Substituted cycloalkene derivatives

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cycloalkene derivatives of formula (I) in which X and Y are a group, in which X and Y together with a carbon atom on ring B to which they are bonded form a ring A, X and Y together represent a ring B substitute, or each of X and Y is a hydrogen atom.

EFFECT: invention relates to a medicinal agent based on the said compounds, which has inhibitory effect on intracellular signal transduction or cell activation induced by an endotoxin.

21 cl, 3 tbl, 191 ex

 

Description

The technical FIELD

The present invention relates to a new compound that has an effect on the inhibition of intracellular signal transduction or cell activation in numerous cells, such as monocytes, macrophages and vascular endothelial cells, and intracellular signal transduction or cell activation induced by endotoxin, and to suppress the generation of inflammatory mediators, such as TNF-α, due to intracellular signal transduction and cell activation, and which is useful as a prophylactic and/or therapeutic agent against various diseases, such as sepsis (septic shock, dissimilatory (widespread or diffuse) intracellular coagulation, multiple organ damage and similar), how to obtain it and use it.

BACKGROUND of INVENTION

Sepsis is the systemic inflammatory response syndrome (SIRS), which occurs due to excessive inflammatory response of a biological object to a bacterial infection, and is a disease that can cause death when it is accompanied by shock or damage to the body. Since to date there are only a few agents that are effective is passed from shock, it is considered a disease that is difficult to prevent and treat. However, because of its high fatality and the number of patients is enormous, the development of therapeutic agents is particularly important (for example, see non-patent document 1).

Endotoxin (lipopolysaccharide, LPS), which is a membrane component of the bacteria active against cells, such as monocytes, macrophages and vascular endothelial cells, induces excessive generation of numerous inflammatory mediators, such as TNF-α, and similarly causes a sudden drop in blood pressure, blood clotting disorders, cardiovascular disorders and similar in addition to the systemic inflammatory response reactions and, thus, exhibits sepsis (see, for example, non-patent document 2). Lipid a, which corresponds to lipopolysaccharide and its partial structure, activates intracellular signal transduction via TLR4 (Toll-like receptor 4), which is the functional receptor cell surface after binding to CD14 (see, for example, non-patent document 3). Accordingly, lipid And initiates numerous responses of cells represented by the generation of inflammatory mediators. Therefore, it is considered that a substance that inhibits intracellular signal transduction is the activation of the cells, caused by endotoxin, and varied responses of cells caused by intracellular signal transduction and cell activation, and different responses of cells represented by excess generation of inflammatory mediators, such as TNF-α, can be an effective prophylactic and therapeutic agent from sepsis (see, for example, non-patent document 3, non-patent document 4, patent document 1 and patent document 2).

Intracellular signal transduction or cell activation induced by endotoxin, and varied responses of cells caused by intracellular signal transduction and cell activation, and various cellular responses submitted by excess generation of inflammatory mediators, such as TNF-α, leading to the development and progression of numerous diseases, such as ischemic brain damage, arteriosclerosis, poor prognosis after coronary angioplasty, heart failure, diabetes, diabetic complications, inflammation of the joints, osteoporosis, osteopenia, autoimmune disease, disorder and tissue rejection after organ transplantation, bacterial infection, viral infection, gastritis, pancreatitis, nephritis, pneumonia, hepatitis and leukemia, in addition to the above-mentioned sepsis (the m, for example, non-patent document 5 and patent document 3).

Therefore, it is considered that a substance that inhibits intracellular signal transduction or cell activation induced by endotoxin, numerous responses of cells induced intracellular signal transduction and cell activation, such as excess generation of inflammatory mediators, such as TNF-α, is effective as a preventive and/or therapeutic agent against various diseases, and, thus, it is desirable to develop an excellent therapeutic agent.

[Non-patent document 1] Iqbal et al., Expert Opin. Emerging Drugs, Vol. 7, 111, 2002.

[Non-patent document 2] Hawkins et el., Current Topics in Medicinal Chemistry, Vol. 4, page 1147, 2004.

[Non-patent document 3] Beutler, Nature, Vol. 430, pages 257-263, 2004.

[Non-patent document 4] Kakutani et al., Inflammation Research, Vol. 48, page 461, 1999.

[Non-patent document 5] Donald N. Cook et al., Nature Immunology. Vol. 5, pages 975-979, 2004.

[Patent document 1] Japanese patent application (Kokai) No. 2000-178246.

[Patent document 2] Japanese patent application (Kokai) No. 2004-2370.

[Patent document 3] international publication WO 00/41698 brochure.

DISCLOSURE of INVENTIONS

The problem addressed by the invention

As the result of conducting extensive studies on pharmacological activity of numerous substituted cyclea Kanovich derivatives with the aim of developing connections, which has an activity of suppressing intracellular signal transduction or cell activation in numerous cells, such as monocytes, macrophages and a variety of endothelial cells, and intracellular signal transduction or cell activation caused by endotoxin, and the suppression of many of the responses of cells induced intracellular signal transduction and cell activation, such as excess generation of inflammatory mediators, such as TNF-α, the inventors of the present invention have found that substituted cycloalkene derivative, having a unique structure, excellent suppressive effect against intracellular signal transduction or cell activation induced by endotoxin, and against the responses of cells induced intracellular signaling transduction and cell activation, such as excess generation of inflammatory mediators, such as TNF-α, and found that it is useful as a prophylactic and/or therapeutic agent against various diseases, such as sepsis, which is associated with intracellular signal transduction or cell activation induced by endotoxin, and responses of cells induced intracellular signal transduction and cell activation is her which led to completion of the present invention.

The present invention provides substituted cycloalkene derivative, which has an activity of suppressing intracellular signal transduction or cell activation induced by endotoxin, and the responses of cells due to signal transduction and cell activation, such as excess generation of inflammatory mediators, such as TNF-α, its pharmacologically acceptable salts, method of its production and medicinal product containing the above-mentioned substituted cycloalkene derivative as an active ingredient, which is excellent for the prevention and/or treatment of numerous diseases caused by intracellular signal transduction or cell activation induced by endotoxin, and called by the responses of cells, including excessive generation inflammatory mediators, such as TNF-α, and the response of cells are called intracellular signal transduction and cell activation.

Resolving problems

Accordingly, the present invention provides

(1) a Compound represented by the General formula (I):

in which X and Y represent a group in which X and Y together with the carbon atom of the ring, which is at they are attached, form a ring And X and Y together represent Deputy ring, or X and Y each represents a hydrogen atom.

1) In the case when X and Y represent a group in which X and Y together with the carbon atom of the ring to which they are attached, form a ring And:

ring a represents

3-7-membered heterocyclyl ring [heterocyclyl ring X and Y independently of one another represent any atom or group selected from a carbon atom, a group NR (R represents a hydrogen atom or a C1-C6alkyl, C2-C6alkenylphenol,2-C6alkylamino or1-C6alkanoyloxy group which may be substituted by a group selected from foster group α), an oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2,

heterocyclyl ring may include unsaturated bond, may form a condensed ring or spirocerca with a 3-7-membered heterocyclyl ring or a 3-7-membered cycloalkyl ring, and ring And including a condensed ring or spirochaete may be substituted by same or different 1 to 4 groups selected from the group consisting of a carbonyl group, tocography, replacement group α, cyclopropyl1-C6alkyl groups,

With1-C6alkyl group which may be sameena-5 groups, selected from foster group α,

With2-C6alkenylphenol group which may be substituted by 1 to 5 groups selected from foster group α, and C2-C6alkylamino group which may be substituted by 1 to 5 groups selected from foster group α],

or

3-7-membered cycloalkyl ring (cycloalkyl ring may include unsaturated bond, may form a condensed ring or spirocerca with a 3-7-membered heterocyclyl ring or a 3-7-membered cycloalkyl ring, and ring And including a condensed ring or spirochaete may be substituted by same or different 1 to 4 groups selected from the group consisting of a substitutional group α, cyclopropyl1-C6alkyl groups,

With1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α,

With2-C6alkenylphenol group which may be substituted by 1 to 5 groups selected from foster group α, and

With2-C6alkylamino group which may be substituted by 1 to 5 groups selected from foster group α).

2) In the case when X and Y together represent Deputy ring:

X and Y represent oxoprop or tocograph,

l and m, independently of one another, represent an integer from 0 to 3, and

l + m is 1 to 3.

R1is

aliphatic hydrocarbon group which may be substituted by a group selected from foster group β and substituting group γ (aliphatic hydrocarbon group is1-C20alkyl group, a C3-C10cycloalkyl group4-C12cycloalkylcarbonyl group3-C6alkenylphenol group or3-C6alkylamino group)

phenyl group which may be substituted by a group selected from foster group δ,

a group having the formula OR4(R4represents a hydrogen atom or an aliphatic hydrocarbon group which may be substituted by a group selected from foster group β and substituting group γ, aliphatic hydrocarbon group has the above-mentioned values) or

halogen atom.

n represents an integer of 0 to 3.

R2represents a hydrogen atom,

With1-C6alkyl group which may be substituted by a group selected from foster group β,

With2-C6alkenylphenol group which may be substituted by a group selected from foster group β, or

With2-C6alkylamino group which may be substituted by a group selected from foster group β.

R3is

phenyl group which may be samewe the and group, selected from foster group ε, or

5 - or 6-membered heteroaryl group which may be substituted by a group selected from foster group ε (heteroaryl group comprises 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom).

R5represents a hydrogen atom,

With1-C6alkyl group which may be substituted by a group selected from foster group β,

With2-C6alkenylphenol group which may be substituted by a group selected from foster group β, or

With2-C6alkylamino group which may be substituted by a group selected from foster group β.

Provided that when R3represents a phenyl group which may be substituted by a group selected from foster group ε, X and Y represent the above-mentioned groups (1) or (2).

Replacement group α represents

the hydroxy-group, halogen atom, With1-C6alkoxygroup, halogeno1-C6alkoxygroup, carboxypropyl,1-C6alkoxycarbonyl group; carbamoyl group which may be substituted by a group selected from C1-C6alkyl group, a C2-C6alkenylphenol group2-C6alkenylphenol group1-C6alkanoyloxy group or2-C6alcanilor onlineu group, and a group having the formula NR6R7.

R6and R7independently from each other, represent a hydrogen atom, a C1-C6alkyl group, a C2-C6alkenylphenol group2-C6alkylamino group1-C6alkanoyloxy group or2-C6alkenylboronic group or together with the nitrogen atom to which they are attached, form heterocyclyl group.

Replacement group β represents

oxoprop, the hydroxy-group, cyclopropyl group1-C6alkoxygroup,1-C6allylthiourea, the nitro-group, halogen atom, cyano, carboxypropyl,1-C10alkoxycarbonyl group1-C6alkanoyloxy group2-C4alkenylboronic group2-C6alkanoyloxy,2-C4alkenylboronic;

carbamoyl group which may be substituted by a group selected from C1-C4alkyl groups, phenyl groups, With1-C7acyl group and1-C4alkoxyphenyl group;

thiocarbamoyl group which may be substituted With1-C4alkyl group or phenyl group;

carbamoyloximes, which may be substituted With1-C4alkyl group or phenyl group;

1-C6alkanolamines,1-C10alkoxycarbonyl group1-C10alkoxycarbonylmethyl and

raidgroup, which may be substituted With1-C4alkyl group or phenyl group.

Replacing the group γ is

heterocyclic group3-C10cycloalkylation,6-C10alloctype,7-C19aralkylated, geterotsiklicheskikh,3-C10cycloalkylation,6-C10killigrew,7-C19arkitip, heterocyclisation, geterotsiklicheskikh group, heterocyclisation group3-C6cycloalkylcarbonyl group6-C10aryloxyalkyl group7-C19aracelikarsaalyna group, heterocalixarenes group6-C10arylcarbamoyl group6-C10arylcarboxamide,6-C10arylcarboxamide,6-C10aryloxypropanolamine group7-C19aracelikarsaalyna group6-C10aryloxypropanolamine,7-C19uralelectropech.ru,3-C10cycloalkylcarbonyl and C6-C10aryl group, which may be for esena group, selected from foster group β.

Replacement group δ is

the hydroxy-group, a nitrogroup, a cyano, a halogen atom, a C1-C6alkyl group, halogeno1-C6alkyl group, a C1-C6alkoxygroup, halogeno1-C6alkoxygroup, carboxypropyl,1-C6alkanoyloxy group1-C6alkoxycarbonyl group1-C6alkanolamines,1-C6allylthiourea, carbamoyl group1-C6alkylcarboxylic group1-C6alkoxycarbonyl1-C6alkylcarboxylic group, 1,3-diarylquinoline1-C6alkyl group, a group having the formula NR6R7(R6and R7have the same meaning as R6and R7replacement group α), C3-C6cycloalkyl group6-C10aryl group and 5-membered heteroaryl group.

Replacement group ε is

the hydroxy-group, a nitrogroup, a cyano, a halogen atom, a C1-C14alkyl group, cyclopropyl1-C14alkyl group, halogeno1-C14alkyl group, a C1-C14alkoxygroup, halogeno1-C14alkoxygroup, carboxypropyl,1-C14alkanoyloxy group1-C14Alcock carbonyloxy group, With1-C14alkanolamines,1-C14allylthiourea, carbamoyl group1-C14alkylcarboxylic group1-C14alkoxycarbonyl1-C14alkylcarboxylic group, 1,3-diarylquinoline1-C14alkyl group, a group having the formula NR6R7(R6and R7have the same meaning as R6and R7replacement group α), C3-C6cycloalkyl group6-C10aryl group and 5-membered heteroaryl group,

or its pharmacologically acceptable salt.

(2) the Compound or its pharmacologically acceptable salt according to the above definition (1)in which l is 0 and m is an integer 1-3,

(3) the Compound or its pharmacologically acceptable salt according to the above definition (1)in which l is 0 and m is equal to 2,

(4) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(3), in which

X and Y together with the carbon atom of the ring To form ring A, and ring a represents

3-7-membered heterocyclyl ring

[heterocyclyl ring X and Y independently of one another represent any atom or group selected from a carbon atom, a group having the formula NR (R represents a hydrogen atom or a C1-the 6alkyl, C2-C6alkenylphenol,2-C6alkylamino or1-C6alkanoyloxy group which may be substituted by a group selected from foster group α), an oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2,

heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring has 1 or 2 oxygen atom and/or nitrogen as heteroatoms), or 5-6-membered cycloalkyl ring, and

ring And including a condensed ring or spirochaete may be substituted by same or different 1 to 4 groups selected from the group consisting of a carbonyl group, tocography, replacement group α, cyclopropyl1-C6alkyl groups and C1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α],

or

3-7-membered saturated cycloalkyl ring

(3-7-membered saturated cycloalkyl ring may be substituted by 1 or 2 groups selected from the group consisting of hydroxy-group, hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group, 1,2,3,4-tetrahydroquinoline group and acetylamino),

(5) the Compound or its pharmacologically ramlau salt according to any one of the above definitions (1)to(3), in which

X and Y represent a group in which X and Y together with the carbon atom of the ring To form ring A, and ring a represents

3-7-membered heterocyclyl ring

[heterocyclyl ring X and Y independently of one another represent any atom or group selected from a carbon atom, oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2,

heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring has 1 or 2 oxygen atom and/or nitrogen as heteroatoms), or

5 - or 6-membered cycloalkyl ring, and

ring And including a condensed ring or spirochaete may be substituted by same or different 1 to 4 groups selected from the group consisting of a carbonyl group, tocography, replacement group α and C1-C6alkyl group which may be substituted by 1-4 groups selected from foster group α],

or

3-5-membered saturated cycloalkyl ring

(3-5-membered saturated cycloalkyl ring may be substituted by 1 or 2 groups selected from the group consisting of hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group, 1,2,3,4-tetrahydroquinoline group and acetylamino gr is PPI),

(6) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(3), in which

X and Y represent a group in which X and Y together with the carbon atom of the ring To form ring A, and ring a represents

3-7-membered heterocyclyl ring

[3-7-membered heterocyclyl ring is oxiran, oxolan, tetrahydrofuran, tetrahydropyran, 1,3-dioxolane, 1,3-dioxane, 1,3-dioxan, 1,3-ditiolan, 1,3-dition, 1,1,3,3-tetraoxo-1,3-ditiolan, 1,3-oxathiolane, 1,3-Ossetian or 1,3-exatape,

data heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (5 - or 6-membered heterocyclyl ring represents tetrahydrofuran, tetrahydropyran, pyrrolidine, piperidine or 1,3-dioxane) or tsiklogeksilnogo ring, and

ring And including a condensed ring or spirochaete may be substituted by 1 or 2 groups selected from the group consisting of a carbonyl group, tocography, replacement group α (replacement group α represents a hydroxy-group and a group having the formula NR6R7and R6and R7independently from each other represent a hydrogen atom or a C1-C6alkanoyloxy group, methyl group, ethyl group and C1-C6alkyl group which is substituted by 1-4 guide what oxypropane],

or

cyclopropyl or cyclopentene ring

(cyclopropyl or cyclopentene ring may be substituted by 1 or 2 groups selected from the group consisting of hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane and 1,2,3,4-tetrahydroquinoline group)

(7) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(3), in which

X and Y represent a group in which X and Y together with the carbon atom of the ring To form ring A, and ring a represents

3-6-membered heterocyclyl ring

{heterocyclyl ring is oxirane, tetrahydrofuran, 1,3-dioxolane, 1,3-dioxane, 1,3-ditiolan, 1,3-dition, 1,3-oxathiolan or 1,3-axation,

data heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (5 - or 6-membered heterocyclyl ring represents tetrahydrofuran, tetrahydropyran or 1,3-dioxane) or tsiklogeksilnogo ring, and

ring And including a condensed ring and spirocerca may be substituted by 1 or 2 groups selected from the group consisting of a substitutional group α [replacement group α represents a hydroxy-group and a group having the formula NR6R7and R6and R7independently from each other presented Aut a hydrogen atom or acetyl group], methyl group, ethyl group, hydroxymethylene group, 1,2-dihydroxyethyl group, 1,2,3-trihydroxypropane group and 1,2,3,4-tetrahydroquinoline group},

(8) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(7), in which

n is 0 or 1, and

R1represents a hydroxy-group, halogen atom, With1-C6alkyl group or a C1-C6alkoxygroup,

(9) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(7), where

n is 0 or 1, and

R1represents a fluorine atom or a methyl group,

(10) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(7), in which

n is 0,

(11) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(10), in which R2is1-C6alkyl group,

(12) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(10), in which R2is1-C4alkyl group,

(13) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(10), in which R2represents ethyl group,

(14) Connect the imposition or its pharmacologically acceptable salt according to any one of the above definitions (1)to(13), in which

R3is

phenyl group which may be substituted by a group selected from foster group ε, or

pyrrolidino group which may be substituted by a group selected from foster group ε, and

replacement group ε represents a halogen atom, a C1-C14alkyl group, halogeno1-C14alkyl group,

(15) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(13), in which

R3is

phenyl group which may be substituted by a group selected from foster group ε, or

pyrrolidino group which may be substituted by a group selected from foster group ε, and

replacement group ε represents a fluorine atom, a chlorine atom, a bromine atom, With3-C8alkyl group, halogeno4-C8alkyl group,

(16) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(13), in which

R3is

phenyl group which may be substituted by a group selected from foster group ε, and

replacement group ε represents a fluorine atom, a chlorine atom and C3-C8alkyl group,

(17) the Compound or its pharmacologically acceptable salt according to any mention of what's above definitions (1)to(16), in which R5represents a hydrogen atom or a C1-C6alkyl group,

(18) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(16), in which R5represents a hydrogen atom or methyl group,

(19) the Compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(16), in which R5represents a hydrogen atom,

(20) Compounds of the following group selected from the above definitions (1) or its pharmacologically acceptable salt:

ethyl 8-[N-(2-chlorophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chlorophenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2-dihydr xitil)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2,3-trihydroxypropane)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2,3,4-tetrahydroquinolin)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(acetamidomethyl-)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3-hydroxy-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,

ethyl 3-acetylamino-9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,

ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-bis(hydroxymethyl)-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,

ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]d is C-6-ene-7-carboxylate,

ethyl 8-[N-(2-heptylphenol)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-bromophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-bromophenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(hydroxymethyl)-8-[N-(2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate and

ethyl 8-[N-(2-chloro-4-forfinal)-N-methylsulfonyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

(21) a Drug containing the compound or its pharmacologically acceptable salt according to any one of the above definitions (1)to(20) as the active ingredient,

(22) the Drug according to the above definition (21) for use in the inhibition of intracellular signal transduction or cell activation induced by endotoxin,

(23) the Drug according to the above definition (21) for use in the suppression of the generation of inflammatory mediators due to intracellular signal transduction or cell activation induced by endotoxin,

(24) the Drug according to the above definition (21) for use as a prophylactic and therapeutic agent from Soboleva is I due to intracellular signal transduction or cell activation, induced by endotoxin,

(25) the Drug according to the above definition (21) for use as a prophylactic and/or therapeutic agent of diseases mediated inflammatory mediator generation which is induced by endotoxin,

(26) the Drug according to the above definition (21) for use as a prophylactic and/or therapeutic agent of diseases mediated inflammatory mediator, which is generated due to intracellular signal transduction or cell activation induced by endotoxin,

(27) the Drug according to the above definition (21) for use as a prophylactic and/or therapeutic agent from sepsis, and

(i) a Method of suppressing intracellular signal transduction induced by endotoxin, and suppress excess generation of inflammatory mediators, such as TNF-α, which is induced by intracellular signal transduction, and (ii) a method of prevention and/or treatment of diseases mediated intracellular signal transduction and inflammatory mediator, which is generated due to intracellular signal transduction, including the introduction of a warm-blooded animal (preferably a human) effetive the amount of the compound according to any of the above definitions (1)to(20) or its pharmacologically acceptable salt.

The EFFECTS of the INVENTION

Substituted cycloalkene derivative according to the present invention, having the General formula (I)has excellent activity suppression of intracellular signal transduction or cell activation induced by endotoxin, and suppress excess generation of inflammatory mediators, such as TNF-α, due to intracellular signal transduction and cell activation, and is useful as a medicine, particularly as a preventive and/or therapeutic agent against ischemic disorders of the brain, hardening of the arteries, poor prognosis after coronary angioplasty, cardiac disorders, diabetes, diabetic complications, inflammation of the joints, osteoporosis, osteopenia, sepsis, autoimmune disease, violations and tissue rejection after organ transplantation, bacterial infections, viral infections, gastritis, pancreatitis, nephritis, pneumonia, hepatitis, leukemia and similar to that induced by the interference of intracellular signal transduction or cell activation and inflammatory mediators due to intracellular signal transduction and cell activation.

The BEST WAY of carrying out the INVENTION

“Halogen atom” in the definition of R1substituting group α, zameshayushei the group β, replacement group δ and substituting group ε includes, for example, fluorine atom, chlorine, bromine or iodine.

As for R1preferably it is fluorine atom or chlorine, more preferably fluorine atom.

As for the replacement group ε, it is preferably fluorine atom, chlorine or bromine, more preferably fluorine atom or chlorine.

“Alkyl group” in the definitions of the group NR, which may be included in ring A, Deputy ring A, R1, R2, R5, R6, R7substituting group β, a proxy group δ and substituting group ε includes linear or branched alkyl group.

“C1-C6alkyl group” definitions “1-C6alkyl group which may be substituted by a group selected from foster group α”in the definition of the group NR, which may be included in ring A; “C1-C6alkyl group” in the definition of “cyclopropyl1-C6alkyl group” in the definition of the substituent of ring A; “C1-C6alkyl group” definitions “1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α”in the definition of the substituent of ring A; “C1-C6alkyl group” definitions “1-C6alkyl group which may be substituted by the group selected from foster group β”in the definition of R2and R5; and “C1-C6alkyl group” in the definitions of the foster group δ, R6and R7imagine, for example, methyl, ethyl, n-sawn, ISO-propyl, n-boutelou, isobutylene, second-boutelou, tert-boutelou, n-pentelow, isopentanol, 2-methylbutanol, neopentyl, 1-ethylpropyl, n-hexoloy, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl or similar.

Among the “C1-C6alkyl groups” group in relation to the NR group, which may be included in ring a, is preferably methyl.

As for the substituent of ring A, they preferably is C1-C4alkyl group.

As for R2they preferably is C1-C4alkyl group, more preferably ethyl.

As for R5they preferably is methyl.

As for R6and R7they preferably is methyl.

As for the replacement of the group of δ, it is preferably1-C4alkyl group.

With1-C14alkyl groups in the definition of the 1-C14alkyl group” and “cyclopropyl1-C14alkyl group” in the definitions of the foster group ε represent, for example, the above-mentioned “C1-C6alkyl group, octyl, nonyl, decyl, dodecyl, tetradecyl or similar.

As for the “With1-C14alkyl group” in the definition of a replacement group ε, it is preferably3-C8alkyl group.

“C1-C20alkyl group” in the definition of R1is, for example, the above-mentioned “C1-C14alkyl group, pentadecyl, hexadecyl, heptadecyl, octadecyl, Needell, eicosyl or similar. Preferably it is C1-C6alkyl group and more preferably a methyl group.

“Alchemilla group” in the definitions of the group NR, which may be included in ring A, Deputy ring A, R1, R2, R5, R6, R7and substituting group α represents a linear or branched alkenylphenol group.

“C3-C6Alchemilla group” in the definition of R1is, for example, 2-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 2-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-ethyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl or 5-hexenyl, preferably3-C4alkenylphenol group.

“C2-C6Alchemilla group” definitions “2-C6Alchemilla group which may be substituted by a group selected from foster group α”in the definition of the group NR, which may be included in ring A, “C2-C6Alchemilla group” definitions “2-C6Alchemilla group which may be substituted by 1 to 5 groups selected from foster group α”in the definition of the substituent of ring A; “C2-C6Alchemilla group” definitions “2-C6Alchemilla group which may be substituted by a group selected from foster group β”in the definition of R2and R5;

and “C2-C6Alchemilla group” in the definitions of R6and R7imagine, for example, vinyl or above “C3-C6alkenylphenol group”, preferably3-C4alkenylphenol group.

“Alchemilla group” in the definitions of the group NR, which may be included in ring A, Deputy ring A, R1, R2, R5, R6, R7and substituting group α represents a linear or branched alkylamino g is the SCP.

“C3-C6Alchemilla group” in the definition of R1is, for example, 2-PROPYNYL, 1-methyl-2-PROPYNYL, 2-butynyl, 1-methyl-2-butenyl, 1-ethyl-2-butinyl, 3-butinyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butinyl, 2-pentenyl, 1-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl or 5-hexenyl, preferably3-C4alkyl group.

“C2-C6Alchemilla group” definitions “2-C6Alchemilla group which may be substituted by a group selected from foster group α”in the definition of the group NR, which may be included in ring A, “C2-C6Alchemilla group” definitions “2-C6Alchemilla group which may be substituted by 1 to 5 groups selected from foster group α”in the definition of the substituent of ring A; “C2-C6Alchemilla group” definitions “2-C6Alchemilla group which may be substituted by a group selected from foster group β”in the definition of R2and R5;

and “C2-C6Alchemilla group” in the definitions of R6and R7imagine, for example, etinilnoy or above “C3-C6alkylamino group”, preferably3-C4alkyne is the function group.

“C3-C6cycloalkyl group” in the definitions of surrogate groups δ and substituting group ε represent, for example, cyclopropyl, cyclopentyl or cyclohexyl.

“3-7-membered cycloalkyl ring” in the definition of a ring And may include unsaturated bond, and such a ring is, for example, cyclopropane, CYCLOBUTANE, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene, Cycloheptane or cycloheptadiene.

The above-mentioned “3-7-membered cycloalkyl ring may form a condensed ring or spirocerca with a 3-7-membered heterocyclyl ring or a 3-7-membered cycloalkyl ring, and so cycloalkenyl ring is, for example, 2-oxa-bicyclo[4.3.0]nonan-8-ilidene, 3-oxa-bicyclo[3.3.0]heptane-7-ilidene, 2,4-dioxaspiro[6.6]undecane-8-ilidene, bicyclo[4.3.0]nonan-7-ilidene, Spiro[6.6]undecane-8-ilidene or similar.

In addition to the described above “3-7-membered cycloalkyl ring cannot form a condensed ring or spirocerca and can be replaced by oxopropoxy or tocography.

As for the aforementioned “cycloalkyl rings”, cycloalkene ring, condensed ring which may be condensed with cycloalkenyl ring, or spirochaete, which is a Spiro associated with cycloalkenyl ring m which may be substituted by same or different 1 to 4 (preferably 1 or 2) groups, selected from the group consisting of a substitutional group α, cyclopropyl1-C6alkyl group, a C1-C6alkyl group which may be substituted by 1-5 groups selected from the group consisting of a substitutional group α, C2-C6alkenylphenol group which may be substituted by 1-5 groups selected from the group consisting of the replacement of the group α, and C2-C6alkenylphenol group which may be substituted by 1-5 groups selected from the group consisting of the replacement of the group α.

Preferred examples of the ring is a 3-hydroxycyclopent, 4-hydroxycyclohexane, 3-hydroxymethylcytosine, 3,4-dihydroxybenzylamine, 4-hydroxymethylcellulose, 4,4-dihydroxyphenylglycol, 3-(1,2-dihydroxyethyl)cyclopentane, 4-(1,2-dihydroxyethyl)cyclohexane, 3,4-bis(1,2-dihydroxyethyl)cyclopentane, 4,4-bis(1,2-dihydroxyethyl)cyclohexane, 3-(1,2,3-trihydroxypropane)cyclopentane, 4-(1,2,3-trihydroxypropane)cyclohexane, 3-(1,2,3,4-tetrahydroquinolin)cyclopentane, 4-(1,2,3,4-tetrahydroquinolin)cyclohexane, 3-ethoxycarbonylphenyl, 4-ethoxycarbonylmethoxy, 4,4-diethoxycarbonyl, 3-carbamoylation, 4-carbamoylphenoxy, 3-acetylaminofluorene, 4-acetylaminofluorene, 3,4-dietilaminometiltselljuloza, 2,3,4,5-tetrahydrooxazolo[4.3.0]nonan (the position of the binding Kohl is ω is an 8-position), 3-oxa-bicyclo[3.3.0]octane (the position of the binding ring b is a 7-position), 2,4-dihydroxymethyl-3-oxa-bicyclo[3.3.0]octane (the position of the binding ring b is a 7-position) and 2,4-dioxaspiro[5.5]undecane (the position of the binding ring b is a 9-position).

“Cycloalkyl ring” in the definition of ring And among the above-mentioned ring is preferably a 3-7-membered cycloalkyl ring which may be substituted by 1 or 2 groups selected from the group consisting of hydroxy-group, hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group, 1,2,3,4-tetrahydroquinoline group and acetylamino, more preferably 3-5-membered saturated cycloalkyl ring which may be substituted by 1 or 2 groups selected from the group consisting of hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane, 1,2,3,4-tetrahydroquinoline and acetylamino and especially preferably cyclopropyl or cyclopentene ring which may be substituted by 1 or 2 groups selected from the group consisting of hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group and 1,2,3,4-tetrahydroquinoline group.

“C3-C10cycloalkyl group” in the definition of R1is, for example, the cycle is propyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

“C4-C12cycloalkylation group” in the definition of R1is, for example, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl or cycloheptylmethyl, preferably4-C8cycloalkylation group, more preferably4-C7cycloalkylation group.

As for the “3-7-membered heterocyclyl rings” in the definition of ring A, X and Y are included in the ring, independently of one another represent any atom or group selected from a carbon atom, a group having the formula NR (R represents a hydrogen atom or a C1-C6alkyl, C2-C6alkenylphenol,2-C6alkylamino or1-C6alkylcarboxylic group which may be substituted by a group selected from foster group α), an oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2preferably any atom or group selected from a carbon atom, oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2. 3-7-membered heterocyclyl ring may include an unsaturated bond.

Examples of such rings are heterocyclyl ring including the nitrogen atom, such as aziridine, azetidine, pyrrolidine, pyrrolin, hypericin and imidazolidin; heterocyclyl ring including an oxygen atom, such as oxirane, oxetane, tetrahydrofuran, oxolan, tetrahydropyran, dihydropyran, oxepin, 1,3-dioxolane, 1,3-dioxane and 1,3-dioxan; heterocyclyl ring including the sulfur atom, a group having the formula SO or a group having the formula SO2such as tieran, tieton, tolan, thiolen, Tian, Tapan, 1,3-ditiolan, 1,3-dition, 1,3-dileepan, 1,3-dioxo-1,3-ditiolan, 1,3-dioxo-1,3-dition, 1,1,3,3-tetraoxo-1,3-ditiolan and 1,1,3,3-tetraoxo-1,3-dition, heterocyclyl ring including an oxygen atom and a sulfur atom such as 1,3-oxathiolane, 1,3-Ossetian and 1,3-exatape; heterocyclyl ring including the nitrogen atom and oxygen atom such as 1,3-oxopyrrolidin and 1.3-oxopyrrolidin, and heterocyclyl ring including the nitrogen atom and sulfur atom, such as 1,3-diaperriding and 1,3-diaperresin.

Preferably it is oxirane, tetrahydrofuran, tetrahydropyran, 1,3-dioxolane, 1,3-dioxane, 1,3-dioxan, 1,3-ditiolan, 1,3-dition, 1,1,3,3-tetraoxo-1,3-ditiolan, 1,3-oxathiolane, 1,3-Ossetian or 1,3-exatape.

More preferably, it is oxirane, tetrahydrofuran, 1,3-dioxolane, 1,3-dioxane, 1,3-ditiolan, 1,3-dition, 1,3-oxathiolan or 1,3-Ossetian.

Even more preferably it is oxirane, 1,3-dioxolane, 1,3-dioxane or 1,3-oxathiolan.

The above-mentioned “3-7-membered, heterocycle is inoe ring may form a condensed ring or spirocerca with a 3-7-membered heterocyclyl ring or a 3-7-membered cycloalkyl ring, preferably may form a condensed or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring has 1 or 2 oxygen atom and/or nitrogen as a heteroatom), or 5 - or 6-membered cycloalkenyl ring and more preferably may form a condensed or spirocerca with tetrahydrofuran, tetrahydropyrane, pyrrolidine, piperidine, 1,3-dioxane or tsiklogeksilnogo ring.

Examples of such heterocyclyl rings are 2,4-dioxa-bicyclo[3.3.0]octane (the position of the binding ring b is a 3-position), 2,4,7-trioxa-bicyclo[3.3.0]octane (the position of the binding ring b is a 3-position), 7,9-dioxa-bicyclo[4.3.0]nonan (the position of the binding ring b is a 8-position), 7-Aza-2,4-dioxa-bicyclo[3.3.0]octane (the position of the binding ring b is a 3-position), 2,4,8,10-tetraoxaspiro[5.5]undecane (the position of the binding ring b is a 3-position) and similar. The position of the binding data of the rings the ring is the same as described above.

In addition to the described above “3-7-membered heterocyclyl ring cannot form a condensed ring or spirochaeta, and can be replaced by oxopropoxy or tocography.

As for the aforementioned “heterocyclyl rings”, heterocyclyl ring is, condensed ring, which is condensed with heterocyclyl ring, or spirochaete, which is a Spiro associated with heterocyclyl ring may be substituted by same or different 1 to 4 (preferably 1 or 2) substituents.

Deputy is a group selected from the group consisting of a carbonyl group, tocography, replacement group α, cyclopropyl1-C6alkyl group, a C1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α, C2-C6alkenylphenol group which may be substituted by 1 to 5 groups selected from foster group α, and C2-C6alkenylphenol group which may be substituted by 1 to 5 groups selected from foster group α.

Deputy preferably is a group selected from the group consisting of a carbonyl group, tocography, replacement group α, cyclopropyl1-C6alkyl groups and C1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α.

More preferably it is a group selected from the group consisting of a carbonyl group, tocography, replacement group α and C1-C6alkyl group which may be substituted by 1-4 groups selected from foster group α.

Even Bo which it is preferably 1 or 2 groups, selected from the group consisting of a carbonyl group, tocography, replacement group α (replacement group α is a hydroxy-group and a group having the formula NR6R7and R6and R7independently from each other, represent a hydrogen atom or a C1-C6alkylcarboxylic group, methyl group, ethyl group and C1-C6alkyl group, substituted by 1-4 hydroxy groups.

Further, preferably is 1 or 2 groups selected from the group consisting of a substitutional group α [replacement group α represents a hydroxy-group and a group having the formula NR6R7(R6and R7independently from each other, represent a hydrogen atom or methylcarbamyl group)], a methyl group, ethyl group, hydroxymethylene group, 1,2-dihydroxyethyl group, 1,2,3-trihydroxypropane group and 1,2,3,4-tetrahydroquinoline group.

As examples can be mentioned

oxiran, oxolan, tetrahydrofuran (traditional name oxolan, according to the IUPAC nomenclature), tetrahydropyran (the traditional name of oxen, according to the IUPAC nomenclature), 1,3-dioxolane, 1,3-dioxane, 1,3-dioxan, 1,3-ditiolan, 1,3-dition, 1,3-oxathiolane, 1,3-axation, 1,3-exatape, tetrahydrooxazolo, tetrahydro-1,3-oxazin, tetrahydrothieno, tetrahydro-1,3-thiazin, 1,1,3,3-tetraoxo-1,3-dition, 2,4,trioxa-bicyclo[3.3.0]octane, 2,4-dithia-7-oxa-bicyclo[3.3.0]octane, 2-thia-4,7-dioxa-bicyclo[3.3.0]octane, 2,4,8,10-tetraoxaspiro[5.5]undecane, 2,4-dithia-8,10-dioxaspiro[5.5]undecane, 2-thia-4,8,10-dioxaspiro[5.5]undecane, 2-hydroxymitragynine, 4-hydroxy-1,3-dioxolane, 4,5-dihydroxy-1,3-dioxolane, 5-hydroxy-1,3-dioxane, 5,5-dihydroxy-1,3-dioxane, 4-hydroxy-1,3-ditiolan, 4,5-dihydroxy-1,3-ditiolan, 5-hydroxy-1,3-dition, 5,5-dihydroxy-1,3-dition, 4-hydroxy-1,1,3,3-tetraoxo-1,3-ditiolan, 4,5-dihydroxy-1,1,3,3-tetraoxo-1,3-ditiolan, 4-hydroxy-1,3-oxathiolan, 5-hydroxy-1,3-axation, 5,5-dihydroxy-1,3-axation, 6,8-dihydroxy-2,4-dioxa-bicyclo[3.3.0]octane, 6,8-dihydroxy-2,4,7-trioxa-bicyclo[3.3.0]octane, 2,3,4,5-tetrahydroxy-7,9-dioxa-bicyclo[4.3.0]nonan, 6,8-dihydroxy-7-Aza-2,4-dioxa-bicyclo[3.3.0]octane, 9-hydroxy-2,4,8,10-tetraoxaspiro[5.5]undecane, 2,3,4,5-tetrahydro-7,9-dithia-bicyclo[4.3.0]nonan, 2,3,4,5-tetrahydro-7-thia-9-oxa-bicyclo[4.3.0]nonan, 2-carboxytetramethyl, 4-carboxy-1,3-dioxolane, 5-carboxy-1,3-dioxane, 4-carboxy-1,3-ditiolan, 5-carboxy-1,3-dition, 4-carboxy-1,1,3,3-tetraoxo-1,3-ditiolan, 4-carboxy-1,3-oxathiolan, 5-carboxy-1,3-axation, 2-methoxycarbonylaminophenyl, 4-methoxycarbonyl-1,3-dioxolane, 5-methoxycarbonyl-1,3-dioxane, 5,5-diethoxycarbonyl-1,3-dioxane, 4-methoxycarbonyl-1,3-ditiolan, 5-methoxycarbonyl-1,3-dition, 5,5-diethoxycarbonyl-1,3-dition, 4-methoxycarbonyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-methoxycarbonyl who -1,3-oxathiolan, 5-methoxycarbonyl-1,3-axation, 5,5-diethoxycarbonyl-1,3-axation, 6,8-diethoxycarbonyl-2,4-dioxa-bicyclo[3.3.0]octane, 6,8-diethoxycarbonyl-2,4,7-trioxa-bicyclo[3.3.0]octane, 6,8-diethoxycarbonyl-7-Aza-2,4-dioxa-bicyclo[3.3.0]octane, 8-methoxycarbonyl-2,4,7,9-tetraoxaspiro[5.5]undecane, 2-ethoxycarbonylmethylene, 4-etoxycarbonyl-1,3-dioxolane, 5-etoxycarbonyl-1,3-dioxane, 5,5-dietoksikarbonil-1,3-dioxane, 4-etoxycarbonyl-1,3-ditiolan, 5-etoxycarbonyl-1,3-dition, 5,5-dietoksikarbonil-1,3-dition, 4-etoxycarbonyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-etoxycarbonyl-1,3-oxathiolan, 5-etoxycarbonyl-1,3-axation, 5,5-dietoksikarbonil-1,3-axation, 6,8-dietoksikarbonil-2,4-dioxa-bicyclo[3.3.0]octane, 6,8-dietoksikarbonil-2,4,7-trioxa-bicyclo[3.3.0]octane, 6,8-dietoksikarbonil-7-Aza-2,4-dioxa-bicyclo[3.3.0]octane, 8-etoxycarbonyl-2,4,7,9-tetraoxaspiro[5.5]undecane, 2-aminotetrahydrofuran, 4-amino-1,3-dioxolane, 4,5-diamino-1,3-dioxolane, 5-amino-1,3-dioxane, 4-amino-1,3-ditiolan, 4,5-diamino-1,3-ditiolan, 5-amino-1,3-dition, 4-amino-1,1,3,3-tetraoxo-1,3-ditiolan, 4-amino-1,3-oxathiolan, 5-amino-1,3-axation,

2-acetylaminofluorene, 4-acetylamino-1,3-dioxolane, 4,5-bis(acetylamino)-1,3-dioxolane, 5-acetylamino-1,3-dioxane, 4-acetylamino-1,3-ditiolan, 4,5-bis(acetylamino)-1,3-ditiolan, 5-acetylamino-1,3-dition, 4-acetylamino-1,1,3,3-tetraoxo-1,3-ditiolan, 4-acetylamino-1,3-oxathiolan, 5-acetylamino-1,3-about satian, 6,8-diatsetilamino-2,4-dioxa-bicyclo[3.3.0]octane, 6,8-diatsetilamino-2,4,7-trioxa-bicyclo[3.3.0]octane, 6,8-diatsetilamino-7-Aza-2,4-dioxa-bicyclo[3.3.0]octane, 8-acetylamino-2,4,7,9-tetraoxaspiro[5.5]undecane,

2-methyltetrahydrofuran, 4-methyl-1,3-dioxolane, 4,5-dimethyl-1,3-dioxolane, 5-methyl-1,3-dioxane, 4-methyl-1,3-ditiolan, 4,5-dimethyl-1,3-ditiolan, 5-methyl-1,3-dition, 4-methyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-methyl-1,3-oxathiolan, 5-methyl-1,3-axation,

5,5-dimethyl-1,3-dioxane, 5,5-dimethyl-1,3-dition, 5,5-dimethyl-1,3-axation,

2-utilityserver, 4-ethyl-1,3-dioxolane, 4,5-diethyl-1,3-dioxolane, 5-ethyl-1,3-dioxane, 4-ethyl-1,3-ditiolan, 4,5-diethyl-1,3-ditiolan, 5-ethyl-1,3-dition, 4-ethyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-ethyl-1,3-oxathiolan, 5-ethyl-1,3-axation,

2-hydroxyethylacrylate, 4-hydroxymethyl-1,3-dioxolane, 5-hydroxymethyl-1,3-dioxane, 5,5-dihydroxymethyl-1,3-dioxane, 4-hydroxymethyl-1,3-ditiolan, 5-hydroxymethyl-1,3-dition, 5,5-dihydroxymethyl-1,3-dition, 4-hydroxymethyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-hydroxymethyl-1,3-oxathiolan, 5-hydroxymethyl-1,3-axation, 5,5-dihydroxymethyl-1,3-axation, 4,5-dihydroxymethyl-1,3-dioxolane, 4,5-dihydroxymethyl-1,3-ditiolan, 4,5-dihydroxymethyl-1,3-oxathiolan, 5,5-dihydroxymethyl-1,3-dioxane, 5,5-dihydroxymethyl-1,3-dition, 5,5-dihydroxymethyl-1,3-axation, 6,8-dihydroxymethyl-2,4,7-trioxa-bicyclo[3.3.0]octane, 6,8-dihydroxymethyl-2,4-dithia-7-oxa-bicyclo[3.3.0]octane,6,8-dihydroxymethyl-2-thia-4,7-dioxa-bicyclo[3.3.0]octane, 6-oxo-8-hydroxymethyl-2,4,7-trioxa-bicyclo[3.3.0]octane,

2-(1,2-dihydroxyethyl)tetrahydrofuran, 4-(1,2-dihydroxyethyl)-1,3-dioxolane, 5-(1,2-dihydroxyethyl)-1,3-dioxane, 5,5-bis(1,2-dihydroxyethyl)-1,3-dioxane, 4-(1,2-dihydroxyethyl)-1,3-ditiolan, 5-(1,2-dihydroxyethyl)-1,3-dition, 5,5-bis(1,2-dihydroxyethyl)-1,3-dition, 4-(1,2-dihydroxyethyl)-1,1,3,3-tetraoxo-1,3-ditiolan, 4-(1,2-dihydroxyethyl)-1,3-oxathiolan, 5-(1,2-dihydroxyethyl)-1,3-axation, 5,5-bis(1,2-dihydroxyethyl)-1,3-axation,

4,5-bis(1,2-dihydroxyethyl)-1,3-dioxolane, 4,5-bis(1,2-dihydroxyethyl)-1,3-ditiolan, 4,5-bis(1,2-dihydroxyethyl)-1,3-oxathiolan,

4,5-bis(1-hydroxyethyl)-1,3-dioxolane, 4,5-bis(1-hydroxypropyl)-1,3-dioxolane,

2-(1,2,3-trihydroxypropane)tetrahydrofuran, 4-(1,2,3-trihydroxypropane)-1,3-dioxolane, 5-(1,2,3-trihydroxypropane)-1,3-dioxane, 5,5-bis(1,2,3-trihydroxypropane)-1,3-dioxane, 4-(1,2,3-trihydroxypropane)-1,3-ditiolan, 5-(1,2,3-trihydroxypropane)-1,3-dition, 5,5-bis(1,2,3-trihydroxypropane)-1,3-dition, 4-(1,2,3-trihydroxypropane)-1,1,3,3-tetraoxo-1,3-ditiolan, 4-(1,2,3-trihydroxypropane)-1,3-oxathiolan, 5-(1,2,3-trihydroxypropane)-1,3-axation, 5,5-bis(1,2,3-trihydroxypropane)-1,3-axation,

2-(1,2,3,4-tetrahydroquinolin)tetrahydrofuran, 4-(1,2,3,4-tetrahydroquinolin)-1,3-dioxolane, 5-(1,2,3,4-tetrahydroquinolin)-1,3-dioxane, 5,5-bis(1,2,3,4-tetrahydroquinolin)-1,3-dioxane, 4-(1,2,3,4-tetrahydroquinolin)-1,3-ditiolan, 5-(1,2,3,4-tetrahydroquinolin)-1,3-dition 5,5-bis(1,2,3,4-tetrahydroquinolin)-1,3-dition, 4-(1,2,3,4-tetrahydroquinolin)-1,1,3,3-tetraoxo-1,3-ditiolan, 4-(1,2,3,4-tetrahydroquinolin)-1,3-oxathiolan, 5-(1,2,3,4-tetrahydroquinolin)-1,3-axation, 5,5-bis(1,2,3,4-tetrahydroquinolin)-1,3-axation,

2-acetilaminostirenului, 4-acetamidomethyl-1,3-dioxolane, 4,5-diacetylene-1,3-dioxolane, 5-acetamidomethyl-1,3-dioxane, 4-acetamidomethyl-1,3-ditiolan, 4,5-diacetylene-1,3-ditiolan, 5-acetamidomethyl-1,3-dition, 4-acetamidomethyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-acetamidomethyl-1,3-oxathiolan, 5-acetamidomethyl-1,3-axation,

4,5-diacetylene-1,3-dioxolane, 4,5-diacetylene-1,3-ditiolan, 4,5-diacetylene-1,3-oxathiolan,

2-vinyltetrahydrofuran, 4-vinyl-1,3-dioxolane, 4,5-divinyl-1,3-dioxolane, 5-vinyl-1,3-dioxane, 4-vinyl-1,3-ditiolan, 4,5-divinyl-1,3-ditiolan, 5-vinyl-1,3-dition, 4-vinyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-vinyl-1,3-oxathiolan, 5-vinyl-1,3-axation,

2-proprietarian, 4-propenyl-1,3-dioxolane, 4,5-dipropyl-1,3-dioxolane, 5-propenyl-1,3-dioxane, 4-propenyl-1,3-ditiolan, 4,5-dipropyl-1,3-ditiolan, 5-propenyl-1,3-dition, 4-propenyl-1,1,3,3-tetraoxo-1,3-ditiolan, 4-propenyl-1,3-oxathiolan, 5-propenyl-1,3-axation,

2-propionylcarnitine, 4-PROPYNYL-1,3-dioxolane, 4,5-dipropyl-1,3-dioxolane, 5-PROPYNYL-1,3-dioxane, 4-PROPYNYL-1,3-ditiolan, 4,5-dipropyl-1,3-ditiolan, 5-PROPYNYL-1,3-dition, 4-PROPYNYL-1,1,3,3-tetraoxo-1,3-CIO is olan, 4-PROPYNYL-1,3-oxathiolan and 5-PROPYNYL-1,3-axation.

“C6-C10aryl group” definitions “6-C10aryl group which may be substituted by a group selected from foster group β” in the definition of a replacement group γ and C6-C10aryl group” in the definitions of surrogate groups δ and substituting group ε are, for example, phenyl or naphthyl.

As for the “With6-C10aryl group which may be substituted by a group selected from foster group β”, “C6-C10aryl group substituted by a Deputy selected from foster group β in able to the replacement position, the Deputy is not limited to one, and they can be many (2-4) are the same or different substituents.

“5 - or 6-membered heteroaryl group” in the definition of R3includes 1-3 heteroatoms selected from nitrogen atom, oxygen and sulfur. As such heteroaryl can be mentioned, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl, and preferably such a group is a furyl, thienyl, pyrrolyl, pyridyl or pyrimidinyl, more preferably pyrrolyl.

“5-membered heteroaryl group” in the definitions of surrogate groups δ and substituting group ε t is aetsa, for example, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, thiazolyl, isothiazolin, oxazolyl, isoxazolyl, thiadiazolyl, thienyl or furyl.

“Halogeno1-C6alkyl group” in the definition of a replacement group δ is, for example, trifluoromethyl or triptorelin.

“Halogeno1-C14alkyl group” in the definition of a replacement group ε is, for example, the above-mentioned “halogen1-C6alkyl group, 4,4,4-tripcomputer, 5,5,5-tryptophanyl, 6,6,6-triptorelin, a 7,7,7-triptorelin or 8,8,8-trifloromethyl, preferably halogeno4-C8alkyl group.

“C1-C6alkoxygroup” in the definition of a replacement group α, a replacement group β and substituting group δ represents a group in which an oxygen atom is linked to the above-mentioned “C1-C6alkyl group, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentox, isopentane, 2-methylbutoxy, 1 ethylpropoxy, 2-ethylpropoxy, neopentane, hexyloxy, 4-methylphenoxy, 3 methylpentane, 2-methylpentane, 3,3-Dimethylbutane, 2,2-Dimethylbutane, 1,1-Dimethylbutane, 1,2-Dimethylbutane, 1,3-Dimethylbutane or 2,3-Dimethylbutane, preferably1-C4alkoxygroup and more preferably1-C2alkoxygroup.

“C1-C4 alkoxygroup” in the definition of a replacement group ε represents a group in which an oxygen atom is linked to the above-mentioned “C1-C14alkyl group”, for example the aforementioned “1-C6alkoxygroup”, octyloxy, nonyloxy, decyloxy, dodecyloxy, tetradecane or similar, preferably With1-C10alkoxygroup and more preferably4-C8alkoxygroup.

“Halogeno1-C6alkoxygroup” in the definitions of the foster group α and substituting group δ represents a group in which one or two or more hydrogen atoms of the aforementioned “C1-C6alkyl group” substituted by the above-mentioned “halogen atom”. Preferably it is halogeno1-C4alkoxygroup, more preferably, deformedarse, triptoreline or 2,2,2-triptoreline and even more preferably triptoreline.

“Halogeno1-C14alkoxygroup” in the definition of a replacement group ε represents a group in which one or two or more hydrogen atoms of the aforementioned “C1-C14alkyl group” substituted by the above-mentioned “halogen atom”. Preferably it is halogeno1-C10alkoxygroup, more preferably, halogeno4-C8alkoxygroup and even more pre is respectfully 4,4,4-triptoreline, 5,5,5-cryptocentrus, 6,6,6-triptoreline, a 7,7,7-cryptolepine or 8,8,8-tripterocalyx.

“C3-C10cycloalkylation” in the definition of a replacement group γ is, for example, cyclopropane, cyclohexyloxy or similar.

“C6-C10arroceros” in the definition of a replacement group γ is, for example, phenoxy or naphthyloxy.

“C7-C19aralkylamines” in the definition of a replacement group γ is, for example, benzyloxy, 1-phenylethylene, 2-phenylethylene, benzhydrylamine or 1 naphthalenyloxy.

“C1-C6allylthiourea” in the definition of a replacement group β and substituting group δ represents a group in which the sulfur atom is linked to the above-mentioned “C1-C6alkyl group and the sulfur atom may be oxidized. Preferably it is C1-C4allylthiourea, for example methylthio, ethylthio, n-propylthio, n-butylthio, methylsulfinyl or methylsulphonyl.

As for the “With1-C14ancilliary” in the definition of a replacement group ε, the sulfur atom is attached to an alkyl group may be oxidized, and it is, for example, the above-mentioned “C1-C6allylthiourea”, n ' Reptilia, 3 methylhexane, n-octylthio, 2,4-dimethylhexane, n-octylthio or 2,3,6-trimethylgallium, preferably the C 1-C10allylthiourea and more preferably4-C8allylthiourea.

As for the “With3-C10cycloalkylation” in the definition of a replacement group γ, the sulfur atom may be oxidized, and it is, for example, cyclopropyl, cyclohexylthio, cyclopentylmethyl or cyclohexylmethyl.

As for the “With6-C10aristocraty” in the definition of a replacement group γ, the sulfur atom may be oxidized, and it is, for example, phenylthio, naphthylthio, phenylsulfinyl or phenylsulfonyl.

As for the “With7-C19arkitip” in the definition of a replacement group γ, the sulfur atom may be oxidized, and it is, for example, benzylthio, feniletilic, benzhydryl, benzylmorphine or benzylmethyl.

“C1-C6alcoolica group” in the definitions of R6, R7substituting group β and substituting group δ represents a group in which a hydrogen atom or a C1-C5an alkyl group linked to a carbonyl group, and it is, for example, formyl, acetyl, propionyl, butyryl, valeryl or pivaloyl.

“C1-C14alcoolica group” in the definition of a replacement group ε is, for example, the above-mentioned “C1-C6alkanoyloxy group”, octanoyl, decanoyl, dodecanoyl or deletion.

“C2-C 4alkenylamine group” in the definition of a replacement group β represents, for example, acryloyl or crotonoyl.

“C2-C6alkenylamine group” in the definitions of R6and R7is, for example, the above-mentioned “C2-C4alkenylboronic group, 1,3-butadienerubber or 3-methyl-2-butylcarbamoyl.

“C6-C10arylcarbamoyl group” in the definition of a replacement group γ is, for example, benzoyl, naphtol or phenylacetyl.

“C1-C6alkoxycarbonyl group” in the definitions of the foster group α and substituting group δ represents a group in which the above-mentioned “C1-C6alkoxygroup” is linked to the carbonyl group, and it is, for example, methoxycarbonyl, etoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxide, tert-butoxycarbonyl or similar.

“C1-C10alkoxycarbonyl group” in the definition of a replacement group β is, for example, the above-mentioned “C1-C6alkoxycarbonyl group”, heptyloxybiphenyl, octyloxybiphenyl, nonintoxicating or decyloxybenzoic.

“C1-C14alkoxycarbonyl group” in the definition of a replacement group ε is, for example, the above-mentioned “C1-C10al is oxycarbonyl group”, dodecyloxybenzoyl or tetradecyltrimethyl, preferably “C1-C10alkoxycarbonyl group, and more preferably4-C8alkoxycarbonyl group.

“C3-C6cycloalkylcarbonyl group” in the definition of a replacement group γ is, for example, cyclopropanecarbonyl, cyclopentanecarbonyl, cyclohexyloxycarbonyl or norbornenedicarboxylic.

“C6-C10aryloxyalkyl group” in the definition of a replacement group γ is, for example, phenoxycarbonyl or naphthalocyanines.

“C7-C19aracelikarsaalyna group” in the definition of a replacement group γ is, for example, benzyloxycarbonyl, benzylaminocarbonyl or 2-ventilatsioonil.

“C2-C6alkanoyloxy” in the definition of a replacement group β represents a group in which2-C6alcoolica group linked to the oxygen atom, and is, for example, acetoxy, propionyloxy, butyryloxy, valeriansee or pivaloyloxy.

“C1-C10alkoxycarbonylmethyl” in the definition of a replacement group β is, for example, methoxycarbonylamino, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, tert-butoxycarbonylamino, n-ventilatsioonile or what-hexyloxyethoxy.

“C6-C10arylcarboxylic” in the definition of a replacement group γ is, for example, benzoyloxy, naphthyloxy or phenylacetate.

“Carbamoyl group which may be substituted by a group selected from C1-C6alkyl group, a C2-C6alkenylphenol group2-C6alkenylphenol group1-C6alkanoyloxy group or2-C6alkenylamine group”in the definition of a replacement group α is carnemolla group or cyclic aminocarbonyl group which may be substituted by 1 or 2 substituents selected from C1-C6alkyl groups such as methyl, ethyl, propyl and similar, With2-C6alkenyl groups such as vinyl, allyl, Isopropenyl and similar, With2-C6etkinlik groups, such as ethinyl and similar, With1-C6alkanoyl groups such as acetyl and similar, and With2-C6alkenylboronic groups, such as acryloyl and similar, preferably, in particular, for example, carnemolla group or cyclic aminocarbonyl group which may be substituted by 1 or 2 substituents selected from C1-C6alkyl groups and C1-C6alkanoyloxy group, more preferably carnemolla group or cyclic amino is arborina group, which is substituted by 1 or 2 C1-C2alkanolamine groups. In particular, it is carbarnoyl, N-methylcarbamoyl, N-ethylcarbazole, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl or N-acetylmuramyl, preferably N-acetylmuramyl.

“Carbamoyl group which may be substituted by a group selected from C1-C4alkyl groups, phenyl groups, With1-C7acyl group and1-C4alkoxyphenyl group”in the definition of a replacement group β is carnemolla group or cyclic aminocarbonyl group which may be substituted by 1 or 2 substituents selected from C1-C4alkyl groups such as methyl, ethyl and similar, phenyl groups, With1-C7acyl groups such as acetyl, propionyl, benzoyl and similar, and With1-C4alkoxyphenyl groups such as methoxyphenyl and similar, in particular, for example, carbarnoyl, N-methylcarbamoyl, N-ethylcarbazole, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl N-phenylcarbamoyl, N-acetylmuramyl, N-benzylcarbamoyl, N-(p-methoxyphenyl)carbarnoyl, 1-pyrrolidinylcarbonyl, piperidinylcarbonyl, 1-piperazinylcarbonyl or morpholinoethyl.

“Thiocarbamoyl group which may be substituted With1-C4alkyl group or phenyl group”in the definition zameshayushei the group β is thiocarbamoyl group, which may be substituted by 1 or 2 substituents selected from C1-C4alkyl groups such as methyl, ethyl and similar, and phenyl groups, in particular, for example, thiocarbamoyl, N-methylthiocarbamate or N-phenylthiocarbamoyl.

“Carbamoyloximes, which may be substituted With1-C4alkyl group or phenyl group”in the definition of a replacement group β is carbamoyloximes, which may be substituted by 1 or 2 substituents selected from C1-C4alkyl groups such as methyl, ethyl and similar, and phenyl groups, in particular, for example, carbamoylated, N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamate or N-phenylcarbamoyloxy.

As for the “group having the formula NR6R7”in determining the replacement group α, a replacement group δ and substituting group ε, R6and R7independently from each other represent a hydrogen atom, a C1-C6alkyl group, a C2-C6alkenylphenol group2-C6alkylamino group1-C6alkanoyloxy group or2-C6alkenylboronic group or, together with the nitrogen atom that is attached to R6and R7form heterocyclyl group. Preferably it is a group, in which R6and R7present at the m of hydrogen, With1-C6alkyl group or a C1-C6alkanoyloxy group, more preferably a group in which R6and R7represent a hydrogen atom, a C1-C4alkyl group or a C1-C4alkanoyloxy group and more preferably a group in which R6and R7represent a hydrogen atom or a C1-C2alkanoyloxy group. In particular, they are amino, methylamino, ethylamino, dimethylamino, diethylamino or acetylamino, preferably acetylamino.

“C1-C6alkanolamines” in the definitions of the foster group β and substituting group δ is, for example, ndimethylacetamide, propionamide, butyramide, valeramide or evaluated.

“C1-C14alkanolamines” in the definition of a replacement group ε is, for example, the above-mentioned “C1-C6alkanolamines”, octanoylthio, decanoylamino, dodecanolide or tetradecanamide.

“C1-C10alkoxycarbonyl group” in the definition of a replacement group β is, for example, methoxycarbonyl, ethoxycarbonyl or tert-butoxycarbonyl.

“Raidgroup, which may be substituted With1-C4alkyl group or phenyl group”in the definition of a replacement group β is, for example, raidgroup, which can the be substituted by 1-3 (preferably 1 or 2) substituents, selected from C1-C4alkyl groups such as methyl group, ethyl group and similar, and phenyl groups, and it is, for example, ureido, 1 methylurea, 3 macilwraith, 3,3-dimethylurea, 1,3-dimethylurea or 3-phenylurea.

“C6-C10arylcarbamoyl” in the definition of a replacement group γ is, for example, benzamide, naftolin or phthalimide.

“C6-C10aryloxyalkanoic group” in the definition of a replacement group γ is, for example, peroxycarboxylic.

“C7-C19aracelikarsaalyna group” in the definition of a replacement group γ is, for example, benzyloxycarbonyl or benzylaminocarbonyl.

“C3-C10cycloalkylcarbonyl” in the definition of a replacement group γ is, for example, cyclopropanecarboxylate or cyclohexyloxycarbonyloxy.

“C6-C10aryloxypropanolamine” in the definition of a replacement group γ is, for example, phenoxycarbonylamino or naphthalocyanines.

“C7-C19uralelectrotyazhmas” in the definition of a replacement group γ is, for example, benzyloxycarbonyloxy, 1 feniltiosemicarbazonele, 2-feniltiosemicarbazonele or benzylaminocarbonyl.

“Heterocyclyl group” in the definition of alwaysa group γ and heterocyclyl group” “geterotsiklicheskikh”, “heterocyclisation”, “geterotsiklicheskikh group”, “heterocyclisation group” and “heterocalixarenes group” represent a 5-8-membered ring (preferably a 5 - or 6-membered ring group or a condensed ring group which contains from 1 to several (preferably 1-4) heteroatoms, such as nitrogen atoms (may be oxidized), oxygen atoms and sulfur atoms. Examples of such “heterocyclyl are pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, furyl, thienyl, oxazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiazolyl, isothiazole, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, pyranyl, tiopronin, dioxines, dioxole, hinely, pyrido[2,3-d]pyrimidyl, 1,5-, 1,6-, 1,7-, 1,8-, 2,6- or 2,7-naphthylidine group, thieno[2,3-d]pyridyl, benzopyranyl, tetrahydrofuryl, tetrahydropyranyl, DIOXOLANYL and dioxane.

Data heterocyclyl group may be substituted at substitutable positions 1-3 substituents selected from C1-C4alkyl groups such as methyl, ethyl and similar hydroxy-group, carbonyl group and C1-C4alkoxygroup, such as methoxy, ethoxy and similar.

“C1 6alkylcarboxylic group” in the definition of a replacement group δ is, for example, methylcarbamoyl, dimethylcarbamoyl or propellerblades.

“C1-C14alkylcarboxylic group” in the definition of a replacement group ε is, for example, the above-mentioned “C1-C6acylcarnitine group”, octylcarbinol, metilcarbamidna, dodecacarbonyl or tetradecylammonium, preferably1-C10acylcarnitine group, and more preferably4-C8acylcarnitine group.

“C1-C6alkoxycarbonyl1-C6alkylcarboxylic group” in the definition of a replacement group δ is, for example, butoxycarbonylmethylene or ethoxycarbonylmethylene.

“C1-C14alkoxycarbonyl1-C14alkylcarboxylic group” in the definition of a replacement group ε is, for example, the above-mentioned “C1-C6alkoxycarbonyl1-C6acylcarnitine group” or octyloxybiphenyl, preferably1-C10alkoxycarbonyl1-C10acylcarnitine group, and more preferably4-C8alkoxycarbonyl4-C8acylcarnitine group.

“1,3-diarylquinoline1-C6alkyl groups which th” in the definition of a replacement group δ is for example, 1,3-diacetylpyridine or 1,3-bis-tert-butoxycarbonylamino.

“1,3-diarylquinoline1-C14alkyl group” in the definition of a replacement group ε is, for example, the above-mentioned 1,3-diarylquinoline1-C6alkyl group, 1,3-diacetylpyridine or 1,3-bis-tert-butoxycarbonylamino, preferably 1,3-diarylquinoline1-C10alkyl group, and more preferably “1,3-diarylquinoline4-C8alkyl group.

X and Y represent a group in which X and Y together with the carbon atom of the ring to which they are attached, form ring A, respectively represent a hydrogen atom or X and Y together represent Deputy ring (Deputy is oxoprop or tocograph) and preferably represent a group in which X and Y together with the carbon atom of the ring to which they are attached, form ring a, or respectively represent a hydrogen atom.

In a preferred example in the case where X and Y represent a group in which X and Y together with the carbon atom of the ring to which they are attached, form ring A, ring a represents a 3-7-membered heterocyclyl ring or a 3-7-membered saturated cycloalkyl ring.

As for heterocyclyl ring, X and Y included what's in the ring, independently from each other represent any atom or group selected from a carbon atom, a group having the formula NR (R represents a hydrogen atom, a C1-C6alkyl group which may be substituted by a group selected from foster group α, C2-C6alkenylphenol group which may be substituted by a group selected from foster group α, C2-C6alkylamino group which may be substituted by a group selected from foster group α, or C1-C6alkanoyloxy group which may be substituted by a group selected from foster group α, oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2,

may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring has 1 or 2 oxygen atom and/or nitrogen as heteroatoms, or a 5 - or 6-membered cycloalkenyl ring,

any ring heterocyclyl ring or condensed ring, which is condensed with heterocyclyl ring, or spirochaete, which is Spiro associated with heterocyclyl ring may be substituted by same or different 1 to 4 groups selected from the group consisting of a carbonyl group, tocography, replacement group α, cyclopropyl1-C6alkiline the group and 1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α.

3-7-membered saturated cycloalkyl ring may be substituted by 1 or 2 groups selected from the group consisting of hydroxy-group, hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group, 1,2,3,4-tetrahydroquinoline group and acetylamino.

Ring And more preferably is a 3-7-membered heterocyclyl ring or 3-to 5-membered cycloalkyl ring.

As for heterocyclyl ring, which is preferable examples of the ring A, X and Y are included in the ring, independently of one another represent any atom or group selected from a carbon atom, oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2,

may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring has 1 or 2 oxygen atom and/or nitrogen as heteroatoms, or a 5 - or 6-membered cycloalkenyl ring, and

any ring heterocyclyl ring or condensed ring, which is condensed with heterocyclyl ring, or spirochaete, which is Spiro associated with heterocyclyl ring may be substituted by the same elerslie 1-4 groups selected from a carbonyl group, tocography, replacement group α and C1-C6alkyl group which may be substituted by 1-4 groups selected from foster group α.

3-5-membered cycloalkyl ring may be substituted by 1 or 2 groups selected from the group consisting of hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group, 1,2,3,4-tetrahydroquinoline group and acetylamino.

Ring And more preferably is heterocyclyl ring or the above-mentioned cyclopropyl or cyclopentene ring, described below.

Examples of such heterocyclyl rings are oxirane, tetrahydrofuran, tetrahydropyran, 1,3-dioxolane, 1,3-dioxane, 1,3-dioxan, 1,3-ditiolan, 1,3-dition, 1,1,3,3-tetraoxo-1,3-ditiolan, 1,3-oxathiolane, 1,3-Ossetian or 1,3-exatape,

data heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring is tetrahydrofuran, tetrahydropyran, pyrrolidine, piperidine or 1,3-dioxane) or tsiklogeksilnogo ring,

any ring heterocyclyl ring, or a condensed ring, which is condensed with heterocyclyl ring, or spirochaete, which is Spiro associated with heterocyclyl ring, can be C maseno 1 or 2 groups selected from the group consisting of a carbonyl group, tocography, replacement group α (replacement group α represents a hydroxy-group and a group having the formula NR6R7and R6and R7independently from each other, represent a hydrogen atom or a C1-C6alkanoyloxy group, methyl group, ethyl group and C1-C6alkyl group which is substituted by 1-4 hydroxy groups.

In addition to the above, cyclopropyl or cyclopentyl ring is cyclopropyl or cyclopentene ring which may be substituted by 1 or 2 groups selected from the group consisting of hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group and 1,2,3,4-tetrahydroquinoline group.

Ring And further preferably is, for example, oxirane, tetrahydrofuran, 1,3-dioxolane, 1,3-dioxane, 1,3-ditiolan, 1,3-dition, 1,3-oxathiolan or 1,3-axation, data heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring is tetrahydrofuran, tetrahydropyran or 1,3-dioxane) or tsiklogeksilnogo ring, and

any ring heterocyclyl ring, or a condensed ring, which is condensed with heterocyclyl ring, or spirochaete, which are the two which is Spiro, associated with heterocyclyl ring may be substituted by 1 or 2 groups selected from the group consisting of a substitutional group α [replacement group α represents a hydroxy-group and a group having the formula NR6R7(R6and R7independently from each other, represent a hydrogen atom or acetyl group)], a methyl group, ethyl group, hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group and 1,2,3,4-tetrahydroquinoline group.

Ring And, particularly preferably, is oxirane, 1,3-dioxolane, 1,3-dioxane or 1,3-oxathiolan, data heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring is tetrahydrofuran, tetrahydropyran or 1,3-dioxane) or tsiklogeksilnogo ring, and

any ring heterocyclyl ring, or a condensed ring, which is condensed with heterocyclyl ring, or spirochaete, which is Spiro associated with heterocyclyl ring may be substituted by 1 or 2 groups selected from the group consisting of a substitutional group α [replacement group α represents a hydroxy-group and a group having the formula NR6R7(R6and R7independently from each other, represent a hydrogen atom or aceti is inuu group)], methyl group, hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group and 1,2,3,4-tetrahydroquinoline group.

Preferred specific examples of ring a are cyclopropyl, 1-hydroxymethylglutaryl, 1,2-dihydroxyethylene, cyclopentyl, 2-hydroxymethylglutaryl, 2,3-dihydroxybenzylamine, 2,3-bis(1,2-dihydroxyethyl)cyclopentyl, 2-(1,2-dihydroxyethyl)cyclopentyl, 2-(1,2,3-trihydroxypropane)cyclopentyl, 2-(1,2,3,4-tetrahydroquinolin)cyclopentyl, oxirane, tetrahydrofuran, tetrahydropyran, 1,3-dioxolane, 1,3-dioxane, 1,3-oxathiolan, 4-hydroxymethyl-1,3-dioxolane, 4,5-dihydroxymethyl-1,3-dioxolane, 4,5-bis(1,2-dihydroxyethyl)-1,3-dioxolane, 4-(1,2-dihydroxyethyl)-1,3-dioxolane, 4-(1,2,3-trihydroxypropane)-1,3-dioxolane, 4-(1,2,3,4-tetrahydroquinolin)-1,3-dioxolane, 4,5-diacetylene-1,3-dioxolane, 5-hydroxy-1,3-dioxane, 5,5-dihydroxymethyl-1,3-dioxane, 5-acetylamino-1,3-dioxane, 5,5-dietoksikarbonil-1,3-dioxane and 2,4,7,9-tetraoxaspiro[5.5]undecane.

More preferred specific examples include 4-hydroxymethyl-1,3-dioxolane, 4,5-dihydroxymethyl-1,3-dioxolane, 4,5-bis(1,2-dihydroxyethyl)-1,3-dioxolane, 4-(1,2-dihydroxyethyl)-1,3-dioxolane, 4-(1,2,3-trihydroxypropane)-1,3-dioxolane, 4-(1,2,3,4-tetrahydroquinolin)-1,3-dioxolane, 4,5-diacetylene-1,3-dioxolane, 5-hydroxy-1,3-dioxane, 5-acetylene is about-1,3-dioxane and 5.5-dihydroxymethyl-1,3-dioxane.

Ring b is a 5-7-membered cycloalkenyl group. Here l and m are parameters to determine the number of ring members, independently from each other represent an integer of 0 to 3, and l+m is 1-3. And l+m is 1-3, indicates that the ring b is a 5-7-membered. Preferably l is 0 and m is an integer 1-3. More preferably it is cyclohexylidene group, in which l is 0 and m is 1.

Among the groups defined as R1preferred is a hydroxy-group, halogen atom, With1-C6an alkyl group or1-C6alkoxygroup, more preferably it is a hydroxy-group, fluorine atom, chlorine atom, methyl group, ethyl group, through the group, a methoxy group or ethoxypropan, more preferable is a fluorine atom or a methyl group.

The number of the substituents n, which is the number of groups R1which are the substituents of ring B, is 0-3, preferably 0 or 1. More preferably n is 0.

Among the groups defined as R2preferred is a1-C6alkyl group which may be substituted by a group selected from foster group β, more preferably1-C6alkyl group, even more preferably1-C4alkyl group and particularly predpochtitelnei is ethyl group.

Among the groups defined as R3, “5 - or 6-membered heteroaryl group” of the “5 - or 6-membered heteroaryl group which may be substituted by a group selected from foster group ε, particularly preferred is pyrrolidine group. That is, preferably, R3the group is phenyl or pyrrolidine group which may be substituted by a group selected from foster group ε. Preferably it is phenyl or pyrrolidine group which may be substituted by a group selected from a halogen atom, a C1-C14alkyl group, halogeno1-C14alkyl group, more preferably phenyl or pyrrolidine group which may be substituted by a group selected from a fluorine atom, chlorine atom, With1-C10alkyl group, halogeno1-C10alkyl groups and cyclopropyl1-C10alkyl group, more preferably phenyl or pyrrolidine group which may be substituted by a group selected from a fluorine atom, chlorine atom, bromine atom With3-C8alkyl group, halogeno4-C8alkyl group and more preferably a phenyl group which may be substituted by a group selected from a fluorine atom, chlorine atom and C3-C8alkyl groups.

In addition to the tale is nomu in case when it is substituted by the Deputy, the position of substitution is preferably 2-position or 4-position.

R3group is, for example, phenyl group, galganovaelena group1-C14alkylphenyl group, cyclopropyl1-C14alkylphenyl group1-C14alkoxyphenyl group1-C14alkoxycarbonylmethyl group, carboxylphenyl group, nitroaniline group, cyanoptila group, halogeno1-C14alkylphenyl group, halogeno1-C14alkoxyphenyl group1-C14alkanolamine group, phenyl group which is substituted 5-membered heteroaryl group, With1-C14alkoxycarbonyl-C1-C14alquilerbarcelona group, 1,3-diarylquinoline-C1-C14alkylphenyl group, phenyl group which is substituted by halogen atom and C1-C14the alkyl, the phenyl group which is substituted by halogen atom and C1-C14alkoxycarbonyl, phenyl group which is substituted by a halogen atom and cyano, phenyl group which is substituted by a halogen atom and a 5-membered heteroaryl group, phenyl group which is substituted by halogen atom and C1-C14alkoxycarbonyl-C1-C14allylcarbamate,

pyrrolidine group, halogenopyrimidines group, With1-C14alkylpyridine group, cyclopropyl1-C14alkylpyridine group1-C14alkoxystyrene group1-C14alkoxycarbonylmethyl group, carboxypropyl group, nitropyrimidine group, cyanopyrrolidine group, halogeno1-C14alkylpyridine group, halogeno1-C14alkoxystyrene group1-C14alkanolamine group, pyrrolidine group, which is substituted 5-membered heteroaryl group, With1-C14alkoxycarbonyl-C1-C14alquilerbarcelona group, 1,3-diarylquinoline-C1-C14alkylpyridine group, pyrrolidine group, which is substituted with halogen and C1-C14the alkyl, pyrrolidine group, which is substituted with halogen and C1-C14alkoxycarbonyl, pyrrolidine group, which is substituted by halogen, cyano, pyrrolidine group, which is substituted with halogen and 5-membered heteroaryl group, pyrrolidine group, which is substituted with halogen and C1-C14alkoxycarbonyl-C1-C14allylcarbamate or similar.

Among them, specific examples are preferably phenyl, 2-forfinal, 2-chlorophenyl, 2-bromophenyl, 2-iopener, 3-forfinal, 3-chlorophenyl, 4-forfinal, 4-chlorophenyl, 2,3-debtor the Nile, 2,3-dichlorophenyl, 2,4-differenl, 2,4-dichlorophenyl, 2,5-differenl, 2,5-dichlorophenyl, 2,6-differenl, 2,6-dichlorophenyl, 3,4-differenl, 3,4-dichlorophenyl, 3,5-differenl, 3,5-dichlorophenyl, 2,4-dibromophenyl, 2,6-dibromophenyl, 4-chloro-2-forfinal, 2-chloro-4-forfinal, 4-bromo-2-forfinal, 2-bromo-4-forfinal, 3-chloro-4-forfinal, 2-bromo-4-chlorophenyl, 5-chloro-2-forfinal, 4-bromo-2-chlorophenyl, 2-chloro-6-forfinal, 2,4-acid, 2,3,4-tryptophanyl, 2,4,5-tryptophanyl, 2,4,6-tryptophanyl, 2-chloro-4,6-differenl, 2,6-dichloro-4-forfinal, 2-bromo-6-chloro-4-forfinal, 2-were 2-ethylphenyl, 2-(n-propyl)phenyl, 2-(n-butyl)phenyl, 2-(n-pentyl)phenyl, 2-(n-hexyl)phenyl, 2-(n-heptyl)phenyl, 2-(n-octyl)phenyl, 2-(n-nonyl)phenyl, 2-(n-decyl)phenyl, 2-(n-undecyl)phenyl, 2-(n-dodecyl)phenyl, 2-(n-tridecyl)phenyl, 2-(n-tetradecyl)phenyl, 2-ethynylphenyl, 2-isopropylphenyl, 2-tert-butylphenyl, 2-second-butylphenyl,

2-methoxyphenyl, 2-ethoxyphenyl, 2-deformational, 2-methylsulfinylphenyl, 2-acetylphenyl, 2-benzylphenol, 2-(morpholine-4-yl)phenyl, 2-[2-(pyridin-4-yl)ethyl]phenyl, 2-[2-(tert-butoxycarbonylamino)ethyl]phenyl, 2-AMINOPHENYL, 2,6-diisopropylphenyl, 2-chloro-4-were, 4-fluoro-3-triptoreline, 4-fluoro-3-methoxyphenyl, 4-chloro-2-ethoxycarbonylphenyl, 2-fluoro-4-methoxyphenyl, 4-chloro-2-were, 2-fluoro-4-were, 2-fluoro-5-were, 2-chloro-4-were, 2-chloro-6-were, 4-tert-butyl-2-chlorophenyl, 2-bromo-4-isopropylphenyl, 4-chloro-2-methoxy-5-IU is ylphenyl, 4-fluoro-2-were, 2-ethyl-4-forfinal, 4-fluoro-2-(n-propyl)phenyl, 2-(n-butyl)-4-forfinal, 4-fluoro-2-(n-pentyl)phenyl, 4-fluoro-2-(n-hexyl)phenyl, 4-fluoro-2-(n-heptyl)phenyl, 4-fluoro-2-(n-octyl)phenyl, 4-fluoro-2-(n-nonyl)phenyl, 2-(n-decyl)-4-forfinal, 4-fluoro-2-(n-undecyl)phenyl, 2-(n-dodecyl)-4-forfinal, 4-fluoro-2-(n-tridecyl)phenyl, 4-fluoro-2-(n-tetradecyl)phenyl, 2-triptoreline, 2-(2,2,2-triptorelin)phenyl, 2-(3,3,3-cryptochromes)phenyl, 2-(4,4,4-trifloromethyl)phenyl, 2-(5,5,5-tryptophanyl)phenyl, 2-(6,6,6-triptorelin)phenyl, 2-(a 7,7,7-triptorelin)phenyl, 2-(8,8,8-trifloromethyl)phenyl, 2-(9,9,9-triptorelin)phenyl, 2-(10,10,10-trifloromethyl)phenyl, 2-cyclopropylethyl, 2-[3-cyclopropyl-(n-propyl)]phenyl, 2-[4-cyclopropyl-(n-butyl)]phenyl, 2-[5-cyclopropyl-(n-pentyl)]phenyl, 2-[6-cyclopropyl-(n-hexyl)]phenyl, 2-[7-cyclopropyl-(n-heptyl)]phenyl, 2-[8-cyclopropyl-(n-octyl)]phenyl, pyrrolyl, 2-forpersonal, 2-chlorpropyl, 2-paperroll, 2,5-differentail, 2,5-dichloropropyl, 2,5-dibromopropyl, 2-chloro-5-forpersonal, 2-methylpyrrole, 2-acylpyrrole, 2-(n-propyl)pyrrolyl, 2-(n-butyl)pyrrolyl, 2-(n-pentyl)pyrrolyl, 2-(n-hexyl)pyrrolyl, 2-(n-heptyl)pyrrolyl, 2-(n-octyl)pyrrolyl, 2-(n-nonyl)pyrrolyl and 2-(n-decyl)pyrrolyl,

more preferably

2-forfinal, 2-chlorophenyl, 2-bromophenyl, 2-iopener, 4-forfinal, 2,4-differenl, 2,4-dichlorophenyl, 2-chloro-4-forfinal, 2-bromo-4-forfinal, 3-chloro-4-forfinal, 2-bromo-4-chlorophenyl, 2,4-dimethoxy the sludge

2-chloro-4,6-differenl, 2,6-dichloro-4-forfinal, 2-bromo-6-chloro-4-forfinal, 2-were 2-ethylphenyl, 2-(n-propyl)phenyl, 2-(n-butyl)phenyl, 2-(n-pentyl)phenyl, 2-(n-hexyl)phenyl, 2-(n-heptyl)phenyl, 2-(n-octyl)phenyl, 2-(n-nonyl)phenyl, 2-(n-decyl)phenyl,

2-ethynylphenyl, 2-second-butylphenyl, 2-methoxyphenyl, 2-methylsulfinylphenyl, 2-benzylphenol, 2-[2-(tert-butoxycarbonylamino)ethyl]phenyl, 4-chloro-2-were, 2-fluoro-5-were, 2-chloro-4-were, 2-chloro-6-were, 4-chloro-2-methoxy-5-were, 4-fluoro-2-were, 2-ethyl-4-forfinal, 4-fluoro-2-(n-propyl)phenyl, 2-(n-butyl)-4-forfinal, 4-fluoro-2-(n-pentyl)phenyl, 4-fluoro-2-(n-hexyl)phenyl, 4-fluoro-2-(n-heptyl)phenyl, 4-fluoro-2-(n-octyl)phenyl, 4-fluoro-2-(n-nonyl)phenyl, 2-(n-decyl)-4-forfinal, 2-(n-butyl)pyrrolyl, 2-(n-pentyl)pyrrolyl, 2-(n-hexyl)pyrrolyl, 2-(n-heptyl)pyrrolyl and 2-(n-octyl)pyrrolyl and

even more preferably

2-chlorophenyl, 2-bromophenyl, 2,4-differenl, 2-chloro-4-forfinal, 2-bromo-4-forfinal, 2-(n-pentyl)phenyl, 2-(n-hexyl)phenyl, 2-(n-heptyl)phenyl, 2-chloro-6-were, 4-fluoro-2-(n-propyl)phenyl, 2-(n-butyl)-4-forfinal, 4-fluoro-2-(n-pentyl)phenyl, 4-fluoro-2-(n-hexyl)phenyl, 4-fluoro-2-(n-heptyl)phenyl and 4-fluoro-2-(n-octyl)phenyl.

As for their (his) pharmacologically acceptable salts”, as the compound having General formula (I) of the present invention, can turn into salt through reaction with acid, when it had the t primary group, such as an amino group, or through reaction with the base when it has an acidic group such as carboxyl group, presents its salts.

Salts of main group are preferably salts of inorganic acids, such as salts kaleidotrope acid, including hydrochloride, hydrobromide and hydroiodide, nitrates, perchlorates, sulfates, phosphates or similar; lower salt alkanesulphonic acid, such as methanesulfonate, triftorbyenzola and aconsultant, salt arylsulfonic acid, such as bansilalpet and p-toluensulfonate, organic acid salts such as acetate, malate, fumarate, succinate, citrates, ascorbates, tartratami, oxalates, maleate or similar, and salts of amino acids such as salt of glycine, lysine, arginine, ornithine, glutamate and aspartate.

On the other hand, salts of the acid groups are preferably alkali metal salts such as sodium salt, potassium salt and lithium salt, salts of alkaline earth metals such as calcium salt and magnesium salt, metal salts, such as aluminium salt and iron salt; inorganic salts such as ammonium salt, amine salts, including organic salts such as tert-octylamine salt, dibenzylamine salt, Martinova salt, glucosamine salt, salt Olkiluoto ester of phenylglycine, atlend the amine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, chloroprocaine salt, Prokaeva salt, diethanolamine salt, N-benzilpenetsillina salt, pieperazinove salt, Tetramethylammonium salt and Tris(hydroxymethyl)aminobutanova salt, and salts with amino acids such as salt of glycine, lysine, arginine salt, ornithine, glutamate and aspartate.

Compounds having General formula (I) according to the present invention, or their pharmaceutically acceptable salts have an asymmetric carbon atom in their molecules, and, thus, there are stereoisomers R-configuration and S-configuration. Each of them, or in connection with any ratio they are also covered by the present invention. With regard to such stereoisomers, the compound (I) can be synthesized by using optically separated parent compound and, optionally, the synthesized compound (I) can optically be separated using conventional methods of splitting or division.

With regard to compounds having General formula (I)or its pharmacologically acceptable salts, according to the present invention are the optical isomers, and each of the optical isomers and mixtures of such isomers are also included in the present from retina.

When the compound having General formula (I)or its pharmacologically acceptable salt is exposed to the atmosphere or precrystallization, they can absorb moisture, resulting in a phenomenon of adhesion of adsorbed water and generation of hydrates. These hydrated compounds and salts are also included in the present invention.

As typical representatives of the compounds of the present invention can be mentioned, for example, compounds listed in the following tables 1-3, but the present invention is not limited to these compounds.

Abbreviations and “ring 1” - “ring 21 in the tables are as follows.

AcAcetyl
BocButoxycarbonyl
BnBenzil
nBun-butyl
sBusecond-butyl
tButert-butyl
cBuCyclobutylamine
nDecn-decane
Flufluoren-1-yl
cPentCyclopentolate
cPrCyclopropylidene
cPrlCyclopropyl
cHeptCyclopeptide
cHexCyclohexylidene
dioxa1,3-dioxane-2-ilidene
dioxa1,3-dioxan-2-ilidene
dioxo1,3-dioxolane-2-ilidene
dithia1,3-dition-2-ilidene
ditio1,3-ditiolan-2-ilidene

2-oxalanilide
EtEthyl
HB1,2,3,4-tetrahydroquinolin
HE1,2-dihydroxyethyl
nHeptn-heptyl
nHexn-hexyl
HMHydroxymethyl
HP1,2,3-trihydroxypropane
MeMethyl
MorMorpholino
nNonn-nonan
O=Oxo
nOctn-octyl
nPentn-pentyl
PhPhenyl
NPrn-propyl
PyrPyrrolyl
PyrdPyridyl
S=Thioxo
oxa2-oxanilide
Ossetia1,3-Ossetian-2-ilidene
ocatio1,3-oxathiolan-2-ilidene
oaks2-acetanilide
hydroxy
oxo2-oxalanilide
ozltetrahydrooxazolo-2-ilidene
ozntetrahydro-1,3-oxazin-2-ilidene

tzltetrahydrothieno-2-ilidene
tzntetrahydro-1,3-thiazin-2-ilidene

In the tables “di” indicates that there are two identical Deputy, and “three” indicates that there are three identical Deputy.

ring:1ring:2ring:3
ring:4ring:5ring:6
ring:7 ring:8ring:9
ring:10ring:11ring:12
ring:13ring:14ring:15
ring:16ring:17ring:18
ring:19ring:20ring:21

The position of the joining rings 1-21 regarding the ring is In the position indicated by the black dot, which is located at the right end of the above-mentioned chemical structure.

The substituents, represented by the abbreviations in the form of X and Y in table 1, shown below.

hydroxyoaksoxoOxa
dioxodioxadioxa
ditiodithia ocatioOssetia
ozlozntzlTzn
3-HM-cPent4-HM-dioxo4-HM-dithio4-HM-ocatio
3,4-DIMM-cPent4,5-dihm-dioxo4,5-dihm-dithio4,5-dihm-ocatio
3,4-Dina-cPent4,5-Dina-dioxo4,5-Dina-dithio4,5-Dina-ocatio
3-HE-cPent4-HE-dioxo4-HE-dithio4-HE-ocatio
3-HP-cPent4-HP-dioxo4-HP-dithio4-HP-ocatio
3-HB-cPent4-HB-dioxo4-HB-dithio 4-HB-ocatio
3,4-disne2NHAc-cPent4,5-disne2NHAc - dioxo4,5-disne2NHAc - dithio4,5-disne2NHAc - ocatio
4-OH-cHex5-OH-dioxa5-OH-dithia5-OH-Ossetia
4-NHAc-cHex5-NHAc-dioxa5-NHAc-dithia5-NHAc-Ossetia
4,4-dime-cHex5,5-dime-dioxa5,5-dime-dithia5,5-dime - Ossetia
4,4-DIMM-cHex5,5-dihm-dioxo5,5-dihm-dithia5,5-dihm-Ossetia
4,4-diso2Et-cHex5,5-diso2Et-dioxa5,5-diso2Et-dithia5,5-diso2Et-Ossetia

tr>
Table 1
Connection # X, YR3
1-1O=Ph
1-2S=Ph
1-3cPrPh
1-4cBuPh
1-5cPentPh
1-6cHexPh
1-7cHeptPh
1-8hydroxyPh
1-9oaksPh
1-10oxoPh
1-11oxaPh
1-12dioxoPh
1-13dioxaPh
1-14dioxaPh
1-15ditioPh
1-16dithiaPh
1-17the ring 1Ph
1-18the ring 2Ph
1-19ocatioPh
1-20OssetiaPh
1-21ozlPh
1-22oznPh
1-23tzlPh
1-24tznPh
1-253-HM-cPentPh
1-264-HM-dioxoPh
1-274-HM-dithioPh

1-284-HM-ocatioPh
1-293,4-DIMM-cPentPh
1-304,5-dihm-dioxoPh
1-314,5-dihm-dithioPh
1-324,5-dihm-ocatioPh
1-333,4-Dina-cPentPh
1-344,5-Dina-dioxoPh
1-354,5-Dina-dithioPh
1-364,5-Dina-ocatioPh
1-373-HE-cPentPh
1-384-HE-dioxoPh
1-394-HE-dithioPh
1-404-HE-ocatio Ph
1-413-HP-cPentPh
1-424-HP-dioxoPh
1-434-HP-dithioPh
1-444-HP-ocatioPh
1-453-HB-cPentPh
1-464-HB-dioxoPh
1-474-HB-dithioPh
1-484-HB-ocatioPh
1-49ring 3Ph
1-50ring 4Ph
1-51ring 5Ph
1-52ring 6Ph
1-53ring 7Ph
1-54ring 8Ph
1-55the ring 9Ph
1-56the ring 10Ph
1-573,4-disne2NHAc-cPentPh
1-584,5-disne2NHAc-dioxoPh
1-594,5-disne2NHAc-dithioPh
1-604,5-disne2NHAc-ocatioPh
1-61the ring 11Ph

1-62the ring 12Ph
1-63the ring 13Ph
1-64the ring 14Ph
1-654-OH-cHexPh
1-665-OH-dioxaPh
1-675-OH-dithiaPh
1-685-OH-OssetiaPh
1-694-NHAc-cHexPh
1-705-NHAc-dioxaPh
1-715-NHAc-dithiaPh
1-725-NHAc-OssetiaPh
1-734,4-dime-cHexPh
1-745,5-dime-dioxaPh
1-755,5-dime-dithiaPh
1-765,5-dime-OssetiaPh
1-774,4-DIMM-cHexPh
1-785,5-dihm-dioxoPh
1-795,5-dihm-dithiaPh
1-805,5-dihm-OssetiaPh
1-81the ring 15Ph
1-82the ring 16Ph
1-83the ring 17Ph
1-84ring 18Ph
1-854,4-diso2Et-cHexPh
1-865,5-diso2Et-dioxaPh
1-875,5-diso2Et-dithiaPh
1-885,5-diso2Et-OssetiaH
1-89O=4-F-Ph
1-90S=4-F-Ph
1-91cPr
1-92cBu4-F-Ph
1-93cPent4-F-Ph
1-94cHex4-F-Ph
1-95cHept4-F-Ph

4-F-Ph
1-96hydroxy4-F-Ph
1-97oaks4-F-Ph
1-98oxo4-F-Ph
1-99oxa4-F-Ph
1-100dioxo4-F-Ph
1-101dioxa4-F-Ph
1-102dioxa4-F-Ph
1-103ditio4-F-Ph
1-104dithia
1-105the ring 14-F-Ph
1-106the ring 24-F-Ph
1-107ocatio4-F-Ph
1-108Ossetia4-F-Ph
1-109ozl4-F-Ph
1-110ozn4-F-Ph
1-111tzl4-F-Ph
1-112tzn4-F-Ph
1-1133-HM-cPent4-F-Ph
1-1144-HM-dioxo4-F-Ph
1-1154-HM-dithio4-F-Ph
1-1164-HM-ocatio4-F-Ph
1-1173,4-DIMM-cPent 4-F-Ph
1-1184,5-dihm-dioxo4-F-Ph
1-1194,5-dihm-dithio4-F-Ph
1-1204,5-dihm-ocatio4-F-Ph
1-1213,4-Dina-cPent4-F-Ph
1-1224,5-Dina-dioxo4-F-Ph
1-1234,5-Dina-dithio4-F-Ph
1-1244,5-Dina-ocatio4-F-Ph
1-1253-HE-cPent4-F-Ph
1-1264-HE-dioxo4-F-Ph
1-1274-HE-dithio4-F-Ph
1-1284-HE-ocatio4-F-Ph
1-1293-HP-cPent4-F-Ph

1-1304-HP-dioxo4-F-Ph
1-1314-HP-dithio4-F-Ph
1-1324-HP-ocatio4-F-Ph
1-1333-HB-cPent4-F-Ph
1-1344-HB-dioxo4-F-Ph
1-1354-HB-dithio4-F-Ph
1-1364-HB-ocatio4-F-Ph
1-137ring 34-F-Ph
1-138ring 44-F-Ph
1-139ring 54-F-Ph
1-140ring 64-F-Ph
1-141ring 74-F-Ph
1-142ring 8 4-F-Ph
1-143the ring 94-F-Ph
1-144the ring 104-F-Ph
1-1453,4-disne2NHAc-cPent4-F-Ph
1-1464,5-disne2NHAc-dioxo4-F-Ph
1-1474,5-disne2NHAc-dithio4-F-Ph
1-1484,5-disne2NHAc-ocatio4-F-Ph
1-149the ring 114-F-Ph
1-150the ring 124-F-Ph
1-151the ring 134-F-Ph
1-152the ring 144-F-Ph
1-1534-OH-cHex4-F-Ph
1-1545-OH-dioxa4-F-Ph
5-OH-dithia4-F-Ph
1-1565-OH-Ossetia4-F-Ph
1-1574-NHAc-cHex4-F-Ph
1-1585-NHAc-dioxa4-F-Ph
1-1595-NHAc-dithia4-F-Ph
1-1605-NHAc-Ossetia4-F-Ph
1-1614,4-dime-cHex4-F-Ph
1-1625,5-dime-dioxa4-F-Ph
1-1635,5-dime-dithia4-F-Ph

1-1645,5-dime-Ossetia4-F-Ph
1-1654,4-DIMM-cHex4-F-Ph
1-1665,5-dihm-dioxo4-F-Ph
1-1675,5-dihm-dithia4-F-Ph
1-1685,5-dihm-Ossetia4-F-Ph
1-169the ring 154-F-Ph
1-170the ring 164-F-Ph
1-171the ring 174-F-Ph
1-172ring 184-F-Ph
1-1734,4-diso2Et-cHex4-F-Ph
1-1745,5-diso2Et-dioxa4-F-Ph
1-1755,5-diso2Et-dithia4-F-Ph
1-1765,5-diso2Et-Ossetia4-F-Ph
1-177O=2-Cl-Ph
1-178S=2-Cl-Ph
1-179 cPr2-Cl-Ph
1-180cBu2-Cl-Ph
1-181cPent2-Cl-Ph
1-182cHex2-Cl-Ph
1-183cHept2-Cl-Ph
1-184hydroxy2-Cl-Ph
1-185oaks2-Cl-Ph
1-186oxo2-Cl-Ph
1-187oxa2-Cl-Ph
1-188dioxo2-Cl-Ph
1-189dioxa2-Cl-Ph
1-190dioxa2-Cl-Ph
1-191ditio2-Cl-Ph
1-192dithia 2-Cl-Ph
1-193the ring 12-Cl-Ph
1-194the ring 22-Cl-Ph
1-195ocatio2-Cl-Ph
1-196Ossetia2-Cl-Ph
1-197ozl2-Cl-Ph

3,4-DIMM-cPent
1-198ozn2-Cl-Ph
1-199tzl2-Cl-Ph
1-200tzn2-Cl-Ph
1-2013-HM-cPent2-Cl-Ph
1-2024-HM-dioxo2-Cl-Ph
1-2034-HM-dithio2-Cl-Ph
1-2044-HM-ocatio2-Cl-Ph
1-2052-Cl-Ph
1-2064,5-dihm-dioxo2-Cl-Ph
1-2074,5-dihm-dithio2-Cl-Ph
1-2084,5-dihm-ocatio2-Cl-Ph
1-2093,4-Dina-cPent2-Cl-Ph
1-2104,5-Dina-dioxo2-Cl-Ph
1-2114,5-Dina-dithio2-Cl-Ph
1-2124,5-Dina-ocatio2-Cl-Ph
1-2133-HE-cPent2-Cl-Ph
1-2144-HE-dioxo2-Cl-Ph
1-2154-HE-dithio2-Cl-Ph
1-2164-HE-ocatio2-Cl-Ph
1-2173-HP-cPent2-Cl-Ph
1-2184-HP-dioxo2-Cl-Ph
1-2194-HP-dithio2-Cl-Ph
1-2204-HP-ocatio2-Cl-Ph
1-2213-HB-cPent2-Cl-Ph
1-2224-HB-dioxo2-Cl-Ph
1-2234-HB-dithio2-Cl-Ph
1-2244-HB-ocatio2-Cl-Ph
1-225ring 32-Cl-Ph
1-226ring 42-Cl-Ph
1-227ring 52-Cl-Ph
1-228ring 62-Cl-Ph
1-229ring 72-Cl-Ph
1-230the number of the TSO 8 2-Cl-Ph
1-231the ring 92-Cl-Ph

5-OH-dioxa
1-232the ring 102-Cl-Ph
1-2333,4-disne2NHAc-cPent2-Cl-Ph
1-2344,5-disne2NHAc-dioxo2-Cl-Ph
1-2 35mm4,5-disne2NHAc-dithio2-Cl-Ph
1-2364,5-disne2NHAc-ocatio2-Cl-Ph
1-237the ring 112-Cl-Ph
1-238the ring 122-Cl-Ph
1-239the ring 132-Cl-Ph
1 to 240the ring 142-Cl-Ph
1-2414-OH-cHex2-Cl-Ph
1-2422-Cl-Ph
1-2435-OH-dithia2-Cl-Ph
1-2445-OH-Ossetia2-Cl-Ph
1-2454-NHAc-cHex2-Cl-Ph
1-2465-NHAc-dioxa2-Cl-Ph
1-2475-NHAc-dithia2-Cl-Ph
1-2485-NHAc-Ossetia2-Cl-Ph
1-2494,4-dime-cHex2-Cl-Ph
1-2505,5-dime-dioxa2-Cl-Ph
1-2515,5-dime-dithia2-Cl-Ph
1-2525,5-dime-Ossetia2-Cl-Ph
1-2534,4-DIMM-cHex2-Cl-Ph
1-2545,5-dihm-dioxo2-Cl-Ph
1-2555,5-dihm-dithia2-Cl-Ph
1-2565,5-dihm-Ossetia2-Cl-Ph
1-257the ring 152-Cl-Ph
1-258the ring 162-Cl-Ph
1-259the ring 172-Cl-Ph
1-260ring 182-Cl-Ph
1-2614,4-diso2Et-cHex2-Cl-Ph
1-2625,5-diso2Et-dioxa2-Cl-Ph
1-2635,5-diso2Et-dithia2-Cl-Ph
1-2645,5-diso2Et-Ossetia2-Cl-Ph
1-265O=2,4-F-Ph

2,4-F-Ph
1-266S=
1-267cPr2,4-F-Ph
1-268cBu2,4-F-Ph
1-269cPent2,4-F-Ph
1-270cHex2,4-F-Ph
1-271cHept2,4-F-Ph
1-272hydroxy2,4-F-Ph
1-273oaks2,4-F-Ph
1-274oxo2,4-F-Ph
1-275oxa2,4-F-Ph
1-276dioxo2,4-F-Ph
1-277dioxa2,4-F-Ph
1-278dioxa2,4-F-Ph
1-279ditio 2,4-F-Ph
1-280dithia2,4-F-Ph
1-281the ring 12,4-F-Ph
1-282the ring 22,4-F-Ph
1-283ocatio2,4-F-Ph
1-284Ossetia2,4-F-Ph
1-285ozl2,4-F-Ph
1-286ozn2,4-F-Ph
1-287tzl2,4-F-Ph
1-288tzn2,4-F-Ph
1-2893-HM-cPent2,4-F-Ph
1-2904-HM-dioxo2,4-F-Ph
1-2914-HM-dithio2,4-F-Ph
1-292 4-HM-ocatio2,4-F-Ph
1-2933,4-DIMM-cPent2,4-F-Ph
1-2944,5-dihm-dioxo2,4-F-Ph
1-2954,5-dihm-dithio2,4-F-Ph
1-2964,5-dihm-ocatio2,4-F-Ph
1-2973,4-Dina-cPent2,4-F-Ph
1-2984,5-Dina-dioxo2,4-F-Ph
1-2994,5-Dina-dithio2,4-F-Ph

1-3004,5-Dina-ocatio2,4-F-Ph
1-3013-HE-cPent2,4-F-Ph
1-3024-HE-dioxo2,4-F-Ph
1-3034-HE-dithio2,4-F-Ph
1-3044-HE-ocatio2,4-F-Ph
1-3053-HP-cPent2,4-F-Ph
1-3064-HP-dioxo2,4-F-Ph
1-3074-HP-dithio2,4-F-Ph
1-3084-HP-ocatio2,4-F-Ph
1-3093-HB-cPent2,4-F-Ph
1-3104-HB-dioxo2,4-F-Ph
1-3114-HB-dithio2,4-F-Ph
1-3124-HB-ocatio2,4-F-Ph
1-313ring 32,4-F-Ph
1-314ring 42,4-F-Ph
1-315ring 52,4-F-Ph
1-316also 6 2,4-F-Ph
1-317ring 72,4-F-Ph
1-318ring 82,4-F-Ph
1-319the ring 92,4-F-Ph
1-320the ring 102,4-F-Ph
1-3213,4-disne2NHAc-cPent2,4-F-Ph
1-3224,5-disne2NHAc-dioxo2,4-F-Ph
1-3234,5-disne2NHAc-dithio2,4-F-Ph
1-3244,5-disne2NHAc-ocatio2,4-F-Ph
1-325the ring 112,4-F-Ph
1-326the ring 122,4-F-Ph
1-327the ring 132,4-F-Ph
1-328 the ring 142,4-F-Ph
1-3294-OH-cHex2,4-F-Ph
1-3305-OH-dioxa2,4-F-Ph
1-3315-OH-dithia2,4-F-Ph
1-3325-OH-Ossetia2,4-F-Ph
1-3334-NHAc-cHex2,4-F-Ph

1-3345-NHAc-dioxa2,4-F-Ph
1-3355-NHAc-dithia2,4-F-Ph
1-3365-NHAc-Ossetia2,4-F-Ph
1-3374,4-dime-cHex2,4-F-Ph
1-3385,5-dime-dioxa2,4-F-Ph
1-3395,5-dime-dithia2,4-F-Ph
-340 5,5-dime-Ossetia2,4-F-Ph
1-3414,4-DIMM-cHex2,4-F-Ph
1-3425,5-dihm-dioxo2,4-F-Ph
1-3435,5-dihm-dithia2,4-F-Ph
1-3445,5-dihm-Ossetia2,4-F-Ph
1-345the ring 152,4-F-Ph
1-346the ring 162,4-F-Ph
1-347the ring 172,4-F-Ph
1-348ring 182,4-F-Ph
1-3494,4-diso2Et-cHex2,4-F-Ph
1-3505,5-diso2Et-dioxa2,4-F-Ph
1-3515,5-diso2Et-dithia2,4-F-Ph
1-3525,5-diso2Et-Ossetia2,4-F-Ph
1-353O=2-Cl-4-F-Ph
1-354S=2-Cl-4-F-Ph
1-355cPr2-Cl-4-F-Ph
1-356cBu2-Cl-4-F-Ph
1-357cPent2-Cl-4-F-Ph
1-358cHex2-Cl-4-F-Ph
1-359cHept2-Cl-4-F-Ph
1-360hydroxy2-Cl-4-F-Ph
1-361oaks2-Cl-4-F-Ph
1-362oxo2-Cl-4-F-Ph
1-363oxa2-Cl-4-F-Ph
1-364dioxo2-Cl-4-F-Ph
1-365dioxa2-Cl-4-F-Ph
1-366dioxa2-Cl-4-F-Ph
1-367ditio2-Cl-4-F-Ph

1-368dithia2-Cl-4-F-Ph
1-369the ring 12-Cl-4-F-Ph
1-370the ring 22-Cl-4-F-Ph
1-371ocatio2-Cl-4-F-Ph
1-372Ossetia2-Cl-4-F-Ph
1-373ozl2-Cl-4-F-Ph
1-374ozn2-Cl-4-F-Ph
1-375tzl2-Cl-4-F-Ph
1-376tzn2-Cl-4-F-Ph
1-377 3-HM-cPent2-Cl-4-F-Ph
1-3784-HM-dioxo2-Cl-4-F-Ph
1-3794-HM-dithio2-Cl-4-F-Ph
1-3804-HM-ocatio2-Cl-4-F-Ph
1-3813,4-DIMM-cPent2-Cl-4-F-Ph
1-3824,5-dihm-dioxo2-Cl-4-F-Ph
1-3834,5-dihm-dithio2-Cl-4-F-Ph
1-3844,5-dihm-ocatio2-Cl-4-F-Ph
1-3853,4-Dina-cPent2-Cl-4-F-Ph
1-3864,5-Dina-dioxo2-Cl-4-F-Ph
1-3874,5-Dina-dithio2-Cl-4-F-Ph
1-3884,5-Dina-ocatio2-Cl-4-F-Ph
1-3893-HE-cPent 2-Cl-4-F-Ph
1-3904-HE-dioxo2-Cl-4-F-Ph
1-3914-HE-dithio2-Cl-4-F-Ph
1-3924-HE-ocatio2-Cl-4-F-Ph
1-3933-HP-cPent2-Cl-4-F-Ph
1-3944-HP-dioxo2-Cl-4-F-Ph
1-3954-HP-dithio2-Cl-4-F-Ph
1-3964-HP-ocatio2-Cl-4-F-Ph
1-3973-HB-cPent2-Cl-4-F-Ph
1-3984-HB-dioxo2-Cl-4-F-Ph
1-3994-HB-dithio2-Cl-4-F-Ph
1-4004-HB-ocatio2-Cl-4-F-Ph
1-401ring 32-Cl-4-F-Ph

1-402ring 42-Cl-4-F-Ph
1-403ring 52-Cl-4-F-Ph
1-404ring 62-Cl-4-F-Ph
1-405ring 72-Cl-4-F-Ph
1-406ring 82-Cl-4-F-Ph
1-407the ring 92-Cl-4-F-Ph
1-408the ring 102-Cl-4-F-Ph
1-4093,4-disne2NHAc-cPent2-Cl-4-F-Ph
1-4104,5-disne2NHAc-dioxo2-Cl-4-F-Ph
1-4114,5-disne2NHAc-dithio2-Cl-4-F-Ph
1-4124,5-disne2NHAc-ocatio2-Cl-4-F-Ph
1-413the ring 112-Cl4-F-Ph
1-414the ring 122-Cl-4-F-Ph
1-415the ring 132-Cl-4-F-Ph
1-416the ring 142-Cl-4-F-Ph
1-4174-OH-cHex2-Cl-4-F-Ph
1-4185-OH-dioxa2-Cl-4-F-Ph
1-4195-OH-dithia2-Cl-4-F-Ph
1-4205-OH-Ossetia2-Cl-4-F-Ph
1-4214-NHAc-cHex2-Cl-4-F-Ph
1-4225-NHAc-dioxa2-Cl-4-F-Ph
1-4235-NHAc-dithia2-Cl-4-F-Ph
1-4245-NHAc-Ossetia2-Cl-4-F-Ph
1-4254,4-dime-cHex2-Cl-4-F-Ph
1-426 5,5-dime-dioxa2-Cl-4-F-Ph
1-4275,5-dime-dithia2-Cl-4-F-Ph
1-4285,5-dime-Ossetia2-Cl-4-F-Ph
1-4294,4-DIMM-cHex2-Cl-4-F-Ph
1-4305,5-dihm-dioxo2-Cl-4-F-Ph
1-4315,5-dihm-dithia2-Cl-4-F-Ph
1-4325,5-dihm-Ossetia2-Cl-4-F-Ph
1-433the ring 152-Cl-4-F-Ph
1-434the ring 162-Cl-4-F-Ph
1-435the ring 172-Cl-4-F-Ph

oxo
1-436ring 182-Cl-4-F-Ph
1-4374,4-diso2Et-cHex1-4385,5-diso2Et-dioxa2-Cl-4-F-Ph
1-4395,5-diso2Et-dithia2-Cl-4-F-Ph
1-4405,5-diso2Et-Ossetia2-Cl-4-F-Ph
1-441O=2-Cl-4-Me-Ph
1-442S=2-Cl-4-Me-Ph
1-443cPr2-Cl-4-Me-Ph
1-444cBu2-Cl-4-Me-Ph
1-445cPent2-Cl-4-Me-Ph
1-446cHex2-Cl-4-Me-Ph
1-447cHept2-Cl-4-Me-Ph
1-448hydroxy2-Cl-4-Me-Ph
1-449oaks2-Cl-4-Me-Ph
1-4502-Cl-4-Me-Ph
1-451oxa2-Cl-4-Me-Ph
1-452dioxo2-Cl-4-Me-Ph
1-453dioxa2-Cl-4-Me-Ph
1-454dioxa2-Cl-4-Me-Ph
1-455ditio2-Cl-4-Me-Ph
1-456dithia2-Cl-4-Me-Ph
1-457the ring 12-Cl-4-Me-Ph
1-458the ring 22-Cl-4-Me-Ph
1-459ocatio2-Cl-4-Me-Ph
1-460Ossetia2-Cl-4-Me-Ph
1-461ozl2-Cl-4-Me-Ph
1-462ozn2-Cl-4-Me-Ph
1-463tzl2-Cl-4-Me-Ph
1-464tzn2-Cl-4-Me-Ph
1-4653-HM-cPent2-Cl-4-Me-Ph
1-4664-HM-dioxo2-Cl-4-Me-Ph
1-4674-HM-dithio2-Cl-4-Me-Ph
1-4684-HM-ocatio2-Cl-4-Me-Ph
1-4693,4-DIMM-cPent2-Cl-4-Me-Ph

1-4704,5-dihm-dioxo2-Cl-4-Me-Ph
1-4714,5-dihm-dithio2-Cl-4-Me-Ph
1-4724,5-dihm-ocatio2-Cl-4-Me-Ph
1-4733,4-Dina-cPent2-Cl-4-Me-Ph
1-4744,5-Dina-dioxo2-Cl-4-Me-Ph
1-4754,5-Dina-dithio2-Cl-4-Me-Ph
1-4764,5-Dina-ocatio2-Cl-4-Me-Ph
1-4773-HE-cPent2-Cl-4-Me-Ph
1-4784-HE-dioxo2-Cl-4-Me-Ph
1-4794-HE-dithio2-Cl-4-Me-Ph
1-4804-HE-ocatio2-Cl-4-Me-Ph
1-4813-HP-cPent2-Cl-4-Me-Ph
1-4824-HP-dioxo2-Cl-4-Me-Ph
1-4834-HP-dithio2-Cl-4-Me-Ph
1-4844-HP-ocatio2-Cl-4-Me-Ph
1-4853-HB-cPent2-Cl-4-Me-Ph
1-4864-HB-dioxo2-Cl-4-Me-Ph
1-487 4-HB-dithio2-Cl-4-Me-Ph
1-4884-HB-ocatio2-Cl-4-Me-Ph
1-489ring 32-Cl-4-Me-Ph
1-490ring 42-Cl-4-Me-Ph
1-491ring 52-Cl-4-Me-Ph
1-492ring 62-Cl-4-Me-Ph
1-493ring 72-Cl-4-Me-Ph
1-494ring 82-Cl-4-Me-Ph
1-495the ring 92-Cl-4-Me-Ph
1-496the ring 102-Cl-4-Me-Ph
1-4973,4-disne2NHAc-cPent2-Cl-4-Me-Ph
1-4984,5-disne2NHAc-dioxo2-Cl-4-Me-Ph
1-4994,5-disne2 NHAc-dithio2-Cl-4-Me-Ph
1-5004,5-disne2NHAc-ocatio2-Cl-4-Me-Ph
1-501the ring 112-Cl-4-Me-Ph
1-502the ring 122-Cl-4-Me-Ph
1-503the ring 132-Cl-4-Me-Ph

1-504the ring 142-Cl-4-Me-Ph
1-5054-OH-cHex2-Cl-4-Me-Ph
1-5065-OH-dioxa2-Cl-4-Me-Ph
1-5075-OH-dithia2-Cl-4-Me-Ph
1-5085-OH-Ossetia2-Cl-4-Me-Ph
1-5094-NHAc-cHex2-Cl-4-Me-Ph
1-5105-NHAc-dioxa2-Cl-4-Me-Ph
1-5115-NHAc-dithia2-Cl-4-Me-Ph
1-5125-NHAc-Ossetia2-Cl-4-Me-Ph
1-5134,4-dime-cHex2-Cl-4-Me-Ph
1-5145,5-dime-dioxa2-Cl-4-Me-Ph
1-5155,5-dime-dithia2-Cl-4-Me-Ph
1-5165,5-dime-Ossetia2-Cl-4-Me-Ph
1-5174,4-DIMM-cHex2-Cl-4-Me-Ph
1-5185,5-dihm-dioxo2-Cl-4-Me-Ph
1-5195,5-dihm-dithia2-Cl-4-Me-Ph
1-5205,5-dihm-Ossetia2-Cl-4-Me-Ph
1-521the ring 152-Cl-4-Me-Ph
1-522the ring 162-Cl-4-Me-Ph
1-52 the ring 172-Cl-4-Me-Ph
1-524ring 182-Cl-4-Me-Ph
1-5254,4-diso2Et-cHex2-Cl-4-Me-Ph
1-5265,5-diso2Et-dioxa2-Cl-4-Me-Ph
1-5275,5-diso2Et-dithia2-Cl-4-Me-Ph
1-5285,5-diso2Et-Ossetia2-Cl-4-Me-Ph
1-529O=2-nBu-Ph
1-530S=2-nBu-Ph
1-531cPr2-nBu-Ph
1-532cBu2-nBu-Ph
1-533cPent2-nBu-Ph
1-534cHex2-nBu-Ph
1-535cHept 2-nBu-Ph
1-536hydroxy2-nBu-Ph
1-537oaks2-nBu-Ph

1-538oxo2-nBu-Ph
1-539oxa2-nBu-Ph
1-540dioxo2-nBu-Ph
1-541dioxa2-nBu-Ph
1-542dioxa2-nBu-Ph
1-543ditio2-nBu-Ph
1-544dithia2-nBu-Ph
1-545the ring 12-nBu-Ph
1-546the ring 22-nBu-Ph
1-547ocatio2-nBu-Ph
1-548Ossetia2-nBu-Ph
1-549ozl2-nBu-Ph
1-550ozn2-nBu-Ph
1-551tzl2-nBu-Ph
1-552tzn2-nBu-Ph
1-5533-HM-cPent2-nBu-Ph
1-5544-HM-dioxo2-nBu-Ph
1-5554-HM-dithio2-nBu-Ph
1-5564-HM-ocatio2-nBu-Ph
1-5573,4-DIMM-cPent2-nBu-Ph
1-5584,5-dihm-dioxo2-nBu-Ph
1-5594,5-dihm-dithio2-nBu-Ph
1-5604,5-dihm-ocatio2-nBu-Ph
1-5613,4-Dina-cPent2-nBu-Ph
1-5624,5-Dina-dioxo2-nBu-Ph
1-5634,5-Dina-dithio2-nBu-Ph
1-5644,5-Dina-ocatio2-nBu-Ph
1-5653-HE-cPent2-nBu-Ph
1-5664-HE-dioxo2-nBu-Ph
1-5674-HE-dithio2-nBu-Ph
1-5684-HE-ocatio2-nBu-Ph
1-5693-HP-cPent2-nBu-Ph
1-5704-HP-dioxo2-nBu-Ph
1-5714-HP-dithio2-nBu-Ph

1-5724-HP-ocatio2nBu-Ph
1-5733-HB-cPent2-nBu-Ph
1-5744-HB-dioxo2-nBu-Ph
1-5754-HB-dithio2-nBu-Ph
1-5764-HB-ocatio2-nBu-Ph
1-577ring 32-nBu-Ph
1-578ring 42-nBu-Ph
1-579ring 52-nBu-Ph
1-580ring 62-nBu-Ph
1-581ring 72-nBu-Ph
1-582ring 82-nBu-Ph
1-583the ring 92-nBu-Ph
1-584the ring 102-nBu-Ph
1-5853,-disne 2NHAc-cPent2-nBu-Ph
1-5864,5-disne2NHAc-dioxo2-nBu-Ph
1-5874,5-disne2NHAc-dithio2-nBu-Ph
1-5884,5-disne2NHAc-ocatio2-nBu-Ph
1-589the ring 112-nBu-Ph
1-590the ring 122-nBu-Ph
1-591the ring 132-nBu-Ph
1-592the ring 142-nBu-Ph
1-5934-OH-cHex2-nBu-Ph
1-5945-OH-dioxa2-nBu-Ph
1-5955-OH-dithia2-nBu-Ph
1-5965-OH-Ossetia2-nBu-Ph
1-5974-NHAc-cHex 2-nBu-Ph
1-5985-NHAc-dioxa2-nBu-Ph
1-5995-NHAc-dithia2-nBu-Ph
1-6005-NHAc-Ossetia2-nBu-Ph
1-6014,4-dime-cHex2-nBu-Ph
1-6025,5-dime-dioxa2-nBu-Ph
1-6035,5-dime-dithia2-nBu-Ph
1-6045,5-dime-Ossetia2-nBu-Ph
1-6054,4-DIMM-cHex2-nBu-Ph

1-6065,5-dihm-dioxo2-nBu-Ph
1-6075,5-dihm-dithia2-nBu-Ph
1-6085,5-dihm-Ossetia2-nBu-Ph
1-609the ring 15 2-nBu-Ph
1-610the ring 162-nBu-Ph
1-611the ring 172-nBu-Ph
1-612ring 182-nBu-Ph
1-6134,4-diso2Et-cHex2-nBu-Ph
1-6145,5-diso2Et-dioxa2-nBu-Ph
1-6155,5-diso2Et-dithia2-nBu-Ph
1-6165,5-diso2Et-Ossetia2-nBu-Ph
1-617O=2-nBu-4-F-Ph
1-618S=2-nBu-4-F-Ph
1-619cPr2-nBu-4-F-Ph
1-620cBu2-nBu-4-F-Ph
1-621cPent2-nBu-4-F-Ph
1-622cHex2-nBu-4-F-Ph
1-623cHept2-nBu-4-F-Ph
1-624hydroxy2-nBu-4-F-Ph
1-625oaks2-nBu-4-F-Ph
1-626oxo2-nBu-4-F-Ph
1-627oxa2-nBu-4-F-Ph
1-628dioxo2-nBu-4-F-Ph
1-629dioxa2-nBu-4-F-Ph
1-630dioxa2-nBu-4-F-Ph
1-631ditio2-nBu-4-F-Ph
1-632dithia2-nBu-4-F-Ph
1-633the ring 12-nBu-4-F-Ph
1-634the ring 22-nBu-4--Ph
1-635ocatio2-nBu-4-F-Ph
1-636Ossetia2-nBu-4-F-Ph
1-637ozl2-nBu-4-F-Ph
1-638ozn2-nBu-4-F-Ph
1-639tzl2-nBu-4-F-Ph

1-640tzn2-nBu-4-F-Ph
1-6413-HM-cPent2-nBu-4-F-Ph
1-6424-HM-dioxo2-nBu-4-F-Ph
1-6434-HM-dithio2-nBu-4-F-Ph
1-6444-HM-ocatio2-nBu-4-F-Ph
1-6453,4-DIMM-cPent2-nBu-4-F-Ph
1-6464,5-dihm-dioxo2-nBu-4-F-Ph
1-6474,5-dihm-dithio2-nBu-4-F-Ph
1-6484,5-dihm-ocatio2-nBu-4-F-Ph
1-6493,4-Dina-cPent2-nBu-4-F-Ph
1-6504,5-Dina-dioxo2-nBu-4-F-Ph
1-6514,5-Dina-dithio2-nBu-4-F-Ph
1-6524,5-Dina-ocatio2-nBu-4-F-Ph
1-6533-HE-cPent2-nBu-4-F-Ph
1-6544-HE-dioxo2-nBu-4-F-Ph
1-6554-HE-dithio2-nBu-4-F-Ph
1-6564-HE-ocatio2-nBu-4-F-Ph
1-6573-HP-cPent2-nBu-4-F-Ph
1-6584-HP-dioxo2-nBu-4-F-Ph
1-6594-HP-dithio2-nBu-4-F-Ph
1-6604-HP-ocatio2-nBu-4-F-Ph
1-6613-HB-cPent2-nBu-4-F-Ph
1-6624-HB-dioxo2-nBu-4-F-Ph
1-6634-HB-dithio2-nBu-4-F-Ph
1-6644-HB-ocatio2-nBu-4-F-Ph
1-665ring 32-nBu-4-F-Ph
1-666ring 42-nBu-4-F-Ph
1-667ring 52-nBu-4-F-Ph
1-668ring 62-nBu-4-F-Ph
1-669ring 72-nBu-4-F-Ph
1-670ring 82-nBu-4-F-Ph
1-671to whom ICO 9 2-nBu-4-F-Ph
1-672the ring 102-nBu-4-F-Ph
1-6733,4-disne2NHAc-cPent2-nBu-4-F-Ph

1-6744,5-disne2NHAc-dioxo2-nBu-4-F-Ph
1-6754,5-disne2NHAc-dithio2-nBu-4-F-Ph
1-6764,5-disne2NHAc-ocatio2-nBu-4-F-Ph
1-677the ring 112-nBu-4-F-Ph
1-678the ring 122-nBu-4-F-Ph
1-679the ring 132-nBu-4-F-Ph
1-680the ring 142-nBu-4-F-Ph
1-6814-OH-cHex2-nBu-4-F-Ph
1-6825-OH-dioxa2-nBu-4-F-Ph
1-6835-OH-dithia2-nBu-4-F-Ph
1-6845-OH-Ossetia2-nBu-4-F-Ph
1-6854-NHAc-cHex2-nBu-4-F-Ph
1-6865-NHAc-dioxa2-nBu-4-F-Ph
1-6875-NHAc-dithia2-nBu-4-F-Ph
1-6885-NHAc-Ossetia2-nBu-4-F-Ph
1-6894,4-dime-cHex2-nBu-4-F-Ph
1-6905,5-dime-dioxa2-nBu-4-F-Ph
1-6915,5-dime-dithia2-nBu-4-F-Ph
1-6925,5-dime-Ossetia2-nBu-4-F-Ph
1-6934,4-DIMM-cHex2-nBu-4-F-Ph
1-6945,5-dihm-dioxo2-nBu-4-F-Ph
1-6955,5-dihm-dithia2-nBu-4-F-Ph
1-6965,5-dihm-Ossetia2-nBu-4-F-Ph
1-697the ring 152-nBu-4-F-Ph
1-698the ring 162-nBu-4-F-Ph
1-699the ring 172-nBu-4-F-Ph
1-700ring 182-nBu-4-F-Ph
1-7014,4-diso2Et-cHex2-nBu-4-F-Ph
1-7025,5-diso2Et-dioxa2-nBu-4-F-Ph
1-7035,5-diso2Et-dithia2-nBu-4-F-Ph
1-7045,5-diso2Et-Ossetia2-nBu-4-F-Ph
1-705O=2-nHex-Ph
1-706S=2-nHex-Ph
1-707cPr2-nHex-Ph

1-708cBu2-nHex-Ph
1-709cPent2-nHex-Ph
1-710cHex2-nHex-Ph
1-711cHept2-nHex-Ph
1-712hydroxy2-nHex-Ph
1-713oaks2-nHex-Ph
1-714oxo2-nHex-Ph
1-715oxa2-nHex-Ph
1-716dioxo2-nHex-Ph
1-717dioxa2-nHex-Ph
1-718dioxa2-nHex-Ph
1-719ditio 2-nHex-Ph
1-720dithia2-nHex-Ph
1-721the ring 12-nHex-Ph
1-722the ring 22-nHex-Ph
1-723ocatio2-nHex-Ph
1-724Ossetia2-nHex-Ph
1-725ozl2-nHex-Ph
1-726ozn2-nHex-Ph
1-727tzl2-nHex-Ph
1-728tzn2-nHex-Ph
1-7293-HM-cPent2-nHex-Ph
1-7304-HM-dioxo2-nHex-Ph
1-7314-HM-dithio2-nHex-Ph
1-7324-HM-ocatio 2-nHex-Ph
1-7333,4-DIMM-cPent2-nHex-Ph
1-7344,5-dihm-dioxo2-nHex-Ph
1-7354,5-dihm-dithio2-nHex-Ph
1-7364,5-dihm-ocatio2-nHex-Ph
1-7373,4-Dina-cPent2-nHex-Ph
1-7384,5-Dina-dioxo2-nHex-Ph
1-7394,5-Dina-dithio2-nHex-Ph
1-7404,5-Dina-ocatio2-nHex-Ph
1-7413-HE-cPent2-nHex-Ph

1-7424-HE-dioxo2-nHex-Ph
1-7434-HE-dithio2-nHex-Ph
1-7444-HE-ocatio 2-nHex-Ph
1-7453-HP-cPent2-nHex-Ph
1-7464-HP-dioxo2-nHex-Ph
1-7474-HP-dithio2-nHex-Ph
1-7484-HP-ocatio2-nHex-Ph
1-7493-HB-cPent2-nHex-Ph
1-7504-HB-dioxo2-nHex-Ph
1-7514-HB-dithio2-nHex-Ph
1-7524-HB-ocatio2-nHex-Ph
1-753ring 32-nHex-Ph
1-754ring 42-nHex-Ph
1-755ring 52-nHex-Ph
1-756ring 62-nHex-Ph
1-757ring 72-nHex-Ph
1-758ring 82-nHex-Ph
1-759the ring 92-nHex-Ph
1-760the ring 102-nHex-Ph
1-7613,4-disne2NHAc-cPent2-nHex-Ph
1-7624,5-disne2NHAc-dioxo2-nHex-Ph
1-7634,5-disne2NHAc-dithio2-nHex-Ph
1-7644,5-disne2NHAc-ocatio2-nHex-Ph
1-765the ring 112-nHex-Ph
1-766the ring 122-nHex-Ph
1-767the ring 132-nHex-Ph
1-768the ring 142-nHex-Ph
1-69 4-OH-cHex2-nHex-Ph
1-7705-OH-dioxa2-nHex-Ph
1-7715-OH-dithia2-nHex-Ph
1-7725-OH-Ossetia2-nHex-Ph
1-7734-NHAc-cHex2-nHex-Ph
1-7745-NHAc-dioxa2-nHex-Ph
1-7755-NHAc-dithia2-nHex-Ph

1-7765-NHAc-Ossetia2-nHex-Ph
1-7774,4-dime-cHex2-nHex-Ph
1-7785,5-dime-dioxa2-nHex-Ph
1-7795,5-dime-dithia2-nHex-Ph
1-7805,5-dime-Ossetia2-nHex-Ph
1-7814,4-DIMM-cHex2-nHex-Ph
1-7825,5-dihm-dioxo2-nHex-Ph
1-7835,5-dihm-dithia2-nHex-Ph
1-7845,5-dihm-Ossetia2-nHex-Ph
1-785the ring 152-nHex-Ph
1-786the ring 162-nHex-Ph
1-787the ring 172-nHex-Ph
1-788ring 182-nHex-Ph
1-7894,4-diso2Et-cHex2-nHex-Ph
1-7905,5-diso2Et-dioxa2-nHex-Ph
1-7915,5-diso2Et-dithia2-nHex-Ph
1-7925,5-diso2Et-Ossetia2-nHex-Ph
1-793O=4-F-2-nHex-Ph
1-794S=4-F-2-nHex-Ph
1-795cPr4-F-2-nHex-Ph
1-796cBu4-F-2-nHex-Ph
1-797cPent4-F-2-nHex-Ph
1-798cHex4-F-2-nHex-Ph
1-799cHept4-F-2-nHex-Ph
1-800hydroxy4-F-2-nHex-Ph
1-801oaks4-F-2-nHex-Ph
1-802oxo4-F-2-nHex-Ph
1-803oxa4-F-2-nHex-Ph
1-804dioxo4-F-2-nHex-Ph
1-805dioxa4-F-2-nHex-Ph
1-806dioxa4-F-2-nHex-Ph
1-807ditio4-F-2-nHex-Ph
1-808dithia4-F-2-nHex-Ph
1-809the ring 14-F-2-nHex-Ph

1-810the ring 24-F-2-nHex-Ph
1-811ocatio4-F-2-nHex-Ph
1-812Ossetia4-F-2-nHex-Ph
1-813ozl4-F-2-nHex-Ph
1-814ozn4-F-2-nHex-Ph
1-815tzl4-F-2-nHex-Ph
1-816tzn4-F-2-nHex-Ph
1-8173-HM-cPent4-F-2-nHex-Ph
1-818 4-HM-dioxo4-F-2-nHex-Ph
1-8194-HM-dithio4-F-2-nHex-Ph
1-8204-HM-ocatio4-F-2-nHex-Ph
1-8213,4-DIMM-cPent4-F-2-nHex-Ph
1-8224,5-dihm-dioxo4-F-2-nHex-Ph
1-8234,5-dihm-dithio4-F-2-nHex-Ph
1-8244,5-dihm-ocatio4-F-2-nHex-Ph
1-8253,4-Dina-cPent4-F-2-nHex-Ph
1-8264,5-Dina-dioxo4-F-2-nHex-Ph
1-8274,5-Dina-dithio4-F-2-nHex-Ph
1-8284,5-Dina-ocatio4-F-2-nHex-Ph
1-8293-HE-cPent4-F-2-nHex-Ph
1-8304-F-2-nHex-Ph
1-8314-HE-dithio4-F-2-nHex-Ph
1-8324-HE-ocatio4-F-2-nHex-Ph
1-8333-HP-cPent4-F-2-nHex-Ph
1-8344-HP-dioxo4-F-2-nHex-Ph
1-8354-HP-dithio4-F-2-nHex-Ph
1-8364-HP-ocatio4-F-2-nHex-Ph
1-8373-HB-cPent4-F-2-nHex-Ph
1-8384-HB-dioxo4-F-2-nHex-Ph
1-8394-HB-dithio4-F-2-nHex-Ph
1-8404-HB-ocatio4-F-2-nHex-Ph
1-841ring 34-F-2-nHex-Ph
1-842ring 4 4-F-2-nHex-Ph
1-843ring 54-F-2-nHex-Ph

1-844ring 64-F-2-nHex-Ph
1-845ring 74-F-2-nHex-Ph
1-846ring 84-F-2-nHex-Ph
1-847the ring 94-F-2-nHex-Ph
1-848the ring 104-F-2-nHex-Ph
1-8493,4-disne2NHAc-cPent4-F-2-nHex-Ph
1-8504,5-disne2NHAc-dioxo4-F-2-nHex-Ph
1-8514,5-disne2NHAc-dithio4-F-2-nHex-Ph
1-8524,5-disne2NHAc-ocatio4-F-2-nHex-Ph
1-853the ring 114-F-2-nHex-Ph
1-854the ring 124-F-2-nHex-Ph
1-855the ring 134-F-2-nHex-Ph
1-856the ring 144-F-2-nHex-Ph
1-8574-OH-cHex4-F-2-nHex-Ph
1-8585-OH-dioxa4-F-2-nHex-Ph
1-8595-OH-dithia4-F-2-nHex-Ph
1-8605-OH-Ossetia4-F-2-nHex-Ph
1-8614-NHAc-cHex4-F-2-nHex-Ph
1-8625-NHAc-dioxa4-F-2-nHex-Ph
1-8635-NHAc-dithia4-F-2-nHex-Ph
1-8645-NHAc-Ossetia4-F-2-nHex-Ph
1-8654,4-dime-cHex4-F-2-nHex-Ph
1-866 5,5-dime-dioxa4-F-2-nHex-Ph
1-8675,5-dime-dithia4-F-2-nHex-Ph
1-8685,5-dime-Ossetia4-F-2-nHex-Ph
1-8694,4-DIMM-cHex4-F-2-nHex-Ph
1-8705,5-dihm-dioxo4-F-2-nHex-Ph
1-8715,5-dihm-dithia4-F-2-nHex-Ph
1-8725,5-dihm-Ossetia4-F-2-nHex-Ph
1-873the ring 154-F-2-nHex-Ph
1-874the ring 164-F-2-nHex-Ph
1-875the ring 174-F-2-nHex-Ph
1-876ring 184-F-2-nHex-Ph
1-8774,4-diso2Et-cHex4-F-2-nHex-Ph

1-8785,5-diso2Et-dioxa4-F-2-nHex-Ph
1-8795,5-diso2Et-dithia4-F-2-nHex-Ph
1-8805,5-diso2Et-Ossetia4-F-2-nHex-Ph
1-881O=2-nHept-Ph
1-882S=2-nHept-Ph
1-883cPr2-nHept-Ph
1-884cBu2-nHept-Ph
1-885cPent2-nHept-Ph
1-886cHex2-nHept-Ph
1-887cHept2-nHept-Ph
1-888hydroxy2-nHept-Ph
1-889oaks2-nHept-Ph
1-890 oxo2-nHept-Ph
1-891oxa2-nHept-Ph
1-892dioxo2-nHept-Ph
1-893dioxa2-nHept-Ph
1-894dioxa2-nHept-Ph
1-895ditio2-nHept-Ph
1-896dithia2-nHept-Ph
1-897the ring 12-nHept-Ph
1-898the ring 22-nHept-Ph
1-899ocatio2-nHept-Ph
1-900Ossetia2-nHept-Ph
1-901ozl2-nHept-Ph
1-902ozn2-nHept-Ph
1-903 tzl2-nHept-Ph
1-904tzn2-nHept-Ph
1-9053-HM-cPent2-nHept-Ph
1-9064-HM-dioxo2-nHept-Ph
1-9074-HM-dithio2-nHept-Ph
1-9084-HM-ocatio2-nHept-Ph
1-9093,4-DIMM-cPent2-nHept-Ph
1-9104,5-dihm-dioxo2-nHept-Ph
1-9114,5-dihm-dithio2-nHept-Ph

1-9124,5-dihm-ocatio2-nHept-Ph
1-9133,4-Dina-cPent2-nHept-Ph
1-9144,5-Dina-dioxo2-nHept-Ph
1-9154,5-Dina-dithio2-nHept-Ph
1-9164,5-Dina-ocatio2-nHept-Ph
1-9173-HE-cPent2-nHept-Ph
1-9184-HE-dioxo2-nHept-Ph
1-9194-HE-dithio2-nHept-Ph
1-9204-HE-ocatio2-nHept-Ph
1-9213-HP-cPent2-nHept-Ph
1-9224-HP-dioxo2-nHept-Ph
1-9234-HP-dithio2-nHept-Ph
1-9244-HP-ocatio2-nHept-Ph
1-9253-HB-cPent2-nHept-Ph
1-9264-HB-dioxo2-nHept-Ph
1-9274-HB-diti is 2-nHept-Ph
1-9284-HB-ocatio2-nHept-Ph
1-929ring 32-nHept-Ph
1-930ring 42-nHept-Ph
1-931ring 52-nHept-Ph
1-932ring 62-nHept-Ph
1-933ring 72-nHept-Ph
1-934ring 82-nHept-Ph
1-935the ring 92-nHept-Ph
1-936the ring 102-nHept-Ph
1-9373,4-disne2NHAc-cPent2-nHept-Ph
1-9384,5-disne2NHAc-dioxo2-nHept-Ph
1-9394,5-disne2NHAc-dithio 2-nHept-Ph
1-9404,5-disne2NHAc-ocatio2-nHept-Ph
1-941the ring 112-nHept-Ph
1-942the ring 122-nHept-Ph
1-943the ring 132-nHept-Ph
1-944the ring 142-nHept-Ph
1-9454-OH-cHex2-nHept-Ph

1-964
1-9465-OH-dioxa2-nHept-Ph
1-9475-OH-dithia2-nHept-Ph
1-9485-OH-Ossetia2-nHept-Ph
1-9494-NHAc-cHex2-nHept-Ph
1-9505-NHAc-dioxa2-nHept-Ph
1-9515-NHAc-dithia 2-nHept-Ph
1-9525-NHAc-Ossetia2-nHept-Ph
1-9534,4-dime-cHex2-nHept-Ph
1-9545,5-dime-dioxa2-nHept-Ph
1-9555,5-dime-dithia2-nHept-Ph
1-9565,5-dime-Ossetia2-nHept-Ph
1-9574,4-DIMM-cHex2-nHept-Ph
1-9585,5-dihm-dioxo2-nHept-Ph
1-9595,5-dihm-dithia2-nHept-Ph
1-9605,5-dihm-Ossetia2-nHept-Ph
1-961the ring 152-nHept-Ph
1-962the ring 162-nHept-Ph
1-963the ring 172-nHept-Ph
ring 182-nHept-Ph
1-9654,4-diso2Et-cHex2-nHept-Ph
1-9665,5-diso2Et-dioxa2-nHept-Ph
1-9675,5-diso2Et-dithia2-nHept-Ph
1-9685,5-diso2Et-Ossetia2-nHept-Ph
1-969O=4-F-2-nHept-Ph
1-970S=4-F-2-nHept-Ph
1-971cPr4-F-2-nHept-Ph
1-972cBu4-F-2-nHept-Ph
1-973cPent4-F-2-nHept-Ph
1-974cHex4-F-2-nHept-Ph
1-975cHept4-F-2-nHept-Ph
1-976 hydroxy4-F-2-nHept-Ph
1-977oaks4-F-2-nHept-Ph
1-978oxo4-F-2-nHept-Ph
1-979oxa4-F-2-nHept-Ph

1-980dioxo4-F-2-nHept-Ph
1-981dioxa4-F-2-nHept-Ph
1-982dioxa4-F-2-nHept-Ph
1-983ditio4-F-2-nHept-Ph
1-984dithia4-F-2-nHept-Ph
1-985the ring 14-F-2-nHept-Ph
1-986the ring 24-F-2-nHept-Ph
1-987ocatio4-F-2-nHept-Ph
1-988 Ossetia4-F-2-nHept-Ph
1-989ozl4-F-2-nHept-Ph
1-990ozn4-F-2-nHept-Ph
1-991tzl4-F-2-nHept-Ph
1-992tzn4-F-2-nHept-Ph
1-9933-HM-cPent4-F-2-nHept-Ph
1-9944-HM-dioxo4-F-2-nHept-Ph
1-9954-HM-dithio4-F-2-nHept-Ph
1-9964-HM-ocatio4-F-2-nHept-Ph
1-9973,4-DIMM-cPent4-F-2-nHept-Ph
1-9984,5-dihm-dioxo4-F-2-nHept-Ph
1-9994,5-dihm-dithio4-F-2-nHept-Ph
1-10004,5-dihm-ocatio 4-F-2-nHept-Ph
1-10013,4-Dina-cPent4-F-2-nHept-Ph
1-10024,5-Dina-dioxo4-F-2-nHept-Ph
1-10034,5-Dina-dithio4-F-2-nHept-Ph
1-10044,5-Dina-ocatio4-F-2-nHept-Ph
1-10053-HE-cPent4-F-2-nHept-Ph
1-10064-HE-dioxo4-F-2-nHept-Ph
1-10074-HE-dithio4-F-2-nHept-Ph
1-10084-HE-ocatio4-F-2-nHept-Ph
1-10093-HP-cPent4-F-2-nHept-Ph
1-10104-HP-dioxo4-F-2-nHept-Ph
1-10114-HP-dithio4-F-2-nHept-Ph
1-10124-HP-ocatio1-10133-HB-cPent4-F-2-nHept-Ph

1-10144-HB-dioxo4-F-2-nHept-Ph
1-10154-HB-dithio4-F-2-nHept-Ph
1-10164-HB-ocatio4-F-2-nHept-Ph
1-1017ring 34-F-2-nHept-Ph
1-1018ring 44-F-2-nHept-Ph
1-1019ring 54-F-2-nHept-Ph
1-1020ring 64-F-2-nHept-Ph
1-1021ring 74-F-2-nHept-Ph
1-1022ring 84-F-2-nHept-Ph
1-1023the ring 94-F-2-nHept-Ph
1-1024to LCO 10 4-F-2-nHept-Ph
1-10253,4-disne2NHAc-cPent4-F-2-nHept-Ph
1-10264,5-disne2NHAc-dioxo4-F-2-nHept-Ph
1-10274,5-disne2NHAc-dithio4-F-2-nHept-Ph
1-10284,5-disne2NHAc-ocatio4-F-2-nHept-Ph
1-1029the ring 114-F-2-nHept-Ph
1-1030the ring 124-F-2-nHept-Ph
1-1031the ring 134-F-2-nHept-Ph
1-1032the ring 144-F-2-nHept-Ph
1-10334-OH-cHex4-F-2-nHept-Ph
1-10345-OH-dioxa4-F-2-nHept-Ph
1-10355-OH-dithia4-F-2-nHept-Ph
1-1036 5-OH-Ossetia4-F-2-nHept-Ph
1-10374-NHAc-cHex4-F-2-nHept-Ph
1-10385-NHAc-dioxa4-F-2-nHept-Ph
1-10395-NHAc-dithia4-F-2-nHept-Ph
1-10405-NHAc-Ossetia4-F-2-nHept-Ph
1-10414,4-dime-cHex4-F-2-nHept-Ph
1-10425,5-dime-dioxa4-F-2-nHept-Ph
1-10435,5-dime-dithia4-F-2-nHept-Ph
1-10445,5-dime-Ossetia4-F-2-nHept-Ph
1-10454,4-DIMM-cHex4-F-2-nHept-Ph
1-10465,5-dihm-dioxo4-F-2-nHept-Ph
1-10475,5-dihm-dithia4-F-2-nHept-Ph

1-10485,5-dihm-Ossetia4-F-2-nHept-Ph
1-1049the ring 154-F-2-nHept-Ph
1-1050the ring 164-F-2-nHept-Ph
1-1051the ring 174-F-2-nHept-Ph
1-1052ring 184-F-2-nHept-Ph
1-10534,4-diso2Et-cHex4-F-2-nHept-Ph
1-10545,5-diso2Et-dioxa4-F-2-nHept-Ph
1-10555,5-diso2Et-dithia4-F-2-nHept-Ph
1-10565,5-diso2Et-Ossetia4-F-2-nHept-Ph
1-1057H,HPyr
1-1058O=Pyr
1-1059S=Pyr
1-1060cPentPyr
1-1061cHexPyr
1-1062dioxoPyr
1-1063dioxaPyr
1-1064ditioPyr
1-1065dithiaPyr
1-1066ocatioPyr
1-1067OssetiaPyr
1-10684-HM-dioxoPyr
1-10694,5-dihm-dioxoPyr
1-10704,5-Dina-dioxoPyr
1-10715-OH-dioxaPyr
1-10725-NHAc-dioxaPyr
1-10735,5-dihm-dioxoPyr
1-1074H,H2-F-Pyr
1-1075O=2-F-Pyr
1-1076S=2-F-Pyr
1-1077cPent2-F-Pyr
1-1078cHex2-F-Pyr
1-1079dioxo2-F-Pyr
1-1080dioxa2-F-Pyr
1-1081ditio2-F-Pyr

1-1082dithia2-F-Pyr
1-1083ocatio2-F-Pyr
1-1084Ossetia2-F-Pyr
1-1085 4-HM-dioxo2-F-Pyr
1-10864,5-dihm-dioxo2-F-Pyr
1-10874,5-Dina-dioxo2-F-Pyr
1-10885-OH-dioxa2-F-Pyr
1-10895-NHAc-dioxa2-F-Pyr
1-10905,5-dihm-dioxo2-F-Pyr
1-1091H,H2-Cl-Pyr
1-1092O=2-Cl-Pyr
1-1093S=2-Cl-Pyr
1-1094cPent2-Cl-Pyr
1-1095cHex2-Cl-Pyr
1-1096dioxo2-Cl-Pyr
1-1097dioxa2-Cl-Pyr
-1098 ditio2-Cl-Pyr
1-1099dithia2-Cl-Pyr
1-1100ocatio2-Cl-Pyr
1-1101Ossetia2-Cl-Pyr
1-11024-HM-dioxo2-Cl-Pyr
1-11034,5-dihm-dioxo2-Cl-Pyr
1-11044,5-Dina-dioxo2-Cl-Pyr
1-11055-OH-dioxa2-Cl-Pyr
1-11065-NHAc-dioxa2-Cl-Pyr
1-11075,5-dihm-dioxo2-Cl-Pyr
1-1108H,H2-Br-Pyr
1-1109O=2-Br-Pyr
1-1110S=2-r-Pyr
1-1111cPent2-Br-Pyr
1-1112cHex2-Br-Pyr
1-1113dioxo2-Br-Pyr
1-1114dioxa2-Br-Pyr
1-1115ditio2-Br-Pyr

1-1116dithia2-Br-Pyr
1-1117ocatio2-Br-Pyr
1-1118Ossetia2-Br-Pyr
1-11194-HM-dioxo2-Br-Pyr
1-11204,5-dihm-dioxo2-Br-Pyr
1-11214,5-Dina-dioxo2-Br-Pyr
1-11225-OH-dioxa2-Br-Pyr
1-11235-NHAc-dioxa2-Br-Pyr
1-11245,5-dihm-dioxo2-Br-Pyr
1-1125H,H2,5-F-Pyr
1-1126O=2,5-F-Pyr
1-1127S=2,5-F-Pyr
1-1128cPent2,5-F-Pyr
1-1129cHex2,5-F-Pyr
1-1130dioxo2,5-F-Pyr
1-1131dioxa2,5-F-Pyr
1-1132ditio2,5-F-Pyr
1-1133dithia2,5-F-Pyr
1-1134ocatio2,5-F-Pyr
1-1135Ossetia 2,5-F-Pyr
1-11364-HM-dioxo2,5-F-Pyr
1-11374,5-dihm-dioxo2,5-F-Pyr
1-11384,5-Dina-dioxo2,5-F-Pyr
1-11395-OH-dioxa2,5-F-Pyr
1-11405-NHAc-dioxa2,5-F-Pyr
1-11415,5-dihm-dioxo2,5-F-Pyr
1-1142H,H2,5-Cl-Pyr
1-1143O=2,5-Cl-Pyr
1-1144S=2,5-Cl-Pyr
1-1145cPent2,5-Cl-Pyr
1-1146cHex2,5-Cl-Pyr
1-1147dioxo2,5-Cl-Pyr
1-1148dioxa2,5-Cl-Pyr
1-1149ditio2,5-Cl-Pyr

1-1150dithia2,5-Cl-Pyr
1-1151ocatio2,5-Cl-Pyr
1-1152Ossetia2,5-Cl-Pyr
1-11534-HM-dioxo2,5-Cl-Pyr
1-11544,5-dihm-dioxo2,5-Cl-Pyr
1-11554,5-Dina-dioxo2,5-Cl-Pyr
1-11565-OH-dioxa2,5-Cl-Pyr
1-11575-NHAc-dioxa2,5-Cl-Pyr
1-11585,5-dihm-dioxo2,5-Cl-Pyr
1-1159H,HA 5-divg-Pyr
1-1160O=2,5-divg-Pyr
1-1161S=2,5-divg-Pyr
1-1162cPent2,5-divg-Pyr
1-1163cHex2,5-divg-Pyr
1-1164dioxo2,5-divg-Pyr
1-1165dioxa2,5-divg-Pyr
1-1166ditio2,5-divg-Pyr
1-1167dithia2,5-divg-Pyr
1-1168ocatio2,5-divg-Pyr
1-1169Ossetia2,5-divg-Pyr
1-11704-HM-dioxo2,5-divg-Pyr
1-11714,5-dihm-dioxo2,5-divg-Pyr
1-1172 4,5-Dina-dioxo2,5-divg-Pyr
1-11735-OH-dioxa2,5-divg-Pyr
1-11745-NHAc-dioxa2,5-divg-Pyr
1-11755,5-dihm-dioxo2,5-divg-Pyr
1-1176H,H2-Me-Pyr
1-1177O=2-Me-Pyr
1-1178S=2-Me-Pyr
1-1179cPent2-Me-Pyr
1-1180cHex2-Me-Pyr
1-1181dioxo2-Me-Pyr
1-1182dioxa2-Me-Pyr
1-1183ditio2-Me-Pyr

1-1210
1-1184dithia 2-Me-Pyr
1-1185ocatio2-Me-Pyr
1-1186Ossetia2-Me-Pyr
1-11874-HM-dioxo2-Me-Pyr
1-11884,5-dihm-dioxo2-Me-Pyr
1-11894,5-Dina-dioxo2-Me-Pyr
1-11905-OH-dioxa2-Me-Pyr
1-11915-NHAc-dioxa2-Me-Pyr
1-11925,5-dihm-dioxo2-Me-Pyr
1-1193H,H2-Et-Pyr
1-1194O=2-Et-Pyr
1-1195S=2-Et-Pyr
1-1196cPent2-Et-Pyr
1-1197 cHex2-Et-Pyr
1-1198dioxo2-Et-Pyr
1-1199dioxa2-Et-Pyr
1-1200ditio2-Et-Pyr
1-1201dithia2-Et-Pyr
1-1202ocatio2-Et-Pyr
1-1203Ossetia2-Et-Pyr
1-12044-HM-dioxo2-Et-Pyr
1-12054,5-dihm-dioxo2-Et-Pyr
1-12064,5-Dina-dioxo2-Et-Pyr
1-12075-OH-dioxa2-Et-Pyr
1-12085-NHAc-dioxa2-Et-Pyr
1-12095,5-dihm-dioxo2-Et-Pyr
H,H2-nPr-Pyr
1-1211O=2-nPr-Pyr
1-1212S=2-nPr-Pyr
1-1213cPent2-nPr-Pyr
1-1214cHex2-nPr-Pyr
1-1215dioxo2-nPr-Pyr
1-1216dioxa2-nPr-Pyr
1-1217ditio2-nPr-Pyr

1-1218dithia2-nPr-Pyr
1-1219ocatio2-nPr-Pyr
1-1220Ossetia2-nPr-Pyr
1-12214-HM-dioxo2-nPr-Pyr
1-12224,5-dim-dioxo 2-nPr-Pyr
1-12234,5-Dina-dioxo2-nPr-Pyr
1-12245-OH-dioxa2-nPr-Pyr
1-12255-NHAc-dioxa2-nPr-Pyr
1-12265,5-dihm-dioxo2-nPr-Pyr
1-1227H,H2-nBu-Pyr
1-1228O=2-nBu-Pyr
1-1229S=2-nBu-Pyr
1-1230cPent2-nBu-Pyr
1-1231cHex2-nBu-Pyr
1-1232dioxo2-nBu-Pyr
1-1233dioxa2-nBu-Pyr
1-1234ditio2-nBu-Pyr
1-1235 dithia2-nBu-Pyr
1-1236ocatio2-nBu-Pyr
1-1237Ossetia2-nBu-Pyr
1-12384-HM-dioxo2-nBu-Pyr
1-12394,5-dihm-dioxo2-nBu-Pyr
1-12404,5-Dina-dioxo2-nBu-Pyr
1-12415-OH-dioxa2-nBu-Pyr
1-12425-NHAc-dioxa2-nBu-Pyr
1-12435,5-dihm-dioxo2-nBu-Pyr
1-1244H,H2-nPent-Pyr
1-1245O=2-nPent-Pyr
1-1246S=2-nPent-Pyr
1-1247cPent2-nPent-Pyr
1-1248cHex2-nPent-Pyr
1-1249dioxo2-nPent-Pyr
1-1250dioxa2-nPent-Pyr
1-1251ditio2-nPent-Pyr

1-1252dithia2-nPent-Pyr
1-1253ocatio2-nPent-Pyr
1-1254Ossetia2-nPent-Pyr
1-12554-HM-dioxo2-nPent-Pyr
1-12564,5-dihm-dioxo2-nPent-Pyr
1-12574,5-Dina-dioxo2-nPent-Pyr
1-12585-OH-dioxa2-nPent-Pyr
1-12595-NHAc-dioxa2-nPent-Pyr
1-12605,5-dihm-dioxo2-nPent-Pyr
1-1261H,H2-nHex-Pyr
1-1262O=2-nHex-Pyr
1-1263S=2-nHex-Pyr
1-1264cPent2-nHex-Pyr
1-1265cHex2-nHex-Pyr
1-1266dioxo2-nHex-Pyr
1-1267dioxa2-nHex-Pyr
1-1268ditio2-nHex-Pyr
1-1269dithia2-nHex-Pyr
1-1270ocatio2-nHex-Pyr
1-1271Ossetia2-nHex-Pyr
1-12724-HM-dioxo2-nHex-Pyr
1-12734,5-dihm-dioxo2-nHex-Pyr
1-12744,5-Dina-dioxo2-nHex-Pyr
1-12755-OH-dioxa2-nHex-Pyr
1-12765-NHAc-dioxa2-nHex-Pyr
1-12775,5-dihm-dioxo2-nHex-Pyr
1-1278H,H2-nHept-Pyr
1-1279O=2-nHept-Pyr
1-1280S=2-nHept-Pyr
1-1281cPent2-nHept-Pyr
1-1282cHex2-nHept-Pyr
1-1283dioxo2-nHept-Pyr
1-1284dioxa2-nHept-Pyr
1-1285 ditio2-nHept-Pyr

1-1286dithia2-nHept-Pyr
1-1287ocatio2-nHept-Pyr
1-1288Ossetia2-nHept-Pyr
1-12894-HM-dioxo2-nHept-Pyr
1-12904,5-dihm-dioxo2-nHept-Pyr
1-12914,5-Dina-dioxo2-nHept-Pyr
1-12925-OH-dioxa2-nHept-Pyr
1-12935-NHAc-dioxa2-nHept-Pyr
1-12945,5-dihm-dioxo2-nHept-Pyr
1-1295H,H2-nOct-Pyr
1-1296O=2-nOct-Pyr
1-1297 S=2-nOct-Pyr
1-1298cPent2-nOct-Pyr
1-1299cHex2-nOct-Pyr
1-1300dioxo2-nOct-Pyr
1-1301dioxa2-nOct-Pyr
1-1302ditio2-nOct-Pyr
1-1303dithia2-nOct-Pyr
1-1304ocatio2-nOct-Pyr
1-1305Ossetia2-nOct-Pyr
1-13064-HM-dioxo2-nOct-Pyr
1-13074,5-dihm-dioxo2-nOct-Pyr
1-13084,5-Dina-dioxo2-nOct-Pyr
1-13095-OH-dioxa2-nOct-Pyr
1-13105-NHAc-dioxa2-nOct-Pyr
1-13115,5-dihm-dioxo2-nOct-Pyr
1-1312H,H2-cPrl-Pyr
1-1313O=2-cPrl-Pyr
1-1314S=2-cPrl-Pyr
1-1315cPent2-cPrl-Pyr
1-1316cHex2-cPrl-Pyr
1-1317dioxo2-cPrl-Pyr
1-1318dioxa2-cPrl-Pyr
1-1319ditio2-cPrl-Pyr

1-1320dithia2-cPrl-Pyr
1-1321ocatio2-cPrl-Pyr
1-13222-cPrl-Pyr
1-13234-HM-dioxo2-cPrl-Pyr
1-13244,5-dihm-dioxo2-cPrl-Pyr
1-13254,5-Dina-dioxo2-cPrl-Pyr
1-13265-OH-dioxa2-cPrl-Pyr
1-13275-NHAc-dioxa2-cPrl-Pyr
1-13285,5-dihm-dioxo2-cPrl-Pyr
1-1329H,H2-Ph-Pyr
1-1330O=2-Ph-Pyr
1-1331S=2-Ph-Pyr
1-1332cPent2-Ph-Pyr
1-1333cHex2-Ph-Pyr
1-1334dioxo2-Ph-Pyr
1-1335dioxa2-Ph-Pyr
1-1336ditio2-Ph-Pyr
1-1337dithia2-Ph-Pyr
1-1338ocatio2-Ph-Pyr
1-1339Ossetia2-Ph-Pyr
1-13404-HM-dioxo2-Ph-Pyr
1-13414,5-dihm-dioxo2-Ph-Pyr
1-13424,5-Dina-dioxo2-Ph-Pyr
1-13435-OH-dioxa2-Ph-Pyr
1-13445-NHAc-dioxa2-Ph-Pyr
1-13455,5-dihm-dioxo2-Ph-Pyr
1-1346H,H2,5-dime-Pyr
1-1347O= 2,5-dime-Pyr
1-1348S=2,5-dime-Pyr
1-1349cPent2,5-dime-Pyr
1-1350cHex2,5-dime-Pyr
1-1351dioxo2,5-dime-Pyr
1-1352dioxa2,5-dime-Pyr
1-1353ditio2,5-dime-Pyr

1-1354dithia2,5-dime-Pyr
1-1355ocatio2,5-dime-Pyr
1-1356Ossetia2,5-dime-Pyr
1-13574-HM-dioxo2,5-dime-Pyr
1-13584,5-dihm-dioxo2,5-dime-Pyr
1-13594,5-Dina-dioxo 2,5-dime-Pyr
1-13605-OH-dioxa2,5-dime-Pyr
1-13615-NHAc-dioxa2,5-dime-Pyr
1-13625,5-dihm-dioxo2,5-dime-Pyr
1-1363O=2-Br-Ph
1-1364S=2-Br-Ph
1-1365cPr2-Br-Ph
1-1366cBu2-Br-Ph
1-1367cPent2-Br-Ph
1-1368cHex2-Br-Ph
1-1369cHept2-Br-Ph
1-1370hydroxy2-Br-Ph
1-1371oaks2-Br-Ph
1-1372oxo 2-Br-Ph
1-1373oxa2-Br-Ph
1-1374dioxo2-Br-Ph
1-1375dioxa2-Br-Ph
1-1376dioxa2-Br-Ph
1-1377ditio2-Br-Ph
1-1378dithia2-Br-Ph
1-1379the ring 12-Br-Ph
1-1380the ring 22-Br-Ph
1-1381ocatio2-Br-Ph
1-1382Ossetia2-Br-Ph
1-1383ozl2-Br-Ph
1-1384ozn2-Br-Ph
1-1385tzl 2-Br-Ph
1-1386tzn2-Br-Ph
1-13873-HM-cPent2-Br-Ph

1-13884-HM-dioxo2-Br-Ph
1-13894-HM-dithio2-Br-Ph
1-13904-HM-ocatio2-Br-Ph
1-13913,4-DIMM-cPent2-Br-Ph
1-13924,5-dihm-dioxo2-Br-Ph
1-13934,5-dihm-dithio2-Br-Ph
1-13944,5-dihm-ocatio2-Br-Ph
1-13953,4-Dina-cPent2-Br-Ph
1-13964,5-Dina-dioxo2-Br-Ph
1-13974,5-Dina-dithio1-13984,5-Dina-ocatio2-Br-Ph
1-13993-HE-cPent2-Br-Ph
1-14004-HE-dioxo2-Br-Ph
1-14014-HE-dithio2-Br-Ph
1-14024-HE-ocatio2-Br-Ph
1-14033-HP-cPent2-Br-Ph
1-14044-HP-dioxo2-Br-Ph
1-14054-HP-dithio2-Br-Ph
1-14064-HP-ocatio2-Br-Ph
1-14073-HB-cPent2-Br-Ph
1-14084-HB-dioxo2-Br-Ph
1-14094-HB-dithio2-Br-Ph
1-1410 4-HB-ocatio2-Br-Ph
1-1411ring 32-Br-Ph
1-1412ring 42-Br-Ph
1-1413ring 52-Br-Ph
1-1414ring 62-Br-Ph
1-1415ring 72-Br-Ph
1-1416ring 82-Br-Ph
1-1417the ring 92-Br-Ph
1-1418the ring 102-Br-Ph
1-14193,4-disne2NHAc-cPent2-Br-Ph
1-14204,5-disne2NHAc-dioxo2-Br-Ph
1-14214,5-disne2NHAc-dithio2-Br-Ph

1-142 4,5-disne2NHAc-ocatio2-Br-Ph
1-1423the ring 112-Br-Ph
1-1424the ring 122-Br-Ph
1-1425the ring 132-Br-Ph
1-1426the ring 142-Br-Ph
1-14274-OH-cHex2-Br-Ph
1-14285-OH-dioxa2-Br-Ph
1-14295-OH-dithia2-Br-Ph
1-14305-OH-Ossetia2-Br-Ph
1-14314-NHAc-cHex2-Br-Ph
1-14325-NHAc-dioxa2-Br-Ph
1-14335-NHAc-dithia2-Br-Ph
1-14345-NHAc-Ossetia 2-Br-Ph
1-14354,4-dime-cHex2-Br-Ph
1-14365,5-dime-dioxa2-Br-Ph
1-14375,5-dime-dithia2-Br-Ph
1-14385,5-dime-Ossetia2-Br-Ph
1-14394,4-DIMM-cHex2-Br-Ph
1-14405,5-dihm-dioxo2-Br-Ph
1-14415,5-dihm-dithia2-Br-Ph
1-14425,5-dihm-Ossetia2-Br-Ph
1-1443the ring 152-Br-Ph
1-1444the ring 162-Br-Ph
1-1445the ring 172-Br-Ph
1-1446ring 182-Br-Ph
1-14474,4-diso2Et-cHex2-Br-Ph
1-14485,5-diso2Et-dioxa2-Br-Ph
1-14495,5-diso2Et-dithia2-Br-Ph
1-14505,5-diso2Et-Ossetia2-Br-Ph
1-1451O=2-Cl-6-Me-Ph
1-1452S=2-Cl-6-Me-Ph
1-1453cPr2-Cl-6-Me-Ph
1-1454cBu2-Cl-6-Me-Ph
1-1455cPent2-Cl-6-Me-Ph

1-1456cHex2-Cl-6-Me-Ph
1-1457cHept2-Cl-6-Me-Ph
1-1458hydroxy2-Cl-6-Me-Ph
1-1459oaks2-Cl-6-Me-Ph
1-1460oxo2-Cl-6-Me-Ph
1-1461oxa2-Cl-6-Me-Ph
1-1462dioxo2-Cl-6-Me-Ph
1-1463dioxa2-Cl-6-Me-Ph
1-1464dioxa2-Cl-6-Me-Ph
1-1465ditio2-Cl-6-Me-Ph
1-1466dithia2-Cl-6-Me-Ph
1-1467the ring 12-Cl-6-Me-Ph
1-1468the ring 22-Cl-6-Me-Ph
1-1469ocatio2-Cl-6-Me-Ph
1-1470Ossetia2-Cl-6-Me-Ph
1-1471ozl 2-Cl-6-Me-Ph
1-1472ozn2-Cl-6-Me-Ph
1-1473tzl2-Cl-6-Me-Ph
1-1474tzn2-Cl-6-Me-Ph
1-14753-HM-cPent2-Cl-6-Me-Ph
1-14764-HM-dioxo2-Cl-6-Me-Ph
1-14774-HM-dithio2-Cl-6-Me-Ph
1-14784-HM-ocatio2-Cl-6-Me-Ph
1-14793,4-DIMM-cPent2-Cl-6-Me-Ph
1-14804,5-dihm-dioxo2-Cl-6-Me-Ph
1-14814,5-dihm-dithio2-Cl-6-Me-Ph
1-14824,5-dihm-ocatio2-Cl-6-Me-Ph
1-14833,4-Dina-cPent2-Cl-6-Me-Ph
1-14844,5-Dina-dioxo2-Cl-6-Me-Ph
1-14854,5-Dina-dithio2-Cl-6-Me-Ph
1-14864,5-Dina-ocatio2-Cl-6-Me-Ph
1-14873-HE-cPent2-Cl-6-Me-Ph
1-14884-HE-dioxo2-Cl-6-Me-Ph
1-14894-HE-dithio2-Cl-6-Me-Ph

1-14904-HE-ocatio2-Cl-6-Me-Ph
1-14913-HP-cPent2-Cl-6-Me-Ph
1-14924-HP-dioxo2-Cl-6-Me-Ph
1-14934-HP-dithio2-Cl-6-Me-Ph
1-14944-HP-ocatio2-Cl-6-Me-Ph
1-14953-HB-cPent2-Cl-6Me-Ph
1-14964-HB-dioxo2-Cl-6-Me-Ph
1-14974-HB-dithio2-Cl-6-Me-Ph
1-14984-HB-ocatio2-Cl-6-Me-Ph
1-1499ring 32-Cl-6-Me-Ph
1-1500ring 42-Cl-6-Me-Ph
1-1501ring 52-Cl-6-Me-Ph
1-1502ring 62-Cl-6-Me-Ph
1-1503ring 72-Cl-6-Me-Ph
1-1504ring 82-Cl-6-Me-Ph
1-1505the ring 92-Cl-6-Me-Ph
1-1506the ring 102-Cl-6-Me-Ph
1-15073,4-disne2NHAc-cPent2-Cl-6-Me-Ph
1-15084,5-disne2NHAc-dioxo2-Cl-6-Me-Ph
1-15094,5-disne2NHAc-dithio2-Cl-6-Me-Ph
1-15104,5-disne2NHAc-ocatio2-Cl-6-Me-Ph
1-1511the ring 112-Cl-6-Me-Ph
1-1512the ring 122-Cl-6-Me-Ph
1-1513the ring 132-Cl-6-Me-Ph
1-1514the ring 142-Cl-6-Me-Ph
1-15154-OH-cHex2-Cl-6-Me-Ph
1-15165-OH-dioxa2-Cl-6-Me-Ph
1-15175-OH-dithia2-Cl-6-Me-Ph
1-15185-OH-Ossetia2-Cl-6-Me-Ph
1-15194-NHAc-cHex2-Cl-6-Me-Ph
1-15205-NHAc-dioxa2-Cl-6-Me-Ph
1-15215-NHAc-dithia2-Cl-6-Me-Ph
1-15225-NHAc-Ossetia2-Cl-6-Me-Ph
1-15234,4-dime-cHex2-Cl-6-Me-Ph

1-15245,5-dime-dioxa2-Cl-6-Me-Ph
1-15255,5-dime-dithia2-Cl-6-Me-Ph
1-15265,5-dime-Ossetia2-Cl-6-Me-Ph
1-15274,4-DIMM-cHex2-Cl-6-Me-Ph
1-15285,5-dihm-dioxo2-Cl-6-Me-Ph
1-15295,5-dihm-dithia2-Cl-6-Me-Ph
1-15305,5-dihm-Ossetia2-Cl-6-Me-Ph
1-1531the ring 15 2-Cl-6-Me-Ph
1-1532the ring 162-Cl-6-Me-Ph
1-1533the ring 172-Cl-6-Me-Ph
1-1534ring 182-Cl-6-Me-Ph
1-15354,4-diso2Et-cHex2-Cl-6-Me-Ph
1-15365,5-diso2Et-dioxa2-Cl-6-Me-Ph
1-15375,5-diso2Et-dithia2-Cl-6-Me-Ph
1-15385,5-diso2Et-Ossetia2-Cl-6-Me-Ph
1-1539O=2-Br-4-F-Ph
1-1540S=2-Br-4-F-Ph
1-1541cPr2-Br-4-F-Ph
1-1542cBu2-Br-4-F-Ph
1-1543cPent2-Br-4-F-Ph
1-1544cHex2-Br-4-F-Ph
1-1545cHept2-Br-4-F-Ph
1-1546hydroxy2-Br-4-F-Ph
1-1547oaks2-Br-4-F-Ph
1-1548oxo2-Br-4-F-Ph
1-1549oxa2-Br-4-F-Ph
1-1550dioxo2-Br-4-F-Ph
1-1551dioxa2-Br-4-F-Ph
1-1552dioxa2-Br-4-F-Ph
1-1553ditio2-Br-4-F-Ph
1-1554dithia2-Br-4-F-Ph
1-1555the ring 12-Br-4-F-Ph
1-1556the ring 2 2-Br-4-F-Ph
1-1557ocatio2-Br-4-F-Ph

1-1558Ossetia2-Br-4-F-Ph
1-1559ozl2-Br-4-F-Ph
1-1560ozn2-Br-4-F-Ph
1-1561tzl2-Br-4-F-Ph
1-1562tzn2-Br-4-F-Ph
1-15633-HM-cPent2-Br-4-F-Ph
1-15644-HM-dioxo2-Br-4-F-Ph
1-15654-HM-dithio2-Br-4-F-Ph
1-15664-HM-ocatio2-Br-4-F-Ph
1-15673,4-DIMM-cPent2-Br-4-F-Ph
1-15684,5-dihm-dioxo2-Br-4F-Ph
1-15694,5-dihm-dithio2-Br-4-F-Ph
1-15704,5-dihm-ocatio2-Br-4-F-Ph
1-15713,4-Dina-cPent2-Br-4-F-Ph
1-15724,5-Dina-dioxo2-Br-4-F-Ph
1-15734,5-Dina-dithio2-Br-4-F-Ph
1-15744,5-Dina-ocatio2-Br-4-F-Ph
1-15753-HE-cPent2-Br-4-F-Ph
1-15764-HE-dioxo2-Br-4-F-Ph
1-15774-HE-dithio2-Br-4-F-Ph
1-15784-HE-ocatio2-Br-4-F-Ph
1-15793-HP-cPent2-Br-4-F-Ph
1-15804-HP-dioxo2-Br-4-F-Ph
1-15814-HP-dithio2-Br-4-F-Ph
1-15824-HP-ocatio2-Br-4-F-Ph
1-15833-HB-cPent2-Br-4-F-Ph
1-15844-HB-dioxo2-Br-4-F-Ph
1-15854-HB-dithio2-Br-4-F-Ph
1-15864-HB-ocatio2-Br-4-F-Ph
1-1587ring 32-Br-4-F-Ph
1-1588ring 42-Br-4-F-Ph
1-1589ring 52-Br-4-F-Ph
1-1590ring 62-Br-4-F-Ph
1-1591ring 72-Br-4-F-Ph

1-1592ring 82-Br-4-F-Ph
1-1593the ring 92-Br-4-F-Ph
1-1594the ring 102-Br-4-F-Ph
1-15953,4-disne2NHAc-cPent2-Br-4-F-Ph
1-15964,5-disne2NHAc-dioxo2-Br-4-F-Ph
1-15974,5-disne2NHAc-dithio2-Br-4-F-Ph
1-15984,5-disne2NHAc-ocatio2-Br-4-F-Ph
1-1599the ring 112-Br-4-F-Ph
1-1600the ring 122-Br-4-F-Ph
1-1601the ring 132-Br-4-F-Ph
1-1602the ring 142-Br-4-F-Ph
1-16034-OH-cHex2-Br-4-F-Ph
1-16045-OH-dioxa2-Br-4-F-Ph
1-16055-OH-dithia2-Br-4-F-Ph
1-16065-OH-Ossetia2-Br-4-F-Ph
1-16074-NHAc-cHex2-Br-4-F-Ph
1-16085-NHAc-dioxa2-Br-4-F-Ph
1-16095-NHAc-dithia2-Br-4-F-Ph
1-16105-NHAc-Ossetia2-Br-4-F-Ph
1-16114,4-dime-cHex2-Br-4-F-Ph
1-16125,5-dime-dioxa2-Br-4-F-Ph
1-16135,5-dime-dithia2-Br-4-F-Ph
1-16145,5-dime-Ossetia2-Br-4-F-Ph
1-16154,4-DIMM-cHex2-Br-4-F-Ph
1-16165,5-dihm-dioxo2-Br-4-F-Ph
1-1617 5,5-dihm-dithia2-Br-4-F-Ph
1-16185,5-dihm-Ossetia2-Br-4-F-Ph
1-1619the ring 152-Br-4-F-Ph
1-1620the ring 162-Br-4-F-Ph
1-1621the ring 172-Br-4-F-Ph
1-1622ring 182-Br-4-F-Ph
1-16234,4-diso2Et-cHex2-Br-4-F-Ph
1-16245,5-diso2Et-dioxa2-Br-4-F-Ph
1-16255,5-diso2Et-dithia2-Br-4-F-Ph

1-16265,5-diso2Et-Ossetia2-Br-4-F-Ph
1-1627O=2-nPent-Ph
1-1628S=2-nPent-Ph
1-1629cPr2-nPent-Ph
1-1630cBu2-nPent-Ph
1-1631cPent2-nPent-Ph
1-1632cHex2-nPent-Ph
1-1633cHept2-nPent-Ph
1-1634hydroxy2-nPent-Ph
1-1635oaks2-nPent-Ph
1-1636oxo2-nPent-Ph
1-1637oxa2-nPent-Ph
1-1638dioxo2-nPent-Ph
1-1639dioxa2-nPent-Ph
1-1640dioxa2-nPent-Ph
1-1641ditio1-1642dithia2-nPent-Ph
1-1643the ring 12-nPent-Ph
1-1644the ring 22-nPent-Ph
1-1645ocatio2-nPent-Ph
1-1646Ossetia2-nPent-Ph
1-1647ozl2-nPent-Ph
1-1648ozn2-nPent-Ph
1-1649tzl2-nPent-Ph
1-1650tzn2-nPent-Ph
1-16513-HM-cPent2-nPent-Ph
1-16524-HM-dioxo2-nPent-Ph
1-16534-HM-dithio2-nPent-Ph
1-16544 Smokstik 2-nPent-Ph
1-16553,4-DIMM-cPent2-nPent-Ph
1-16564,5-dihm-dioxo2-nPent-Ph
1-16574,5-dihm-dithio2-nPent-Ph
1-16584,5-dihm-ocatio2-nPent-Ph
1-16593,4-Dina-cPent2-nPent-Ph

1-16604,5-Dina-dioxo2-nPent-Ph
1-16614,5-Dina-dithio2-nPent-Ph
1-16624,5-Dina-ocatio2-nPent-Ph
1-16633-HE-cPent2-nPent-Ph
1-16644-HE-dioxo2-nPent-Ph
1-16654-HE-dithio2-nPent-Ph
1-1666 4-HE-ocatio2-nPent-Ph
1-16673-HP-cPent2-nPent-Ph
1-16684-HP-dioxo2-nPent-Ph
1-16694-HP-dithio2-nPent-Ph
1-16704-HP-ocatio2-nPent-Ph
1-16713-HB-cPent2-nPent-Ph
1-16724-HB-dioxo2-nPent-Ph
1-16734-HB-dithio2-nPent-Ph
1-16744-HB-ocatio2-nPent-Ph
1-1675ring 32-nPent-Ph
1-1676ring 42-nPent-Ph
1-1677ring 52-nPent-Ph
1-1678ring 6 2-nPent-Ph
1-1679ring 72-nPent-Ph
1-1680ring 82-nPent-Ph
1-1681the ring 92-nPent-Ph
1-1682the ring 102-nPent-Ph
1-16833,4-disne2NHAc-cPent2-nPent-Ph
1-16844,5-disne2NHAc-dioxo2-nPent-Ph
1-16854,5-disne2NHAc-dithio2-nPent-Ph
1-16864,5-disne2NHAc-ocatio2-nPent-Ph
1-1687the ring 112-nPent-Ph
1-1688the ring 122-nPent-Ph
1-1689the ring 132-nPent-Ph
1-1690the ring 14 2-nPent-Ph
1-16914-OH-cHex2-nPent-Ph
1-16925-OH-dioxa2-nPent-Ph
1-16935-OH-dithia2-nPent-Ph

1-16945-OH-Ossetia2-nPent-Ph
1-16954-NHAc-cHex2-nPent-Ph
1-16965-NHAc-dioxa2-nPent-Ph
1-16975-NHAc-dithia2-nPent-Ph
1-16985-NHAc-Ossetia2-nPent-Ph
1-16994,4-dime-cHex2-nPent-Ph
1-17005,5-dime-dioxa2-nPent-Ph
1-17015,5-dime-dithia2-nPent-Ph
1-17025,5-dime-axat is and 2-nPent-Ph
1-17034,4-DIMM-cHex2-nPent-Ph
1-17045,5-dihm-dioxo2-nPent-Ph
1-17055,5-dihm-dithia2-nPent-Ph
1-17065,5-dihm-Ossetia2-nPent-Ph
1-1707the ring 152-nPent-Ph
1-1708the ring 162-nPent-Ph
1-1709the ring 172-nPent-Ph
1-1710ring 182-nPent-Ph
1-17114,4-diso2Et-cHex2-nPent-Ph
1-17125,5-diso2Et-dioxa2-nPent-Ph
1-17135,5-diso2Et-dithia2-nPent-Ph
1-17145,5-d the CO 2Et-Ossetia2-nPent-Ph
1-1715O=4-F-2-nPent-Ph
1-1716S=4-F-2-nPent-Ph
1-1717cPr4-F-2-nPent-Ph
1-1718cBu4-F-2-nPent-Ph
1-1719cPent4-F-2-nPent-Ph
1-1720cHex4-F-2-nPent-Ph
1-1721cHept4-F-2-nPent-Ph
1-1722hydroxy4-F-2-nPent-Ph
1-1723oaks4-F-2-nPent-Ph
1-1724oxo4-F-2-nPent-Ph
1-1725oxa4-F-2-nPent-Ph
1-1726dioxo4-F-2-nPent-Ph
1-1727dioxa4-F-2-nPent-Ph

1-1728dioxa4-F-2-nPent-Ph
1-1729ditio4-F-2-nPent-Ph
1-1730dithia4-F-2-nPent-Ph
1-1731the ring 14-F-2-nPent-Ph
1-1732the ring 24-F-2-nPent-Ph
1-1733ocatio4-F-2-nPent-Ph
1-1734Ossetia4-F-2-nPent-Ph
1-1735ozl4-F-2-nPent-Ph
1-1736ozn4-F-2-nPent-Ph
1-1737tzl4-F-2-nPent-Ph
1-1738tzn4-F-2-nPent-Ph
3-HM-cPent4-F-2-nPent-Ph
1-17404-HM-dioxo4-F-2-nPent-Ph
1-17414-HM-dithio4-F-2-nPent-Ph
1-17424-HM-ocatio4-F-2-nPent-Ph
1-17433,4-DIMM-cPent4-F-2-nPent-Ph
1-17444,5-dihm-dioxo4-F-2-nPent-Ph
1-17454,5-dihm-dithio4-F-2-nPent-Ph
1-17464,5-dihm-ocatio4-F-2-nPent-Ph
1-17473,4-Dina-cPent4-F-2-nPent-Ph
1-17484,5-Dina-dioxo4-F-2-nPent-Ph
1-17494,5-Dina-dithio4-F-2-nPent-Ph
1-17504,5-Dina-ocatio4-F-2-nPent-Ph
1-17513-HE-cPent4-F-2-nPent-Ph
1-17524-HE-dioxo4-F-2-nPent-Ph
1-17534-HE-dithio4-F-2-nPent-Ph
1-17544-HE-ocatio4-F-2-nPent-Ph
1-17553-HP-cPent4-F-2-nPent-Ph
1-17564-HP-dioxo4-F-2-nPent-Ph
1-17574-HP-dithio4-F-2-nPent-Ph
1-17584-HP-ocatio4-F-2-nPent-Ph
1-17593-HB-cPent4-F-2-nPent-Ph
1-17604-HB-dioxo4-F-2-nPent-Ph
1-17614-HB-dithio4-F-2-nPent-Ph

4-F-2-nPent-Ph
1-17624-HB-ocatio4--2-nPent-Ph
1-1763ring 34-F-2-nPent-Ph
1-1764ring 44-F-2-nPent-Ph
1-1765ring 54-F-2-nPent-Ph
1-1766ring 64-F-2-nPent-Ph
1-1767ring 74-F-2-nPent-Ph
1-1768ring 84-F-2-nPent-Ph
1-1769the ring 94-F-2-nPent-Ph
1-1770the ring 104-F-2-nPent-Ph
1-17713,4-disne2NHAc-cPent4-F-2-nPent-Ph
1-17724,5-disne2NHAc-dioxo4-F-2-nPent-Ph
1-17734,5-disne2NHAc-dithio4-F-2-nPent-Ph
1-17744,5-disne2NHAc-ocatio
1-1775the ring 114-F-2-nPent-Ph
1-1776the ring 124-F-2-nPent-Ph
1-1777the ring 134-F-2-nPent-Ph
1-1778the ring 144-F-2-nPent-Ph
1-17794-OH-cHex4-F-2-nPent-Ph
1-17805-OH-dioxa4-F-2-nPent-Ph
1-17815-OH-dithia4-F-2-nPent-Ph
1-17825-OH-Ossetia4-F-2-nPent-Ph
1-17834-NHAc-cHex4-F-2-nPent-Ph
1-17845-NHAc-dioxa4-F-2-nPent-Ph
1-17855-NHAc-dithia4-F-2-nPent-Ph
1-17865-NHAc-Ossetia4-F-2-nPent-Ph
1-17874,4-dime-cHex4-F-2-nPent-Ph
1-17885,5-dime-dioxa4-F-2-nPent-Ph
1-17895,5-dime-dithia4-F-2-nPent-Ph
1-17905,5-dime-Ossetia4-F-2-nPent-Ph
1-17914,4-DIMM-cHex4-F-2-nPent-Ph
1-17925,5-dihm-dioxo4-F-2-nPent-Ph
1-17935,5-dihm-dithia4-F-2-nPent-Ph
1-17945,5-dihm-Ossetia4-F-2-nPent-Ph
1-1795the ring 154-F-2-nPent-Ph

1-1796the ring 164-F-2-nPent-Ph
1-1797the ring 174-F-2-nPent-Ph
1-1798 ring 184-F-2-nPent-Ph
1-17994,4-diso2Et-cHex4-F-2-nPent-Ph
1-18005,5-diso2Et-dioxa4-F-2-nPent-Ph
1-18015,5-diso2Et-dithia4-F-2-nPent-Ph
1-18025,5-diso2Et-Ossetia4-F-2-nPent-Ph
1-1803O=2-nOct-Ph
1-1804S=2-nOct-Ph
1-1805cPr2-nOct-Ph
1-1806cBu2-nOct-Ph
1-1807cPent2-nOct-Ph
1-1808cHex2-nOct-Ph
1-1809cHept2-nOct-Ph
1-1810hydroxy 2-nOct-Ph
1-1811oaks2-nOct-Ph
1-1812oxo2-nOct-Ph
1-1813oxa2-nOct-Ph
1-1814dioxo2-nOct-Ph
1-1815dioxa2-nOct-Ph
1-1816dioxa2-nOct-Ph
1-1817ditio2-nOct-Ph
1-1818dithia2-nOct-Ph
1-1819the ring 12-nOct-Ph
1-1820the ring 22-nOct-Ph
1-1821ocatio2-nOct-Ph
1-1822Ossetia2-nOct-Ph
1-1823ol 2-nOct-Ph
1-1824ozn2-nOct-Ph
1-1825tzl2-nOct-Ph
1-1826tzn2-nOct-Ph
1-18273-HM-cPent2-nOct-Ph
1-18284-HM-dioxo2-nOct-Ph
1-18294-HM-dithio2-nOct-Ph

2-nOct-Ph
1-18304-HM-ocatio2-nOct-Ph
1-18313,4-DIMM-cPent2-nOct-Ph
1-18324,5-dihm-dioxo2-nOct-Ph
1-18334,5-dihm-dithio2-nOct-Ph
1-18344,5-dihm-ocatio2-nOct-Ph
1-18353,4-Dina-cPent
1-18364,5-Dina-dioxo2-nOct-Ph
1-18374,5-Dina-dithio2-nOct-Ph
1-18384,5-Dina-ocatio2-nOct-Ph
1-18393-HE-cPent2-nOct-Ph
1-18404-HE-dioxo2-nOct-Ph
1-18414-HE-dithio2-nOct-Ph
1-18424-HE-ocatio2-nOct-Ph
1-18433-HP-cPent2-nOct-Ph
1-18444-HP-dioxo2-nOct-Ph
1-18454-HP-dithio2-nOct-Ph
1-18464-HP-ocatio2-nOct-Ph
1-18473-HB-cPent2-nOct-Ph
1-18484-HB-dioxo2-nOct-Ph
1-18494-HB-dithio2-nOct-Ph
1-18504-HB-ocatio2-nOct-Ph
1-1851ring 32-nOct-Ph
1-1852ring 42-nOct-Ph
1-1853ring 52-nOct-Ph
1-1854ring 62-nOct-Ph
1-1855ring 72-nOct-Ph
1-1856ring 82-nOct-Ph
1-1857the ring 92-nOct-Ph
1-1858the ring 102-nOct-Ph
1-18593,4-disne2NHAc-cPent2-nOct-Ph
1-18604,5-dis 2NHAc-dioxo2-nOct-Ph
1-18614,5-disne2NHAc-dithio2-nOct-Ph
1-18624,5-disne2NHAc-ocatio2-nOct-Ph
1-1863the ring 112-nOct-Ph

1-1864the ring 122-nOct-Ph
1-1865the ring 132-nOct-Ph
1-1866the ring 142-nOct-Ph
1-18674-OH-cHex2-nOct-Ph
1-18685-OH-dioxa2-nOct-Ph
1-18695-OH-dithia2-nOct-Ph
1-18705-OH-Ossetia2-nOct-Ph
1-18714-NHAc-cHex2-nOct-Ph
1-18725-NHAc-dioxa2-nOct-Ph
1-18735-NHAc-dithia2-nOct-Ph
1-18745-NHAc-Ossetia2-nOct-Ph
1-18754,4-dime-cHex2-nOct-Ph
1-18765,5-dime-dioxa2-nOct-Ph
1-18775,5-dime-dithia2-nOct-Ph
1-18785,5-dime-Ossetia2-nOct-Ph
1-18794,4-DIMM-cHex2-nOct-Ph
1-18805,5-dihm-dioxo2-nOct-Ph
1-18815,5-dihm-dithia2-nOct-Ph
1-18825,5-dihm-Ossetia2-nOct-Ph
1-1883the ring 152-nOct-Ph
1-1884 the ring 162-nOct-Ph
1-1885the ring 172-nOct-Ph
1-1886ring 182-nOct-Ph
1-18874,4-diso2Et-cHex2-nOct-Ph
1-18885,5-diso2Et-dioxa2-nOct-Ph
1-18895,5-diso2Et-dithia2-nOct-Ph
1-18905,5-diso2Et-Ossetia2-nOct-Ph
1-1891O=4-F-2-nOct-Ph
1-1892S=4-F-2-nOct-Ph
1-1893cPr4-F-2-nOct-Ph
1-1894cBu4-F-2-nOct-Ph
1-1895cPent4-F-2-nOct-Ph
1-1896cHex 4-F-2-nOct-Ph
1-1897cHept4-F-2-nOct-Ph

1-1898hydroxy4-F-2-nOct-Ph
1-1899oaks4-F-2-nOct-Ph
1-1900oxo4-F-2-nOct-Ph
1-1901oxa4-F-2-nOct-Ph
1-1902dioxo4-F-2-nOct-Ph
1-1903dioxa4-F-2-nOct-Ph
1-1904dioxa4-F-2-nOct-Ph
1-1905ditio4-F-2-nOct-Ph
1-1906dithia4-F-2-nOct-Ph
1-1907the ring 14-F-2-nOct-Ph
1-1908the ring 24F-2-nOct-Ph
1-1909ocatio4-F-2-nOct-Ph
1-1910Ossetia4-F-2-nOct-Ph
1-1911ozl4-F-2-nOct-Ph
1-1912ozn4-F-2-nOct-Ph
1-1913tzl4-F-2-nOct-Ph
1-1914tzn4-F-2-nOct-Ph
1-19153-HM-cPent4-F-2-nOct-Ph
1-19164-HM-dioxo4-F-2-nOct-Ph
1-19174-HM-dithio4-F-2-nOct-Ph
1-19184-HM-ocatio4-F-2-nOct-Ph
1-19193,4-DIMM-cPent4-F-2-nOct-Ph
1-19204,5-dihm-dioxo4-F-2-nOct-Ph
1-1921 4,5-dihm-dithio4-F-2-nOct-Ph
1-19224,5-dihm-ocatio4-F-2-nOct-Ph
1-19233,4-Dina-cPent4-F-2-nOct-Ph
1-19244,5-Dina-dioxo4-F-2-nOct-Ph
1-19254,5-Dina-dithio4-F-2-nOct-Ph
1-19264,5-Dina-ocatio4-F-2-nOct-Ph
1-19273-HE-cPent4-F-2-nOct-Ph
1-19284-HE-dioxo4-F-2-nOct-Ph
1-19294-HE-dithio4-F-2-nOct-Ph
1-19304-HE-ocatio4-F-2-nOct-Ph
1-19313-HP-cPent4-F-2-nOct-Ph

1-19324-HP-dioxo4-F-2-nOct-Ph
1-19334-HP-dithio4-F-2-nOct-Ph
1-19344-HP-ocatio4-F-2-nOct-Ph
1-19353-HB-cPent4-F-2-nOct-Ph
1-19364-HB-dioxo4-F-2-nOct-Ph
1-19374-HB-dithio4-F-2-nOct-Ph
1-19384-HB-ocatio4-F-2-nOct-Ph
1-1939ring 34-F-2-nOct-Ph
1-1940ring 44-F-2-nOct-Ph
1-1941ring 54-F-2-nOct-Ph
1-1942ring 64-F-2-nOct-Ph
1-1943ring 74-F-2-nOct-Ph
1-1944ring 84-F-2-nOct-Ph
1-1945 the ring 94-F-2-nOct-Ph
1-1946the ring 104-F-2-nOct-Ph
1-19473,4-disne2NHAc-cPent4-F-2-nOct-Ph
1-19484,5-disne2NHAc-dioxo4-F-2-nOct-Ph
1-19494,5-disne2NHAc-dithio4-F-2-nOct-Ph
1-19504,5-disne2NHAc-ocatio4-F-2-nOct-Ph
1-1951the ring 114-F-2-nOct-Ph
1-1952the ring 124-F-2-nOct-Ph
1-1953the ring 134-F-2-nOct-Ph
1-1954the ring 144-F-2-nOct-Ph
1-19554-OH-cHex4-F-2-nOct-Ph
1-19565-OH-dioxa4-F-2-nOct-Ph
11957 5-OH-dithia4-F-2-nOct-Ph
1-19585-OH-Ossetia4-F-2-nOct-Ph
1-19594-NHAc-cHex4-F-2-nOct-Ph
1-19605-NHAc-dioxa4-F-2-nOct-Ph
1-19615-NHAc-dithia4-F-2-nOct-Ph
1-19625-NHAc-Ossetia4-F-2-nOct-Ph
1-19634,4-dime-cHex4-F-2-nOct-Ph
1-19645,5-dime-dioxa4-F-2-nOct-Ph
1-19655,5-dime-dithia4-F-2-nOct-Ph

1-19665,5-dime-Ossetia4-F-2-nOct-Ph
1-19674,4-DIMM-cHex4-F-2-nOct-Ph
1-19685,5-dihm-dioxo 4-F-2-nOct-Ph
1-19695,5-dihm-dithia4-F-2-nOct-Ph
1-19705,5-dihm-Ossetia4-F-2-nOct-Ph
1-1971the ring 154-F-2-nOct-Ph
1-1972the ring 164-F-2-nOct-Ph
1-1973the ring 174-F-2-nOct-Ph
1-1974ring 184-F-2-nOct-Ph
1-19754,4-diso2Et-cHex4-F-2-nOct-Ph
1-19765,5-diso2Et-dioxa4-F-2-nOct-Ph
1-19775,5-diso2Et-dithia4-F-2-nOct-Ph
1-1978O=2-nPr-Ph
1-1979S=2-nPr-Ph
1-1980cPr2-nPr-h
1-1981cBu2-nPr-Ph
1-1982cPent2-nPr-Ph
1-1983cHex2-nPr-Ph
1-1984cHept2-nPr-Ph
1-1985hydroxy2-nPr-Ph
1-1986oaks2-nPr-Ph
1-1987oxo2-nPr-Ph
1-1988oxa2-nPr-Ph
1-1989dioxo2-nPr-Ph
1-1990dioxa2-nPr-Ph
1-1991dioxa2-nPr-Ph
1-1992ditio2-nPr-Ph
1-1993dithia2-nPr-P
1-1994the ring 12-nPr-Ph
1-1995the ring 22-nPr-Ph
1-1996ocatio2-nPr-Ph
1-1997Ossetia2-nPr-Ph
1-1998ozl2-nPr-Ph
1-1999ozn2-nPr-Ph

1-2000tzl2-nPr-Ph
1-2001tzn2-nPr-Ph
1-20023-HM-cPent2-nPr-Ph
1-20034-HM-dioxo2-nPr-Ph
1-20044-HM-dithio2-nPr-Ph
1-20054-HM-ocatio2-nPr-Ph
3,4-DIMM-cPent2-nPr-Ph
1-20074,5-dihm-dioxo2-nPr-Ph
1-20084,5-dihm-dithio2-nPr-Ph
1-20094,5-dihm-ocatio2-nPr-Ph
1-20103,4-Dina-cPent2-nPr-Ph
1-20114,5-Dina-dioxo2-nPr-Ph
1-20124,5-Dina-dithio2-nPr-Ph
1-20134,5-Dina-ocatio2-nPr-Ph
1-20143-HE-cPent2-nPr-Ph
1-20154-HE-dioxo2-nPr-Ph
1-20164-HE-dithio2-nPr-Ph
1-20174-HE-ocatio2-nPr-Ph
1-2018 3-HP-cPent2-nPr-Ph
1-20194-HP-dioxo2-nPr-Ph
1-20204-HP-dithio2-nPr-Ph
1-20214-HP-ocatio2-nPr-Ph
1-20223-HB-cPent2-nPr-Ph
1-20234-HB-dioxo2-nPr-Ph
1-20244-HB-dithio2-nPr-Ph
1-20254-HB-ocatio2-nPr-Ph
1-2026ring 32-nPr-Ph
1-2027ring 42-nPr-Ph
1-2028ring 52-nPr-Ph
1-2029ring 62-nPr-Ph
1-2030ring 72-nPr-Ph
1-2031ring 82-nPr-Ph
1-2032the ring 92-nPr-Ph
1-2033the ring 102-nPr-Ph

1-20343,4-disne2NHAc-cPent2-nPr-Ph
1-20354,5-disne2NHAc-dioxo2-nPr-Ph
1-20364,5-disne2NHAc-dithio2-nPr-Ph
1-20374,5-disne2NHAc-ocatio2-nPr-Ph
1-2038the ring 112-nPr-Ph
1-2039the ring 122-nPr-Ph
1-2040the ring 132-nPr-Ph
1-2041the ring 142-nPr-Ph
1-20424-OH-cHex 2-nPr-Ph
1-20435-OH-dioxa2-nPr-Ph
1-20445-OH-dithia2-nPr-Ph
1-20455-OH-Ossetia2-nPr-Ph
1-20464-NHAc-cHex2-nPr-Ph
1-20475-NHAc-dioxa2-nPr-Ph
1-20485-NHAc-dithia2-nPr-Ph
1-20495-NHAc-Ossetia2-nPr-Ph
1-20504,4-dime-cHex2-nPr-Ph
1-20515,5-dime-dioxa2-nPr-Ph
1-20525,5-dime-dithia2-nPr-Ph
1-20535,5-dime-Ossetia2-nPr-Ph
1-20544,4-DIMM-cHex2-nPr-Ph
1-20555,5-dihm-dioxo2-nPr-Ph
1-20565,5-dihm-dithia2-nPr-Ph
1-20575,5-dihm-Ossetia2-nPr-Ph
1-2058the ring 152-nPr-Ph
1-2059the ring 162-nPr-Ph
1-2060the ring 172-nPr-Ph
1-2061ring 182-nPr-Ph
1-20624,4-diso2Et-cHex2-nPr-Ph
1-20635,5-diso2Et-dioxa2-nPr-Ph
1-20645,5-diso2Et-dithia2-nPr-Ph
1-20655,5-diso2Et-Ossetia2-nPr-Ph
1-2066O=4-F-2-nPr-Ph
1-2067S=4-F-2-nPr-Ph

1-2068cPr4-F-2-nPr-Ph
1-2069cBu4-F-2-nPr-Ph
1-2070cPent4-F-2-nPr-Ph
1-2071cHex4-F-2-nPr-Ph
1-2072cHept4-F-2-nPr-Ph
1-2073hydroxy4-F-2-nPr-Ph
1-2074oaks4-F-2-nPr-Ph
1-2075oxo4-F-2-nPr-Ph
1-2076oxa4-F-2-nPr-Ph
1-2077dioxo4-F-2-nPr-Ph
1-2078dioxa4-F-2-nPr-Ph
1-2079diocese 4-F-2-nPr-Ph
1-2080ditio4-F-2-nPr-Ph
1-2081dithia4-F-2-nPr-Ph
1-2082the ring 14-F-2-nPr-Ph
1-2083the ring 24-F-2-nPr-Ph
1-2084ocatio4-F-2-nPr-Ph
1-2085Ossetia4-F-2-nPr-Ph
1-2086ozl4-F-2-nPr-Ph
1-2087ozn4-F-2-nPr-Ph
1-2088tzl4-F-2-nPr-Ph
1-2089tzn4-F-2-nPr-Ph
1-20903-HM-cPent4-F-2-nPr-Ph
1-20914-HM-dioxo4-F-2-nPr-Ph
1-20924-HM-dithio4-F-2-nPr-Ph
1-20934-HM-ocatio4-F-2-nPr-Ph
1-20943,4-DIMM-cPent4-F-2-nPr-Ph
1-20954,5-dihm-dioxo4-F-2-nPr-Ph
1-20964,5-dihm-dithio4-F-2-nPr-Ph
1-20974,5-dihm-ocatio4-F-2-nPr-Ph
1-20983,4-Dina-cPent4-F-2-nPr-Ph
1-20994,5-Dina-dioxo4-F-2-nPr-Ph
1-21004,5-Dina-dithio4-F-2-nPr-Ph
1-21014,5-Dina-ocatio4-F-2-nPr-Ph

td align="center"> 1-2128
1-21023-HE-cPent4-F-2-nPr-Ph
1-21034-HE-dioxo 4-F-2-nPr-Ph
1-21044-HE-dithio4-F-2-nPr-Ph
1-21054-HE-ocatio4-F-2-nPr-Ph
1-21063-HP-cPent4-F-2-nPr-Ph
1-21074-HP-dioxo4-F-2-nPr-Ph
1-21084-HP-dithio4-F-2-nPr-Ph
1-21094-HP-ocatio4-F-2-nPr-Ph
1-21103-HB-cPent4-F-2-nPr-Ph
1-21114-HB-dioxo4-F-2-nPr-Ph
1-21124-HB-dithio4-F-2-nPr-Ph
1-21134-HB-ocatio4-F-2-nPr-Ph
1-2114ring 34-F-2-nPr-Ph
1-2115ring 44-F-2-nPr-Ph
1-2116ring 54-F-2-nPr-Ph
1-2117ring 64-F-2-nPr-Ph
1-2118ring 74-F-2-nPr-Ph
1-2119ring 84-F-2-nPr-Ph
1-2120the ring 94-F-2-nPr-Ph
1-2121the ring 104-F-2-nPr-Ph
1-21223,4-disne2NHAc-cPent4-F-2-nPr-Ph
1-21234,5-disne2NHAc-dioxo4-F-2-nPr-Ph
1-21244,5-disne2NHAc-dithio4-F-2-nPr-Ph
1-21254,5-disne2NHAc-ocatio4-F-2-nPr-Ph
1-2126the ring 114-F-2-nPr-Ph
1-2127the ring 124-F-2-nPr-Ph
the ring 134-F-2-nPr-Ph
1-2129the ring 144-F-2-nPr-Ph
1-21304-OH-cHex4-F-2-nPr-Ph
1-21315-OH-dioxa4-F-2-nPr-Ph
1-21325-OH-dithia4-F-2-nPr-Ph
1-21335-OH-Ossetia4-F-2-nPr-Ph
1-21344-NHAc-cHex4-F-2-nPr-Ph
1-21355-NHAc-dioxa4-F-2-nPr-Ph

1-2164
1-21365-NHAc-dithia4-F-2-nPr-Ph
1-21375-NHAc-Ossetia4-F-2-nPr-Ph
1-21384,4-dime-cHex4-F-2-nPr-Ph
1-21395,5-dime-dioxa4-F-2-nPr-P
1-21405,5-dime-dithia4-F-2-nPr-Ph
1-21415,5-dime-Ossetia4-F-2-nPr-Ph
1-21424,4-DIMM-cHex4-F-2-nPr-Ph
1-21435,5-dihm-dioxo4-F-2-nPr-Ph
1-21445,5-dihm-dithia4-F-2-nPr-Ph
1-21455,5-dihm-Ossetia4-F-2-nPr-Ph
1-2146the ring 154-F-2-nPr-Ph
1-2147the ring 164-F-2-nPr-Ph
1-2148the ring 174-F-2-nPr-Ph
1-2149ring 184-F-2-nPr-Ph
1-21504,4-diso2Et-cHex4-F-2-nPr-Ph
1-21515,5-diso2Et-dioxa1-21525,5-diso2Et-dithia4-F-2-nPr-Ph
1-21535,5-diso2Et-Ossetia4-F-2-nPr-Ph
1-2154the ring 192-Cl-Ph
1-2155the ring 202-Cl-Ph
1-2156the ring 212-Cl-Ph
1-2157the ring 192-Br-Ph
1-2158the ring 202-Br-Ph
1-2159the ring 212-Br-Ph
1-2160the ring 192-Cl-6-Me-Ph
1-2161the ring 202-Cl-6-Me-Ph
1-2162the ring 212-Cl-6-Me-Ph
1-2163the ring 192-Cl-4-F-Ph
the ring 202-Cl-4-F-Ph
1-2165the ring 212-Cl-4-F-Ph
1-2166the ring 192,4-F
1-2167the ring 202,4-F
1-2168the ring 212,4-F
1-2169the ring 192-Br-4-F-Ph

1-2170the ring 202-Br-4-F-Ph
1-2171the ring 212-Br-4-F-Ph
1-2172the ring 192-nBu-4-F-Ph
1-2173the ring 202-nBu-4-F-Ph
1-2174the ring 212-nBu-4-F-Ph
1-2175the ring 192-nPent-Ph
1-2176the ring 202-nPent-Ph
1-2177the ring 212-nPent-Ph
1-2178the ring 194-F-2-nPent-Ph
1-2179the ring 204-F-2-nPent-Ph
1-2180the ring 214-F-2-nPent-Ph
1-2181the ring 192-nHex-Ph
1-2182the ring 202-nHex-Ph
1-2183the ring 212-nHex-Ph
1-2184the ring 194-F-2-nHex-Ph
1-2185the ring 204-F-2-nHex-Ph
1-2186the ring 214-F-2-nHex-Ph
1-2187the ring 192-nHept-Ph
1-21882-nHept-Ph
1-2189the ring 212-nHept-Ph
1-2190the ring 194-F-2-nHept-Ph
1-2191the ring 204-F-2-nHept-Ph
1-2192the ring 214-F-2-nHept-Ph
1-2193the ring 192-nOct-Ph
1-2194the ring 202-nOct-Ph
1-2195the ring 212-nOct-Ph
1-2196the ring 194-F-2-nOct-Ph
1-2197the ring 204-F-2-nOct-Ph
1-2198the ring 214-F-2-nOct-Ph
1-2199the ring 19Ph
1-2200the ring 20 Ph
1-2201the ring 21Ph
1-2202the ring 194-F-Ph
1-2203the ring 204-F-Ph

1-2204the ring 214-F-Ph
1-2205the ring 192-Cl-4-Me-Ph
1-2206the ring 202-Cl-4-Me-Ph
1-2207the ring 212-Cl-4-Me-Ph
1-2208the ring 192-nBu-Ph
1-2209the ring 202-nBu-Ph
1-2210the ring 212-nBu-Ph
1-2211the ring 192-nPr-Ph
1-2212the ring 202-nPr-Ph/td>
1-2213the ring 212-nPr-Ph
1-2214the ring 194-F-2-nPr-Ph
1-2215the ring 204-F-2-nPr-Ph
1-2216the ring 214-F-2-nPr-Ph
1-2217dioxo2-F-Ph
1-22184-HM-dioxo2-F-Ph
1-22194,5-dihm-dioxo2-F-Ph
1-22204,5-Dina-dioxo2-F-Ph
1-2221the ring 192-F-Ph
1-2222the ring 202-F-Ph
1-2223the ring 212-F-Ph
1-2224dioxo2-I-Ph
1-2225 4-HM-dioxo2-I-Ph
1-22264,5-dihm-dioxo2-I-Ph
1-22274,5-Dina-dioxo2-I-Ph
1-2228the ring 192-I-Ph
1-2229the ring 202-I-Ph
1-2230the ring 212-I-Ph
1-2231dioxo4-Cl-Ph
1-22324-HM-dioxo4-Cl-Ph
1-22334,5-dihm-dioxo4-Cl-Ph
1-22344,5-Dina-dioxo4-Cl-Ph
1-2235the ring 194-Cl-Ph
1-2236the ring 204-Cl-Ph
1-2237the ring 214-Cl-Ph

1-2238dioxo2-Me-Ph
1-22394-HM-dioxo2-Me-Ph
1-22404,5-dihm-dioxo2-Me-Ph
1-22414,5-Dina-dioxo2-Me-Ph
1-2242the ring 192-Me-Ph
1-2243the ring 202-Me-Ph
1-2244the ring 212-Me-Ph
1-2245dioxo2-Et-Ph
1-22464-HM-dioxo2-Et-Ph
1-22474,5-dihm-dioxo2-Et-Ph
1-22484,5-Dina-dioxo2-Et-Ph
1-2249the ring 192-E-Ph
1-2250the ring 202-Et-Ph
1-2251the ring 212-Et-Ph
1-2252dioxo2-C≡CH-Ph
1-22534-HM-dioxo2-C≡CH-Ph
1-22544,5-dihm-dioxo2-C≡CH-Ph
1-22554,5-Dina-dioxo2-C≡CH-Ph
1-2256the ring 192-C≡CH-Ph
1-2257the ring 202-C≡CH-Ph
1-2258the ring 212-C≡CH-Ph
1-2259dioxo2-iPr-Ph
1-22604-HM-dioxo2-iPr-Ph
1-22614,5-dihm-dioxo2-iPr-Ph
1-2262 4,5-Dina-dioxo2-iPr-Ph
1-2263the ring 192-iPr-Ph
1-2264the ring 202-iPr-Ph
1-2265the ring 212-iPr-Ph
1-2266dioxo2-tBu-Ph
1-22674-HM-dioxo2-tBu-Ph
1-22684,5-dihm-dioxo2-tBu-Ph
1-22694,5-Dina-dioxo2-tBu-Ph
1-2270the ring 192-tBu-Ph

1-2271the ring 202-tBu-Ph
1-2272the ring 212-tBu-Ph
1-2273dioxo2-sBu-Ph
1-22744-HM-dioxo2-sBu-Ph
1-22754,5-dihm-dioxo2-sBu-Ph
1-22764,5-Dina-dioxo2-sBu-Ph
1-2277the ring 192-sBu-Ph
1-2278the ring 202-sBu-Ph
1-2279the ring 212-sBu-Ph
1-2280dioxo2-OMe-Ph
1-22814-HM-dioxo2-OMe-Ph
1-22824,5-dihm-dioxo2-OMe-Ph
1-22834,5-Dina-dioxo2-OMe-Ph
1-2284the ring 192-OMe-Ph
1-2285the ring 202-OMe-Ph
1-2286number is CH 21 2-OMe-Ph
1-2287dioxo2-OEt-Ph
1-22884-HM-dioxo2-OEt-Ph
1-22894,5-dihm-dioxo2-OEt-Ph
1-22904,5-Dina-dioxo2-OEt-Ph
1-2291the ring 192-OEt-Ph
1-2292the ring 202-OEt-Ph
1-2293the ring 212-OEt-Ph
1-2294dioxo2-OCHF2-Ph
1-22954-HM-dioxo2-OCHF2-Ph
1-22964,5-dihm-dioxo2-OCHF2-Ph
1-22974,5-Dina-dioxo2-OCHF2-Ph
1-2298the ring 19 2-OCHF2-Ph
1-2299the ring 202-OCHF2-Ph
1-2300the ring 212-OCHF2-Ph
1-2301dioxo2-SMe-Ph
1-23024-HM-dioxo2-SMe-Ph
1-23034,5-dihm-dioxo2-SMe-Ph
1-23044,5-Dina-dioxo2-SMe-Ph

1-2305the ring 192-SMe-Ph
1-2306the ring 202-SMe-Ph
1-2307the ring 212-SMe-Ph
1-2308dioxo2-Ac-Ph
1-23094-HM-dioxo2-Ac-Ph
1-23104,5-dihm-is ioxo 2-Ac-Ph
1-23114,5-Dina-dioxo2-Ac-Ph
1-2312the ring 192-Ac-Ph
1-2313the ring 202-Ac-Ph
1-2314the ring 212-Ac-Ph
1-2315dioxo2-Bn-Ph
1-23164-HM-dioxo2-Bn-Ph
1-23174,5-dihm-dioxo2-Bn-Ph
1-23184,5-Dina-dioxo2-Bn-Ph
1-2319the ring 192-Bn-Ph
1-2320the ring 202-Bn-Ph
1-2321the ring 212-Bn-Ph
1-2322dioxo2-Mor-Ph
4-HM-dioxo2-Mor-Ph
1-23244,5-dihm-dioxo2-Mor-Ph
1-23254,5-Dina-dioxo2-Mor-Ph
1-2326the ring 192-Mor-Ph
1-2327the ring 202-Mor-Ph
1-2328the ring 212-Mor-Ph
1-2329dioxoFlu
1-23304-HM-dioxoFlu
1-23314,5-dihm-dioxoFlu
1-23324,5-Dina-dioxoFlu
1-2333the ring 19Flu
1-2334the ring 20Flu
1-2335the ring 21 Flu
1-2336dioxo2-CH2CH2Pyrd-Ph
1-23374-HM-dioxo2-CH2CH2Pyrd-Ph
1-23384,5-dihm-dioxo2-CH2CH2Pyrd-Ph

1-23394,5-Dina-dioxo2-CH2CH2Pyrd-Ph
1-2340the ring 192-CH2CH2Pyrd-Ph
1-2341the ring 202-CH2CH2Pyrd-Ph
1-2342the ring 212-CH2CH2Pyrd-Ph
1-2343dioxo2-CH2CH2NHBoc-Ph
1-23444-HM-dioxo2-CH2CH2NHBoc-Ph
1-23454,5-dihm-dioxo2-CH2CH2NHBoc-Ph
1-23464,5-Dina-dioxo2-CH2CH2NHBoc-Ph
1-2347the ring 192-CH2CH2NHBoc-Ph
1-2348the ring 202-CH2CH2NHBoc-Ph
1-2349the ring 212-CH2CH2NHBoc-Ph
1-2350dioxo2-NH2-Ph
1-23514-HM-dioxo2-NH2-Ph
1-23524,5-dihm-dioxo2-NH2-Ph
1-23534,5-Dina-dioxo2-NH2-Ph
1-2354the ring 192-NH2-Ph
1-2355the ring 202-NH2-Ph
1-2356the ring 212-NH2-Ph
1-2357 dioxo4-F-2-Me-Ph
1-23584-HM-dioxo4-F-2-Me-Ph
1-23594,5-dihm-dioxo4-F-2-Me-Ph
1-23604,5-Dina-dioxo4-F-2-Me-Ph
1-2361the ring 194-F-2-Me-Ph
1-2362the ring 204-F-2-Me-Ph
1-2363the ring 214-F-2-Me-Ph
1-2364dioxo3-Cl-4-F-Ph
1-23654-HM-dioxo3-Cl-4-F-Ph
1-23664,5-dihm-dioxo3-Cl-4-F-Ph
1-23674,5-Dina-dioxo3-Cl-4-F-Ph
1-2368the ring 193-Cl-4-F-Ph
1-2369the ring 20 3-Cl-4-F-Ph
1-2370the ring 213-Cl-4-F-Ph
1-2371dioxo4-F-3-CF3-Ph
1-23724-HM-dioxo4-F-3-CF3-Ph

1-23734,5-dihm-dioxo4-F-3-CF3-Ph
1-23744,5-Dina-dioxo4-F-3-CF3-Ph
1-2375the ring 194-F-3-CF3-Ph
1-2376the ring 204-F-3-CF3-Ph
1-2377the ring 214-F-3-CF3-Ph
1-2378dioxo4-F-3-OMe-Ph
1-23794-HM-dioxo4-F-3-OMe-Ph
1-23804,5-dihm-dioxo4-F-3-OMe-Ph
1-23814,5-Dina-dioxo4-F-3-OMe-Ph
1-2382the ring 194-F-3-OMe-Ph
1-2383the ring 204-F-3-OMe-Ph
1-2384the ring 214-F-3-OMe-Ph
1-2385dioxo3,4-F-Ph
1-23864-HM-dioxo3,4-F-Ph
1-23874,5-dihm-dioxo3,4-F-Ph
1-23884,5-Dina-dioxo3,4-F-Ph
1-2389the ring 193,4-F-Ph
1-2390the ring 203,4-F-Ph
1-2391the ring 213,4-F-Ph
1-2392dioxo2,4-dime-Ph
1-2393 4-HM-dioxo2,4-dime-Ph
1-23944,5-dihm-dioxo2,4-dime-Ph
1-23954,5-Dina-dioxo2,4-dime-Ph
1-2396the ring 192,4-dime-Ph
1-2397the ring 202,4-dime-Ph
1-2398the ring 212,4-dime-Ph
1-2399dioxo4-Cl-2-F-Ph
1-24004-HM-dioxo4-Cl-2-F-Ph
1-24014,5-dihm-dioxo4-Cl-2-F-Ph
1-24024,5-Dina-dioxo4-Cl-2-F-Ph
1-2403the ring 194-Cl-2-F-Ph
1-2404the ring 204-Cl-2-F-Ph
1-2405Kohl is about 21 4-Cl-2-F-Ph
1-2406dioxo2-Br-4-Cl-Ph

1-24074-HM-dioxo2-Br-4-Cl-Ph
1-24084,5-dihm-dioxo2-Br-4-Cl-Ph
1-24094,5-Dina-dioxo2-Br-4-Cl-Ph
1-2410the ring 192-Br-4-Cl-Ph
1-2411the ring 202-Br-4-Cl-Ph
1-2412the ring 212-Br-4-Cl-Ph
1-2413dioxo4-Cl-2-Me-Ph
1-24144-HM-dioxo4-Cl-2-Me-Ph
1-24154,5-dihm-dioxo4-Cl-2-Me-Ph
1-24164,5-Dina-dioxo4-Cl-2-Me-Ph
1-417 the ring 194-Cl-2-Me-Ph
1-2418the ring 204-Cl-2-Me-Ph
1-2419the ring 214-Cl-2-Me-Ph
1-2420dioxo4-Cl-2-CO2Me-Ph
1-24214-HM-dioxo4-Cl-2-CO2Me-Ph
1-24224,5-dihm-dioxo4-Cl-2-CO2Me-Ph
1-24234,5-Dina-dioxo4-Cl-2-CO2Me-Ph
1-2424the ring 194-Cl-2-CO2Me-Ph
1-2425the ring 204-Cl-2-CO2Me-Ph
1-2426the ring 214-Cl-2-CO2Me-Ph
1-2427dioxo3,4-Cl-Ph
1-24284-HM-dioxo3,4-is Cl-Ph
1-24294,5-dihm-dioxo3,4-Cl-Ph
1-24304,5-Dina-dioxo3,4-Cl-Ph
1-2431the ring 193,4-Cl-Ph
1-2432the ring 203,4-Cl-Ph
1-2433the ring 213,4-Cl-Ph
1-2434dioxo2,5-F-Ph
1-24354-HM-dioxo2,5-F-Ph
1-24364,5-dihm-dioxo2,5-F-Ph
1-24374,5-Dina-dioxo2,5-F-Ph
1-2438the ring 192,5-F-Ph
1-2439the ring 202,5-F-Ph
1-2440the ring 212,5-F-Ph
1-2441dioxo2,6-F-Ph
1-24424-HM-dioxo2,6-F-Ph
1-24434,5-dihm-dioxo2,6-F-Ph
1-24444,5-Dina-dioxo2,6-F-Ph
1-2445the ring 192,6-F-Ph
1-2446the ring 202,6-F-Ph
1-2447the ring 212,6-F-Ph
1-2448dioxo2-F-4-Me-Ph
1-24494-HM-dioxo2-F-4-Me-Ph
1-24504,5-dihm-dioxo2-F-4-Me-Ph
1-24514,5-Dina-dioxo2-F-4-Me-Ph
1-2452the ring 19 2-F-4-Me-Ph
1-2453the ring 202-F-4-Me-Ph
1-2454the ring 212-F-4-Me-Ph
1-2455dioxo2-F-5-Me-Ph
1-24564-HM-dioxo2-F-5-Me-Ph
1-24574,5-dihm-dioxo2-F-5-Me-Ph
1-24584,5-Dina-dioxo2-F-5-Me-Ph
1-2459the ring 192-F-5-Me-Ph
1-2460the ring 202-F-5-Me-Ph
1-2461the ring 212-F-5-Me-Ph
1-2462dioxo2-F-4-OMe-Ph
1-24634-HM-dioxo2-F-4-OMe-Ph
1-24644,5-dihm-dioxo2-F-4-OMe-Ph
1-24654,5-Dina-dioxo2-F-4-OMe-Ph
1-2466the ring 192-F-4-OMe-Ph
1-2467the ring 202-F-4-OMe-Ph
1-2468the ring 212-F-4-OMe-Ph
1-2469dioxo5-Cl-2-F-Ph
1-24704-HM-dioxo5-Cl-2-F-Ph
1-24714,5-dihm-dioxo5-Cl-2-F-Ph
1-24724,5-Dina-dioxo5-Cl-2-F-Ph
1-2473the ring 195-Cl-2-F-Ph
1-2474the ring 205-Cl-2-F-Ph

1-2475the ring 215-Cl-2-F-Ph
1-2476 dioxo2,3,4-triF-Ph
1-24774-HM-dioxo2,3,4-triF-Ph
1-24784,5-dihm-dioxo2,3,4-triF-Ph
1-24794,5-Dina-dioxo2,3,4-triF-Ph
1-2480the ring 192,3,4-triF-Ph
1-2481the ring 202,3,4-triF-Ph
1-2482the ring 212,3,4-triF-Ph
1-2483dioxo2,4,5-triF-Ph
1-24844-HM-dioxo2,4,5-triF-Ph
1-2485 4,5-dihm-dioxo2,4,5-triF-Ph
1-24864,5-Dina-dioxo2,4,5-triF-Ph
1-2487the ring 192,4,5-triF-Ph
1-2488the ring 202,4,5-triF-Ph
1-2489the ring 212,4,5-triF-Ph
1-2490dioxo2,4,6-triF-Ph
1-24914-HM-dioxo2,4,6-triF-Ph
1-24924,5-dihm-dioxo2,4,6-triF-Ph
1-24934,5-Dina-dioxo2,4,6-triF-Ph
1-294 the ring 192,4,6-triF-Ph
1-2495the ring 202,4,6-triF-Ph
1-2496the ring 212,4,6-triF-Ph
1-2497dioxo2,4-Cl-Ph
1-24984-HM-dioxo2,4-Cl-Ph
1-24994,5-dihm-dioxo2,4-Cl-Ph
1-25004,5-Dina-dioxo2,4-Cl-Ph
1-2501the ring 192,4-Cl-Ph
1-2502the ring 202,4-Cl-Ph
1-2503 the ring 212,4-Cl-Ph
1-2504dioxo4-Br-2-Cl-Ph
1-25054-HM-dioxo4-Br-2-Cl-Ph
1-25064,5-dihm-dioxo4-Br-2-Cl-Ph
1-25074,5-Dina-dioxo4-Br-2-Cl-Ph
1-2508the ring 194-Br-2-Cl-Ph

td align="center"> 1-2526
1-2509the ring 204-Br-2-Cl-Ph
1-2510the ring 214-Br-2-Cl-Ph
1-2511dioxo4-tBu-2-Cl-Ph
1-25124-HM-dioxo4-tBu-2-Cl-Ph
1-25134,5-dihm-dioxo 4-tBu-2-Cl-Ph
1-25144,5-Dina-dioxo4-tBu-2-Cl-Ph
1-2515the ring 194-tBu-2-Cl-Ph
1-2516the ring 204-tBu-2-Cl-Ph
1-2517the ring 214-tBu-2-Cl-Ph
1-2518dioxo2-Cl-6-F-Ph
1-25194-HM-dioxo2-Cl-6-F-Ph
1-25204,5-dihm-dioxo2-Cl-6-F-Ph
1-25214,5-Dina-dioxo2-Cl-6-F-Ph
1-2522the ring 192-Cl-6-F-Ph
1-2523the ring 202-Cl-6-F-Ph
1-2524the ring 212-Cl-6-F-Ph
1-2525dioxo2,6-Cl-Ph
4-HM-dioxo2,6-Cl-Ph
1-25274,5-dihm-dioxo2,6-Cl-Ph
1-25284,5-Dina-dioxo2,6-Cl-Ph
1-2529the ring 192,6-Cl-Ph
1-2530the ring 202,6-Cl-Ph
1-2531the ring 212,6-Cl-Ph
1-2532dioxo2,3-Cl-Ph
1-25334-HM-dioxo2,3-Cl-Ph
1-25344,5-dihm-dioxo2,3-Cl-Ph
1-25354,5-Dina-dioxo2,3-Cl-Ph
1-2536the ring 192,3-Cl-Ph
1-2537the ring 202,3-Cl-Ph
1-238 the ring 212,3-Cl-Ph
1-2539dioxo2,5-Cl-Ph
1-25404-HM-dioxo2,5-Cl-Ph
1-25414,5-dihm-dioxo2,5-Cl-Ph
1-25424,5-Dina-dioxo2,5-Cl-Ph

4-Cl-2-OMe-5-Me-Ph
1-2543the ring 192,5-Cl-Ph
1-2544the ring 202,5-Cl-Ph
1-2545the ring 212,5-Cl-Ph
1-2546dioxo2-Cl-4,6-F-Ph
1-25474-HM-dioxo2-Cl-4,6-F-Ph
1-25484,5-dihm-dioxo2-Cl-4,6-F-Ph
1-25494,5-Dina-dioxo1-2550the ring 192-Cl-4,6-F-Ph
1-2551the ring 202-Cl-4,6-F-Ph
1-2552the ring 212-Cl-4,6-F-Ph
1-2553dioxo2,6-Cl-4-F-Ph
1-25544-HM-dioxo2,6-Cl-4-F-Ph
1-25554,5-dihm-dioxo2,6-Cl-4-F-Ph
1-25564,5-Dina-dioxo2,6-Cl-4-F-Ph
1-2557the ring 192,6-Cl-4-F-Ph
1-2558the ring 202,6-Cl-4-F-Ph
1-2559the ring 212,6-Cl-4-F-Ph
1-2560dioxo2-Br-6-Cl-4-F-Ph
1-25614-HM-dioxo 2-Br-6-Cl-4-F-Ph
1-25624,5-dihm-dioxo2-Br-6-Cl-4-F-Ph
1-25634,5-Dina-dioxo2-Br-6-Cl-4-F-Ph
1-2564the ring 192-Br-6-Cl-4-F-Ph
1-2565the ring 202-Br-6-Cl-4-F-Ph
1-2566the ring 212-Br-6-Cl-4-F-Ph
1-2567dioxo4-Cl-2-OMe-5-Me-Ph
1-25684-HM-dioxo4-Cl-2-OMe-5-Me-Ph
1-25694,5-dihm-dioxo4-Cl-2-OMe-5-Me-Ph
1-25704,5-Dina-dioxo4-Cl-2-OMe-5-Me-Ph
1-2571the ring 194-Cl-2-OMe-5-Me-Ph
1-2572the ring 204-Cl-2-OMe-5-Me-Ph
1-2573the ring 21
1-2574dioxo2,4-divg-Ph
1-25754-HM-dioxo2,4-divg-Ph
1-25764,5-dihm-dioxo2,4-divg-Ph

2-nNon-Ph
1-25774,5-Dina-dioxo2,4-divg-Ph
1-2578the ring 192,4-divg-Ph
1-2579the ring 202,4-divg-Ph
1-2580the ring 212,4-divg-Ph
1-2581dioxo2,6-divg-Ph
1-25824-HM-dioxo2,6-divg-Ph
1-25834,5-dihm-dioxo2,6-divg-Ph
1-25844,5-Dina-dioxo2,6-divg-Ph
1-2585 the ring 192,6-divg-Ph
1-2586the ring 202,6-divg-Ph
1-2587the ring 212,6-divg-Ph
1-2588dioxo2-Br-4-iPr-Ph
1-25894-HM-dioxo2-Br-4-iPr-Ph
1-25904,5-dihm-dioxo2-Br-4-iPr-Ph
1-25914,5-Dina-dioxo2-Br-4-iPr-Ph
1-2592the ring 192-Br-4-iPr-Ph
1-2593the ring 202-Br-4-iPr-Ph
1-2594the ring 212-Br-4-iPr-Ph
1-2595dioxo2-nNon-Ph
1-25964-HM-dioxo2-nNon-Ph
1-25974,5-dihm-dioxo
1-25984,5-Dina-dioxo2-nNon-Ph
1-2599the ring 192-nNon-Ph
1-2600the ring 202-nNon-Ph
1-2601the ring 212-nNon-Ph
1-2602dioxo4-F-2-nNon-Ph
1-26034-HM-dioxo4-F-2-nNon-Ph
1-26044,5-dihm-dioxo4-F-2-nNon-Ph
1-26054,5-Dina-dioxo4-F-2-nNon-Ph
1-2606the ring 194-F-2-nNon-Ph
1-2607the ring 204-F-2-nNon-Ph
1-2608the ring 214-F-2-nNon-Ph
1-2609dioxo2-nDec-Ph
1-26104-HM-dioxo2-nDec-Ph

1-26114,5-dihm-dioxo2-nDec-Ph
1-26124,5-Dina-dioxo2-nDec-Ph
1-2613the ring 192-nDec-Ph
1-2614the ring 202-nDec-Ph
1-2615the ring 212-nDec-Ph
1-2616dioxo4-F-2-nDec-Ph
1-26174-HM-dioxo4-F-2-nDec-Ph
1-26184,5-dihm-dioxo4-F-2-nDec-Ph
1-26194,5-Dina-dioxo4-F-2-nDec-Ph
1-2620the ring 19 4-F-2-nDec-Ph
1-2621the ring 204-F-2-nDec-Ph
1-2622the ring 214-F-2-nDec-Ph
1-2623dioxo2-Et-4-F-Ph
1-26244-HM-dioxo2-Et-4-F-Ph
1-26254,5-dihm-dioxo2-Et-4-F-Ph
1-26264,5-Dina-dioxo2-Et-4-F-Ph
1-2627the ring 192-Et-4-F-Ph
1-2628the ring 202-Et-4-F-Ph
1-2629the ring 212-Et-4-F-Ph
Table 2
Connection # X, YR3/td>
2-1dioxo2-Cl-Ph
2-24-HM-dioxo2-Cl-Ph
2-34,5-dihm-dioxo2-Cl-Ph
2-44,5-Dina-dioxo2-Cl-Ph
2-5dioxo2-Br-Ph
2-64-HM-dioxo2-Br-Ph
2-74,5-dihm-dioxo2-Br-Ph
2-84,5-Dina-dioxo2-Br-Ph

2-9dioxo2-Cl-6-Me-Ph
2-104-HM-dioxo2-Cl-6-Me-Ph
2-114,5-dihm-dioxo2-l-6-Me-Ph
2-124,5-Dina-dioxo2-Cl-6-Me-Ph
2-13dioxo2-Cl-4-F-Ph
2-144-HM-dioxo2-Cl-4-F-Ph
2-154,5-dihm-dioxo2-Cl-4-F-Ph
2-164,5-Dina-dioxo2-Cl-4-F-Ph
2-17dioxo2,4-F
2-184-HM-dioxo2,4-F
2-194,5-dihm-dioxo2,4-F
2-204,5-Dina-dioxo2,4-F
2-21dioxo2-Br-4-F-Ph
2-224-HM-dioxo2-Br-4-F-Ph
2-234,5-dihm-dioxo2-Br-4-F-Ph
2-244,5-Dina-dioxo2-Br-4-F-Ph
2-25dioxo2-nBu-4-F-Ph
2-264-HM-dioxo2-nBu-4-F-Ph
2-274,5-dihm-dioxo2-nBu-4-F-Ph
2-284,5-Dina-dioxo2-nBu-4-F-Ph
2-29dioxo2-nPent-Ph
2-304-HM-dioxo2-nPent-Ph
2-314,5-dihm-dioxo2-nPent-Ph
2-324,5-Dina-dioxo2-nPent-Ph
2-33dioxo4-F-2-nPent-Ph
2-344-HM-dioxo4-F-2-nPent-Ph
2-354,5-dihm-dioxo4-F-2-nPent-Ph
2-36 4,5-Dina-dioxo4-F-2-nPent-Ph
2-37dioxo2-nHex-Ph
2-384-HM-dioxo2-nHex-Ph
2-394,5-dihm-dioxo2-nHex-Ph
2-404,5-Dina-dioxo2-nHex-Ph
2-41dioxo4-F-2-nHex-Ph
2-424-HM-dioxo4-F-2-nHex-Ph

2-434,5-dihm-dioxo4-F-2-nHex-Ph
2-444,5-Dina-dioxo4-F-2-nHex-Ph
2-45dioxo2-nHept-Ph
2-464-HM-dioxo2-nHept-Ph
2-474,5-dihm-dioxo2-nHept-Ph
-48 4,5-Dina-dioxo2-nHept-Ph
2-49dioxo4-F-2-nHept-Ph
2-504-HM-dioxo4-F-2-nHept-Ph
2-514,5-dihm-dioxo4-F-2-nHept-Ph
2-524,5-Dina-dioxo4-F-2-nHept-Ph
2-53dioxo2-nOct-Ph
2-544-HM-dioxo2-nOct-Ph
2-554,5-dihm-dioxo2-nOct-Ph
2-564,5-Dina-dioxo2-nOct-Ph
2-57dioxo4-F-2-nOct-Ph
2-584-HM-dioxo4-F-2-nOct-Ph
2-594,5-dihm-dioxo4-F-2-nOct-Ph
2-60 4,5-Dina-dioxo4-F-2-nOct-Ph
2-61dioxoPh
2-624-HM-dioxoPh
2-634,5-dihm-dioxoPh
2-644,5-Dina-dioxoPh
2-65dioxo4-F-Ph
2-664-HM-dioxo4-F-Ph
2-674,5-dihm-dioxo4-F-Ph
2-684,5-Dina-dioxo4-F-Ph
2-69dioxo2-Cl-4-Me-Ph
2-704-HM-dioxo2-Cl-4-Me-Ph
2-714,5-dihm-dioxo2-Cl-4-Me-Ph
2-724,5-Dina-dioxo2-Cl-4-Me-Ph
2-73dioxo2-nBu-Ph
2-744-HM-dioxo2-nBu-Ph
2-754,5-dihm-dioxo2-nBu-Ph
2-764,5-Dina-dioxo2-nBu-Ph

2-77dioxo2-nPr-Ph
2-784-HM-dioxo2-nPr-Ph
2-794,5-dihm-dioxo2-nPr-Ph
2-804,5-Dina-dioxo2-nPr-Ph
2-81dioxo4-F-2-nPr-Ph
2-824-HM-dioxo 4-F-2-nPr-Ph
2-834,5-dihm-dioxo4-F-2-nPr-Ph
2-844,5-Dina-dioxo4-F-2-nPr-Ph
Table 3
Connection # X, YR2R3
3-1dioxoMe2-Cl-Ph
3-24-HM-dioxoMe2-Cl-Ph
3-34,5-dihm-dioxoMe2-Cl-Ph
3-44,5-Dina-dioxoMe2-Cl-Ph
3-5dioxo nPr2-Cl-Ph
3-64-HM-dioxonPr2-Cl-Ph
3-74,5-dihm-dioxonPr2-Cl-Ph
3-84,5-Dina-dioxonPr2-Cl-Ph
3-9dioxonBu2-Cl-Ph
3-104-HM-dioxonBu2-Cl-Ph
3-114,5-dihm-dioxonBu2-Cl-Ph
3-124,5-Dina-dioxonBu2-Cl-Ph
3-13dioxoiPr 2-Cl-Ph
3-144-HM-dioxoiPr2-Cl-Ph
3-154,5-dihm-dioxoiPr2-Cl-Ph
3-164,5-Dina-dioxoiPr2-Cl-Ph
3-17dioxotBu2-Cl-Ph
3-184-HM-dioxotBu2-Cl-Ph

3-194,5-dihm-dioxotBu2-Cl-Ph
3-204,5-Dina-dioxotBu2-Cl-Ph
3-21dioxoCH2SLA2-Cl-Ph
4-HM-dioxoCH2OAc2-Cl-Ph
3-234,5-dihm-dioxoCH2OAc2-Cl-Ph
3-244,5-Dina-dioxoCH2OAc2-Cl-Ph
3-25dioxoMe2-Br-Ph
3-264-HM-dioxoMe2-Br-Ph
3-274,5-dihm-dioxoMe2-Br-Ph
3-284,5-Dina-dioxoMe2-Br-Ph
3-29dioxonPr2-Br-Ph
3-304-HM-dioxonPr2-Br-Ph
3-314,5-dihm-dioxonPr 2-Br-Ph
3-324,5-Dina-dioxonPr2-Br-Ph
3-33dioxonBu2-Br-Ph
3-344-HM-dioxonBu2-Br-Ph
3-354,5-dihm-dioxonBu2-Br-Ph
3-364,5-Dina-dioxonBu2-Br-Ph
3-37dioxoiPr2-Br-Ph
3-384-HM-dioxoiPr2-Br-Ph
3-394,5-dihm-dioxoiPr2-Br-Ph
3-404,5-Dina-dioxoiPr2-Br-Ph
3-41dioxo tBu2-Br-Ph
3-424-HM-dioxotBu2-Br-Ph
3-434,5-dihm-dioxotBu2-Br-Ph
3-444,5-Dina-dioxotBu2-Br-Ph
3-45dioxoCH2SLA2-Br-Ph
3-464-HM-dioxoCH2SLA2-Br-Ph
3-474,5-dihm-dioxoCH2SLA2-Br-Ph
3-484,5-Dina-dioxoCH2OAc2-Br-Ph
3-49dioxoMe2-Cl-6-Me-Ph
3-504-HM-dioxoMe2-Cl-6-Me-Ph
3-514,5-dihm-dioxoMe2-Cl-6-Me-Ph
3-524,5-Dina-dioxoMe2-Cl-6-Me-Ph

3-53dioxonPr2-Cl-6-Me-Ph
3-544-HM-dioxonPr2-Cl-6-Me-Ph
3-554,5-dihm-dioxonPr2-Cl-6-Me-Ph
3-564,5-Dina-dioxonPr2-Cl-6-Me-Ph
3-57dioxonBu2-Cl-6-Me-Ph
358 for4-HM-dioxonBu2-Cl-6-Me-Ph
3-594,5-dihm-dioxonBu2-Cl-6-Me-Ph
3-60 4,5-Dina-dioxonBu2-Cl-6-Me-Ph
3-61dioxoiPr2-Cl-6-Me-Ph
3-624-HM-dioxoiPr2-Cl-6-Me-Ph
3-634,5-dihm-dioxoiPr2-Cl-6-Me-Ph
3-644,5-Dina-dioxoiPr2-Cl-6-Me-Ph
3-65dioxotBu2-Cl-6-Me-Ph
3-664-HM-dioxotBu2-Cl-6-Me-Ph
3-674,5-dihm-dioxotBu2-Cl-6-Me-Ph
3-684,5-Dina-dioxotBu2-Cl-6-Me-Ph
3-69dioxoCH2SLA 2-Cl-6-Me-Ph
3-704-HM-dioxoCH2SLA2-Cl-6-Me-Ph
3-714,5-dihm-dioxoCH2SLA2-Cl-6-Me-Ph
3-724,5-Dina-dioxoCH2OAc2-Cl-6-Me-Ph
3-73dioxoMe2-Cl-4-F-Ph
3-744-HM-dioxoMe2-Cl-4-F-Ph
3-754,5-dihm-dioxoMe2-Cl-4-F-Ph
3-764,5-Dina-dioxoMe2-Cl-4-F-Ph
3-77dioxonPr2-Cl-4-F-Ph
3-784-HM-dioxonPr2-Cl-4-F-Ph
3-79 4,5-dihm-dioxonPr2-Cl-4-F-Ph
3-804,5-Dina-dioxonPr2-Cl-4-F-Ph
3-81dioxonBu2-Cl-4-F-Ph
3-824-HM-dioxonBu2-Cl-4-F-Ph
3-834,5-dihm-dioxonBu2-Cl-4-F-Ph
3-844,5-Dina-dioxonBu2-Cl-4-F-Ph
3-85dioxoiPr2-Cl-4-F-Ph
3-864-HM-dioxoiPr2-Cl-4-F-Ph

3-98
3-874,5-dihm-dioxoiPr2-Cl-4-F-Ph
3-884,5-Dina-dioxo iPr2-Cl-4-F-Ph
3-89dioxotBu2-Cl-4-F-Ph
3-904-HM-dioxotBu2-Cl-4-F-Ph
3-914,5-dihm-dioxotBu2-Cl-4-F-Ph
3-924,5-Dina-dioxotBu2-Cl-4-F-Ph
3-93dioxoCH2SLA2-Cl-4-F-Ph
3-944-HM-dioxoCH2SLA2-Cl-4-F-Ph
3-954,5-dihm-dioxoCH2SLA2-Cl-4-F-Ph
3-964,5-Dina-dioxoCH2OAc2-Cl-4-F-Ph
3-97dioxoMe2,4-F-Ph
4-HM-dioxoMe2,4-F-Ph
3-994,5-dihm-dioxoMe2,4-F-Ph
3-1004,5-Dina-dioxoMe2,4-F-Ph
3-101dioxonPr2,4-F-Ph
3-1024-HM-dioxonPr2,4-F-Ph
3-1034,5-dihm-dioxonPr2,4-F-Ph
3-1044,5-Dina-dioxonPr2,4-F-Ph
3-105dioxonBu2,4-F-Ph
3-1064-HM-dioxonBu2,4-F-Ph
3-1074,5-dihm-dioxonB 2,4-F-Ph
3-1084,5-Dina-dioxonBu2,4-F-Ph
3-109dioxoiPr2,4-F-Ph
3-1104-HM-dioxoiPr2,4-F-Ph
3-1114,5-dihm-dioxoiPr2,4-F-Ph
3-1124,5-Dina-dioxoiPr2,4-F-Ph
3-113dioxotBu2,4-F-Ph
3-1144-HM-dioxotBu2,4-F-Ph
3 through 1154,5-dihm-dioxotBu2,4-F-Ph
3-1164,5-Dina-dioxotBu2,4-F-Ph
3-17 dioxoCH2SLA2,4-F-Ph
3-1184-HM-dioxoCH2SLA2,4-F-Ph
3-1194,5-dihm-dioxoCH2SLA2,4-F-Ph
3-1204,5-Dina-dioxoCH2OAc2,4-F-Ph

3-121dioxoMe2-Br-4-F-Ph
3-1224-HM-dioxoMe2-Br-4-F-Ph
3-1234,5-dihm-dioxoMe2-Br-4-F-Ph
3-1244,5-Dina-dioxoMe2-Br-4-F-Ph
3-125dioxonPr2-Br-4-F-Ph
3-1264-HM-dioxonPr2-Br-4-F-Ph
3-1274,5-dihm-dioxonPr2-Br-4-F-Ph
3-1284,5-Dina-dioxonPr2-Br-4-F-Ph
3-129dioxonBu2-Br-4-F-Ph
3-1304-HM-dioxonBu2-Br-4-F-Ph
3-1314,5-dihm-dioxonBu2-Br-4-F-Ph
3-1324,5-Dina-dioxonBu2-Br-4-F-Ph
3-133dioxoiPr2-Br-4-F-Ph
3-1344-HM-dioxoiPr2-Br-4-F-Ph
3-1354,5-dihm-dioxoiPr 2-Br-4-F-Ph
3-1364,5-Dina-dioxoiPr2-Br-4-F-Ph
3-137dioxotBu2-Br-4-F-Ph
3-1384-HM-dioxotBu2-Br-4-F-Ph
3-1394,5-dihm-dioxotBu2-Br-4-F-Ph
3-1404,5-Dina-dioxotBu2-Br-4-F-Ph
3-141dioxoCH2SLA2-Br-4-F-Ph
3-1424-HM-dioxoCH2SLA2-Br-4-F-Ph
3-1434,5-dihm-dioxoCH2SLA2-Br-4-F-Ph
3-1444,5-Dina-dioxoCH2OAc2-Br-4-F-Ph
3-145dioxoMe2-nBu-4-F-Ph
3-1464-HM-dioxoMe2-nBu-4-F-Ph
3-1474,5-dihm-dioxoMe2-nBu-4-F-Ph
3-1484,5-Dina-dioxoMe2-nBu-4-F-Ph
3-149dioxonPr2-nBu-4-F-Ph
3-1504-HM-dioxonPr2-nBu-4-F-Ph
3-1514,5-dihm-dioxonPr2-nBu-4-F-Ph
3-1524,5-Dina-dioxonPr2-nBu-4-F-Ph
3-153dioxonBu2-nBu-4-F-Ph
3-1544-HM-dioxo nBu2-nBu-4-F-Ph

3-1554,5-dihm-dioxonBu2-nBu-4-F-Ph
3-1564,5-Dina-dioxonBu2-nBu-4-F-Ph
3-157dioxoiPr2-nBu-4-F-Ph
3-1584-HM-dioxoiPr2-nBu-4-F-Ph
3-1594,5-dihm-dioxoiPr2-nBu-4-F-Ph
3-1604,5-Dina-dioxoiPr2-nBu-4-F-Ph
3-161dioxotBu2-nBu-4-F-Ph
3-1624-HM-dioxotBu2-nBu-4-F-Ph
3-1634,5-dihm-dioxotBu 2-nBu-4-F-Ph
3-1644,5-Dina-dioxotBu2-nBu-4-F-Ph
3-165dioxoCH2SLA2-nBu-4-F-Ph
3-1664-HM-dioxoCH2SLA2-nBu-4-F-Ph
3-1674,5-dihm-dioxoCH2SLA2-nBu-4-F-Ph
3-1684,5-Dina-dioxoCH2OAc2-nBu-4-F-Ph
3-169dioxoMe2-nPent-Ph
3-1704-HM-dioxoMe2-nPent-Ph
3-1714,5-dihm-dioxoMe2-nPent-Ph
3-1724,5-Dina-dioxoMe2-nPent-Ph
3-173dioxonPr2-nPent-Ph
3-1744-HM-dioxonPr2-nPent-Ph
3-1754,5-dihm-dioxonPr2-nPent-Ph
3-1764,5-Dina-dioxonPr2-nPent-Ph
3-177dioxonBu2-nPent-Ph
3-1784-HM-dioxonBu2-nPent-Ph
3-1794,5-dihm-dioxonBu2-nPent-Ph
3-1804,5-Dina-dioxonBu2-nPent-Ph
3-181dioxoiPr2-nPent-Ph
3-1824-HM-dioxoiPr 2-nPent-Ph
3-1834,5-dihm-dioxoiPr2-nPent-Ph
3-1844,5-Dina-dioxoiPr2-nPent-Ph
3-185dioxotBu2-nPent-Ph
3-1864-HM-dioxotBu2-nPent-Ph
3-1874,5-dihm-dioxotBu2-nPent-Ph
3-1884,5-Dina-dioxotBu2-nPent-Ph

3-189dioxoCH2SLA2-nPent-Ph
3-1904-HM-dioxoCH2SLA2-nPent-Ph
3-1914,5-dihm-dioxoCH2SLA 2-nPent-Ph
3-1924,5-Dina-dioxoCH2OAc2-nPent-Ph
3-193dioxoMe4-F-2-nPent-Ph
3-1944-HM-dioxoMe4-F-2-nPent-Ph
3-1954,5-dihm-dioxoMe4-F-2-nPent-Ph
3-1964,5-Dina-dioxoMe4-F-2-nPent-Ph
3-197dioxonPr4-F-2-nPent-Ph
3-1984-HM-dioxonPr4-F-2-nPent-Ph
3-1994,5-dihm-dioxonPr4-F-2-nPent-Ph
3-2004,5-Dina-dioxonPr4-F-2-nPent-Ph
3-201 dioxonBu4-F-2-nPent-Ph
3-2024-HM-dioxonBu4-F-2-nPent-Ph
3-2034,5-dihm-dioxonBu4-F-2-nPent-Ph
3-2044,5-Dina-dioxonBu4-F-2-nPent-Ph
3-205dioxoiPr4-F-2-nPent-Ph
3-2064-HM-dioxoiPr4-F-2-nPent-Ph
3-2074,5-dihm-dioxoiPr4-F-2-nPent-Ph
3-2084,5-Dina-dioxoiPr4-F-2-nPent-Ph
3-209dioxotBu4-F-2-nPent-Ph
3-2104-HM-dioxotBu 4-F-2-nPent-Ph
3-2114,5-dihm-dioxotBu4-F-2-nPent-Ph
3-2124,5-Dina-dioxotBu4-F-2-nPent-Ph
3-213dioxoCH2SLA4-F-2-nPent-Ph
3-2144-HM-dioxoCH2SLA4-F-2-nPent-Ph
3-2154,5-dihm-dioxoCH2SLA4-F-2-nPent-Ph
3-2164,5-Dina-dioxoCH2OAc4-F-2-nPent-Ph
3-217dioxoMe2-nHex-Ph
3-2184-HM-dioxoMe2-nHex-Ph
3-2194,5-dihm-dioxoMe2-nHex-Ph
3-2204,5-Dina-dioxoMe2-nHex-Ph
3-221dioxonPr2-nHex-Ph
3-2224-HM-dioxonPr2-nHex-Ph

3-2234,5-dihm-dioxonPr2-nHex-Ph
3-2244,5-Dina-dioxonPr2-nHex-Ph
3-225dioxonBu2-nHex-Ph
3-2264-HM-dioxonBu2-nHex-Ph
3-2274,5-dihm-dioxonBu2-nHex-Ph
3-2284,5-Dina-dioxonBu2-nHex-Ph
3-229dioxo iPr2-nHex-Ph
3-2304-HM-dioxoiPr2-nHex-Ph
3-2314,5-dihm-dioxoiPr2-nHex-Ph
3-2324,5-Dina-dioxoiPr2-nHex-Ph
3-233dioxotBu2-nHex-Ph
3-2344-HM-dioxotBu2-nHex-Ph
3-2354,5-dihm-dioxotBu2-nHex-Ph
3-2364,5-Dina-dioxotBu2-nHex-Ph
3-237dioxoCH2SLA2-nHex-Ph
3-2384-HM-dioxoCH2SLA2-nHex-Ph
3-2394,5-dihm-dioxoCH2SLA2-nHex-Ph
3-2404,5-Dina-dioxoCH2OAc2-nHex-Ph
3-241dioxoMe4-F-nHex-Ph
3-2424-HM-dioxoMe4-F-nHex-Ph
3-2434,5-dihm-dioxoMe4-F-nHex-Ph
3-2444,5-Dina-dioxoMe4-F-nHex-Ph
3-245dioxonPr4-F-nHex-Ph
3-2464-HM-dioxonPr4-F-nHex-Ph
3-2474,5-dihm-dioxonPr4-F-nHex-Ph
3-2484.5 to the ine-dioxo nPr4-F-nHex-Ph
3-249dioxonBu4-F-nHex-Ph
3-2504-HM-dioxonBu4-F-nHex-Ph
3-2514,5-dihm-dioxonBu4-F-nHex-Ph
3-2524,5-Dina-dioxonBu4-F-nHex-Ph
3-253dioxoiPr4-F-nHex-Ph
3-2544-HM-dioxoiPr4-F-nHex-Ph
3-2554,5-dihm-dioxoiPr4-F-nHex-Ph
3-2564,5-Dina-dioxoiPr4-F-nHex-Ph
3-257dioxotBu4-F-nHex-Ph

table width="90%" border="1" cellpadding="0" cellspacing="0" frame="all"> 3-2584-HM-dioxotBu4-F-nHex-Ph3-2594,5-dihm-dioxotBu4-F-nHex-Ph3-2604,5-Dina-dioxotBu4-F-nHex-Ph3-261dioxoCH2SLA4-F-nHex-Ph3-2624-HM-dioxoCH2SLA4-F-nHex-Ph3-2634,5-dihm-dioxoCH2SLA4-F-nHex-Ph3-2644,5-Dina-dioxoCH2OAc4-F-nHex-Ph3-265dioxoMe2-nHept-Ph3-2664-HM-dioxoMe2-nHept-Ph3-267 4,5-dihm-dioxoMe2-nHept-Ph3-2684,5-Dina-dioxoMe2-nHept-Ph3-269dioxonPr2-nHept-Ph3-2704-HM-dioxonPr2-nHept-Ph3-2714,5-dihm-dioxonPr2-nHept-Ph3-2724,5-Dina-dioxonPr2-nHept-Ph3-273dioxonBu2-nHept-Ph3-2744-HM-dioxonBu2-nHept-Ph3-2754,5-dihm-dioxonBu2-nHept-Ph3-2764,5-Dina-dioxonBu2-nHept-Ph 3-277dioxoiPr2-nHept-Ph3-2784-HM-dioxoiPr2-nHept-Ph3-2794,5-dihm-dioxoiPr2-nHept-Ph3-2804,5-Dina-dioxoiPr2-nHept-Ph3-281dioxotBu2-nHept-Ph3-2824-HM-dioxotBu2-nHept-Ph3-2834,5-dihm-dioxotBu2-nHept-Ph3-2844,5-Dina-dioxotBu2-nHept-Ph3-285dioxoCH2SLA2-nHept-Ph3-2864-HM-dioxo CH2SLA2-nHept-Ph3-2874,5-dihm-dioxoCH2SLA2-nHept-Ph3-2884,5-Dina-dioxoCH2OAc2-nHept-Ph3-289dioxoMe4-F-2-nHept-Ph3-2904-HM-dioxoMe4-F-2-nHept-Ph

3-324
3-2914,5-dihm-dioxoMe4-F-2-nHept-Ph
3-2924,5-Dina-dioxoMe4-F-2-nHept-Ph
3-293dioxonPr4-F-2-nHept-Ph
3-2944-HM-dioxonPr4-F-2-nHept-Ph
3-2954,5-dihm-dioxo nPr4-F-2-nHept-Ph
3-2964,5-Dina-dioxonPr4-F-2-nHept-Ph
3-297dioxonBu4-F-2-nHept-Ph
3-2984-HM-dioxonBu4-F-2-nHept-Ph
3-2994,5-dihm-dioxonBu4-F-2-nHept-Ph
3 to 3004,5-Dina-dioxonBu4-F-2-nHept-Ph
3-301dioxoiPr4-F-2-nHept-Ph
3-3024-HM-dioxoiPr4-F-2-nHept-Ph
3-3034,5-dihm-dioxoiPr4-F-2-nHept-Ph
3-3044,5-Dina-dioxoiPr4-F-2-nHept-Ph
3-305dioxotBu4-F-2-nHept-Ph
3-3064-HM-dioxotBu4-F-2-nHept-Ph
3-3074,5-dihm-dioxotBu4-F-2-nHept-Ph
3-3084,5-Dina-dioxotBu4-F-2-nHept-Ph
3-309dioxoCH2SLA4-F-2-nHept-Ph
3-3104-HM-dioxoCH2SLA4-F-2-nHept-Ph
3-3114,5-dihm-dioxoCH2SLA4-F-2-nHept-Ph
3-3124,5-Dina-dioxoCH2OAc4-F-2-nHept-Ph
3-313dioxoMe2-nOct-Ph
3-314Me2-nOct-Ph
3-3154,5-dihm-dioxoMe2-nOct-Ph
3-3164,5-Dina-dioxoMe2-nOct-Ph
3-317dioxonPr2-nOct-Ph
3-3184-HM-dioxonPr2-nOct-Ph
3-3194,5-dihm-dioxonPr2-nOct-Ph
3-3204,5-Dina-dioxonPr2-nOct-Ph
3-321dioxonBu2-nOct-Ph
3-3224-HM-dioxonBu2-nOct-Ph
3-3234,5-dihm-dioxonBu2-nOct-Ph
4,5-Dina-dioxonBu2-nOct-Ph

3-325dioxoiPr2-nOct-Ph
3-3264-HM-dioxoiPr2-nOct-Ph
3-3274,5-dihm-dioxoiPr2-nOct-Ph
3-3284,5-Dina-dioxoiPr2-nOct-Ph
3-329dioxotBu2-nOct-Ph
3-3304-HM-dioxotBu2-nOct-Ph
3-3314,5-dihm-dioxotBu2-nOct-Ph
3-3324,5-Dina-dioxotBu2-nOct-Ph
3-333 CH2SLA2-nOct-Ph
3-3344-HM-dioxoCH2SLA2-nOct-Ph
3-3354,5-dihm-dioxoCH2SLA2-nOct-Ph
3-3364,5-Dina-dioxoCH2OAc2-nOct-Ph
3-337dioxoMe4-F-2-nOct-Ph
3-3384-HM-dioxoMe4-F-2-nOct-Ph
3-3394,5-dihm-dioxoMe4-F-2-nOct-Ph
3-3404,5-Dina-dioxoMe4-F-2-nOct-Ph
3-341dioxonPr4-F-2-nOct-Ph
3-3424-HM-dioxonPr 4-F-2-nOct-Ph
3-3434,5-dihm-dioxonPr4-F-2-nOct-Ph
3-3444,5-Dina-dioxonPr4-F-2-nOct-Ph
3-345dioxonBu4-F-2-nOct-Ph
3-3464-HM-dioxonBu4-F-2-nOct-Ph
3-3474,5-dihm-dioxonBu4-F-2-nOct-Ph
3-3484,5-Dina-dioxonBu4-F-2-nOct-Ph
3-349dioxoiPr4-F-2-nOct-Ph
3-3504-HM-dioxoiPr4-F-2-nOct-Ph
3-3514,5-dihm-dioxoiPr4-F-2-nOct-Ph
3-352 4,5-Dina-dioxoiPr4-F-2-nOct-Ph
3-353dioxotBu4-F-2-nOct-Ph
3-3544-HM-dioxotBu4-F-2-nOct-Ph
3-3554,5-dihm-dioxotBu4-F-2-nOct-Ph
3-3564,5-Dina-dioxotBu4-F-2-nOct-Ph
3-357dioxoCH2SLA4-F-2-nOct-Ph
3-3584-HM-dioxoCH2SLA4-F-2-nOct-Ph

3-3594,5-dihm-dioxoCH2SLA4-F-2-nOct-Ph
3-3604,5-Dina-dioxoCH2OAc4-F-2-nOct-Ph
3-361 dioxoMePh
3-3624-HM-dioxoMePh
3-3634,5-dihm-dioxoMePh
3-3644,5-Dina-dioxoMePh
3-365dioxonPrPh
3-3664-HM-dioxonPrPh
3-3674,5-dihm-dioxonPrPh
3-3684,5-Dina-dioxonPrPh
3-369dioxonBuPh
3-3704-HM-dioxonBuPh
3-3714,5-dihm-dioxonBuPh
3-3724,5-Dina-dioxonBuPh
3-373dioxoiPrPh
3-3744-HM-dioxoiPrPh
3-3754,5-dihm-dioxoiPrPh
3-3764,5-Dina-dioxoiPrPh
3-377dioxotBuPh
3-3784-HM-dioxotBuPh
3-3794,5-dihm-dioxotBuPh
3-3804,5-Dina-dioxotBuPh
3-381dioxoCH2SLAPh
3-3824-HM-dioxoCH2SLAPh
3-3834,5-dihm-dioxoCH2SLAPh
3-3844,5-Dina-dioxoCH2OAcPh
3-385dioxoMe4-F-Ph
3-3864-HM-dioxoMe4-F-Ph
3-3874,5-dihm-dioxoMe4-F-Ph
3-3884,5-Dina-dioxoMe4-F-Ph
3-389dioxonPr4-F-Ph
3-3904-HM-dioxonPr 4-F-Ph
3-3914,5-dihm-dioxonPr4-F-Ph
3-3924,5-Dina-dioxonPr4-F-Ph

4,5-Dina-dioxo
3-393dioxonBu4-F-Ph
3-3944-HM-dioxonBu4-F-Ph
3-3954,5-dihm-dioxonBu4-F-Ph
3-3964,5-Dina-dioxonBu4-F-Ph
3-397dioxoiPr4-F-Ph
3-3984-HM-dioxoiPr4-F-Ph
3-3994,5-dihm-dioxoiPr4-F-Ph
3-400iPr4-F-Ph
3-401dioxotBu4-F-Ph
3-4024-HM-dioxotBu4-F-Ph
3-4034,5-dihm-dioxotBu4-F-Ph
3-4044,5-Dina-dioxotBu4-F-Ph
3-405dioxoCH2SLA4-F-Ph
3-4064-HM-dioxoCH2SLA4-F-Ph
3-4074,5-dihm-dioxoCH2SLA4-F-Ph
3-4084,5-Dina-dioxoCH2OAc4-F-Ph
3-409dioxoMe 2-Cl-4-Me-Ph
3-4104-HM-dioxoMe2-Cl-4-Me-Ph
3-4114,5-dihm-dioxoMe2-Cl-4-Me-Ph
3-4124,5-Dina-dioxoMe2-Cl-4-Me-Ph
3-413dioxonPr2-Cl-4-Me-Ph
3-4144-HM-dioxonPr2-Cl-4-Me-Ph
3-4154,5-dihm-dioxonPr2-Cl-4-Me-Ph
3-4164,5-Dina-dioxonPr2-Cl-4-Me-Ph
3-417dioxonBu2-Cl-4-Me-Ph
3-4184-HM-dioxonBu2-Cl-4-Me-Ph
3-41945-DIMM-dioxo nBu2-Cl-4-Me-Ph
3-4204,5-Dina-dioxonBu2-Cl-4-Me-Ph
3-421dioxoiPr2-Cl-4-Me-Ph
3-4224-HM-dioxoiPr2-Cl-4-Me-Ph
3-4234,5-dihm-dioxoiPr2-Cl-4-Me-Ph
3-4244,5-Dina-dioxoiPr2-Cl-4-Me-Ph
3-425dioxotBu2-Cl-4-Me-Ph
3-4264-HM-dioxotBu2-Cl-4-Me-Ph

3-4274,5-dihm-dioxotBu2-Cl-4-Me-Ph
3-4284,5-Dina-dioxo tBu2-Cl-4-Me-Ph
3-429dioxoCH2SLA2-Cl-4-Me-Ph
3-4304-HM-dioxoCH2SLA2-Cl-4-Me-Ph
3-4314,5-dihm-dioxoCH2SLA2-Cl-4-Me-Ph
3-4324,5-Dina-dioxoCH2OAc2-Cl-4-Me-Ph
3-433dioxoMe2-nBu-Ph
3-4344-HM-dioxoMe2-nBu-Ph
3-4354,5-dihm-dioxoMe2-nBu-Ph
3-4364,5-Dina-dioxoMe2-nBu-Ph
3-437dioxonPr2-nBu-Ph
3-4384-HM-dioxonPr2-nBu-Ph
3-4394,5-dihm-dioxonPr2-nBu-Ph
3-4404,5-Dina-dioxonPr2-nBu-Ph
3-441dioxonBu2-nBu-Ph
3-4424-HM-dioxonBu2-nBu-Ph
3-4434,5-dihm-dioxonBu2-nBu-Ph
3-4444,5-Dina-dioxonBu2-nBu-Ph
3-445dioxoiPr2-nBu-Ph
3-4464-HM-dioxoiPr2-nBu-Ph
3-4474,5-dihm-dioxoiPr 2-nBu-Ph
3-4484,5-Dina-dioxoiPr2-nBu-Ph
3-449dioxotBu2-nBu-Ph
3-4504-HM-dioxotBu2-nBu-Ph
3-4514,5-dihm-dioxotBu2-nBu-Ph
3-4524,5-Dina-dioxotBu2-nBu-Ph
3-453dioxoCH2SLA2-nBu-Ph
3-4544-HM-dioxoCH2SLA2-nBu-Ph
3-4554,5-dihm-dioxoCH2SLA2-nBu-Ph
3-4564,5-Dina-dioxoCH2OAc2-nBu-Ph
3-457 dioxoMe2-nPr-Ph
3-4584-HM-dioxoMe2-nPr-Ph
3-4594,5-dihm-dioxoMe2-nPr-Ph
3-4604,5-Dina-dioxoMe2-nPr-Ph

2-nPr-Ph tBu
3-461dioxonPr2-nPr-Ph
3-4624-HM-dioxonPr2-nPr-Ph
3-4634,5-dihm-dioxonPr2-nPr-Ph
3-4644,5-Dina-dioxonPr2-nPr-Ph
3-465dioxonBu2-nPr-Ph
3-4664-HM-dioxonBu
3-4674,5-dihm-dioxonBu2-nPr-Ph
3-4684,5-Dina-dioxonBu2-nPr-Ph
3-469dioxoiPr2-nPr-Ph
3-4704-HM-dioxoiPr2-nPr-Ph
3-4714,5-dihm-dioxoiPr2-nPr-Ph
3-4724,5-Dina-dioxoiPr2-nPr-Ph
3-473dioxotBu2-nPr-Ph
3-4744-HM-dioxotBu2-nPr-Ph
3-4754,5-dihm-dioxotBu2-nPr-Ph
3-4764,5-Dina-dioxo2-nPr-Ph
3-477dioxoCH2SLA2-nPr-Ph
3-4784-HM-dioxoCH2SLA2-nPr-Ph
3-4794,5-dihm-dioxoCH2SLA2-nPr-Ph
3-4804,5-Dina-dioxoCH2OAc2-nPr-Ph
3-481dioxoMe4-F-2-nPr-Ph
3-4824-HM-dioxoMe4-F-2-nPr-Ph
3-4834,5-dihm-dioxoMe4-F-2-nPr-Ph
3-4844,5-Dina-dioxoMe4-F-2-nPr-Ph
3-485dioxonPr4-F-2-nPr-Ph
3-4864-HM-dioxonPr4-F-2-nPr-Ph
3-4874,5-dihm-dioxonPr4-F-2-nPr-Ph
3-4884,5-Dina-dioxonPr4-F-2-nPr-Ph
3-489dioxonBu4-F-2-nPr-Ph
3-4904-HM-dioxonBu4-F-2-nPr-Ph
3-4914,5-dihm-dioxonBu4-F-2-nPr-Ph
3-4924,5-Dina-dioxonBu4-F-2-nPr-Ph
3-493dioxoiPr4-F-2-nPr-Ph
3-4944-HM-dioxoiPr4-F-2-nPr-Ph

3-495 4,5-dihm-dioxoiPr4-F-2-nPr-Ph
3-4964,5-Dina-dioxoiPr4-F-2-nPr-Ph
3-497dioxotBu4-F-2-nPr-Ph
3-4984-HM-dioxotBu4-F-2-nPr-Ph
3-4994,5-dihm-dioxotBu4-F-2-nPr-Ph
3-5004,5-Dina-dioxotBu4-F-2-nPr-Ph
3-501dioxoCH2SLA4-F-2-nPr-Ph
3-5024-HM-dioxoCH2SLA4-F-2-nPr-Ph
3-5034,5-dihm-dioxoCH2SLA4-F-2-nPr-Ph
3-5044,5-Dina-dioxo CH2OAc4-F-2-nPr-Ph

In the compounds having General formula (I) of the present invention, the preferred compounds may be mentioned are illustrated by the examples of compound No.: 1-12, 1-13, 1-19, 1-20, 1-26, 1-28, 1-30, 1-32, 1-34, 1-36, 1-38, 1-40, 1-42, 1-44, 1-46, 1-48, 1-50, 1-54, 1-58, 1-60, 1-62, 1-66, 1-68, 1-70, 1-72, 1-74, 1-78, 1-80, 1-82, 1-86, 1-100, 1-101, 1-107, 1-108, 1-114, 1-116, 1-118, 1-120, 1-122, 1-124, 1-126, 1-128, 1-130, 1-132, 1-134, 1-136, 1-138, 1-142, 1-146, 1-148, 1-150, 1-154, 1-156, 1-158, 1-160, 1-162, 1-166, 1-168, 1-170, 1-174, 1-188, 1-189, 1-195, 1-196, 1-202, 1-204, 1-206, 1-208, 1-210, 1-212, 1-214, 1-216, 1-218, 1-220, 1-222, 1-224, 1-226, 1-230, 1-234, 1-236, 1-238, 1-242, 1-244, 1-246, 1-248, 1-250, 1-254, 1-256, 1-258, 1-262, 1-276, 1-277, 1-283, 1-284, 1-290, 1-292, 1-294, 1-296, 1-298, 1-300, 1-302, 1-304, 1-306, 1-308, 1-310, 1-312, 1-314, 1-318, 1-322, 1-324, 1-326, 1-330, 1-332, 1-334, 1-336, 1-338, 1-342, 1-344, 1-346, 1-350, 1-353, 1-355, 1-360 to 1-369, 1-371, 1-372, 1-378, 1-380, 1-382, 1-384, 1-386, 1-388, 1-390, 1-392, 1-394, 1-396, 1-398, 1-400, 1-402, 1-406, 1-410, 1-412, 1-414, 1-418, 1-420, 1-422, 1-424, 1-426, 1-430, 1-432, 1-434, 1-438, 1-452, 1-453, 1-459, 1-460, 1-466, 1-468, 1-470, 1-472, 1-474, 1-476, 1-478, 1-480, 1-482, 1-484, 1-486, 1-488, 1-490, 1-494, 1-498, 1-500, 1-502, 1-506, 1-508, 1-510, 1-512, 1-514, 1-518, 1-520, 1-522, 1-526, 1-540, 1-541, 1-547, 1-548, 1-554, 1-556, 1-558, 1-560, 1-562, 1-564, 1-566, 1-568, 1-570, 1-572, 1-574, 1-576, 1-578, 1-582, 1-586, 1-588, 1-590, 1-594, 1-596, 1-598, 1-600, 1-602, 1-604, 1-606, 1-608, 1-610, 1-614, 1-628, 1-629, 1-635, 1-636, 1-642, 1-644, 1-646, 1-648, 1-650, 1-652, 1-654, 1-656, 1-658, 1-660, 1-662, 1-664, 1-666, 1-670, 1-674, 1-676, 1-678, 1-682, 1-684, 1-686, 1-688, 1-690, 1-694, 1-696, 1-698, 1-702, 1-712 to 1-720, 1-723, 1-724, 1-730, 1-732, 1-734, 1-736, 1-738, 1-740, 1-742, 1-744, 1-746, 1-748, 1-750, 1-752, 1-754, 1-758, 1-762, 1-764, 1-766, 1-770, 1-772, 1-774, 1-776, 1-778, 1-782, 1-784, 1-786, 1-790, 1-804, 1-805, 1-811, 1-812, 1-818, 1-820, 1-822, 1-824, 1-826, 1-828, 1-830, 1-832, 1834, 1-836, 1-838, 1-840, 1-842, 1-846, 1-850, 1-852, 1-854, 1-858, 1-860, 1-862, 1-864, 1-866, 1-870, 1-872, 1-874, 1-878, 1-888 to 1-896, 1-899, 1-900, 1-906, 1-908, 1-910, 1-912, 1-914, 1-916, 1-918, 1-920, 1-922, 1-924, 1-926, 1-928, 1-930, 1-934, 1-938, 1-940, 1-942, 1-946, 1-948, 1-950, 1-952, 1-954, 1-958, 1-960, 1-962, 1-966, 1-980, 1-981, 1-987, 1-988, 1-994, 1-996, 1-998, 1-1000, 1-1002, 1-1004, 1-1006, 1-1008, 1-1010, 1-1012, 1-1014, 1-1016, 1-1018, 1-1022, 1-1026, 1-1028, 1-1030, 1-1034, 1-1036, 1-1038, 1-1040, 1-1042, 1-1046, 1-1048, 1-1050, 1-1054, 1-1057, 1-1062, 1-1063, 1-1066, 1-1067 to 1-1070, 1-1074, 1-1079, 1-1080, 1-1083, 1-1085 to 1-1087, 1-1091, 1-1096, 1-1097, 1-1100, 1-1102 to 1-1104, 1-1108, 1-1113, 1-1114, 1-1117, 1-1119 to 1-1121, 1-1125, 1-1130, 1-1131, 1-1134, 1-1136 to 1-1138, 1-1142, 1-1147, 1-1148, 1-1151, 1-1153 to 1-1155, 1-1159, 1-1164, 1-1165, 1-1168, 1-1170 to 1-1172, 1-1176, 1-1181, 1-1182, 1-1185, 1-1187 to 1-1189, 1-1193, 1-1198, 1-1199, 1-1202, 1-1204 to 1-1206, 1-1210, 1-1215, 1-1216, 1-1219, 1-1221 to 1-1223, 1-1227, 1-1232, 1-1233, 1-1236, 1-1238 to 1-1240, 1-1244, 1-1249, 1-1250, 1-1253, 1-1255 to 1-1257, 1-1261, 1-1266, 1-1267, 1-1270, 1-1272 to 1-1274, 1-1278, 1-1283, 1-1284, 1-1287, 1-1289 to 1-1291, 1-1295, 1-1300, 1-1301, 1-1304, 1-1306 to 1-1308, 1-1312, 1-1317, 1-1318, 1-1321, 1-1323 to 1-1325, 1-1329, 1-1334, 1-1335, 1-1337, 1-1340 to 1-1342, 1-1346, 1-1351, 1-1352, 1-1355, 1-1357 to 1-1359, 1-1374, 1-1375, 1-1381, 1-1382, 1-1388, 1-1390, 1-1392, 1-1394, 1-1396, 1-1398, 1-1400, 1-1402, 1-1404, 1-1406, 1-1408, 1-1410, 1-1412, 1-1416, 1-1420, 1-1422, 1-1428, 1-1430, 1-1432, 1-1434, 1-1436, 1-1440, 1-1442, 1-1444, 1-1448, 1-1462, 1-1463, 1-1469, 1-1470, 1-1476, 1-1478, 1-1480, 1-1482, 1-1484, 1-1486, 1-1488, 1-1490, 1-1492, 1-1494, 1-1496, 1-1498, 1-1500, 1-1504, 1-1508, 1-1510, 1-1516, 1-1518, 1-1520, 1-1522, 1-1524, 1-1528, 1-1530, 1-1532, 1-1536, 1-1550, 1-1551, 1-1557, 1-1558, 1-1564, 1-1566, 1-1568, 1-1570, 1-1572, 1-1574, 1-1576, 1-1578, 1-1580, 1-1582, 1-1584, 1-1586, 1-1588, 1-1592, 1-1596, 1-1598, 1-1604, 1-1606, 1-1608, 1-1610, 1-1612, 1-1616, 1-1618, 1-1620, 1-1624, 1-1638, 1-1639, 1-1645, 1-1646, 1-1652, 1-1654, 1-1656, 1-1658, 1-1660, 1-1662, 1-1664, 1-1666, 1-1668, 1-1670, 1-1672, 1-1674, 1-1676, 1-1680, 1-1684, 1-1686, 1-1692, 1-1694, 1-1696, 1-1698, 1-1700, 1-704, 1-1706, 1-1708, 1-1712, 1-1726, 1-1727, 1-1733, 1-1734, 1-1740, 1-1742, 1-1744, 1-1746, 1-1748, 1-1750, 1-1752, 1-1754, 1-1756, 1-1758, 1-1760, 1-1762, 1-1764, 1-1768, 1-1772, 1-1774, 1-1780, 1-1782, 1-1784, 1-1786, 1-1788, 1-1792, 1-1794, 1-1796, 1-1800, 1-1814, 1-1815, 1-1821, 1-1822, 1-1828, 1-1830, 1-1832, 1-1834, 1-1836, 1-1838, 1-1840, 1-1842, 1-1844, 1-1846, 1-1848, 1-1850, 1-1852, 1-1856, 1-1860, 1-1862, 1-1868, 1-1870, 1-1872, 1-1874, 1-1876, 1-1880, 1-1882, 1-1884, 1-1888, 1-1902, 1-1903, 1-1909, 1-1910, 1-1916, 1-1918, 1-1920, 1-1922, 1-1924, 1-1926, 1-1928, 1-1930, 1-1932, 1-1934, 1-1936, 1-1938, 1-1940, 1-1944, 1-1948, 1-1950, 1-1956, 1-1958, 1-1960, 1-1962, 1-1964, 1-1968, 1-1970, 1-1972, 1-1976, 1-1989, 1-1990, 1-1996, 1-1997, 1-2003, 1-2005, 1-2007, 1-2009, 1-2011, 1-2013, 1-2015, 1-2017, 1-2019, 1-2021, 1-2023, 1-2025, 1-2027, 1-2031, 1-2035, 1-2037, 1-2043, 1-2045, 1-2047, 1-2049, 1-2051, 1-2055, 1-2057, 1-2059, 1-2063, 1-2077, 1-2078, 1-2084, 1-2085, 1-2091, 1-2093, 1-2095, 1-2097, 1-2099, 1-2101, 1-2103, 1-2105, 1-2107, 1-2109, 1-2111, 1-2113, 1-2115, 1-2119, 1-2123, 1-2125, 1-2131, 1-2133, 1-2135, 1-2137, 1-2139, 1-2143, 1-2145, 1-2147, 1-2151, 1-2154, 1-2157, 1-2160, 1-2163, 1-2166, 1-2169, 1-2172, 1-2175, 1-2178, 1-2181, 1-2184, 1-2187, 1-2190, 1-2193, 1-2196, 1-2199, 1-2202, 1-2205, 1-2208, 1-2211, 1-2214, 1-2217 to 1-2221, 1-2224 to 1-2228, 1-2231 to 1-2235, 1-2238 to 1-2242, 1-2245 to 1-2249, 1-2252 to 1-2256, 1-2259 to 1-2263, 1-2266 to 1-2270, 1-2273 to 1-2277, 1-2280 to 1-2284, 1-2287 to 1-2291, 1-2294 to 1-2298, 1-2301 to 1-2305, 1-2308 to 1-2312, 1-2315 to 1-2319, 1-2322 to 1-2326, 1-2329 to 1-2333, 1-2336 to 1-2340, 1-2343 to 1-2347, 1-2350 to 1-2354, 1-2357 to 1-2361, 1-2364 to 1-2368, 1-2371 to 1-2375, 1-2378 to 1-2382, 1-2385 to 1-2389, 1-2392 to 1-2396, 1-2399 to 1-2403, 1-2406 to 1-2410, 1-2413 to 1-2417, 1-2420 to 1-2424, 1-2427 to 1-2431, 1-2434 to 1-2438, 1-2441 to 1-2445, 1-2448 to 1-2452, 1-2455 to 1-2459, 1-2462 to 1-2466, 1-2469 to 1-2473, 1-2476 to 1-2480, 1-2483 to 1-2487, 1-2490 to 1-2494, 1-2497 to 1-2501, 1-2504 to 1-2508, 1-2511 to 1-2515, 1-2518 to 1-2522, 1-2525 to 1-2529, 1-2532 to 1-2536, 1-2539 to 1-2543, 1-2546 to 1-2550, 1-2553 to 1-2557, 1-2560 to 1-2564, 1-2567 to 1-2571, 1-2574 to 1-2578, 1-2581 what about 1-2585, 1-2588 to 1-2592, 1-2595 to 1-2599, 1-2602 to 1-2606, 1-2609 to 1-2613, 1-2616 to 1-2620, 1-2623 to 1-2627,

2-3, 2-4, 2-7, 2-8, 2-11, 2-12, 2-15, 2-16, 2-19, 2-20, 2-23, 2-24, 2-27, 2-28, 2-31, 2-32, 2-35, 2-36, 2-39, 2-40, 2-43, 2-44, 2-47, 2-48, 2-51, 2-52, 2-59, 2-60, 2-83, 2-84,

3-3, 3-4, 3-7, 3-8, 3-11, 3-12, 3-15, 3-16, 3-27, 3-28, 3-31, 3-32, 3-35, 3-36, 3-39, 3-40, 3-51, 3-52, 3-55, 3-56, 3-59, 3-60, 3-63, 3-64, 3-75, 3-76, 3-79, 3-80, 3-83, 3-84, 3-87, 3-88, 3-99, 3-100, 3-103, 3-104, 3-107, 3-108, 3-111, 3-112, 3-123, 3-124, 3-127, 3-128, 3-131, 3-132, 3-135, 3-136, 3-147, 3-148, 3-151, 3-152, 3-155, 3-156, 3-159, 3-160, 3-171, 3-172, 3-175, 3-176, 3-179, 3-180, 3-183, 3-184, 3-195, 3-196, 3-199, 3-200, 3-203, 3-204, 3-207, 3-208, 3-219, 3-220, 3-223, 3-224, 3-227, 3-228, 3-231, 3-232, 3-243, 3-244, 3-247, 3-248, 3-251, 3-252, 3-255, 3-256, 3-267, 3-268, 3-271, 3-272, 3-275, 3-276, 3-279, 3-280, 3-291, 3-292, 3-295, 3-296, 3-299, 3 to 300, 3-303, 3-304, 3-339, 3-340, 3-343, 3-344, 3-347, 3-348, 3-351, 3-352, 3-483, 3-484, 3-487, 3-488, 3-491, 3-492, 3-495 and 3-496,

more preferably can be illustrated by examples mentioned compound No.: 1-12, 1-26, 1-30, 1-34, 1-38, 1-42, 1-46, 1-58, 1-66, 1-70, 1-78, 1-100, 1-114, 1-118, 1-122, 1-126, 1-130, 1-134, 1-146, 1-154, 1-158, 1-166, 1-188, 1-202, 1-206, 1-210, 1-214, 1-218, 1-222, 1-234, 1-242, 1-246, 1-254, 1-276, 1-290, 1-294, 1-298, 1-302, 1-306, 1-310, 1-322, 1-330, 1-334, 1-342, 1-364, 1-378, 1-382, 1-386, 1-390, 1-394, 1-398, 1-410, 1-418, 1-422, 1-430, 1-452, 1-466, 1-470, 1-474, 1-478, 1-482, 1-486, 1-498, 1-506, 1-510, 1-518, 1-540, 1-554, 1-558, 1-562, 1-566, 1-570, 1-574, 1-586, 1-594, 1-598, 1-604, 1-606, 1-628, 1-642, 1-646, 1-650, 1-654, 1-658, 1-662, 1-674, 1-682, 1-686, 1-694, 1-716, 1-730, 1-734, 1-738, 1-742, 1-746, 1-750, 1-762, 1-770, 1-774, 1-782, 1-804, 1-818, 1-822, 1-826, 1-830, 1-834, 1-838, 1-850, 1-858, 1-862, 1-870, 1-892, 1-906, 1-910, 1-914, 1-918, 1-922, 1-926, 1-938, 1-946, 1-950, 1-958, 1-980, 1-994, 1-998, 1-1002, 1-1006, 1-1010, 1-1014, 1-1026, 1-1034, 1-1038, 1-1046, 1-1227, 1-1232, 1-1239, 1-1240, 1-1244, 1-1249, 1-1256, 1-1257, 1-1261, 1-1266, 1-1273, 1-1274, 1-1278, 1-1283, 1-1290, 1-1291, 1-1295, 1-1300, 1-1307, 1-1308, 1-1374, 1-1388, 1-1392 1-1396, 1-1400, 1-1404, 1-1408, 1-1420, 1-1428, 1-1432, 1-1440, 1-1462, 1-1476, 1-1480, 1-1484, 1-1488, 1-1492, 1-1496, 1-1508, 1-1516, 1-1520, 1-1528, 1-1550, 1-1564, 1-1568, 1-1572, 1-1576, 1-1580, 1-1584, 1-1596, 1-1604, 1-1608, 1-1616, 1-1638, 1-1652, 1-1656, 1-1660, 1-1664, 1-1668, 1-1672, 1-1684, 1-1692, 1-1696, 1-1704, 1-1726, 1-1740, 1-1744, 1-1748, 1-1752, 1-1756, 1-1760, 1-1772, 1-1780, 1-1784, 1-1792, 1-1814, 1-1828, 1-1832, 1-1836, 1-1840, 1-1844, 1-1848, 1-1860, 1-1868, 1-1872, 1-1880, 1-1902, 1-1916, 1-1920, 1-1924, 1-1928, 1-1932, 1-1936, 1-1948, 1-1956, 1-1960, 1-1968, 1-1989, 1-2003, 1-2007, 1-2011, 1-2015, 1-2019, 1-2023, 1-2035, 1-2043, 1-2047, 1-2055, 1-2077, 1-2091, 1-2095, 1-2099, 1-2103, 1-2107, 1-2111, 1-2123, 1-2131, 1-2135, 1-2143, 1-2219, 1-2220, 1-2226, 1-2227, 1-2233, 1-2234, 1-2240, 1-2241, 1-2247, 1-2248, 1-2254, 1-2255, 1-2261, 1-2262, 1-2268, 1-2269, 1-2275, 1-2276, 1-2282, 1-2283, 1-2289, 1-2290, 1-2296, 1-2297, 1-2303, 1-2304, 1-2310, 1-2311, 1-2317, 1-2318, 1-2324, 1-2325, 1-2331, 1-2332, 1-2338, 1-2339, 1-2345, 1-2346, 1-2352, 1-2353, 1-2359, 1-2360, 1-2366, 1-2367, 1-2373, 1-2374, 1-2380, 1-2381, 1-2387, 1-2388, 1-2394, 1-2395, 1-2401, 1-2402, 1-2408, 1-2409, 1-2415, 1-2416, 1-2422, 1-2423, 1-2429, 1-2430, 1-2436, 1-2437, 1-2443, 1-2444, 1-2450, 1-2451, 1-2457, 1-2458, 1-2464, 1-2465, 1-2471, 1-2472, 1-2478, 1-2479, 1-2485, 1-2486, 1-2492, 1-2493, 1-2499, 1-2500, 1-2506, 1-2507, 1-2513, 1-2514, 1-2520, 1-2521, 1-2527, 1-2528, 1-2534, 1-2535, 1-2541, 1-2542, 1-2548, 1-2549, 1-2555, 1-2556, 1-2562, 1-2563, 1-2569, 1-2570, 1-2576, 1-2577, 1-2583, 1-2584, 1-2590, 1-2591, 1-2597, 1-2598, 1-2604, 1-2605, 1-2611, 1-2612, 1-2618, 1-2619, 1-2625, 1-2626,

2-3, 2-7, 2-11, 2-15, 2-19, 2-23, 2-27, 2-31, 2-35, 2-39, 2-43, 2-47, 2-51, 2-59, 2-83,

3-7, 3-31, 3-55, 3-79, 3-103, 3-127, 3-151, 3-175, 3-199, 3-223, 3-247, 3-271, 3-295, 3-343 and 3-487

even more preferably may be mentioned

illustrated with example compound No. 1-206: ethyl 8-[N-(2-chlorophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-210: ethyl 8-[N-(2-chlorophenylsulfonyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-294: ethyl 8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-298: ethyl 8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated example of connection # 1-378: ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-hydroxymethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-382: ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-386:

ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-390: ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-394: ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2,3-trihydroxypropane)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-398: ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2,3,4-tetrahydroquinolin)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-410: ethyl 2,3-bis(acetamidomethyl)-8-[N-(2-chloro-4-forfinal)who sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated example of connection # 1-418: ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3-hydroxy-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,

illustrated with example compound No. 1-422: ethyl 3-acetylamino-9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,

illustrated with example compound No. 1-430: ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-bis(hydroxymethyl)-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,

illustrated with example compound No. 1-646: ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-650: ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-734: ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-738: ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-822: ethyl 8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-826: ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-1,4-is oxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-910: ethyl 8-[N-(2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-914: ethyl 8-[N-(2-heptylphenol)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-998: ethyl 8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1002: ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1392: ethyl 8-[N-(2-bromophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1396: ethyl 8-[N-(2-bromophenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1480: ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1484: ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1568: ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxine who yl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1572: ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1656: ethyl 2,3-bis(hydroxymethyl)-8-[N-(2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1660: ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1744: ethyl 8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1748: ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1920: ethyl 8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-1924: ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-2095: ethyl 8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,

illustrated with example compound No. 1-2099: ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-propylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate and

illustrated with example compound No. 2-15: ethyl 8-[N-(2-chloro-4-forfinal)-N-methylsulfonyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate.

The compound having General formula (I)according to the present invention can be easily obtained in accordance with the method And the method shown here below.

Method a is a method of obtaining compounds having General formula (I), by introducing a cyclic Catala at the initial stage of receipt.

The method is a method of obtaining compounds having General formula (I), by introducing a cyclic Catala on the final receipt.

The method is a method of obtaining compounds having General formula (I), by inserting R5at the final stage of receipt.

Method And

Method In

Method

In the above-mentioned method And the method With the ring A, ring B, X, Y, R1, R2, R3, R5, m and n have the same meaning defined above, L represents a leaving or delete the group, and Z represents a protective group.

In the reaction of method A - method when the connection as reactive substrate has a group such as amino group, a hydroxy-group and/or carboxyl group, which inhibits PR is naznacheniju to the implementation of the reaction, these groups may be protected if necessary, the protective group. The protective group (s), which inhibits designed to implement the reaction is not limited as long as it is a protective group that is generally used for the reaction, it may be, for example, a protective group described in “Protective Groups in Organic Synthesis, 3rdedition, by T.W. Greene &P. G. M. Wuts; Jhn Wiley & Sons, Inc.

The protective group of the amino group can be used without specific limitations, yet it is a protective group that is generally used as a protective group of amino group, and preferably can be mentioned formyl group mentioned above With1-C6acylcarnitine group; the above-mentioned arylcarbamoyl group; the above-mentioned1-C6alkoxycarbonyl group; the above-mentioned1-C6alcoolica group, which is substituted with halogen; kalkilya groups such as benzyl, phenethyl, 3-phenylpropyl, 4-phenylbutyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthylmethyl or 9-antimetal; the above aracelikarsaalyna group and similar.

The protective group of the hydroxy-group can be used without specific limitations, yet it is a protective group commonly used as a protective group hydro is a system of groups, and preferably can be mentioned formyl, C1-C6alkylcarboxylic groups such as acetyl, arylcarboxamide, such as benzoline group, and alkoxysilane alkoxymethyl groups such as 2-methoxyethoxymethyl.

The protective group of the carboxyl group can be used without particular limitations, for now it is a group that is typically used as a protective group of carboxyl group, and preferably can be mentioned the above-mentioned1-C6alkyl group and kalkilya groups such as benzyl, phenethyl and phenylpropyl.

Additionally, if necessary, the protective groups groups which inhibit intended to implement the reaction can be chipped off. The reaction of the removal of these protective groups, which is a desirable reaction may be conducted in accordance with generally accepted procedures used in the field of synthetic organic chemistry (for example, the procedure described in the above publication, "Protective Groups in Organic Synthesis", 3rdedition, by T.W. Greene &P. G. M. Wuts; Jhn Wiley & Sons, Inc.).

Method And

Stage 1 of the method And is the stage of reaction of the ketone compound (1) with compound (2) or compound (3), which is compound (2)having an end group, a substituted trimethylsilyloxy group (described as TMS on Omanthai above), in an inert solvent in the presence of acid, to obtain a cyclic catalogo connection (4).

For this stage you can choose the reaction of the cyclic in (protection) ketone, which is widely used in organic synthesis, and this stage can be carried out in accordance with the procedures described in T.W. Greene. P. G. Wuts; "Protective Groups in Organic Synthesis”, 3rdedition, 1999, Chapter 4, page 293-368, John Wiley & Sons, Inc., and similar, or in accordance with similar procedures.

Here cyclic catalinae compound (4) can also be obtained using the following procedure (stage 1' method A).

Stage 1' method And is the stage of the reaction dimethylketene connection (5) with compound (2) or compound (3) in an inert solvent in the presence of acid, to obtain a cyclic catalogo connection (4). This reaction can be carried out in accordance with the same procedure or on the basis of the procedure stage 1.

Stage 2 of the method And is the stage of enable cyclic Catalina the compound (4)obtained by using the stage 1 or stage 1', to be subjected to the reaction of Dickman obtaining clinocerinae connection (7).

At this stage you can choose the reaction of dikman, which usually widely used in organic synthesis, and this reaction can be carried out in accordance with proceed the swarm, described in "Chemical Pharmaceutical Bulletin (Chem. Pharm. Bull.), Vol. 29, PP. 3238-3248 (1981), and similar or on the basis of this procedure.

In this case ketoamine compound (7) can also be obtained using the following procedure (stage 2' method A).

Stage 2' method And is the stage of reaction of the ketone compound (6) with dialkylammonium, in an inert solvent in the presence of a base, to obtain keeeping connection (7).

At this stage you can apply the response of the introduction of ester groups, which are usually widely used in organic synthesis, and this reaction can be carried out in accordance with the procedure described in Canadian Journal of Chemistry (Can. J. Chem.), Vol. 70, PP. 1406-1426 (1992), or equivalent, or on the basis of this procedure.

Stage 3 method And is the stage of anodirovaniya keeeping compound (7)obtained in stage 2 or stage 2', in an inert solvent in the presence of a base to obtain compound (8)having a leaving or remove the group L.

This stage can be carried out in accordance with the procedure described in Journal of American Chemical Society (J. Am. Chem. Soc.), Vol 120, PP. 3664-3670 (1998), and similar or on the basis of this procedure.

“Leaving group” in the definition of L is usually a group that is removed in the form of a nucleophilic residue, and can be mentioned, for example, halogen atoms, the e as a fluorine atom, chlorine, bromine and iodine; lower alkanesulfonyl, such as methanesulfonate, econsultancy; halogeno low alkanesulfonyl, such as tripterocalyx, pentafluoroethanesulfonyl, and arylsulfonate, such as benzosulfimide, p-toluensulfonate and p-nitrobenzenesulfonate. Preferably it is halogeno lowest alkanesulfonyl, particularly preferably triftormetilfullerenov.

The inert solvent is not particularly limited, while it did not inhibit the reaction and dissolves to some extent the source material, and can be mentioned, for example, aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylethylenediamine ether; amides, such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone and hexamethylphosphorotriamide, or mixtures of these solvents. Preferably it is a halogenated hydrocarbon, preferably dichloromethane.

Used the base includes inorganic bases such as carbonates, alkaline metal is in, such as sodium carbonate, potassium carbonate and lithium carbonate; bicarbonates of alkali metals such as sodium bicarbonate, potassium bicarbonate and lithium bicarbonate; alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; alkali metal fluorides such as sodium fluoride and potassium fluoride; organic bases such as alkoxides of alkali metals such as sodium methoxide, ethoxide sodium, potassium methoxide, ethoxide potassium tert-piperonyl potassium and lithium methoxide; N-methylmorpholine, triethylamine, Tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinedione, picoline, 4-(N,N-dimethylamino)pyridine, 2,6-di(tert-butyl)-4-methylpyridine, quinoline, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), preferably hydrides of alkali metals or organic bases and more preferably the hydride sodium or diisopropylethylamine.

The reaction temperature varies depending on the starting compounds and the reaction reagent, and the reaction is carried out at temperatures from -100°C to 100°C., preferably from -78°C. to 50°C.

The reaction time varies depending on the reaction temperature, the starting compound, the reaction reagent or the type dissolve the I, and usually it is in the interval from 1 minute to 48 hours, preferably from 5 minutes to 12 hours.

Stage 4 method And is the stage of interaction of the compound (8)having a leaving group L, obtained in stage 3, with tilenum compound (9) in an inert solvent in the presence of a base, to obtain the compounds (10).

“Protective group” sulfanilic group in the definition of Z is not particularly limited, as long as it is a protective group sulfanilic group, which usually widely used in organic synthesis, and can be mentioned, for example, alcoholnye groups, such as formyl, acetyl, propionyl, butyryl, and arylcarbamoyl groups such as the benzoyl, α-naphtol, β-naphtol, pyridyl, toenail and furor. Preferably it is a group which forms a pharmacologically acceptable ester, and more preferably acetyl group.

Used inert solvent is not particularly limited, while it did not inhibit the reaction and dissolves to some extent the source material, and can be mentioned, for example, aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxa is, dimethoxyethane and diethylethylenediamine ether; aprotic polar solvents such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide or mixtures of these solvents. Preferably it is an aprotic polar solvent, preferably N,N-dimethylformamide.

Used the base includes inorganic bases such as carbonates of alkali metals, for example sodium carbonate, potassium carbonate and lithium carbonate; bicarbonates of alkali metals such as sodium bicarbonate, potassium bicarbonate and lithium bicarbonate; hydrides of alkali metals such as lithium hydride, sodium hydride and potassium hydride; alkali metal fluorides such as sodium fluoride and potassium fluoride; organic bases such as alkoxides of alkali metals such as sodium methoxide, ethoxide sodium, potassium methoxide, ethoxide potassium tert-piperonyl potassium and lithium methoxide; N-methylmorpholine, triethylamine, Tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinedione, picoline, 4-(N,N-dimethylamino)pyridine, 2,6-di(tert-butyl)-4-methylpyridine, quinoline, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), preferably hydride of an alkali metal, more preferred is entrusted sodium hydride or potassium hydride.

The reaction temperature varies depending on the starting compounds and the reaction reagent, and the reaction is carried out at a temperature from -78°C to 100°C, preferably from -20°C. to 50°C.

The reaction time varies depending on the reaction temperature, the starting compound, the reaction reagent or the type of solvent, and usually it is in the interval from 1 minute to 120 hours, preferably from 10 minutes to 72 hours.

Stage 5 method And is the stage of removal of the protective group sulfanilic group of compound (10)obtained in stage 4, in an inert solvent to obtain the compound (11).

This stage is the stage of removal of the protective group sulfanilic group, which is widely used in organic synthesis, and is conducted in accordance with the procedure described in the above-mentioned work “Protective Groups in Organic Synthesis, 3rdedition, by T.W. Greene &P. G. M. Wuts; Jhn Wiley & Sons, Inc., and similar, or on the basis of this procedure, and may preferably be conducted using the procedures for removing protection in an inert solvent in the presence of a base.

Used inert solvent is not particularly limited, while it did not inhibit the reaction and dissolves to some extent the source material, and can be mentioned, for example, aromatic hydrocarbons such as benzo is l, toluene and xylene; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylethylenediamine ether; alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, Isobutanol, tert-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and 2-methoxyethanol; amides, such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone and hexamethylphosphorotriamide; sulfoxidov, such as dimethyl sulfoxide and sulfolane or any mixture of these solvents, and is preferably an alcohol, and more preferably methanol or ethanol.

Used the base include carbonates of alkali metals such as sodium carbonate, potassium carbonate and lithium carbonate; bicarbonates of alkali metals such as sodium bicarbonate, potassium bicarbonate and lithium bicarbonate; organic bases such as alkoxides of alkali metals such as sodium methoxide, ethoxide sodium, potassium methoxide, ethoxide potassium tert-piperonyl potassium and lithium methoxide; N-methylmorpholine, triethylamine, Tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinedione, picoline, 4-(N,N-d is methylamino)pyridine, 2,6-di(tert-butyl)-4-methylpyridine, quinoline, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), preferably the carbonates of alkali metals and more preferably potassium carbonate.

The reaction temperature varies depending on the starting compounds and the reaction reagent, and the reaction is carried out at a temperature from -78°C to 100°C, preferably from -20°C. to 50°C.

The reaction time varies depending on the reaction temperature, the starting compound, the reaction reagent or the type of solvent, and it usually takes from 1 minute to 24 hours, preferably from 5 minutes to 5 hours.

Stage 6 of the method And is the stage of chlorosulfonylisocyanate Tilney group of the compound (11)obtained at stage 5, in an inert solvent to obtain compound (12).

This stage can be carried out in accordance with the procedure described in "Journal of Organic Chemistry (J. Org. Chem.), Vol 16, PP. 621-625 (1951) and similar, or on the basis of this procedure.

Used inert solvent is not particularly limited, while it did not inhibit the reaction and dissolves to some extent the source material, and can be mentioned, for example, aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, is hloroform, carbon tetrachloride, dichloroethane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylethylenediamine ether; alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, Isobutanol, tert-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and 2-methoxyethanol; aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide; NITRILES such as acetonitrile; esters such as methyl acetate and ethyl acetate; carboxylic acids such as formic acid, acetic acid, propionic acid and triperoxonane acid; water; or mixtures of these solvents. Preferably, a solvent, a mixture of carboxylic acid and water or a mixture of nitrile and water, more preferably a solvent mixture of acetic acid and water or a mixture of acetonitrile and water.

The reaction temperature varies depending on the starting compounds and the reaction reagent, and the reaction is carried out at a temperature from -78°C to 100°C, preferably from -20°C. to 50°C.

The reaction time varies depending on the reaction temperature, the starting compound, the reaction reagent or the type of solvent, and it usually takes from 1 minute to 12 hours, preferably about the 5 minutes to 1 hour.

Stage 7 method And is the stage of interaction of the compound (12)obtained at stage 6, with aminoven compound (13) in an inert solvent in the presence or in the absence of a base, to obtain the compounds of General formula (I).

Used inert solvent is not particularly limited, while it did not inhibit the reaction and dissolves to some extent the source material, and can be mentioned, for example, aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride and dichloroethane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylethylenediamine ether; aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide; NITRILES such as acetonitrile; esters such as methyl acetate and ethyl acetate, or mixtures of these solvents. Preferably it is an ester, preferably ethyl acetate.

Used base includes hydrides of alkali metals such as lithium hydride, sodium hydride and potassium hydride; and organic bases such as N-methylmorpholine, triethylamine, Tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinedione,picoline, 4-(N,N-dimethylamino)pyridine, 2,6-di(tert-butyl)-4-methylpyridine, quinoline, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), preferably organic bases and more preferably triethylamine.

The reaction temperature varies depending on the starting compounds and the reaction reagent, and the reaction is carried out at a temperature from -78°C to 100°C, preferably from -20°C. to 50°C.

The reaction time varies depending on the reaction temperature, the starting compound, the reaction reagent or the type of solvent, and it usually is in the range from 1 minute to 120 hours, preferably from 10 minutes to 48 hours.

Method In

Step 8 of the method is In the stage of hydrolysis of cyclic catalogo compound (14)obtained in method A, in an inert solvent in the presence of acid to obtain the ketone compound (15).

At this stage you can apply stage unprotect cyclic catalogo connection, which is widely used in organic synthesis, and can be carried out in accordance with the procedure described in the above-mentioned work by T.W. Greene, O. G. Wuts “Protective Groups in Organic Synthesis, 3rdedition, 1999, Chapter 4, PP. 293-368, Jhn Wiley & Sons, Inc., and the same, or on the basis of this procedure.

Stage 9 of the method which is the stage of obtaining dimethylketene connection (16) with a ketone compound (15), get on stage 8, in an inert solvent in the presence of acid.

For this stage you can choose the reaction dimethylthiazole (protection) ketone, which is widely used in organic synthesis, and can be carried out in accordance with the procedure described in the above-mentioned T.W. Greene. O. G. Wut, "Protective Groups in Organic Synthesis", 3rdedition, 1999, Chapter 4, PP. 293-368, John Wiley & Sons, Inc., and similar, or on the basis of this procedure.

Step 10 of the method is the stage In the reaction of the ketone compound (15)obtained at stage 8, with compound (2) or compound (3) in an inert solvent in the presence of acid to obtain compounds having General formula (I).

The reaction can be carried out in accordance with the procedure similar to stage 1.

Stage 10' method is In stage reaction dimethylketene compound (16)obtained at stage 9, with compound (2) or compound (3) in an inert solvent in the presence of acid to obtain compounds having General formula (I).

The reaction can be carried out in accordance with the procedure similar to stage 1'.

Method

Stage 11 method in the case when R5cyclic catalogo compound (14)obtained in method A, or compounds having General formula (I)obtained in the method, represents a hydrogen atom, it is the stage of its reaction with R 5-L (17) in an inert solvent in the presence of a base to obtain the compounds having General formula (I), which is replaced by the desired group R5.

R5and L have the same values as described above, a “leaving group” in the definition of L represents a group which is removed in the form of a nucleophilic residue, and can be mentioned, for example, halogen atoms such as fluorine atom, chlorine, bromine and iodine; lower alkanesulfonyl, such as methanesulfonate, econsultancy; halogeno low alkanesulfonyl, such as tripterocalyx, pentafluoroethanesulfonyl; arylsulfonate, such as benzosulfimide, p-toluensulfonate and p-nitrobenzenesulfonate. Preferably it is a halogen atom, particularly preferably an iodine atom.

Used inert solvent is not particularly limited, while it did not inhibit the reaction and dissolves to some extent the source material, and includes, for example, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane; aprotic polar solvents such as dimethylformamide, dimethylacetamide and dimethyl sulfoxide; NITRILES such as acetonitrile; esters, such as Metalac the tat and ethyl acetate; aromatic hydrocarbons, such as benzene, toluene and xylene; aliphatic hydrocarbons such as pentane, hexane and heptane, preferably ethers, ketones or aprotic polar solvents, and more preferably tetrahydrofuran, acetone or dimethylformamide.

Used the base include carbonates of alkali metals such as sodium carbonate, potassium carbonate and lithium carbonate; bicarbonates of alkali metals such as sodium bicarbonate, potassium bicarbonate and lithium bicarbonate; organic bases such as alkoxides of alkali metals such as sodium methoxide, ethoxide sodium, potassium methoxide, ethoxide potassium tert-piperonyl potassium and lithium methoxide; N-methylmorpholine, triethylamine, Tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinedione, picoline, 4-(N,N-dimethylamino)pyridine, 2,6-di(tert-butyl)-4-methylpyridine, quinoline, N,N-dimethylaniline, N,N-diethylaniline, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), preferably the carbonates of alkali metals and more preferably potassium carbonate.

The reaction temperature varies depending on the starting compounds and the reaction reagent, and the reaction is carried out at a temperature from -78°C to 150°C, preferably from -20°C. to 100°C.

<> The reaction time varies depending on the reaction temperature, the starting compound, the reaction reagent or the type of solvent, and usually it is in the interval from 1 minute to 24 hours, preferably from 10 minutes to 5 hours.

After each of the above-mentioned reaction is completed, the desired connection is allocated from the reaction mixture in accordance with conventional procedures.

For example, if necessary, the reaction mixture is neutralized, and after filtration to remove insoluble substances when it exists, the reaction solution is extracted with an organic solvent such as ethyl acetate, which is not miscible with water. Then, after washing the reaction solution with water and similar, the organic layer containing the desired compound is separated and dried over anhydrous magnesium sulfate and similar, and then the solvent evaporated giving the desired connection.

Get the desired connection may, if necessary, be separated and purified using conventional procedures such as recrystallization and pereosazhdeniya, or by using procedures that are typically used for separation and purification of organic compounds, such as an appropriate combination of the method of the adsorption column chromatography using silica gel, about the of n aluminum or Florisil magnesium-silica type as the substrate; method using a synthetic adsorbent agent, such as a distribution column chromatography, in which the use of Sephadex LH-20 (manufactured by Pharmacia), Amberlite XAD-11 (manufactured by Rohm and Haas) or Diaion HP-20 (manufactured by Mitshubishi Chemical Corporation) as a substrate; the method using ion-exchange chromatography or column chromatography with normal or reversed phase, using silica gel or alkylated silica gel (preferably high performance liquid chromatography and elution with appropriate solvent.

The parent compound, such as(1), (2), (3), (5), (6), (9), (13) and (17), as a reactive substance of the present invention, the known or can be easily obtained in accordance with known procedures.

The compound having General formula (I)according to the present invention or its pharmacologically acceptable salts possess excellent activity suppression of intracellular signal transduction or cell activation in numerous cells, such as monocytes, macrophages and vascular endothelial cells, and intracellular signal transduction and cell activation induced by endotoxin, and the suppression of many of the responses of cells caused by intracellular signal tra is cuccia and cell activation such as excess generation of inflammatory mediators, such as TNF-α. Therefore, the compound and its salt useful as a medicine, particularly as a preventive and therapeutic agent against various diseases associated with intracellular signal transduction or cell activation induced by endotoxin, and with a variety of responses of cells (for example, excess generation of inflammatory mediators, such as TNF-α), which are induced intracellular signal transduction and cell activation. As such drugs may be mentioned preventive and/or therapeutic agent against ischemic brain damage, arteriosclerosis, poor prognosis after coronary angioplasty, cardiac disorders, diabetes, diabetic complications, inflammation of the joints, osteoporosis, osteopenia, sepsis, autoimmune diseases, disorders and tissue rejection after organ transplantation, bacterial infections, viral infections, gastritis, pancreatitis, nephritis, pneumonia, hepatitis, or leukemia.

In the case where the compound having General formula (I)according to the present invention or its pharmacologically acceptable salts are used as a prophylactic or therapeutic agent of the above-mentioned diseases, it can be mixed with excipients, diluents and similar, which are themselves pharmacologically acceptable, and administered orally in the form of tablets, capsules, granules, powders or syrups, or injected parenterally in the form of injectable preparation for subcutaneous injection, intramuscular injection or intravenous injection, or suppository.

Data pharmaceutical drugs get in accordance with known processes using additives include excipients (for example, there can be mentioned organic excipients, such as derivatives of sugars, such as lactose, sucrose, glucose, mannitol or sorbitol; starch derivatives such as corn starch, potato starch, α-starch or dextrin; cellulose derivatives such as crystalline cellulose; Arabian gum; dextran; or pullulan, and inorganic excipients such as silicate derivatives such as light silicic anhydride, synthetic aluminum silicate, calcium silicate, metamagnetic; phosphates, for example, acidic phosphate calcium, carbonates, e.g. calcium carbonate; salts of sulfuric acid, such as calcium sulfate), lubricants (for example, can be mentioned stearic acid, metal salts and stearic acid such as calcium stearate or magnesium stearate; talc; to Llodra silicon dioxide; waxes, such as beeswax or spermaceti; boric acid; adipic acid; sulfates such as sodium sulfate; glycol; fumaric acid; sodium benzoate; DL leucine; laurilsulfate, such as sodium lauryl sulfate or lauryl sulfate, magnesium; silicic acids such as silicic anhydride or silicate hydrate; and the above-mentioned starch derivatives), binders (for example, can be mentioned hydroxypropylcellulose, hypromellose, polyvinylpyrrolidone, macrogol, and compounds similar to the above excipients), dezintegriruetsja agents (for example, there may be mentioned cellulose derivatives such as low-substituted hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose or internally cross crosslinked sodium carboxymethylcellulose; or chemically modified starches or cellulose, such as carboximetilkrahmal, sodium carboximetilkrahmal or transversely crosslinked polyvinylpyrrolidone), emulsifiers (for example, colloidal clay, such as bentonite or bee resin; metal hydroxides such as magnesium hydroxide or aluminum hydroxide; anionic surfactants such as sodium lauryl sulfate or calcium stearate; cationic surfactants such as benzalkonium chloride; and nonionic over OSTO-active substances, such as polyoxyethyleneglycol ether; polyoxyethylenesorbitan a fatty acid ester or sucrose ester of fatty acids), stabilisers (for example, there may be mentioned esters of peroxybenzoyl acid, such as methylparaben or propylparaben; alcohols such as chlorobutanol, benzyl alcohol or phenethyl alcohol, benzalkonium chloride; phenols such as phenol or cresol; thimerosal; dehydroacetic acid; and sorbic acid) and corrigentov (for example, can be referred to commonly used sweeteners, podnikatel or aromatic substances) or thinners.

Dosage amount varies depending on the symptoms and age, and it is desirable that the compound of the present invention was administered orally or parenterally to an adult person with a lower limit of 0.01 mg/kg (preferably 0.10 mg/kg) and the upper limit of 1000 mg/kg (preferably 100 mg/kg) a day, once a day or several times by parts, depending on the symptoms.

EXAMPLES

Hereinafter the present invention will be described in detail with reference to examples and examples, tests, however, the scope of the present invention is not limited to them.

Example 1

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-364)

(1A) Ethyl 8-AOC-who tilsley-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate

19,97 g (a 55.4 mmol) ethyl 8-tripterocalyx-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate [compound described as compound 6 in Tetrahedron Letter, Vol. 39, pp. 6139-6142 (1998)] was dissolved in 200 ml of dimethylformamide and thereto were added to 9.50 g (83.1 mmol) thioacetate potassium under stirring with ice cooling, followed by stirring at room temperature for 91 hours. To the reaction solution was added ice water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 17:3), with 7,15 g specified in the title compounds as a pale brown oil (yield: 45%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,20 (2H, square, 7 Hz), 4.04 the-of 3.96 (4H, m), 2,73-of 2.66 (4H, m), of 2.34 (3H, s)to 1.87 (2H, t, J=6 Hz), of 1.28 (3H, t, J=7 Hz).

(1b) Ethyl 8-mercapto-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate

7,14 g (24,9 mmol) ethyl 8-acetylmethadol-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate obtained in (1A), was dissolved in 145 ml of methanol and thereto was added 2.58 g (to 18.7 mmol) of potassium carbonate under stirring with ice cooling, followed by stirring at the same temperature for 1 hour and then at room temperature for 1 hour. The reaction rastvoromeshalke by adding 1 to N. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 9:1), obtaining 5,63 g specified in the title compounds as a pale yellow oil (yield: 92%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,32 (1H, s), is 4.21 (2H, square, 7 Hz), 4.04 the-3,95 (4H, m), 2,72-to 2.67 (2H, m), 2,59-to 2.57 (2H, m), equal to 1.82 (2H, t, J=7 Hz), of 1.30 (3H, t, J=7 Hz).

(1C) Ethyl 8-chlorosulfonyl-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate

To a saturated solution, obtained by blowing (ozonation) gaseous chlorine in 80 ml of a mixture acetonitrile-water (1:1) for 20 minutes, was added a solution of 5.00 g (20,5 mmol) ethyl 8-mercapto-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate obtained in (1b) in 10 ml of acetonitrile with stirring under ice cooling. Then chlorine gas was blown through the reaction solution for 10 minutes at the same temperature. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), to receive the receiving of 5.83 g specified in the title compounds as colorless oil (yield: 92%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,30 (2H, square, 7 Hz), 4,05-3,98 (4H, m), 2.91 in-of 2.86 (2H, m), 2.71 to 2,69 (2H, m)of 1.93 (2H, t, J=7 Hz), of 1.34 (3H, t, J=7 Hz).

(1d) Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

To a solution of 197 mg (1.35 mmol) of 2-chloro-4-foronline and 0.20 ml (1,42 mmol) of triethylamine in 5 ml of ethyl acetate was added dropwise a solution of 400 mg (1,29 mmol) ethyl 8-chlorosulfonyl-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate obtained in (1C) in 3 ml of ethyl acetate with stirring under ice cooling, followed by stirring at room temperature for 48 hours. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 3:1) and the obtained solid is then washed with a solution of a mixture of hexane-isopropyl ether (1:1), with 325 mg specified in the title compound as a white powder (yield: 60%).

The melting point 117-119°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,16 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,98 (2H, m), 6,83 (1H, s), 4,43-to 4.41 (1H, m), 4.26 deaths-4,01 (5H, m), 3.95 to 3,88 (1H, m), 2,56 at 2.45 (2H, m), 2,24-2,11 (1H, m), 1,88 and 1.80 (1H, m), of 1.27 (3H, t, J=7 Hz).

Example 2

Ethyl 8-(N-finals livemail)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-12)

In accordance with the process described in example (1d), aniline was used instead of 2-chloro-4-foranyone, obtaining specified in the title compound as an amorphous substance (yield: 81%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,37-7,31 (4H, m), 7,21-to 7.15 (1H, m), to 6.95 (1H, s), 6,85-6,87 (1H, m), 4,30-4,20 (3H, m), 4,13-4,01 (3H, m), 3,94-3,88 (1H, m), 2,48-to 2.41 (1H, m), 2,31 (1H, TD, J=14 Hz, 3 Hz), 2,10-2,00 (1H, m), 1,86 and 1.80 (1H, m)is 1.31 (3H, t, J=7 Hz).

Example 3

Ethyl 8-[N-(2-butylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-540)

In accordance with the process described in example (1d), 2-butylaniline was used instead of 2-chloro-4-foranyone, obtaining specified in the title compounds as colorless oil (yield: 56%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,55-7,52 (1H, m), 7,22-7,17 (2H, m), 7,13-was 7.08 (1H, m), 6,85-6,84 (1H, m), 6,63 (1H, s), 4,47-of 4.44 (1H, m), 4,25-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2.71 to 2,62 (2H, m), 2,54-of 2.38 (2H, m), 2,19-of 2.09 (1H, m), 1,86-1,81 (1H, m), 1,62-of 1.53 (2H, m), 1,45 is 1.34 (2H, m)of 1.26 (3H, t, J=7 Hz), of 0.95 (3H, t, J=7 Hz).

Example 4

Ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate(see examplecompound No. 1-716)

In accordance with the process described in example (1d), 2-hexylaniline was used instead of 2-chloro-4-foranyone, obtaining ukazannoj is in the title compounds as a pale yellow oil (yield: 82%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,55-7,52 (1H, m), 7,22-7,17 (2H, m), 7,13-was 7.08 (1H, m), 6,85-6,84 (1H, m), 6,63 (1H, s), 4,47-of 4.44 (1H, m), 4,25-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2,70-2,61 (2H, m), 2,54-of 2.38 (2H, m), 2,19-of 2.09 (1H, m), 1,86-1,81 (1H, m), 1,64-and 1.54 (2H, m), 1.41 to 1,24 (6H, m)of 1.26 (3H, t, J=7 Hz), 0,91-of 0.85 (3H, m).

Example 5

Ethyl 8-[N-(2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-892)

In accordance with the process described in example (1d), 2-heptylaniline was used instead of 2-chloro-4-foranyone, obtaining specified in the title compounds as a pale yellow oil (yield: 87%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,55-7,52 (1H, m), 7,22-7,17 (2H, m), 7,13-was 7.08 (1H, m), 6,85-6,84 (1H, m), 6,63 (1H, s), 4,47-of 4.44 (1H, m), 4,25-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2,69-2,61 (2H, m), 2,54-of 2.38 (2H, m), 2,19-of 2.09 (1H, m), 1,86-1,81 (1H, m), 1,64-and 1.54 (2H, m), 1,42 is 1.23 (8H, m)of 1.26 (3H, t, J=7 Hz), to 0.88 (3H, t, J=7 Hz).

Example 6

Ethyl 8-[N-(1H-pyrrol-1-yl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1062)

In accordance with the process described in example (1d), 1N-pyrrol-1-ylamine was used instead of 2-chloro-4-foranyone, obtaining specified in the title compound as a white powder (yield: 33%).

The melting point 115-117°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

with 8.05 (1H, s), of 6.99 (2H, t, J=2 Hz), 6,94 (1H, s), 6,17 (2H, the, J=2 Hz), 4,55-4,51 (1H, m), 4,30 (2H, square, J=7 Hz), 4,14-a 4.03 (3H, m), 3,98-to 3.89 (1H, m), of 2.51 is 2.44 (1H, m), 2.26 and-2,05 (2H, m), 1,89 of-1.83 (1H, m)of 1.35 (3H, t, J=7 Hz).

Example 7

Ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3-oxo-1-cyclohexen-1-carboxylate (example compound No. 1-353)

To 2.55 g (6,07 mmol) ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 1 was added 100 ml of a mixture of 1 N. hydrochloric acid-tetrahydrofuran (1:1) and the reaction mixture was stirred at room temperature for 64 hours. Tetrahydrofuran drove away under reduced pressure, the residue was extracted by adding ethyl acetate, the organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 4:1), obtaining 2,19 g specified in the title compounds as a pale brown powder (yield: 96%).

The melting point of 128-130°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.69 (1H, DD, J=9 Hz, 5 Hz), 7,20 (1H, DD, J=8 Hz, 3 Hz), to 7.09-7.03 is (1H, m)6,91 (2H, s), and 4.68 (1H, DD, J=5 Hz, 2 Hz), 4,28-4,18 (2H, m), 3,21-to 3.09 (1H, m), 2,80-of 2.72 (1H, m), 2.57 m-2,49 (1H, m), 2,44-2,31 (1H, m)of 1.28 (3H, t, J=7 Hz).

Example 8

Ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate (the shown example compound No. 1-365)

100 mg (0.27 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3-oxo-1-cyclohexen-1-carboxylate obtained in example 7, was dissolved in 2 ml of toluene, and thereto was added 0.04 ml (0.54 mmol) of propane-1,3-diol and 68 mg (0.27 mmol)ofp-toluensulfonate pyridinium, followed by heating at the boiling point under reflux for 1 hour. After cooling the reaction solution to room temperature was added a saturated aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1) and then the resulting solid was washed with hexane, to obtain 60 mg specified in the title compound as a white powder (yield: 51%).

The melting point of 120-121°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), was 7.36 (1H, s), 7,14 (1H, DD, J=8 Hz, 3 Hz), 7,01 (1H, DD, J=7 Hz, 2 Hz), 6,98 (1H, s), 4,45-4,39 (1H, m), 4,27-4,12 (2H, m), 4,11-a-3.84 (4H, m), 2,46-to 2.06 (4H, m), 1,92-to 1.67 (2H,, m)of 1.28 (3H, t, J=7 Hz).

Example 9

Ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethyl-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate (example compound No. 1-426)

In accordance with the process described in example 8, 2,2-DIMETHYLPROPANE-1,3-diol was used instead of propane-1,3-diol, to obtain specified in the title compounds as a pale brown oil (yield: 64%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.64 (1H, DD, J=9 Hz, 5 Hz), 7,31 (1H, s), 7,13 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality-6,94 (2H, m), 4,45-4,39 (1H, m), 4,27-4,12 (2H, m), 3,69-of 3.46 (4H, m), 2,42-2,11 (4H, m)of 1.28 (3H, t, J=7 Hz), of 1.03 (3H, s), of 0.97 (3H, s).

Example 10

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-367)

100 mg (0.27 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3-oxo-1-cyclohexen-1-carboxylate obtained in example 7, was dissolved in 1 ml of dichloromethane and thereto was added 0,034 ml (0,405 mmol) ethane-1,2-dithiol and 0.025 ml (0,203 mmol) of titlefirst of boron TRIFLUORIDE under stirring with ice cooling, followed by stirring at room temperature for 1 hour. To the reaction solution was added 1 N. aqueous solution of sodium hydroxide and the mixture was extracted with diethyl ether. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The resulting solid is washed with diethyl ether and then hexane, to obtain 325 mg specified in the header connect the deposits in the form of a white powder (yield: 76%).

The melting point 160-161°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7,14 (1H, DD, J=8 Hz, 3 Hz), 7,10 (1H, s),? 7.04 baby mortality-of 6.96 (2H, m), and 4.40 (1H, d, J=5 Hz), 4,25-4,10 (2H, m), 3,52-3,26 (4H, m), 2,82-of 2.72 (1H, m), 2,58-of 2.50 (1H, m), 2,33-of 2.24 (1H, m), 2,11 of 1.99 (1H, m)of 1.27 (3H, t, J=7 Hz).

Example 11

Ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,5-Diaspora[5.5]undec-7-ene-8-carboxylate (example compound No. 1-368)

In accordance with the process described in example 10, propane-1,3-dithiol used instead of ethane-1,2-dithiol, obtaining specified in the title compound as an amorphous substance (yield: 72%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7,40 (1H, s), 7,14 (1H, DD, J= 8 Hz, 3 Hz), 7.03 is-of 6.96 (1H, m)6,94 (1H, s), 4,51 (1H, d, J=5 Hz), 4,24-4,11 (2H, m), 3,17-of 3.07 (1H, m), 2,98-2,77 (3H, m), 2,61 is 2.51 (1H, m), 2,47-of 2.38 (1H, m), a 2.36-of 2.27 (1H, m), 2,25-to 2.13 (1H, m), 2,12-of 1.95 (2H, m)of 1.27 (3H, t, J=7 Hz).

Example 12

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1-oxa-4-Diaspora[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-371)

In accordance with the process described in example 10, 2-mercaptoethanol used instead of ethane-1,2-dithiol, obtaining specified in the title compound as a white powder (yield: 61%).

The melting point of 133-134°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7,14 (1H, DD, J=8 Hz, 3 Hz), 706 (0,4H, C)? 7.04 baby mortality-of 6.96 (2,6H, m), 4,46 (0,4H, DD, J=5 Hz, 3 Hz), 4,39-4,01 (4,6H, m), 3,23-of 3.06 (2H, m), 2.77-to of 2.51 (1,6H, m), 2,45-2,36 (0,4H, m), 2,20-2,00 (2H, m)of 1.27 (3H, t, J=7 Hz).

Example 13

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,1,4,4-tetraoxo-1λ6, / 4λ6-Diaspora[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-369)

80 mg (0.18 mmol) of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-Diaspora[4.5]Dec-6-ene-7-carboxylate obtained in example 10, was dissolved in 2 ml dichloromethane, was added 91 mg (1,08 mmol) of sodium bicarbonate and then 239 mg (0.90 mmol)ofm-chloroperbenzoic acid (65%) under stirring with ice cooling, followed by stirring at room temperature for 5 hours. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to thin-layer chromatography on silica gel (solvent: hexane:ethyl acetate = 1:1), to obtain 42 mg specified in the title compound as a white powder (yield: 45%).

The melting point of 88-90°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), to 7.15 (1H, DD, J=8 Hz, 3 Hz), 7,06-6,98 (2H, m), 6,92 (1H, s), of 4.57 (1H, d, J=5 Hz), 4.26 deaths-of 4.16 (2H, m), 3,79-of 3.60 (4H, m), 3,14 are 2.98 (1H, m), 2,69-2,60 (1H, m), 2,45-of 2.36 (1H, m), 2,29-of 2.16 (1H, m)of 1.28 (3H, t, J=7 G is).

Example 14

Ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-1-oxaspiro[2.5]Oct-4-ene-5-carboxylate (example compound No. 1-360)

50 mg (0.133 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3-oxo-1-cyclohexen-1-carboxylate obtained in example 7, and 0.01 ml (0,146 mmol) of dibromomethane was dissolved in 1 ml of tetrahydrofuran, and thereto was added dropwise to 0.18 ml (0,279 mmol)n-utility/hexane solution (1,58 M) at -78°C., followed by stirring at room temperature for 4 hours. After cooling the reaction solution with ice was added a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to thin-layer chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), to obtain 7 mg specified in the title compound as a yellow oil (yield: 14%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9 Hz, 5 Hz), to 7.15 (1H, DD, J=8 Hz, 3 Hz), 7,07-6,91 (2H, m), 6,60 (1H, s), 4,50 (1H, d, J=4 Hz), 4,27-4,06 (2H, m), 2,98 of 2.92 (1H, m), 2.91 in-2,88 (1H, m), 2,83-2,70 (1H, m), 2,68 at 2.59 (1H, m), 2.21 are 2,07 (2H, m), 1,25 (3H, t, J=7 Hz).

Example 15

Ethyl (2S)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-hydroxymethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (Pref the Albanian example compound No. 1-378)

100 mg (0.27 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3-oxo-1-cyclohexen-1-carboxylate obtained in example 7, and 69 mg (0.35 mmol) of (R)-2,3-dihydroxybenzoate was dissolved in 2 ml dichloromethane and successively added to 0.19 ml (1.05 mmol) of isopropoxytitanium and 2 μl (0.014 mmol) trimethylsilyltrifluoromethane under stirring with ice cooling, followed by stirring at the same temperature for 1 hour. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 1:1), to obtain 121 mg of ethyl (2R)-2-benzoyloxymethyl-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate as a pale yellow oil (yield: 81%).

Next, 121 mg (0.22 mmol) of this compound was dissolved in 2 ml of methanol-tetrahydrofuran (1:1) and to the solution was added 0.5 ml (0.50 mmol) of 1 N. aqueous sodium hydroxide solution under stirring with ice cooling, followed by stirring at the same temperature for 30 minutes. To the reaction solution were added water and the mixture was extracted with ethyl acetate. Organic is the cue layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 1:1), to obtain 41 mg specified in the title compound as an amorphous substance (yield: 41%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.64 (1H, DD, J=9 Hz, 5 Hz), 7,14 (1H, DD, J=8 Hz, 3 Hz), 7,06-6,97 (2H, m), 6.89 in (0,25H, C)6,86 (0,25H, (C), 6,80 (0,25H, (C), 6,78 (0,25H, (C), 4,43-or 4.31 (1,75H, m), 4.26 deaths-was 4.02 (3,25H, m), 3.95 to a 3.87 (0,75H, m), 3,85-of 3.77 (1H, m), 3.75 to 3,69 (0,25H, m), 3,68-3,59 (1H, m), 2,65-of 2.38 (2H, m), 2,25-2,11 (1H, m), 2,11-2,05 (0,25H, m), 2,03-1,97 (0,25H, m), 1,94-1,81 (1,5H, m)of 1.26 (3H, t, J=7 Hz).

Example 16

Ethyl (2R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-hydroxymethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-378)

(16A) Ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate

6,1 g (16.2 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3-oxo-1-cyclohexen-1-carboxylate obtained in example 7, was dissolved in 120 ml of methanol and thereto was sequentially added 4.1 g (16.2 mmol)ofp-toluensulfonate pyridine and 8,86 ml (81.0 mmol) trimethoxymethane under stirring with ice cooling, followed by stirring at room temperature over night. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried n the d anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), to obtain 6.0 g specified in the title compound as a white powder (yield: 88%).

The melting point 97-98°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7,14 (1H, DD, J=8 Hz, 3 Hz), 7,07-6,97 (3H, m)to 4.41 (1H, d, J=4 Hz), 4,28-4,12 (2H, m), 3,29 (3H, s), 3,23 (3H, s), 2,47-of 2.38 (1H, m), 2,31-of 2.21 (1H, m), 2,18-to 2.06 (1H, m), 2,01-of 1.93 (1H, m)of 1.28 (3H, t, J=7 Hz).

(16b) Ethyl (2R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-hydroxymethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

342 mg (0.81 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in (16A), and 206 mg (1.05 mmol) of (S)-2,3-dihydroxybenzoate was dissolved in 7 ml of dichloromethane and thereto was sequentially added of 0.56 ml (3,15 mmol) of isopropoxytitanium and 7 µl level (0.041 mol) trimethylsilyltrifluoromethane under stirring with ice cooling, followed by stirring at the same temperature for 1 hour. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:this is laatat = 1:1), to obtain 410 mg of ethyl (2S)-2-benzoyloxymethyl-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate as a colourless oil (yield: 91%).

Next, 410 mg (0,74 mmol) of this compound was dissolved in 10 ml of methanol-tetrahydrofuran (1:1) and thereto was added 3 ml (3.0 mmol) of 1 N. aqueous sodium hydroxide solution, followed by stirring at room temperature for 15 minutes. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 1:1), to obtain 293 mg specified in the title compound as an amorphous substance (yield: 88%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.64 (1H, DD, J=9 Hz, 5 Hz), 7,14 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality-to 6.95 (2H, m), 6.89 in (0,42H, C)6,86 (0,02H, C)6,80 (0,02H, C), 6,78 (0,42H, (C), 4,43-or 4.31 (1,5H, m), 4.26 deaths-was 4.02 (2,5H, m), 3.96 points-3,89 (1H, m), 3,83-of 3.77 (0,5H, m), 3.75 to 3,69 (0,5H, m), 3,68-3,59 (1H, m), 2,65-to 2.41 (2H, m), 2,25-2,10 (1H, m), 1.93 and-1,82 (1H, m), 1.77 in-1,67 (0,5H, users), 1,58 (0,5H, users), of 1.26 (3H, t, J=7 Hz).

Example 17

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-382)

In accordance with% som, described in example (16b), 1,4-di-About-benzoyl-D-threitol used instead of (S)-2,3-dihydroxybenzoate, obtaining specified in the title compound as an amorphous substance (yield: 44%).

<an Alternative procedure>

(17A) Ethyl (2R,3R)-2,3-bis(benzoyloxymethyl)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

of 1.46 g (is 3.08 mmol) of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol obtained in reference example 18, suspended in 2 ml of acetonitrile and thereto was sequentially added 0.04 ml (0.24 mmol) trimethylsilyltrifluoromethane and a solution of 1.00 g (2,37 mmol) ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), in 5 ml of acetonitrile under stirring with ice cooling, followed by stirring at the same temperature for 1 hour. The reaction solution was concentrated under reduced pressure, the residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), to obtain 1.50 g specified in the title compounds as a pale yellow powder (yield: 92%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

8,10-8,04 (4H, m), 7.68 per-EUR 7.57 (3H, m), 7,49-7,44 (4H, m), 7,16 (1H, dt, J=8.0 Hz, 2.6 Hz), 7,05-7,00 (2H, m), 6.87 in (1H, d, J=14,0 Hz), 4,66-4,07 (9H, m), 2,63 is 2.44 (2H, m), 2,25-2,19 (1H, m), of 1.94 (1H, t, J=15.2 Hz), to 1.19 (3H, t, J=7,0 Hz).

(17b) Ethyl (2R,3R)-8-[N-2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

1.50 g (2,18 mmol) ethyl (2R,3R)-2,3-bis(benzoyloxymethyl)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in (17A), was dissolved in 10 ml of methanol-tetrahydrofuran (4:1), and thereto was added 10 ml (10.0 mmol) 1 N. aqueous sodium hydroxide solution under stirring with ice cooling, followed by stirring at the same temperature for 15 minutes. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 1:1), with 900 mg specified in the title compound as a white amorphous substance (yield: 86%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-to 7.64 (1H, m), 7,16 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,99 (2H, m), 6,91-6,90 (0,5H, m), 6,85-6,84 (0,5H, m), 4,43-to 4.41 (1H, m), 4,27-4.09 to (3,5H, m), 4,05-4,01 (0,5H, m), 3,93-3,81 (2H, m), 3.75 to at 3.69 (2H,, m), 2,59 at 2.45 (2H, m), 2,23 of 1.50 (4H, m), 1,29-1,24 (3H, m).

Example 18

Ethyl (2S,3S)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-382)

In accordance with the process described in example (16b), 1,4-di-About-benzoyl-L-threitol used instead of (S)-2,3-dihydro what dipropylacetate, obtaining specified in the title compound as an amorphous substance (yield: 34%).

<an Alternative procedure>

In accordance with the process described in example 17 (alternative procedure), 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-L-threitol obtained in reference example 19 was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compound as an amorphous substance (yield: 73%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-to 7.64 (1H, m), 7,16 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,99 (2H, m), 6,91-6,90 (0,5H, m), 6,85-6,84 (0,5H, m), 4,43-to 4.41 (1H, m), 4,27-4.09 to (3,5H, m), 4,05-4,01 (0,5H, m), 3,93-3,81 (2H, m), 3.75 to at 3.69 (2H,, m), 2,59 at 2.45 (2H, m), 2,23 of 1.50 (4H, m), 1,29-1,24 (3H, m).

Example 19

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-meso-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-382)

200 mg (0.47 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), and 290 mg (0.61 mmol) of 1,4-di-About-benzoyl-2,3-di-About- (trimethylsilyl)-meso-erythritol obtained in reference example 1 was dissolved in 4 ml of dichloromethane and thereto were added 4 μl (0,024 mmol) trimethylsilyltrifluoromethane under stirring with ice cooling, followed by stirring at the same temperature during the 1 hour. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), to obtain 171 mg of ethylmeso-2,3-bis[(benzoyloxy)methyl]-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate as an amorphous substance (yield: 53%).

Next, 170 mg (0.25 mmol) of this compound was dissolved in 10 ml of methanol-tetrahydrofuran (1:1) and thereto was added 3 ml (3.0 mmol) of 1 N. aqueous sodium hydroxide solution under stirring with ice cooling, followed by stirring at the same temperature for 15 minutes. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 1:3), with 105 mg specified in the title compound as an amorphous substance (yield: 89%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.64 (1H, DD, J=9 Hz, 5 Hz), to 7.15 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality-to 6.95 (2H, m), 6,93 (0,4H, C), 6,72 (0,6H, s), 4,49-4,33 (2,4H, m), 4,32-4.26 deaths (0,6H, m), 4,25-4,07 (2H, m, 3,93-3,70 (4H, m), 2,69-2,58 (0,4H, m), 2,58-2,35 (3,6H, m), 2,24-of 2.09 (1H, m), 1,99-1,91 (0,6H, m), 1,90-1,83 (0,4H, m)of 1.27 (3H, t, J=7 Hz).

Example 20

Ethyl (2R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-((1R)-1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-390)

300 mg (0.71 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), and 436 mg (1,42 mmol) (4R,5R)-2,2-dimethyl-4,5-bis[(trimethylsilyl)oxy]methyl[1.3]dioxolane were dissolved in 12 ml of dichloromethane and thereto was added 26 μl (0,142 mmol) trimethylsilyltrifluoromethane under stirring with ice cooling, followed by stirring at room temperature for 90 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with dichloromethane. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 4:1), to obtain 90 mg of ethyl (2R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-((4R)-2,2-dimethyl[1.3]dioxolane-4-yl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate as an amorphous substance (yield: 24%).

Further to 85 mg (0,163 mmol) of this compound was added 4 ml of a mixture of acetic sour is a-water (1:1), followed by stirring at room temperature over night. The reaction solution was neutralized by adding saturated aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only ethyl acetate), to obtain 46 mg specified in the title compound as an amorphous substance (yield: 59%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-to 7.64 (1H, m), 7,19-to 7.15 (1H, m), 7,06-6,98 (2H, m), 6,89-to 6.80 (1H, m), 4,43-to 4.41 (1H, m), of 4.38-4,08 (4H, m), a 4.03-3.95 to (0,7H, m), 3,86 (0,3H, t, J=8 Hz), of 3.77-3,63 (3H, m), 2,67-is 2.37 (3H, m), 2,22-1,84 (3H, m), 1.30 and 1,25 (3H, m).

Example 21

Ethyl (2R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-((2R)-1,2,3-trihydroxypropane)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-394)

547 mg (1.07 mmol) 1,3,4,5,7-Penta-About-trimethylsilyl-D-arabitol obtained in reference example 2, was dissolved in 3 ml of nitromethane, to the resulting solution was added 13 ml (0,007 mmol) trimethylsilyltrifluoromethane and then added 300 mg (0.71 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A) under stirring with cooling the receiving ice, followed by stirring at the same temperature for 1 hour. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with dichloromethane. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only ethyl acetate), to obtain 151 mg specified in the title compound as an amorphous substance (yield: 42%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,19-to 7.15 (1H, m), 7,10-6,99 (2H, m)6,86 (0,5H, s), 6,82-6,80 (0,5H, m), 4,42-4,39 (1H, m), 4,28-3,65 (9H, m), 3,20-of 1.40 (3H, usher.), 2.57 m) is 2.43 (2H, m), 2,23-of 2.09 (1H, m), 1,92-to 1.82 (1H, m), 1,29-1,25 (3H, m).

Example 22

Ethyl (2R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-((1S,2R,3R)-1,2,3,4-tetrahydroquinolin)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-398)

200 mg (0.47 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), and 434 mg (0.71 mmol) of 1,2,3,4,5,6-hexa-About- (trimethylsilyl)-D-mannitol was dissolved in 4 ml of dichloromethane, the resulting solution was sequentially added to 0.12 ml (0.47 mmol) of isopropoxytitanium and 4 μl (0,024 mmol) trimethylsilyltrifluoromethane when premesis the Institute with ice cooling, followed by stirring at room temperature over night. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: dichloromethane-methanol = 10:1), to obtain 130 mg specified in the title compound as an amorphous substance (yield: 51%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

a 7.62 (1H, DD, J=9 Hz, 5 Hz), 7,22 for 7.12 (2H, m),? 7.04 baby mortality-of 6.96 (1H, m), 6,88-6,84 (0,2H, m), 6,80-6,77 (0,4H, m), 6,76 (0,4H, C), to 4.41-or 4.31 (1H, m), 4,25-a 4.03 (4H, m), 3,98-3,63 (6H, m), 2,54-to 2.41 (2H, m), 2,22-of 2.08 (1H, m), 1,92-of 1.81 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 23

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis((1R)-1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-386)

In accordance with the process described in example 19, 1,6-di-About-benzoyl-2,3,4,5-Tetra-About- (trimethylsilyl)-D-mannitol, obtained in reference example 3 was used instead of 1,4-di-About-benzoyl-2,3-di-About- (trimethylsilyl)-meso-erythritol, obtaining specified in the title compound as a white powder (yield: 11%).

The melting point of 55-56°C.

1H-NMR spectrum (400 MHz, CDCl3 ) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7,20-7,13 (2H, m), 7,06-7,00 (1H, m), 6,80 (0,5H, s), 6,78 (0,5H, C)to 4.38 (1H, d, J=5 Hz), 4.26 deaths-of 4.00 (5H, m), 3,98-3,88 (1,5H, m), a 3.87-3,65 (5,5H, m), 2,78-of 2.56 (2H, m), 2,55-to 2.40 (2H, m), 2,23-of 2.09 (1H, m), 1,92 and 1.80 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 24

Ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3-hydroxy-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate (example compound No. 1-418)

In accordance with the process described in example 19 2-trimethylsilyloxy-1-trimethylsilylmethylamine-1-carboxylate obtained in reference example 4 was used instead of 1,4-di-About-benzoyl-2,3-di-About- (trimethylsilyl)-meso-erythritol, obtaining specified in the title compound as an amorphous substance (yield: 17%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-to 7.64 (1H, m), 7,52-7,51 (0,5H, m), 7.18 in-7,15 (1H, m), 7,08-6,99 (2,5H, m), 4,45 was 4.42 (1H, m), or 4.31-of 4.05 (4H, m), 3,88-3,74 (2H, m), 3.72 points-3,63 (1H, m), 2,78-2,52 (1H, usher.), 2,48-of 1.97 (4H, m), 1,31-of 1.26 (3H, m).

Example 25

Ethyl 12-[N-(2-chloro-4-forfinal)sulfamoyl]-2,4,8,5-tetraoxaspiro[5.2.5.2]hexadec-10-EN-11-carboxylate (example compound No. 1-434)

100 mg (0,266 mmol) ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3-oxo-1-cyclohexen-1-carboxylate obtained in example 7, and 156 mg (0,532 mmol) of 5,5-bis[(trimethylsilyl)oxy]methyl[1.3]dioxane was dissolved in 2 ml dichloromethane and C thereto was added 10 μl (,053 mmol) trimethylsilyltrifluoromethane, followed by stirring at the same temperature for 30 minutes, and then at room temperature for 2 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with dichloromethane. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1) and the resulting solid is then washed with isopropyl ether, to obtain 49 mg specified in the title compound as a white powder (yield: 52%).

The melting point 156-157°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,98 (2H, m), a 4.83 (1H, d, J=6 Hz), 4,78 (1H, d, J=6 Hz), of 4.44 was 4.42 (1H, m), 4,29-to 4.14 (2H, m), a 3.87-3,70 (8H, m), 2,44-of 2.38 (1H, m), 2,32 amounts to 2.24 (1H, m), 2,18-of 2.08 (2H, m)of 1.28 (3H, t, J=7 Hz).

Example 26

Ethyl 3-acetylamino-9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate (example compound No. 1-422)

500 mg (1,19 mmol) ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), and 205 mg (1.54 mmol)ofN-(2-hydroxy-1-hydroxymethylation)ndimethylacetamide was dissolved in 20 ml of dichloromethane and thereto was sequentially added 0,84 ml (4,74 mmol) of isopropoxytitanium and 43 μl (0.24 mm is l) trimethylsilyltrifluoromethane under stirring with ice cooling, followed by stirring at the same temperature for 30 minutes and then at room temperature for 66 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with dichloromethane. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: ethyl acetate-methanol = 39:1), with 288 mg specified in the title compound as an amorphous substance (yield: 50%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,62-7,60 (0,5H, m), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,99 (2H, m), 6,93-6,91 (0,5H, m), 6.35mm (1H, userd, J=8 Hz), 4,46 was 4.42 (1H, m), 4,35-4,11 (4H, m), a 4.03-of 3.95 (1H, m), 3,82-3,70 (2H, m), 2,60-2,55 (0,5H, m), 2,48 is 2.01 (3H, m)to 2.06 (3H, s), 1,95-1,90 (0,5H, m)of 1.30 (3H, t, J=7 Hz).

Example 27

Ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-bis(hydroxymethyl)-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate (example compound No. 1-430)

500 mg (1,19 mmol) ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), and 1.0 g (of 2.38 mmol) of 1,3-bis[(trimethylsilyl)oxy]-2,2-bis[(trimethylsilyl)oxy]methylpropane was dissolved in 10 ml of dichloromethane and thereto was added 10 μl (0.06 mmol) trimethylsilyltrifluoromethane sulfonate under stirring with ice cooling, followed by stirring at the same temperature for 2 hours. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only ethyl acetate), to obtain 510 mg specified in the title compound as an amorphous substance (yield: 87%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,28 (1H, s), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,11 (1H, s), 7,07-6,98 (1H, m), 4,42 (1H, d, J=4 Hz), 4,30-4,10 (2H, m), 3,92-3,68 (8H, m), 2,54-of 2.36 (3H, m), 2,34-of 2.23 (1H, m), 2,21-2,07 (2H, m)of 1.28 (3H, t, J=7 Hz).

Example 28

Triethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,5-dioxaspiro[5.5]undec-7-ene-3,3,8-tricarboxylate (example compound No. 1-438)

In accordance with the process described in example 27, diethyl-2,2-bis[(trimethylsilyl)oxy]methylmalonate obtained in reference example 5 was used instead of 1,3-bis[(trimethylsilyl)oxy]-2,2-bis[(trimethylsilyl)oxy]methylpropane, obtaining specified in the title compound as an amorphous substance (yield: 42%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7.23 percent-7,21 (1H, m), 7,16 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality-6,99 (1H, m), 6,97 (1H, s), 4,43 is 4.36 (3H, m), or 4.31-4,13 (8H, m), 2,44-is 2.37 (1H, m) 2,33 was 2.25 (1H, m), 2,19-to 2.06 (2H, m), 1,283 (3H, t, J=7 Hz), 1,280 (6H, t, J=7 Hz).

Example 29

Ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]Spiro[2.5]Oct-4-ene-5-carboxylate (example compound No. 1-355)

(29A) Ethyl 3-[1-(2-ethoxycarbonylethyl)cyclopropyl]propionate

to 24.5 ml (24.5 mmol) of 1.0 M solution of diethylzinc/hexane was added to 30 ml of dichloromethane, and then was added a solution of 1.89 ml (24.5 mmol) triperoxonane acid in 10 ml of dichloromethane under stirring with ice cooling. The reaction solution was stirred at the same temperature for 20 minutes, then was added a solution of 1.97 ml (24.5 mmol) diiodomethane in 10 ml of dichloromethane and was stirred for 20 minutes and then was added a solution of 1.40 g (6,13 mmol) diethyl-4-methylenetetrahydrofolate (compounds described in J.A.C.S. 107, 13, 3981-3997 (1985)) in 10 ml of dichloromethane. After stirring the reaction solution for 6 hours at room temperature to the reaction solution was added ice water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 5:1), to obtain 1.48 g specified in the title compound as a brown oil (yield: 99%).

1H-YAM who-spectrum (400 MHz, CDCl3) δ ppm:

4,10 (2H, square, J=7 Hz), 3,37-2,31 (4H, m), 1.60-to of 1.53 (4H, m), 1,25 (6H, t, J=7 Hz), 0,31 (4H, s).

(29b) Ethyl 6-hydroximino[2.5]Oct-5-ene-5-carboxylate

of 1.46 g (6,03 mmol) ethyl 3-[1-(2-ethoxycarbonylethyl)cyclopropyl]propionate obtained in (29A), was dissolved in 60 ml of tetrahydrofuran, and thereto was added 1.35 g (12.1 mmol) of tert-butoxide potassium, followed by stirring at room temperature for 1 hour. The reaction solution was cooled with ice and acidified by adding 1 N. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only ethyl acetate), obtaining of 1.05 g specified in the title compound as a yellow oil (yield: 89%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

12,23 (0,7H, s), 4.26 deaths-4.09 to (2H, m), 3,50 (0,3H, DD, J=10 Hz, 6 Hz), 2.57 m-2,42 (0,7H, m), a 2.36 (2H, t, J=6 Hz), 2,03-1,94 (0,3H, m), 1,66-of 1.52 (1H, m)to 1.48 (2H, t, J=6 Hz), 1.28 (in, 3H, J=7 Hz), 0,60-0,30 (4H, m).

(29s) Ethyl 6-triftoratsetilatsetonom[2.5]Oct-5-ene-5-carboxylate

1,05 g (5,35 mmol) ethyl 6-hydroximino[2.5]Oct-5-ene-5-carboxylate obtained in (29b), was dissolved in 30 ml of dichloromethane and successively added 0,99 ml (of 5.89 mmol) diisopropylethylamine and 1.40 ml (8,03 mmol) triftormetilfullerenov anhydride with PE is emiliania at S. After stirring the reaction solution for 3 hours at the same temperature it was heated to room temperature. The reaction solution was poured into saturated aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only ethyl acetate), to obtain 1.56 g specified in the title compound as a brown oil (yield: 89%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4.26 deaths (2H, square, J=7 Hz), 2.57 m) is 2.46 (2H, m), 2,35-to 2.29 (2H, m), 1.60-to of 1.53 (2H, m)of 1.32 (3H, t, J=7 Hz), 0,49-0,40 (4H, m).

(29d) Ethyl 6-mercaptopurine[2.5]Oct-5-ene-5-carboxylate

In accordance with the process described in example (1A), ethyl 6-triftoratsetilatsetonom[2.5]Oct-5-ene-5-carboxylate obtained in (29s)was used instead of ethyl 8-tripterocalyx-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate, to obtain ethyl 6-acetylsulfapyridine[2.5]Oct-5-ene-5-carboxylate as a pale yellow oil (yield: 58%).

Next, 700 mg (2,75 mmol) of this compound was dissolved in 14 ml of ethanol and thereto was added a 2.75 ml (11 mmol) of 4 n solution of hydrogen chloride/dioxane under stirring with ice cooling, followed by stirring at room temperature in ECENA 4 hours. The reaction solution was concentrated under reduced pressure and the residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 10:1), obtaining 300 mg specified in the title compounds as a pale yellow oil (yield: 51%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,19 (2H, square, J=7 Hz), 4,12 (1H, s), to 2.57 (2H, t, J=6 Hz), 2,22-to 2.18 (2H, m)of 1.46 (2H, t, J=6 Hz), of 1.29 (3H, t, J=7 Hz), 0,40-0,33 (4H, m).

(A) Ethyl 6-(chlorosulfonyl)Spiro[2.5]Oct-5-ene-5-carboxylate

7 ml of acetic acid was added to 651 mg (to 4.23 mmol) tetrahydrate sodium perborate, the mixture was heated to 50°C. and to it was added a solution of 300 mg (1,41 mmol) ethyl 6-mercaptopurine[2.5]Oct-5-ene-5-carboxylate obtained in (29d), in 3 ml of acetic acid, followed by stirring at the same temperature for 2 hours and then at 80°C for 3 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. To the residue was added 5 ml of thionyl chloride and the mixture was heated at the boiling point under reflux for 2 hours. The reaction solution was again cooled to room temperature and concentrated under reduced pressure. To the residue was added ice water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration at below the nom pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 5:1), to obtain 195 mg specified in the title compounds as colorless oil (yield: 50%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 4.28 (2H, square, J=7 Hz), 2.77-to 2,69 (2H, m), 2,43-of 2.38 (2H, m)of 1.62 (2H, t, J=6 Hz), of 1.33 (3H, t, J=7 Hz), 0,52-0,46 (4H, m).

(29f) Ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]Spiro[2.5]Oct-4-ene-5-carboxylate

In accordance with the process described in example 1(d), ethyl 6-(chlorosulfonyl)Spiro[2.5]Oct-5-ene-5-carboxylate obtained in (e)was used instead of ethyl 8-chlorosulfonyl-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate, to obtain the specified title compound as a white powder (yield: 17%).

Melting point: 125-126°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.69 (1H, DD, J=9 Hz, 5 Hz), 7,13 (1H, DD, J=8 Hz, 3 Hz), 7.03 is-of 6.96 (2H, m), to 6.58 (1H, s), a 4.53 (1H, d, J=5 Hz), 4,20-Android 4.04 (2H, m), 2,62-of 2.50 (2H, m), 1,98-of 1.85 (1H, m)of 1.23 (3H, t, J=7 Hz), 1,22-1,13 (1H, m), 1,09 is 0.99 (2H, m), 0,93-0,80 (2H, m).

Example 30

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1-oxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemye the diastereoisomer), (the highly polar diastereoisomer) (example compound No. 1-362)

(30A) 7-(1,3-Dioxane-2-yl)-5-[2-(1,3-dioxane-2-yl)ethyl]heptane-1,5-diol

430 mg (5 mmol) of γ-butyrolactone was dissolved in 10 ml of tetrahydrofuran, and thereto was added 22 ml (11 mmol) of 0.5 M solution of bromo is a (1,3-dioxane-2-retil)magnesium/tetrahydrofuran, under stirring with ice cooling, followed by stirring at 50°C for 3 hours. After cooling the reaction solution with ice was added a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: ethyl acetate:ethanol = 10:1), to obtain 880 mg specified in the title compounds as colorless oil (yield: 55%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,51 (2H, t, J=5 Hz), 4,08 (4H, DD, J=10 Hz, 4 Hz), 3,79-3,70 (4H, m), 3,61 (2H, t, J=6 Hz), 2.13 and is 2.00 (2H, m), 1,68-of 1.56 (12H, m), 1,55-1,49 (2H, m), 1,37-of 1.29 (2H, m).

(30b) of 2-(2-{2-[2-(1,3-Dioxane-2-yl)ethyl]tetrahydrofuran-2-yl}ethyl)-1,3-dioxane

2,60 g (8.17 mmol) of 7-(1,3-dioxane-2-yl)-5-[2-(1,3-dioxane-2-yl)ethyl]heptane-1,5-diol, obtained in (30A), was dissolved in 45 ml of pyridine and thereto was added a solution of 1.64 g (8,58 mmol)p-toluensulfonate in 15 ml of pyridine, with stirring and with ice cooling, followed by stirring at the same temperature for 1 hour and at room temperature for 3 hours. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed concentrate what risovaniem under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 1:1), to obtain 1.31 g specified in the title compounds as colorless oil (yield: 53%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,50 (2H, t, J=5 Hz), 4.09 to (2H, DD, J=11 Hz, 5 Hz), 3,83-3,68 (6H, m), 2,15 of 1.99 (2H, m), 1,92-to 1.82 (2H, m), 1,73 is 1.48 (12H, m), 1,38-of 1.29 (2H, m).

(30C) Ethyl 3-[2-(2-ethoxycarbonylethyl)tetrahydrofuran-2-yl]propionate

1.31 g (43,6 mmol) of 2-(2-{2-[2-(1,3-dioxane-2-yl)ethyl]tetrahydrofuran-2-yl}ethyl)-1,3-dioxane obtained in (30b), was dissolved in 15 ml of acetone, and thereto was added and 16.3 ml (43,6 mmol) of Jones reagent, under stirring with ice cooling, followed by stirring at room temperature for 3 hours. The reaction solution was cooled with ice and then the reaction was stopped by adding isopropyl alcohol. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was dissolved in 15 ml of ethanol and added 0,76 ml (10.5 mmol) of thionyl chloride, followed by stirring overnight at room temperature. The reaction solution was concentrated under reduced pressure and the residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate 1:1), to obtain 610 mg specified in the title compound as a yellow oil (yield: 51%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 4.13 (4H, square, J=7 Hz), of 3.78 (2H, t, J=7 Hz), 2,37-2,31 (4H, m), 1,95-to 1.87 (2H, m), 1,86-to 1.79 (4H, m), 1,71 (2H, t, J=7 Hz), of 1.26 (6H, t, J=7 Hz).

(30d) Ethyl 8-oxo-1-oxaspiro[4.5]decane-7-carboxylate

610 mg (2,24 mmol) ethyl 3-[2-(2-ethoxycarbonylethyl)tetrahydrofuran-2-yl]propionate obtained in (30C), was dissolved in 18 ml of tetrahydrofuran, and thereto was added 503 mg (4,48 mmol)tert-butoxide potassium, followed by heating at the boiling point under reflux for 1 hour. After cooling the reaction solution with ice, the reaction solution was acidified by adding 1 N. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), to obtain 340 mg specified in the title compounds as colorless oil (yield: 67%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

12,24 (1H, s), 4.26 deaths-of 4.12 (2H, m), 3.96 points-with 3.79 (2H, m), 2,63-2,47 (1H, m), 2,43-2,12 (3H, m), 2.05 is is 1.86 (2H, m), 1,86 is 1.60 (4H, m)of 1.30 (3H, t, J=7 Hz).

(30e) Ethyl 8-tripterocalyx-1 oxaspiro[4.5]Dec-7-ene-7-carboxylate

To a suspension of 72 mg of 55% sodium hydride (1,65 mmol)/3 ml di is loretana solution was added 340 mg (1.50 mmol) of ethyl 8-oxo-1-oxaspiro[4.5]decane-7-carboxylate, obtained in (29d), in 4 ml of dichloromethane under stirring with ice cooling, followed by stirring at the same temperature for 1 hour. Next, the reaction solution was cooled to-C and to it was added, and 0.28 ml (1,65 mmol) triftormetilfullerenov anhydride. The mixture was stirred for 1 hour at the same temperature, and then heated to room temperature. After adding ice water to the reaction solution to terminate the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only ethyl acetate), to obtain 480 mg specified in the title compounds as a pale yellow oil (yield: 89%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4.26 deaths (2H, square, J=7 Hz), 3,92-3,81 (2H, m), 2,74-2,63 (1H, m), 2,62-2,48 (2H, m), 2,45-of 2.34 (1H, m), 2,04 by 1.68 (6H, m)of 1.32 (3H, t, J=7 Hz).

(30f) Ethyl 8-acetylthio-1 oxaspiro[4.5]Dec-7-ene-7-carboxylate

In accordance with the process described in example (1A), ethyl 8-tripterocalyx-1 oxaspiro[4.5]Dec-7-ene-7-carboxylate obtained in (30e)was used instead of ethyl 8-tripterocalyx-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate, to obtain the specified title compound as a yellow oil (yield: 32%)./p>

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,18 (2H, square, J=7 Hz), 3,91-a 3.83 (2H, m), 2,65-2,60 (1H, m), 2,60 is 2.51 (2H, m), is 2.40 to 2.35 (1H, m), 2,32 (2,6H, C)to 2.29 (0,4H, C), 2,00-of 1.93 (2H, m), 1,87-to 1.67 (4H, m)of 1.28 (3H, t, J= 7 Hz).

(30g) Ethyl 8-mercapto-1-oxaspiro[4.5]Dec-7-ene-7-carboxylate

120 mg (0.42 mmol) of ethyl 8-acetylthio-1 oxaspiro[4.5]Dec-7-ene-7-carboxylate obtained in (30f), was dissolved in 3 ml of ethanol and thereto was added 1 ml (4 mmol) of 4 n solution of hydrogen chloride/dioxane, followed by stirring at room temperature for 4 hours. The reaction solution was concentrated under reduced pressure and the residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 3:1), with 100 mg specified in the title compounds as a pale yellow oil (yield: 98%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,24-4,16 (2H, m), 4,12 (1H, s), 3,91-of 3.80 (2H, m), 2,84-a 2.71 (1H, m), 2,52-of 2.34 (3H, m), 2,01-1,90 (2H, m), 1,82 is 1.58 (4H, m)of 1.23 (3H, t, J=7 Hz).

(30h) Ethyl 8-chlorosulfonyl-1 oxaspiro[4.5]Dec-7-ene-7-carboxylate

100 mg (0.41 mmol) of ethyl 8-mercapto-1-oxaspiro[4.5]Dec-7-ene-7-carboxylate obtained in (30f), was dissolved in 4 ml mixture of acetic acid and water (acetic acid:water = 1:1) and through the reaction solution was purged with gaseous chlorine under stirring with ice cooling for 15 minutes. To the reaction solution was added ice water and the mixture was extracted with ethylacetate is. The organic layer was washed with water and dried over anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 3:1), to obtain 108 mg specified in the title compounds as colorless oil (yield: 85%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 4.28 (2H, square, J=7 Hz), 3,88 (2H, t, J=7 Hz), 2,92-of 2.81 (1H, m), 2.77-to of 2.66 (1H, m), 1,58 (2H, m), 2.06 to 1,89 (3H, m)1,80 (2H, t, 7 Hz), 1.77 in-1,67 (1H, m)of 1.34 (3H, t, J=7 Hz).

(30i) Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1-oxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemye the diastereoisomer), (the highly polar diastereoisomer)

To a solution of 57 mg (0,39 mmol) of 2-chloro-4-foronline and 0.05 ml (0,39 mmol) of triethylamine in 1 ml of ethyl acetate was added dropwise a solution of 108 mg (0.35 mmol) of ethyl 8-chlorosulfonyl-1 oxaspiro[4.5]Dec-7-ene-7-carboxylate obtained in (29h), in 2 ml of ethyl acetate under stirring with ice cooling, followed by stirring at room temperature over night. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to thin-layer chromatography on silica gel (solvent: hexane:ethyl acetate = 3:1), to obtain 12 mg nikopolamus is the diastereoisomer, specified in the title compound, a white powder and 20 mg of highly polar diastereoisomer specified in the title compound, as an amorphous substance (yield: 8%, 14%).

(Iskopaemye the diastereoisomer)

Melting point: 112-114°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7,14 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality-6,97 (1H, m), to 6.95 (1H, s), make 6.90 (1H, s), of 4.45 (1H, DD, J=6 Hz, 2 Hz), 4,22-4,10 (2H, m), 3.96 points-3,88 (1H, m), 3,86-with 3.79 (1H, m), 2,41 is 2.33 (1H, m), 2,29-to 2.18 (1H, m), 2.13 and is 2.01 (4H, m), 1,94-to 1.79 (2H, m), 1,25 (3H, t, J=7 Hz).

(The highly polar diastereoisomer)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,13 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality-of 6.96 (2H, m), to 6.95 (1H, s), 4,36 (1H, d, J=5 Hz), 4,22-4,10 (2H, m), a 4.03-of 3.96 (1H, m), 3,93-of 3.85 (1H, m), 2,56-2,48 (1H, m), 2.40 a-to 2.29 (1H, m), 2.06 to and 1.63 (6H, m)of 1.26 (3H, t, J=7 Hz).

Example 31

Ethyl 6-[N-(1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1057)

To a solution of 1.0 g (12,18 mmol) 1H-pyrrol-1-ylamine and 1.8 ml (13,40 mmol) of triethylamine in 60 ml of ethyl acetate was added dropwise a solution of 3.6 g (12,18 mmol) ethyl 2-chlorosulfonyl-1-cyclohexene-1-carboxylate (the compound disclosed in the description of Japanese patent application (Kokai) No. 2000-178246) in 12 ml of ethyl acetate under stirring with ice cooling, followed by stirring at room temperature over night. To the reaction solution were added water and the mixture of extras who were garofali with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 3:1) and the resulting solid was then washed with isopropyl ether to obtain 1.9 grams specified in the title compound as a white powder (yield: 52%).

Melting point: 85-86°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 8.15 (1H, s), 7,44-7,42 (1H, m), 7,02 (2H, t, J=2 Hz), 6,17 (2H, t, J=2 Hz), 4,57-4,56 (1H, m), the 4.29 (2H, square, J=7 Hz), 2,52 is 2.46 (2H, m), 2,32-of 2.23 (1H, m), 1.93 and-of 1.66 (3H, m)of 1.34 (3H, t, J=7 Hz).

Example 32

Ethyl 6-[N-(2-methyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1176)

In accordance with the process described in example 31, 2-methyl-1N-pyrrol-1-ylamine was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compound as a white powder (yield: 32%).

Melting point: 100-101°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.95 (1H, s), 7,43-7,39 (1H, m), 7.03 is-6,99 (1H, m), 6,07 (1H, t, J=4 Hz), 5,88 of 5.84 (1H, m), 4,60-4,55 (1H, m), 4.26 deaths (2H, square, J=7 Hz), 2,56 is 2.43 (2H, m), 2,34-of 2.20 (1H, m)to 2.29 (3H, s), 1,95-of 1.66 (3H, m), of 1.33 (3H, t, J=7 Hz).

Example 33

Ethyl 6-[N-(2-ethyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (see example is soedineniya No. 1-1193)

In accordance with the process described in example 31, 2-ethyl-1N-pyrrol-1-ylamine was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compound as a white powder (yield: 51%).

Melting point: 77-78°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.97 (1H, s), 7,46-7,41 (1H, m),? 7.04 baby mortality-7,01 (1H, m), 6,13 (1H, t, J=4 Hz), of 5.92-by 5.87 (1H, m), 4,62-of 4.57 (1H, m), 4,28 (2H, square, J=7 Hz), 2,79-of 2.64 (2H, m), 2,58-to 2.42 (2H, m), 2,35-of 2.21 (1H, m), 1,95-of 1.65 (3H, m)of 1.33 (3H, t, J=7 Hz), 1,24 (3H, t, J=8 Hz).

Example 34

Ethyl 6-[N-(2-propyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1210)

In accordance with the process described in example 31, 2-propyl-1N-pyrrol-1-ylamine was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compound as a white powder (yield: 31%).

Melting point: 66-68°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.97 (1H, s), 7,46-7,41 (1H, m),? 7.04 baby mortality-7,01 (1H, m), 6,12 (1H, t, J=3 Hz), of 5.92-by 5.87 (1H, m), 4,62-of 4.57 (1H, m), 4,27 (2H, square, J=7 Hz), 2,73-2,62 (2H, m), 2.57 m) is 2.43 (2H, m), 2,34-of 2.21 (1H, m), 1,95-1,63 (5H, m)of 1.33 (3H, t, J=7 Hz), 0,99 (3H, t, J=7 Hz).

Example 35

Ethyl 6-[N-(2-butyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1227)

In accordance with the process described in example 31, 2-BU the Il-1 N-pyrrol-1-ylamine was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compound as a white powder (yield: 26%).

Melting point: 49-50°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,94 (1H, s), 7,43-7,39 (1H, m), 7,01-6,98 (1H, m), 6,11-between 6.08 (1H, m), of 5.89-to 5.85 (1H, m), 4,60-4,55 (1H, m), 4.26 deaths (2H, square, J=7 Hz), 2.71 to to 2.65 (2H, m), 2,56 is 2.43 (2H, m), 2,33-of 2.20 (1H, m), 1,94-1,57 (5H, m), of 1.45 and 1.35 (2H, m)of 1.32 (3H, t, J=7 Hz), of 0.93 (3H, t, J=7 Hz).

Example 36

Ethyl 6-[N-(2-pentyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1244)

In accordance with the process described in example 31, 2-pentyl-1N-pyrrol-1-ylamine, obtained in reference example 6 was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compound as a white powder (yield: 33%).

Melting point: 60-61°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.96 (1H, s), 7,46-7,41 (1H, m),? 7.04 baby mortality-7,00 (1H, m), 6,12 (1H, t, J=3 Hz), of 5.92 and 5.86 (1H, m), 4,62-4,56 (1H, m), 4,28 (2H, square, J=7 Hz), 2,72-to 2.65 (2H, m), 2.57 m) is 2.44 (2H, m), 2,34-of 2.21 (1H, m), 1,95-to 1.59 (5H, m), 1,42-1,29 (4 H, m)of 1.34 (3H, t, J=7 Hz), to 0.89 (3H, t, J=7 Hz).

Example 37

Ethyl 6-[N-(2-hexyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1261)

In accordance with the process described in example 31, 2-hexyl-1N-pyrrol-1-ylamine, obtained the reference example 7, used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compound as a yellow oil (yield: 46%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.93 (1H, s), 7,43-7,39 (1H, m), 7,01-6,98 (1H, m), 6,12-between 6.08 (1H, m), of 5.89-to 5.85 (1H, m), 4,60-4,55 (1H, m), 4,27 (2H, square, J=' Hz), 2.71 to of 2.64 (2H, m), 2,56 is 2.43 (2H, m), 2,33-of 2.21 (1H, m), 1,91 is 1.58 (5H, m), 1,42-of 1.27 (6H, m)of 1.33 (3H, t, J=7 Hz), to 0.88 (3H, t, J=7 Hz).

Example 38

Ethyl 6-[N-(2-heptyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1278)

In accordance with the process described in example 31, 2-heptyl-1N-pyrrol-1-ylamine, obtained in reference example 8 was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compounds as colorless oil (yield: 13%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.97 (1H, s), 7,46-7,41 (1H, m),? 7.04 baby mortality-7,01 (1H, m), 6,11 (1H, t, J=3 Hz), 5,96 and 5.86 (1H, m), 4,62-4,56 (1H, m), 4,28 (2H, square, J=7 Hz), 2,72-2,62 (2H, m), 2,58 is 2.43 (2H, m), 2,35-of 2.21 (1H, m), 1,94-to 1.59 (5H, m), 1.41 to 1,22 (8H, m)of 1.33 (3H, t, J=7 Hz), to 0.88 (3H, t, J=7 Hz).

Example 39

Ethyl 6-[N-(2-octyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1295)

In accordance with the process described in example 31, 2-octyl-1N-pyrrol-1-ylamine, obtained in reference example 8 was used instead of 1N-pyrrol-1-ylamine, to receive the drug specified in the title compounds as a pale yellow oil (yield: 18%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.96 (1H, s), 7,46-7,41 (1H, m),? 7.04 baby mortality-7,00 (1H, m), 6,11 (1H, t, J=4 Hz), 5,91 and 5.86 (1H, m), br4.61-of 4.57 (1H, m), 4,28 (2H, square, J=7 Hz), 2.71 to of 2.64 (2H, m), 2.57 m) is 2.44 (2H, m), 2,34-of 2.20 (1H, m), 1,95 is 1.58 (5H, m), 1,42-1,19 (10H, m)of 1.33 (3H, t, J=7 Hz), to 0.88 (3H, t, J=7 Hz).

Example 40

Ethyl 6-[N-(2-cyclopropyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1312)

In accordance with the process described in example 31, 2-cyclopropyl-1N-pyrrol-1-ylamine, obtained in reference example 10 was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compounds as a pale pink powder (yield: 42%).

Melting point: 95-96°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,87 (1H, s), 7,41-7,37 (1H, m), 6,98-to 6.95 (1H, m), 6,05-of 6.02 (1H, m), 5,69-to 5.66 (1H, m), 4,66-br4.61 (1H, m), 4,25 (2H, square, J=7 Hz), 2,60 is 2.43 (2H, m), 2,34-of 2.20 (1H, m), 2.05 is-to 1.87 (2H, m), 1,82 by 1.68 (2H, m), of 1.31 (3H, t, J=7 Hz), 0,94-of 0.82 (2H, m), 0,73-0,65 (1H, m), 0,59-0,51 (1H, m).

Example 41

Ethyl 6-[N-(2-phenyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1329)

In accordance with the process described in example 31, 2-phenyl-1N-pyrrol-1-ylamine was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compounds as a pale yellow powder (yield: 21%).

Melting point: 160-161 the C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.99 (1H, s), EUR 7.57 (2H, d, J=8 Hz), 7,39 (2H, t, J=8 Hz), 7,33-7,27 (2H, m), 7,14-7,11 (1H, m), 6,32-6,28 (1H, m), and 6.25 (1H, t, J=4 Hz), 4,22 (2H, square, J=7 Hz), 4,18-to 4.14 (1H, m), 2,44 of-2.32 (1H, m), 2,24-2,07 (2H, m), 1.91 a is 1.75 (1H, m), 1,67-is 1.51 (1H, m), 1,40-of 1.29 (1H, m)of 1.28 (3H, t, J=7 Hz).

Example 42

Ethyl 6-[N-(2,5-dimethyl-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1346)

In accordance with the process described in example 31, 2,5-dimethyl-1N-pyrrol-1-ylamine was used instead of 1N-pyrrol-1-ylamine, obtaining specified in the title compound as a white powder (yield: 29%).

Melting point: 96-97°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,88 (1H, s), 7,40-to 7.35 (1H, m), of 5.75 (2H, s), 4,58-to 4.52 (1H, m), 4,24 (2H, square, J=7 Hz), 2,69-2,61 (1H, m), 2,53-to 2.42 (1H, m), 2,33-2,19 (1H, m), and 2.26 (6H, s), 2,02 is 1.91 (1H, m), 1,86-of 1.73 (2H, m)of 1.30 (3H, t, J=7 Hz).

Example 43

Ethyl 6-[N-(2-chloro-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1091)

150 mg (0,503 mmol) ethyl 6-[N-(1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate obtained in example 31 was dissolved in 3 ml of tetrahydrofuran, and thereto was added 70 mg (0,528 mmol)Nchlorosuccinimide, under stirring with ice cooling, followed by stirring at room temperature over night. To actionname the solution was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to thin-layer chromatography on silicagel Le (solvent: hexane:ethyl acetate = 2:1) and the resulting solid was then washed with isopropyl ether to obtain 50 mg specified in the title compound as a white powder (yield: 30%).

Melting point: 60-61°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to $ 7.91 (1H, s), 7,43-7,37 (1H, m),? 7.04 baby mortality (1H, DD, J=4 Hz, 2 Hz), 6,14 (1H, t, J=4 Hz), 6,10 (1H, DD, J=4 Hz, 2 Hz), 4,65-br4.61 (1H, m), 4.26 deaths (2H, square, J=7 Hz), 2,61 is 2.44 (2H, m), 2,33-of 2.21 (1H, m), 2.05 is-1,90 (1H, m), 1,83-1,71 (2H, m)of 1.30 (3H, t, J=7 Hz).

Example 44

Ethyl 6-[N-(2-bromo-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1108)

In accordance with the process described in example 43,N-bromosuccinimide was used instead ofNchlorosuccinimide, obtaining specified in the title compound as a white powder (yield: 50%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.85 (1H, s), 7,42-7,38 (1H, m), to 7.15 (1H, DD, J=4 Hz, 2 Hz), 6.22 per 6,17 (2H, m), 4,67-to 4.62 (1H, m), 4,25 (2H, square, J=7 Hz), 2,60 is 2.44 (2H, m), 2,33-of 2.20 (1H, m), 2.05 is-of 1.92 (1H, m), 1,83 is 1.70 (2H, m)of 1.30 (3H, t, J=7 Hz).

Example 45

Ethyl 6-[N-(2,5-dichloro-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (see primeramente No. 1-1142)

In accordance with the process described in example 42, 2.1 equivalentNchlorosuccinimide used relatively ethyl 6-[N-(1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate obtained in example 31, with the receipt specified in the title compounds as a pale yellow oil (yield: 25%).

Melting point: 144-145°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

8,08 (1H,s), 7,39-7,33 (1H, m), 6,07 (2H, s), 4,89 of 4.83 (1H, m), 4,24 (2H, square, J=7 Hz), 2,67-of 2.58 (1H, m), 2,52-to 2.42 (1H, m), 2,31-2,19 (1H, m), 2,03-of 1.88 (1H, m), 1,87-1,72 (2H, m)of 1.29 (3H, t, J=7 Hz).

Example 46

Ethyl 6-[N-(2,5-dibromo-1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate (example compound No. 1-1159)

In accordance with the process described in example 44, 2.1 equivalentN-bromosuccinimide used relatively ethyl 6-[N-(1H-pyrrol-1-yl)sulfamoyl]-1-cyclohexen-1-carboxylate obtained in example 31, with the receipt specified in the title compound as a white powder (yield: 3%).

Melting point: 123-124°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

with 8.05 (1H, s), 7,40-to 7.35 (1H, m), 6,24 (2H, s), 5,02-of 4.95 (1H, m), 4,25 (2H, square, J=7 Hz), 2,69-2,60 (1H, m), 2,53-to 2.42 (1H, m), 2,33-2,19 (1H, m), 2,02-1,90 (1H, m), 1,87-1,72 (2H, m)of 1.29 (3H, t, J=7 Hz).

Example 47

tert-Butyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxyl the t (example compound No. 3-89)

(47A) 8-[N-(2-Chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylic acid

1.8 g (4,29 mmol) ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 1 was dissolved in 60 ml of water-tetrahydrofuran (1:1) and thereto was added 900 mg (21,45 mmol) of lithium hydroxide, followed by stirring for 7 hours at 50°C. the Reaction solution was cooled with ice, and then it was acidified by adding 1 N. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was washed with hexane, obtaining 1,43 g specified in the title compounds as a pale brown powder (yield: 85%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9 Hz, 5 Hz), 7,16 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality-6,93 (3H, m), 4,36 (1H, d, J=5 Hz), 4,16-was 4.02 (3H, m), 3,97-3,88 (1H, m), 2.57 m at 2.45 (3H, m), 2,25-to 2.13 (1H, m), 1,90-to 1.82 (1H, m).

(47b) of tert-Butyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

100 mg (0.26 mmol) of 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylic acid obtained in (47A), was dissolved in 2 ml of toluene, and thereto was added 1 ml of di-tert-butylacetateN,N-dimethylformamide, followed by stirring the ri 100°C for 3 hours. After cooling the reaction solution to room temperature was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to thin-layer chromatography on silica gel (solvent: dichloromethane:methanol = 1:50), with 52 mg specified in the title compound as a white amorphous substance (yield: 45%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.64 (1H, DD, J=9 Hz, 5 Hz), to 7.15 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,98 (2H, m), of 6.71 (1H, s), 4,42-to 4.38 (1H, m), 4,13-4,01 (3H, m), 3.95 to 3,88 (1H, m), of 2.51-2.40 a (2H, m), 2,21-2,10 (1H, m), 1,86-to 1.79 (1H, m), of 1.46 (9H, s).

In accordance with the process described in example (47b), various corresponding acetals used instead of di-tert-butylacetateN,N-dimethylformamide for synthesis of compounds of examples 48-51.

Example 48

Methyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 3-73)

White powder (yield: 50%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,16 (1H, DD, J=8 Hz, 3 Hz), 7,06-6,99 (1H, m), 6,98 (1H, s), at 6.84 (1H, s), 4,43-to 4.38 (1H, m), 4,15-3,99 (3H, m), 3.95 to 3,88 (1H, m), of 3.73 (3H, s), 2,56 is 2.43 (2H, m), 2,24-2,12 (1H, m), 1,88-to 1.79 (1H, m).

Example 49

Propyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro the[4.5]Dec-6-ene-7-carboxylate (example compound No. 3-77)

White amorphous substance (yield: 18%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,16 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,97 (2H, m), for 6.81 (1H, s), 4,42 (1H, d, J=5 Hz), 4,16-3,99 (5H, m), 3.95 to 3,88 (1H, m), 2,55 is 2.44 (2H, m), 2,24-2,11 (1H, m), 1,88-of 1.81 (1H, m), 1,71 is 1.60 (2H, m)to 0.94 (3H, t, J=7 Hz).

Example 50

Butyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 3-81)

White powder (yield: 26%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,16 (1H, DD, J=8 Hz, 3 Hz), 7,05-of 6.96 (2H, m), to 6.80 (1H, s), 4,42 (1H, d, J=5 Hz), 4,20-4,00 (5H, m), 3.95 to a 3.87 (1H, m), 2,55 is 2.44 (2H, m), 2,24-2,11 (1H, m), 1,88 and 1.80 (1H, m), 1,66-of 1.57 (2H, m), USD 1.43-1,32 (2H, m)of 0.93 (3H, t, J=7 Hz).

Example 51

Isopropyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 3-85)

White powder (yield: 21%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,16 (1H, DD, J=8 Hz, 3 Hz), 7,06-6,98 (2H, m), 6,78 (1H, s), 5,11-4,99 (1H, m), 4,42 (1H, d, J=5 Hz), 4,15-3,99 (3H, m), 3.95 to 3,88 (1H, m), 2,55 is 2.43 (2H, m), 2,24-2,11 (1H, m), 1,99-to 1.79 (1H, m)of 1.26 (3H, d, J=2 Hz), 1,24 (3H, d, J=2 Hz).

Example 52

Acetoxymethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 3-93)

1 g (2.55 mmol)of 8-[ N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylic acid obtained in example (47A), was dissolved in 20 ml of acetonitrile and thereto were added to 0.50 ml (5,10 mmol) Bromeliaceae, 499 mg (1.53 mmol) of cesium carbonate and 471 mg (1.28 mmol) of tetrabutylammonium iodide, followed by stirring at room temperature for 1 hour. To the reaction solution was added 0.1 G. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: dichloromethane:methanol = 49:1), obtaining 833 mg specified in the title compound as an amorphous substance (yield: 70%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,18 (1H, DD, J=8 Hz, 3 Hz), 7,08-7,02 (1H, m), 7,01 (1H, s), 6,92 (1H, s)5,80 (2H, s)to 4.41 (1H, DD, J=6 Hz, 2 Hz), 4,15-4,01 (3H, m), 3,94-3,88 (1H, m), 2,48 (1H, TD, J=14 Hz, 4 Hz), 2,44-is 2.37 (1H, m), 2,22 with 2.14 (1H, m), 2,12 (3H, s), 1.85 to to 1.79 (1H, m).

In accordance with the process described in example (1d), various corresponding anilines used instead of 2-chloro-4-foronline for the synthesis of compounds of examples 53-121.

Example 53

Ethyl 8-[N-(2-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2217)

Oil (yield: 61%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 to 7.62 (1H, m), 7,17-to 7.09 (3H, m), of 6.96 (1H, d, J=3 Hz), 6,83 (1H, t, J=1 Hz), 4,43-and 4.40 (1H, m), 4,24-4,01 (5H, m), 3.95 to the 3.89 (1H, m), 2,55-to 2.41 (2H, m), 2,21-2,10 (1H, m), 1,89-of 1.81 (1H, m)of 1.27 (3H, t, J=7 Hz).

Example 54

Ethyl 8-[N-(2-chlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-188)

Pale brown powder (yield: 69%).

Melting point: 157-160°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.70 (1H, DD, J=8 Hz, 1 Hz), 7,39 (1H, DD, J=8 Hz, 2 Hz), 7,31-7,26 (1H, m), 7,10-7,05 (2H, m), 6,83 (1H, t, J=1 Hz), 4,49-to 4.46 (1H, m), 4,24-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2,60-2,48 (2H, m), 2,24-2,13 (1H, m), 1,88-of 1.81 (1H, m)of 1.24 (3H, t, J=7 Hz).

Example 55

Ethyl 8-[N-(2-bromophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1374)

Oil (yield: 59%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.70 (1H, DD, J=8 Hz, 1 Hz), 7,55 (1H, DD, J=8 Hz, 2 Hz), of 7.36-7,30 (1H, m),? 7.04 baby mortality-6,98 (2H, m), 6,83 (1H, t, J=1 Hz), 4,50-4,47 (1H, m), 4,23-4,01 (5H, m), 3.95 to 3,88 (1H, m), 2,62-2,49 (2H, m), 2,24-2,13 (1H, m), 1,88-of 1.81 (1H, m)of 1.24 (3H, t, J=7 Hz).

Example 56

Ethyl 8-[N-(2-itfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2224)

Amorphous substance (yield: 53%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,79 (1H, DD, J=8 Hz, 1 Hz), and 7.7 (1H, DD, J=8 Hz, 1 Hz), 7,38-7,33 (1H, m), 6,88-PC 6.82 (3H, m), 4,49 (1H, d, J=5 Hz), 4,24-4,01 (5H, m), 3.95 to 3,88 (1H, m), 2,63-2,49 (2H, m), 2,24 and 2.13 (1H, m), 1,88-of 1.81 (1H, m)of 1.24 (3H, t, J=7 Hz).

Example 57

Ethyl 8-[N-(4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-100)

White powder (yield: 87%).

Melting point: 141-146°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,38-7,33 (2H, m), 7,07-7,01 (3H, m), 6.87 in (1H, t, J=1 Hz), 4,30-is 4.21 (3H, m), 4,14-4,01 (3H, m), 3.95 to the 3.89 (1H, m), 2,45-of 2.38 (1H, m), and 2.27 (1H, TD, J=14 Hz, 3 Hz), 2,09 of 1.99 (1H, m), 1,87 and 1.80 (1H, m), 1,33 (3H, t, J=7 Hz).

Example 58

Ethyl 8-[N-(4-chlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2231)

White powder (yield: 81%).

Melting point: 153-156°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,31 (4H, s), 7,03 (1H, s), 6.87 in (1H, t, J=1 Hz), 4,29-4,19 (3H, m), 4,14-was 4.02 (3H, m), 3.95 to the 3.89 (1H, m), 2,47-to 2.40 (1H, m), and 2.27 (1H, TD, J=14 Hz, 3 Hz), 2,10-2,00 (1H, m), 1,88-of 1.81 (1H, m)of 1.32 (3H, t, J=7 Hz).

Example 59

Ethyl 8-[N-(2-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2238)

White powder (yield: 75%).

Melting point: 101-104°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,56-7,53 (1H, m), 7.23 percent-to 7.18 (2H, m), 7,11-7,06 (1H, m), 6,85 (1H, t, J=1 Hz), 6,62 (1H, s), of 4.44 (1H, DD, J=6 Hz, 2 Hz), 4,25-4,01 (5H, m), 3.95 to the 3.89 (1H, m), 2,5-2,48 (1H, m), 2,42 (1H, TD, J=14 Hz, 4 Hz), was 2.34 (3H, s), 2,19-of 2.09 (1H, m), 1,88-of 1.81 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 60

Ethyl 8-[N-(2-ethylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2245)

White powder (yield: 66%).

Melting point: 83-87°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

rate of 7.54 (1H, DD, J=8 Hz, 1 Hz), 7,25-7,19 (2H, m), 7,14 (1H, TD, J=7 Hz, 1 Hz), 6,85 (1H, s), 6,63 (1H, s), 4,47 (1H, DD, J=6 Hz, 2 Hz), 4,25-was 4.02 (5H, m), 2,75-of 2.66 (2H, m), 2,54-2,48 (1H, m), 2,43 (1H, TD, J=14 Hz, 4 Hz), 2,19-2,11 (1H, m), 1,87-of 1.81 (1H, m), 1,28-of 1.23 (6H, m).

Example 61

Ethyl 8-[N-(2-propylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1989)

Oil (yield: 53%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,55-7,52 (1H, m), 7.23 percent-to 7.18 (2H, m), 7,14-to 7.09 (1H, m), 6,85 (1H, t, J=1 Hz), only 6.64 (1H, s), 4,48-of 4.44 (1H, m), 4,24-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2,67-2,62 (2H, m), 2,54-2,39 (2H, m), 2,20-2,10 (1H, m), 1,87-of 1.81 (1H, m), 1,69 is 1.58 (2H, m)of 1.26 (3H, t, J=7 Hz), 0,99 (3H, t, J=7 Hz).

Example 62

Ethyl 8-[N-(2-ethynylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2252)

Oil (yield: 19%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=8 Hz, 1 Hz), 7,47 (1H, DD, J=8 Hz, 2 Hz), 7,37 (1H, TD, J=8 Hz, 2 Hz), 7,21 (1H, s), 7,07 (1H, TD, J=8 Hz, 1 Hz), PC 6.82 (1H, t, J=1 Hz), to 4.52 figure-4.49 (1H, m), 4,22-4,01 (5H, m), 3.95 to 3,88 (1H, m), 3,49 (1H, s), 2,65-2,0 (2H, m), 2,24 and 2.13 (1H, m), 1,88-of 1.81 (1H, m)to 1.22 (3H, t, J=7 Hz).

Example 63

Ethyl 8-[N-(2-isopropylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2259)

Pale brown powder (yield: 65%).

Melting point: 115-118°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,53-7,49 (1H, m), 7,34-7,30 (1H, m), 7.23 percent-7,17 (2H, m)6,86 (1H, s), 6,69 (1H, s), 4,47 (1H, DD, J=6 Hz, 2 Hz), 4,27-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 3.33 and-3,24 (1H, m), 2,53-2,47 (1H, m), 2,42 (1H, TD, J=14 Hz, 3 Hz), 2,18-2,10 (1H, m), 1,86-of 1.81 (1H, m), 1,29-to 1.21 (9H, m).

Example 64

Ethyl 8-[N-(2-tert-butylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2266)

White powder (yield: 53%).

Melting point: 117-120°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

was 7.45 (1H, DD, J=8 Hz, 1 Hz), 7,38 (1H, DD, J=8 Hz, 2 Hz), 7.23 percent (1H, TD, J=8 Hz, 2 Hz), 7,12-7,07 (1H, m)6,86 (1H, t, J=1 Hz), only 6.64 (1H, s), with 4.64-br4.61 (1H, m), 4,24-a 4.03 (5H, m), 3,97-are 3.90 (1H, m), 2,65 of $ 2.53 (2H, m), 2,28-to 2.18 (1H, m), 1,90 of-1.83 (1H, m)of 1.45 (9H, s)of 1.23 (3H, t, J=7 Hz).

Example 65

Ethyl 8-[N-(2-Deut-butylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2273)

Oil (yield: 71%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,54-7,49 (1H, m), 7,29-7,16 (3H, m)6,86 (1H, dt, J=5 Hz, 1 Hz), of 6.68 (1H, d, J=10 Hz), 4,47-of 4.44 (1H, m), 4,27-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 3,12-2,95 (1H, m), 2,53-2,35 (H, m), 2,19-2,07 (1H, m), 1,86 and 1.80 (1H, m), 1.70 to 1.55V (2H, m), 1,31-1,19 (6H, m), 0,91-to 0.80 (3H, m).

Example 66

Ethyl 8-[N-(2-methoxyphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2280)

White powder (yield: 70%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

EUR 7.57 (1H, DD, J=8 Hz, 2 Hz), 7,11-7,05 (2H, m), of 6.96 (1H, TD, J=8 Hz, 1 Hz), 6.89 in (1H, DD, J=8 Hz, 1 Hz), 6,79 (1H, t, J=1 Hz), of 4.44 (1H, d, J=4 Hz), 4,21-4,00 (5H, m), 3,94-a-3.84 (4H, m), 2,58 (1H, TD, J=14 Hz, 4 Hz), 2,50 is 2.43 (1H, m), 2,18-of 2.08 (1H, m), 1,84-to 1.77 (1H, m)of 1.23 (3H, t, J=7 Hz).

Example 67

Ethyl 8-[N-(2-ethoxyphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2287)

White powder (yield: 60%).

Melting point: 129-134°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,58 (1H, DD, J=8 Hz, 2 Hz), 7,12 (1H, s), 7,06 (1H, TD, J=8 Hz, 2 Hz), to 6.95 (1H, TD, J=8 Hz, 2 Hz), 6.87 in (1H, DD, J=8 Hz, 1 Hz), 6,79 (1H, t, J=1 Hz), 4,45 was 4.42 (1H, m), 4,20-of 4.00 (7H, m), 3,94-a 3.87 (1H, m), 2.57 m (1H, TD, J=14 Hz, 4 Hz), 2,50 is 2.44 (1H, m), 2,18-of 2.08 (1H, m), 1.85 to of 1.78 (1H, m)of 1.45 (3H, t, J=7 Hz), of 1.23 (3H, t, J=7 Hz).

Example 68

Ethyl 8-[N-(2-deformational)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2294)

White powder (yield: 48%).

Melting point: 85-88°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.69 (1H, DD, J=8 Hz, 2 Hz), 7,25-was 7.08 (4H, m), at 6.84 (1H, s), 6,57 1H, DD, J=74 Hz, 73 Hz), of 4.44-to 4.41 (1H, m), 4,21-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2.57 m) is 2.44 (2H, m), 2,21-2,10 (1H, m), 1,90-to 1.82 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 69

Ethyl 8-[N-(2-methylsulfinylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2301)

White powder (yield: 56%).

Melting point: 93-95°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.70 (1H, s), 7,63 (1H, DD, J=8 Hz, 1 Hz), 7,51 (1H, DD, J=8 Hz, 2 Hz), 7,33-7,28 (1H, m), was 7.08 (1H, TD, J=8 Hz, 1 Hz), PC 6.82 (1H, square, J=1 Hz), 4,50 (1H, d, J=4 Hz), 4,21-4,01 (5H, m), 3.95 to 3,88 (1H, m), 2,65-of 2.50 (2H, m), of 2.38 (3H, s), 2,23-2,12 (1H, m), 1,88-of 1.81 (1H, m), 1,25-to 1.21 (3H, m).

Example 70

Ethyl 8-[N-(2-acetylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2308)

Oil (yield: 25%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

11,46 (1H, s), to $ 7.91 (1H, DD, J=8 Hz, 1 Hz), the 7.85 (1H, DD, J=8 Hz, 1 Hz), to 7.59-rate of 7.54 (1H, m), 7,15-7,10 (1H, m), to 6.80 (1H, t, J=1 Hz), 4,50-4,47 (1H, m), 4,16-4,00 (5H, m), 3,94-3,88 (1H, m), 2,68 at 2.59 (4H, m), 2,56-2,49 (1H, m), 2,20-of 2.09 (1H, m), 1,87 and 1.80 (1H, m), 1,25 (3H, t, J=7 Hz).

Example 71

Ethyl 8-[N-(2-benzoylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2315)

White powder (yield: 73%).

Melting point: 127-129°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,58 (1H, DD, J=8 Hz, 1 Hz), 7,32-7,13 (8H, m), to 6.80 (1H, s), 6,50 (1H, s), 4,36 (1H, DD, =6 Hz, 2 Hz), 4,23-of 4.00 (7H, m), 3,93-a 3.87 (1H, m), a 2.36 (1H, TD, J=14 Hz, 4 Hz), 2,19 and 2.13 (1H, m), 2,03-of 1.94 (1H, m), 1,76 is 1.70 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 72

Ethyl 8-{N-[2-(morpholine-4-yl)phenyl]sulfamoyl}-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2322)

White powder (yield: 71%).

Melting point: 118-121°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

8,10 (1H, s), 7,58 (1H, DD, J=8 Hz, 2 Hz), 7.23 percent (1H, DD, J=8 Hz, 2 Hz), 7,20-to 7.15 (1H, m), 7,07 (1H, TD, J=8 Hz, 2 Hz), PC 6.82 (1H, t, 1 Hz), 4,47-of 4.44 (1H, m), 4,15-4,00 (5H, m), 3.95 to of 3.85 (5H, m), 2,92-and 2.83 (4H, m), 2,59-of 2.50 (2H, m), 2,24-2,12 (1H, m), 1,90-to 1.82 (1H, m)of 1.23 (3H, t, J=7 Hz).

Example 73

Ethyl 8-[N-(9H-fluoren-1-yl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2329)

Pale brown powder (yield: 60%).

Melting point: 156 to 160°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

for 7.78 (1H, d, J=7 Hz), a 7.62 (1H, d, J=8 Hz), 7,58 (1H, d, J=7 Hz), 7,54 (1H, d, J=8 Hz), 7,42-7,37 (2H, m), 7,34 (1H, TD, J=7 Hz, 1 Hz), 6,92 (1H, s)6,86 (1H, s), of 4.45 (1H, DD, J=6 Hz, 2 Hz), 4,22-4,00 (5H, m), of 3.96 (2H, s), 3,94-to 3.89 (1H, m), 2,56-of 2.50 (1H, m), is 2.37 (1H, TD, J=14 Hz, 3 Hz), 2,17-of 2.08 (1H, m), 1,88-to 1.82 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 74

Ethyl 8-(N-{2-[2-(pyridin-4-yl)ethyl]phenyl}sulfamoyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2336)

White powder (yield: 26%).

Melting point: 77-80°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

8,50-of 8.47 (2H, m), 7,54-7,52 (1H, m), 7,26-7,22 (1H, m), 7,19-7,13 (4H, m), 6.89 in (1H, t, J=1 Hz), to 6.80 (1H, s), 4,43 (1H, DD, J=6 Hz, 3 Hz), 4,25-4,18 (2H, m), 4,14-a 4.03 (3H, m), 3.96 points-are 3.90 (1H, m), 3,15-3,00 (2H, m), 2,99-2,89 (2H, m), 2,54-2,48 (1H, m), 2,33 (1H, TD, J=14 Hz, 3 Hz), 2,17-of 2.09 (1H, m), 1,88-to 1.82 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 75

Ethyl 8-(N-{2-[2-(tert-butoxycarbonylamino)ethyl]phenyl}sulfamoyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2343)

Amorphous substance (yield: 65%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

of 8.00 (1H, s), a 7.62 (1H, d, J=8 Hz), 7,24 (1H, TD, J=8 Hz, 2 Hz), 7,17 (1H, d, J=7 Hz), 7,10 (1H, t, J=7 Hz), 6,83 (1H, s), the 4.90 (1H, users), to 4.46 (1H, d, J=5 Hz), 4,23-4,01 (5H, m), 3,94-3,88 (1H, m,), with 3.27 (2H, square, J=7 Hz), 2,96-and 2.83 (2H, m), 2,59-2,52 (2H, m), 2,18-of 2.09 (1H, m), 1,83-of 1.78 (1H, m), 1,48-of 1.41 (9H, m)of 1.27 (3H, t, J=7 Hz).

Example 76

Ethyl 8-[N-(2-AMINOPHENYL)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2350)

Oil (yield: 13%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,39 (1H, DD, J=8 Hz, 2 Hz), 7,11-7,06 (1H, m), 6.89 in (1H, t, J=1 Hz), 6,79-of 6.73 (2H, m), 4,46 (1H, DD, J=6 Hz, 3 Hz), or 4.31-3,86 (3H, m), 4,28 (2H, square, J=7 Hz), 4,11-was 4.02 (3H, m), 3.95 to the 3.89 (1H, m), 2,48-to 2.41 (1H, m), 2,24 (1H, TD, J=14 Hz, 3 Hz), 2,13-2,03 (1H, m), 1,86-to 1.79 (1H, m)of 1.32 (3H, t, J=7 Hz).

Example 77

Ethyl 8-[N-(2,4-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound is 1-276)

White powder (yield: 74%).

Melting point: 128-131°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.64-EUR 7.57 (1H, m), 6,97 (1H, users), 6,93-6,86 (2H, m), at 6.84 (1H, t, J=1 Hz), 4,36 (1H, DD, J=6 Hz, 2 Hz), 4,28-was 4.02 (5H, m), 3.95 to 3,90 (1H, m), 2,53 is 2.46 (1H, m), is 2.40 (1H, TD, J=14 Hz, 4 Hz), 2,21-2,10 (1H, m), 1,88-of 1.81 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 78

Ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1550)

Pale yellow powder (yield: 48%).

Melting point: 106-111°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9 Hz, 5 Hz), 7,32 (1H, DD, J=8 Hz, 3 Hz), 7,10? 7.04 baby mortality (1H, m)6,94 (1H, s), PC 6.82 (1H, t, J=1 Hz), 4,46-4,43 (1H, m), 4.26 deaths-4,01 (5H, m), 3.95 to the 3.89 (1H, m), 2.57 m-2,47 (2H, m), 2,24 and 2.13 (1H, m), 1,87-of 1.81 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 79

Ethyl 8-[N-(4-fluoro-2-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2357)

White powder (yield: 79%).

Melting point: 103-105°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), of 6.96-6,85 (3H, m), only 6.64 (1H, users), 4,39 (1H, DD, J=6 Hz, 3 Hz), 4,27-4,18 (2H, m), 4,14-was 4.02 (3H, m), 3.96 points-to 3.89 (1H, m), 2,52 at 2.45 (1H, m), 2.40 a-2,31 (4H, m), 2,18-of 2.08 (1H, m), 1,87 and 1.80 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 80

Ethyl 8-[N-(3-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound is 1-2364)

Pale brown powder (yield: 81%).

Melting point: 111-118°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,47 (1H, DD, J=6 Hz, 3 Hz), 7,29-of 7.25 (1H, m), 7,15-to 7.09 (2H, m), to 6.88 (1H, s), 4,28 (2H, square, J=7 Hz), 4,21-4,18 (1H, m), 4,14-was 4.02 (3H, m), 3.96 points-to 3.89 (1H, m), 2,49-to 2.41 (1H, m), of 2.25 (1H, TD, J=14 Hz, 3 Hz), 2,12 is 2.01 (1H, m), 1,89-to 1.82 (1H, m)of 1.34 (3H, t, J=7 Hz).

Example 81

Ethyl 8-[N-(4-fluoro-3-triptoreline)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2371)

White powder (yield: 78%).

Melting point: 109-111°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.64-EUR 7.57 (2H, m), 7,27-7,17 (2H, m), 6.89 in (1H, s), 4,28 (2H, square, J=7 Hz), 4,19-4,16 (1H, m), 4,14-a 4.03 (3H, m), 3.96 points-to 3.89 (1H, m), 2,49-to 2.42 (1H, m), and 2.26 (1H, TD, J=14 Hz, 3 Hz), 2,13-2,03 (1H, m), 1,89-1,83 (1H, m)of 1.34 (3H, t, J=7 Hz).

Example 82

Ethyl 8-[N-(4-fluoro-3-methoxyphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2378)

Oil (yield: 72%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.09 (1H, DD, J=7 Hz, 2 Hz), 7,03 (1H, DD, J=11 Hz, 9 Hz), of 6.96 (1H, users), 6,88-6,83 (2H, m), 4,30-to 4.23 (3H, m), 4,14-was 4.02 (3H, m), 3.95 to the 3.89 (4H, m), 2,46-of 2.38 (1H, m), and 2.27 (1H, TD, J=14 Hz, 3 Hz), 2,10-2,00 (1H, m), 1,88-of 1.81 (1H, m)of 1.33 (3H, t, J=7 Hz).

Example 83

Ethyl 8-[N-(3,4-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2385)

Pale brown powder (yield: 94%).

Melting point: 118-121°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,33-7,26 (1H, m), 7.18 in-7,06 (3H, m), 6.89 in (1H, s), 4,28 (2H, square, J=7 Hz), 4,19 (1H, DD, J=5 Hz, 3 Hz), 4,14-was 4.02 (3H, m), 3.96 points-to 3.89 (1H, m), 2,48-to 2.41 (1H, m), of 2.25 (1H, TD, J=14 Hz, 3 Hz), 2,11-a 2.01 (1H, m), 1,89-to 1.82 (1H, m)of 1.34 (3H, t, J=7 Hz).

Example 84

Ethyl 8-[N-(2,4-acid)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2392)

White powder (yield: 49%).

Melting point: 118-121°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,47 was 7.45 (1H, m), is 6.78 (2H, d, J=9.8 Hz), 6,50-6,47 (2H, m), to 4.38 (1H, d, J=4,7 Hz), 4,21-of 3.80 (12H, m)to 2.54 (1H, dt, J=14,2 Hz, 7.2 Hz), 2,45-of 2.38 (1H, m), 2,14-of 2.08 (1H, m), 1,81 to 1.76 (1H, m), 1,25 (3H, t, J=7,0 Hz).

Example 85

Ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-628)

Brown oil (yield: 82%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), 6,94 (1H, DD, J=10 Hz, 3 Hz), 6,92-6,86 (2H, m), 6,60 (1H, s)to 4.41 (1H, DD, J=6 Hz, 2 Hz), 4,28-4,18 (2H, m), 4,14-was 4.02 (3H, m), 3.96 points-to 3.89 (1H, m), of 2,75 2,63 (2H, m), 2,52-2,45 (1H, m), is 2.37 (1H, dt, J=14 Hz, 3 Hz), 2,18-of 2.08 (1H, m), 1,87 and 1.80 (1H, m), 1,63-of 1.52 (2H, m), of 1.44 and 1.35 (2H, m)of 1.29 (3H, t, J=7 Hz), of 0.95 (3H, t, J=8 Hz).

Example 86

Ethyl 8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound is 1-1726)

Brown oil (yield: 78%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), 6,94 (1H, DD, J=10 Hz, 3 Hz), 6,92-6,85 (2H, m), is 6.61 (1H, s), and 4.40 (1H, DD, J=6 Hz, 2 Hz), 4,27-4,18 (2H, m), 4,14-was 4.02 (3H, m), 3.95 to 3,90 (1H, m), was 2.76-2,61 (2H, m), 2,52-2,45 (1H, m), is 2.37 (1H, dt, J=14 Hz, 3 Hz), 2,18-of 2.09 (1H, m), 1,87-of 1.81 (1H, m), 1,65-of 1.52 (2H, m), 1,39-of 1.32 (4H, m)of 1.30 (3H, t, J=7 Hz), of 0.90 (3H, t, J=7 Hz).

Example 87

Ethyl 8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-804)

Pale brown oil (yield: 58%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), of 6.96-6,85 (3H, m), is 6.61 (1H, s), and 4.40 (1H, DD, J=6 Hz, 2 Hz), 4,28-4,18 (2H, m), 4,14-was 4.02 (3H, m), 3.95 to the 3.89 (1H, m), was 2.76-2,61 (2H, m), 2,52 at 2.45 (1H, m), is 2.37 (1H, TD, J=14 Hz, 3 Hz), 2,18-of 2.08 (1H, m), 1,87-of 1.81 (1H, m), 1,63-of 1.52 (2H, m), 1,42-1,25 (9H, m), 0,91-of 0.85 (3H, m).

Example 88

Ethyl 8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-980)

Pale-yellow oil (yield: 85%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), of 6.96-6.87 in (3H, m), 6,63 (1H, s)to 4.41 (1H, DD, J=6 Hz, 2 Hz), 4,27-4,19 (2H, m), 4,14-3,91 (4H, m), was 2.76-2,62 (2H, m), 2,52 is 2.46 (1H, m), is 2.37 (1H, dt, J=14 Hz, 3 Hz), 2,18-2,09 (1H, m)of 1.84 (1H, dt, J=13 Hz, 4 Hz), 1,62-of 1.55 (2H, m), 1,40-1,24 (11H, m)to 0.88 (3H, t, J=7 Hz).

Example 89

Ethyl 8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-1,4-d is oxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1902)

Pale-yellow oil (yield: 72%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), of 6.96-6.87 in (3H, m), 6,62 (1H, s), and 4.40 (1H, DD, J=6 Hz, 2 Hz), 4,27-4,19 (2H, m), 4,15-are 3.90 (4H, m), 2,74-2,62 (2H, m), 2,52 is 2.46 (1H, m), is 2.37 (1H, dt, J=14 Hz, 3 Hz), 2,18-2,10 (1H, m), 1,86-of 1.81 (1H, m), 1,63-of 1.53 (2H, m), 1,40-1,24 (13H, m)to 0.88 (3H, t, J=7 Hz).

Example 90

Ethyl 8-[N-(4-fluoro-2-nonylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2602)

A pale orange oil (yield: 82%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), 6,94 (1H, DD, J=9 Hz, 3 Hz), 6,92-6,85 (2H, m), 6,62 (1H, s), and 4.40 (1H, DD, J=6 Hz, 2 Hz), 4,28-4,17 (2H, m), 4,15-a 4.03 (3H, m), 3.95 to 3,90 (1H, m), 2,75-2,62 (2H, m), 2,52-2,45 (1H, m), is 2.37 (1H, TD, J=14 Hz, 3 Hz), 2,18-of 2.09 (1H, m), 1,86-of 1.81 (1H, m), 1,63-of 1.53 (2H, m), 1,39-1,22 (15H, m)to 0.88 (3H, t, J=7 Hz).

Example 91

Ethyl 8-[N-(2-decyl-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2616)

Pale-yellow oil (yield: 83%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), 6,94 (1H, DD, J=9 Hz, 3 Hz), 6,92-6,85 (2H, m), 6,62 (1H, s), and 4.40 (1H, DD, J=5 Hz, 3 Hz), 4,28-4,17 (2H, m), 4,15-a 4.03 (3H, m), 3.95 to 3,90 (1H, m), 2,75-2,62 (2H, m), of 2.51 at 2.45 (1H, m), is 2.37 (1H, TD, J=14 Hz, 3 Hz), 2,18-of 2.09 (1H, m), 1,86-of 1.81 (1H, m), 1,63-of 1.53 (2H, m), 1,39-1,22 (17H, m)to 0.88 (3H, t, J=7 Hz).

Example 92

Ethyl 8-[N-(4-chloro-2-forfinal)sulfamoyl]-1,4-di is suspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2399)

White powder (yield: 65%).

Melting point: 130-133°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

a 7.62-7,56 (1H, m), 7.18 in-7,11 (2H, m), 7,02 (1H, s), at 6.84 (1H, t, J=1 Hz), 4,37 (1H, DD, J=6 Hz, 2 Hz), 4,25-was 4.02 (5H, m), 3.96 points-to 3.89 (1H, m), 2,55-2,48 (1H, m), 2,42 (1H, TD, J=14 Hz, 4 Hz), 2.21 are 2,11 (1H, m), 1,88-to 1.82 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 93

Ethyl 8-[N-(2-bromo-4-chlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2406)

Pale brown powder (yield: 51%).

Melting point: 100-110°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.64 (1H, d, J=9 Hz), 7,56 (1H, d, J=3 Hz), 7,31 (1H, DD, J=9 Hz, 3 Hz), 7,02 (1H, s), 6,83 (1H, t, J=1 Hz), 4,47-4,43 (1H, m), 4,23-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2,58-2,48 (2H, m), 2,24 with 2.14 (1H, m), 1,89-to 1.82 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 94

Ethyl 8-[N-(4-chloro-2-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2413)

White powder (yield: 74%).

Melting point: 123-126°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, d, J=9 Hz), 4,21-to 4.15 (2H, m)6,86 (1H, t, J=1 Hz), of 6.65 (1H, s), to 4.38 (1H, DD, J=6 Hz, 3 Hz), 4,24-to 4.15 (2H, m), 4,14-was 4.02 (3H, m), 3.96 points-to 3.89 (1H, m), 2,54-2,47 (1H, m), 2,41 of-2.32 (4H, m), 2,19-of 2.09 (1H, m), 1,88-to 1.82 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 95

Ethyl 8-[N-(4-chloro-2-ethoxycarbonylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (see example is soedineniya No. 1-2420)

White powder (yield: 46%).

Melting point: 131-134°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

10,48 (1H, s), of 8.00 (1H, d, J=3 Hz), 7,79 (1H, d, J=9 Hz), to 7.50 (1H, DD, J=9 Hz, 3 Hz), to 6.80 (1H, t, J=1 Hz), 4,47 (1H, DD, J=6 Hz, 2 Hz), 4,14-4,01 (5H, m), 3.95 to 3,88 (4H, m), 2,66-of 2.50 (2H, m), 2,22-2,11 (1H, m), 1,88-of 1.81 (1H, m), 1,25 (3H, t, J=7 Hz).

Example 96

Ethyl 8-[N-(3,4-dichlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2427)

White powder (yield: 66%).

Melting point: 163-164°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, d, J=2 Hz), 7,41 (1H, d, J=9 Hz), 7.23 percent (1H, DD, J=9 Hz, 3 Hz), 7,16 (1H, s), to 6.88 (1H, t, J=1 Hz), 4,27 (2H, square, J=7 Hz), is 4.21 (1H, square, J=3 Hz), 4,14-was 4.02 (3H, m), 3.96 points-3,88 (1H, m), 2,50 is 2.43 (1H, m), and 2.27 (1H, TD, J=14 Hz, 3 Hz), 2,13-2,03 (1H, m), 1,89-to 1.82 (1H, m)of 1.33 (3H, t, J=7 Hz).

Example 97

Ethyl 8-[N-(2,5-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2434)

Pale brown powder (yield: 61%).

Melting point: 125-128°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,45-7,41 (1H, m), 7,09-7,00 (2H, m)6,86 (1H, s), 6,80-6,74 (1H, m)to 4.41 (1H, DD, J=6 Hz, 2 Hz), 4.26 deaths-was 4.02 (5H, m), 3.95 to 3,90 (1H, m), 2,58-2,52 (1H, m)2,44 (1H, TD, J=14 Hz, 3 Hz), 2,23 with 2.14 (1H, m), 1,89-of 1.84 (1H, m)of 1.28 (3H, t, J=7 Hz).

Example 98

Ethyl 8-[N-(2,6-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (Pref the Albanian example compound No. 1-2441)

White powder (yield: 56%).

Melting point: 129-131°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,25-to 7.18 (1H, m), 7,01-to 6.95 (2H, m), 6.89 in-6,87 (2H, m), with 4.64 (1H, DD, J=5 Hz, 2 Hz), or 4.31-is 4.21 (2H, m), 4,15-a 4.03 (3H, m), 3.96 points-3,91 (1H, m), 2,63-to 2.57 (1H, m), a 2.36 (1H, TD, J=14 Hz, 3 Hz), 2.26 and-2,17 (1H, m,), 1,87-to 1.82 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 99

Ethyl 8-[N-(2-fluoro-4-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2448)

White powder (yield: 69%).

Melting point: 136-138°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,49 (1H, t, J=9 Hz), 6,95-6,92 (2H, m)6,86 (1H, d, J=2 Hz), 6,83 (1H, s), 4,40-4,37 (1H, m), 4.26 deaths-to 4.15 (2H, m), 4,13-4,01 (3H, m), 3,94-to 3.89 (1H, m), of 2.51-2.40 a (2H, m), 2,32 (3H, s), 2,18-of 2.09 (1H, m), 1,86-of 1.81 (1H, m)of 1.27 (3H, t, J=7 Hz).

Example 100

Ethyl 8-[N-(2-fluoro-5-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2455)

Oil (yield: 63%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

the 7.43 (1H, DD, J=8 Hz, 2 Hz), 6,98 (1H, DD, J=10 Hz, 8 Hz), 6,91-6,87 (2H, m), 6,83 (1H, t, J=1 Hz), 4,42 (1H, DD, J=6 Hz, 2 Hz), 4.26 deaths-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2,54-to 2.42 (2H, m), 2,20-2,12 (1H, m,), 1,87-to 1.82 (1H, m)of 1.27 (3H, t, J=7 Hz).

Example 101

Ethyl 8-[N-(2-fluoro-4-methoxyphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2462)

Pale to enevy powder (yield: 57%).

Melting point: 167-169°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.50 (1H, t, J=9 Hz), PC 6.82 (1H, t, J=1 Hz), 6,79 (1H, users), of 6.71 is 6.67 (2H, m), of 4.38 is 4.35 (1H, m), 4,28-4,19 (2H, m), 4,14-4,01 (3H, m), 3.95 to 3,88 (1H, m), with 3.79 (3H, s), 2,49-of 2.36 (2H, m), 2,18-of 2.08 (1H, m), 1,86-to 1.79 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 102

Ethyl 8-[N-(5-chloro-2-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2469)

White powder (yield: 55%).

Melting point: 88-90°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,68-the 7.65 (1H, m), 7,07-7,01 (3H, m)6,86 (1H, s), and 4.40 (1H, DD, J=6 Hz, 2 Hz), 4,27-to 4.15 (2H, m), 4,14-a 4.03 (3H, m), 3.96 points-are 3.90 (1H, m), 2,58-2,52 (1H, m), 2,43 (1H, TD, J=14 Hz, 3 Hz), 2,23-to 2.15 (1H, m), 1,89-of 1.84 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 103

Ethyl 8-[N-(2,3,4-tryptophanyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2476)

White powder (yield: 71%).

Melting point: 149-152°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,41-7,34 (1H, m), 7,14 (1H, users), 7,02-6,93 (1H, m), 6,85 (1H, t, J=1 Hz), 4,36 (1H, DD, J=6 Hz, 2 Hz), 4,28-4,20 (2H, m), 4,14-was 4.02 (3H, m), 3.96 points-are 3.90 (1H, m), 2,55 is 2.46 (1H, m), of 2.38 (1H, TD, J=14 Hz, 4 Hz), 2,22-2,12 (1H, m), 1,89-to 1.82 (1H, m)is 1.31 (3H, t, J=7 Hz).

Example 104

Ethyl 8-[N-(2,4,5-tryptophanyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2483)

White powder (yield: 72%.

Melting point: 104-107°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,60-7,52 (1H, m), 7,05-6,97 (2H, m)6,86 (1H, t, J=1 Hz), 4,35 (1H, DD, J=6 Hz, 2 Hz), 4,28-4,19 (2H, m), 4,15-was 4.02 (3H, m), 3.96 points-are 3.90 (1H, m), 2,56-2,49 (1H, m), of 2.38 (1H, TD, J=14 Hz, 4 Hz), 2,23-2,12 (1H, m), 1,90 of-1.83 (1H, m)of 1.30 (3H, t, J=7 Hz).

Example 105

Ethyl 8-[N-(2,4,6-tryptophanyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2490)

White powder (yield: 61%).

Melting point: 131-133°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,91 (1H, s), to 6.88 (1H, t, J=1 Hz), 6,80-6,72 (2H, m), 4,55 (1H, DD, J=6 Hz, 3 Hz), or 4.31-to 4.23 (2H, m), 4,14-a 4.03 (3H, m), 3.96 points-are 3.90 (1H, m), 2,62 is 2.55 (1H, m), 2,32 (1H, TD, J=14 Hz, 3 Hz), 2,25-to 2.15 (1H, m), 1,88-of 1.81 (1H, m)is 1.31 (3H, t, J=7 Hz).

Example 106

Ethyl 8-[N-(2,4-dichlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2497)

Pale brown powder (yield: 67%).

Melting point: 109-111°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, d, J=9 Hz), 7,41 (1H, d, J=2 Hz), 7,28-7,24 (1H, m), 7,07 (1H, s), 6,83 (1H, s), 4,46 was 4.42 (1H, m), 4,24-was 4.02 (5H, m), 3,98-to 3.89 (1H, m), 2,56 is 2.46 (2H, m), 2,24 and 2.13 (1H, m), 1,89-to 1.82 (1H, m), of 1.26 (3H, t, J=7 Hz).

Example 107

Ethyl 8-[N-(4-bromo-2-chlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2504)

White powder (yield: 74%).

Point PL is the exercise: 102-107°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

to 7.59 (1H, d, J=9 Hz), 7,55 (1H, d, J=2 Hz), 7,40 (1H, DD, J=9 Hz, 2 Hz), was 7.08 (1H, s), 6,83 (1H, s), of 4.44 (1H, d, J=5 Hz), 4,23-was 4.02 (5H, m), 3.95 to the 3.89 (1H, m), 2,55-2,47 (2H, m), 2,23 with 2.14 (1H, m), 1,89 of-1.83 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 108

Ethyl 8-[N-(2-chloro-4-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-452)

Pale brown powder (yield: 69%).

Melting point: 130-135°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

EUR 7.57 (1H, d, J=9 Hz), 7,20 (1H, d, J=2 Hz), 7,10-7,06 (1H, m), 6,97 (1H, s), for 6.81 (1H, d, J=1 Hz), of 4.44 (1H, d, J=5 Hz), 4,25-4,00 (5H, m), 3.95 to a 3.87 (1H, m), 2,59 at 2.45 (2H, m), 2,31 (3H, s), 2,22-2,10 (1H, m), 1,87-to 1.79 (1H, m), 1,25 (3H, t, J=7 Hz).

Example 109

Ethyl 8-[N-(4-tert-butyl-2-chlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2511)

Amorphous substance (yield: 49%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.61 (1H, d, J=9 Hz), 7,38 (1H, d, J=2 Hz), 7,29 (1H, DD, J=9 Hz, 2 Hz), 7,00 (1H, s), PC 6.82 (1H, s), 4,46 (1H, d, J=4 Hz), 4,23-4,01 (5H, m), 3.95 to 3,88 (1H, m), 2,59-2,47 (2H, m), 2.23 to-2,12 (1H, m), 1,87 and 1.80 (1H, m)of 1.29 (9H, s), 1,25-to 1.21 (3H, m).

Example 110

Ethyl 8-[N-(2-chloro-6-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2518)

Amorphous substance (yield: 62%).

1H-NMR spectrum (400 MHz, CDCl3) δ is d:

7,27-7,24 (1H, m), 7,21-to 7.15 (1H, m), 7,12-7,06 (1H, m), 6,98 (1H, s)6,86 (1H, s), 4,77-4,74 (1H, m), 4,30-is 4.21 (2H, m), 4,15-a 4.03 (3H, m), 3.96 points-are 3.90 (1H, m), 2,67-2,60 (1H, m), of 2.38 (1H, TD, J=14 Hz, 3 Hz), 2,28-2,17 (1H, m), 1,88-of 1.81 (1H, m)of 1.29 (3H, t, J=7 Hz).

Example 111

Ethyl 8-[N-(2,6-dichlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2525)

Amorphous substance (yield: 24%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,39 (1H, s), 7,38 (1H, s), 7,27 (1H, s), 7,17 (1H, t, J=8 Hz), 6.87 in (1H, s), 4,88 (1H, DD, J=5 Hz, 3 Hz), the 4.29 (2H, square, J=7 Hz), 4,15-a 4.03 (3H, m), 3.96 points-3,91 (1H, m), 2,68-2,62 (1H, m), 2,31 (1H, TD, J=14 Hz, 3 Hz), 2.26 and-to 2.18 (1H, m), 1,88-to 1.82 (1H, m)is 1.31 (3H, t, J=7 Hz).

Example 112

Ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1462)

Amorphous substance (yield: 55%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,29-of 7.23 (1H, m), 7,20-to 7.09 (3H, m), at 6.84 (1H, t, J=1 Hz), 4.80 to of 4.77 (1H, m), 4,30-4,20 (2H, m), 4,13-4,00 (3H, m), 3.95 to the 3.89 (1H, m), 2,58 is 2.46 (4H, m), 2,33 (1H, TD, J=14 Hz, 3 Hz), 2,25-and 2.14 (1H, m), 1.85 to-of 1.78 (1H, m)of 1.28 (3H, t, J=7 Hz).

Example 113

Ethyl 8-[N-(2,3-dichlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2532)

Amorphous substance (yield: 70%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66-to 7.61 (1H, m), 7,26-7,19 (3H, m), 6,83 (1H, s), 4,46 (1H, d, J=5 Hz), 4,22-4,01 (5H, m), 3.95 to the 3.89(1H, m), 2.57 m-2,48 (2H, m), 2,25-and 2.14 (1H, m), 1,89-to 1.82 (1H, m), 1,25 (3H, t, J=7 Hz).

Example 114

Ethyl 8-[N-(2,5-dichlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2539)

White powder (yield: 78%).

Melting point: 120-124°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,72 (1H, d, J=2 Hz), 7,31 (1H, d, J=9 Hz), 7,11 (1H, s), 7,05 (1H, DD, J=9 Hz, 2 Hz), 6,86 (1H, s), 4,46 (1H, DD, J=6 Hz, 2 Hz), 4,25-a 4.03 (5H, m), 3.95 to 3,90 (1H, m), 2,58-2,48 (2H, m), 2.26 and-2,17 (1H, m), 1,90-of 1.84 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 115

Ethyl 8-[N-(2-chloro-4,6-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2546)

Oil (yield: 29%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,07-7,03 (1H, m), of 6.99 (1H, s), 6,91-6,83 (2H, m), of 4.67 (1H, DD, J=5 Hz, 3 Hz), or 4.31-to 4.23 (2H, m), 4,14-a 4.03 (3H, m), 3,97-are 3.90 (1H, m), 2,65-to 2.57 (1H, m), 2,34 (1H, TD, J=14 Hz, 3 Hz), 2,27-2,17 (1H, m), 1,88-of 1.81 (1H, m)is 1.31 (3H, t, J=7 Hz).

Example 116

Ethyl 8-[N-(2,6-dichloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2553)

Amorphous substance (yield: 39%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,22 (1H, s), 7,17 (2H, d, J=7 Hz), to 6.88 (1H, t, J=1 Hz), 4,84-to 4.81 (1H, m), the 4.29 (2H, square, J=7 Hz), 4,14-a 4.03 (3H, m), 3,97-are 3.90 (1H, m), 2,67-2,60 (1H, m), 2,34-2,17 (2H, m), 1,88-of 1.81 (1H, m)of 1.33 (3H, t, J=7 Hz).

Example 117

Ethyl 8-[N-(2-b is ω-6-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2560)

Amorphous substance (yield: 46%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.35 (1H, DD, J=7.5 Hz, 2.8 Hz), 7.24 to 7,21 (2H, m), 7,24 (1H, s), the 4.90 (1H, d, J=5,1 Hz), 4,30 (2H, square, J=7,2 Hz), 4,14-to 3.92 (4H, m), 2,67-2,62 (1H, m), 2,33-to 2.18 (2H, m), 1,88-of 1.84 (1H, m)of 1.33 (3H, t, J=6,6 Hz).

Example 118

Ethyl 8-[N-(4-chloro-2-methoxy-5-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2567)

White powder (yield: 54%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.43 (1H, s), of 6.96 (1H, s), 6.87 in (1H, s), 6,78 (1H, t, J=1 Hz)to 4.41 (1H, DD, J=6 Hz, 2 Hz), 4,20-4,00 (5H, m), 3,94-3,88 (1H, m), 3,85 (3H, s), 2,58 is 2.43 (2H, m), 2,31 (3H, s), 2,20-of 2.08 (1H, m), 1.85 to of 1.78 (1H, m), 1,25 (3H, t, J=7 Hz).

Example 119

Ethyl 8-[N-(2,4-dibromophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2574)

Oil (yield: 56%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

of 7.70 (1H, d, J=2 Hz), to 7.59 (1H, d, J=9 Hz), 7,44 (1H, DD, J=9 Hz, 2 Hz), 7,02 (1H, s), 6,83 (1H, s), 4,47-of 4.44 (1H, m), 4,23-was 4.02 (5H, m), 3.95 to 3,90 (1H, m), 2.57 m-2,49 (2H, m), 2,23-to 2.15 (1H, m), 1,88-to 1.83 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 120

Ethyl 8-[N-(2,6-dibromophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2581)

Amorphous substance (yield: 41%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

to 7.61 (2H, d, J=8 Hz) 7,26 (1H, users), 7,02 (1H, t, J=8 Hz), to 6.88 (1H, s), 5,02-5,00 (1H, m), the 4.29 (2H, square, J=7 Hz), 4,15-3,91 (4H, m), 2,70-of 2.64 (1H, m), 2,33-2,19 (2H, m), 1,87 of-1.83 (1H, m)of 1.32 (3H, t, J=7 Hz).

Example 121

Ethyl 8-[N-(2-bromo-4-isopropylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2588)

White powder (yield: 51%).

Melting point: 130-134°C.

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

of 7.60 (1H, d, J=8 Hz), 7,40 (1H, d, J=2 Hz), 7,18 (1H, DD, J=8 Hz, 2 Hz), 6,94 (1H, s), PC 6.82 (1H, s), 4,48-to 4.46 (1H, m), 4,24-4,01 (5H, m), 3,94-3,88 (1H, m), 2,89-and 2.83 (1H, m), 2,60-2,47 (2H, m), 2,22-to 2.13 (1H, m), 1,86-of 1.81 (1H, m), 1,25-to 1.21 (9H, m).

Example 122

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak) (high-polar compound, second peak) (example compound No. 1-364)

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 1 was subjected to high performance liquid chromatography (HPLC) (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers and respectively have been received and iskopaemoe connection (first peak), and high-polar compound (second peak) in the form of a white powder. According to the results of HPLC analysis of two optical out is', obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 1:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak): 6.1 minutes
high-polar compound (second peak): 10.5 minutes
iskopaemoe connection (first peak)
melting point:116-117°C

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9,2 Hz, 5.3 Hz), 7,17 (1H, DD, J=7,8 Hz, 2.7 Hz), 7,05-7,00 (2H, m), 6,83 (1H, s), 4,43 (1H, d, J=5.4 Hz), 4.26 deaths-are 3.90 (6H, m), 2,55-2,47 (2H, m), 4,15-2,47 (1H, m), was 4.02 and 2.13 (1H, m)of 1.27 (3H, t, J=7,0 Hz).

High-polar compound(second peak)
Melting point:116-117°C

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9,0 Hz, 5.5 Hz), 7,17 (1H, DD, J=8.0 Hz, 2.9 Hz), 7,06-7,00 (2H, m), at 6.84 (1H, s), 4,43 (1H, d, J=5.4 Hz), 4.26 deaths-are 3.90 (6H, m), 2,55-2,47 (2H, m), 1,13-of 2.23 (1H, m), 1,87 of-1.83 (1H, m)of 1.27 (3H, t, J=6,6 Hz).

Example 123

Ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate

(123a) Ethyl 7-tripterocalyx-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate

In accordance with the process described in example (30e), ethyl 7-oxo-1,4-dioxaspiro[4.5]decane-8-carboxylate [compound described as the connection s in the patent Application U.S. No. US 2004/259914 A1] was used instead of ethyl 8-oxo-1-oxaspiro[4.5]decane-7-carboxylate, to obtain the specified title compound as a white powder (yield: 96%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 4.28 (2H, square, J=7 Hz), 4.04 the-of 3.96 (4H, m), 2,65-2,61 (4H, m), 1,82-of 1.78 (2H, m)of 1.32 (3H, t, J=7 Hz).

(123b) Ethyl 7-acetylmethadol-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate

In accordance with the process described in example (1A), ethyl 7-tripterocalyx-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate obtained in (123A)was used instead of ethyl 8-tripterocalyx-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate to obtain specified in the connection header in the form bled the brown oil (yield: 83%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

is 4.21 (2H, square, 7 Hz), 4.04 the-of 3.96 (4H, m), 2,72-to 2.65 (4H, m), 2,32 (3H, s), of 1.85 (2H, t, J=7 Hz), of 1.29 (3H, t, J=7 Hz).

(S) Ethyl 7-mercapto-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate

In accordance with the process described in example (1b), ethyl 7-acetylmethadol-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate obtained in (123b)was used instead of ethyl 8-acetylmethadol-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate, to obtain the specified title compound as a pale brown powder (yield: 85%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,22 (2H, square, 7 Hz), 4,20 (1H, s), as 4.02-of 3.95 (4H, m), 2,69-of 2.66 (2H, m), 2,61-of 2.56 (2H, m), 1,82-of 1.78 (2H, m)of 1.30 (3H, t, J=7 Hz).

(123d) Ethyl 7-chlorosulfonyl-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate

In accordance with the process described in example (1C), ethyl 7-mercapto-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate obtained in (C)was used instead of ethyl 8-mercapto-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate, to obtain the specified title compound as a colourless oil (yield: 62%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

or 4.31 (2H, square, 7 Hz), 4.09 to 4,00 (4H, m), 2,82-by 2.73 (4H, m)to 1.86 (2H, t, J=7 Hz), of 1.35 (3H, t, J=7 Hz).

(E) Ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate

In accordance with the process described in example (1d), ethyl 7-chlorosulfonyl-1,4-dioxaspiro[4.5]Dec-7-ene-8-carboxylate, receiving the tion in (123d), used instead of ethyl 8-chlorosulfonyl-1,4-dioxaspiro[4.5]Dec-7-ene-7-carboxylate, to obtain the specified title compound as a white powder (yield: 61%).

Melting point: 120-122°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,81 (1H, s), 7,66 (1H, DD, J=9 Hz, 5 Hz), 7,14-7,10 (2H, m), 6,98-6,92 (1H, m), 4,71-of 4.67 (1H, m), 4,22-of 3.96 (6H, m), 2,75-of 2.56 (3H, m), 2,08-2,02 (1H, m)of 1.24 (3H, t, J=7 Hz).

Example 124

Ethyl 2-bromacil-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), 1-bromo-2,3-bis[(trimethylsilyl)oxy]propane was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compound as a white amorphous substance (yield: 100%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9,2 and 5.3 Hz), 7,17 (1H, DD, J=7,8 and 2.8 Hz), 7,05-6,99 (2H, m), 6,86-6,77 (1H, m), 4.53-in-a-3.84 (6H, m), 3,53-and 3.31 (2H, m), 2,66-to 2.41 (2H, m), 2,24-2,12 (1H, m), 1,89 is 1.86 (1H, m), 1,28-1,24 (3H, m).

Example 125

Ethyl (2S)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-methoxycarbonylmethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), methyl-(S)-3,4-bis[(trimethylsilyl)oxy]butyrate obtained in reference example 20 was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-t is aitola, obtaining specified in the title compounds as colorless oil (yield: 96%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9,0 Hz, 5.4 Hz), 7,16 (1H, DD, J=7.9 Hz, 2.8 Hz), 7,05-6,98 (2H, m), 6,88-6,76 (1H, m), 4.63 to-4,58 (1H, m), 4,47-to 4.41 (1H, m), 4,32-4,10 (3H, m), 3,84-3,59 (4H, m), 2,85-2,39 (4H, m), 2.21 are of 2.16 (1H, m,), 1,89 and 1.80 (1H, m), 1,29-1,24 (3H, m).

Example 126

Ethyl 3-[N-(2-chloro-4-forfinal)sulfamoyl]-7,12-dioxaspiro[5.6]dodec-1-EN-2-carboxylate (example compound No. 1-366)

34 mg (0.61 mmol) of 1,4-butanediol was dissolved in 5 ml dichloromethane and successively added of 0.32 ml (1,83 mmol) of isopropoxytitanium, 200 mg (0.47 mmol) of ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), and 4 μl (0,024 mmol) trimethylsilyltrifluoromethane, under stirring with ice cooling, followed by stirring at the same temperature for 2 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 3:1) and the resulting substance was washed with hexane, to receive the of 6 mg specified in the title compound as a white powder (yield: 3%).

Melting point: 142-144°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9 Hz, 5 Hz), 7,16 (1H, DD, J=8 Hz, 3 Hz),? 7.04 baby mortality (1H, s), 7.03 is-6,98 (2H, m), of 4.44-and 4.40 (1H, m), 4,27-4,11 (2H, m), 3,91-3,62 (4H, m), 2,46-of 2.38 (1H, m), 2,31-of 2.21 (1H, m), 2,17-of 1.94 (2H, m), 1,71 is 1.58 (4H, m)of 1.27 (3H, t, J=7 Hz).

Example 127

Ethyl 4-[N-(2-chloro-4-forfinal)sulfamoyl]-3A',4',6',6A'-tetrahydrofuro[cyclohex-2-ene-1,2'-furo[3,4-d][1.3]dioxol]-3-carboxylate (example compound No. 1-402)

In accordance with the process described in example 21, 1,4-anhydrous-2,3-di-About- (trimethylsilyl)-meso-erythritol obtained in reference example 21 was used instead of 1,3,4,5,7-Penta-About-trimethylsilyl-D-arabitol, obtaining specified in the title compound as a white powder (yield: 56%).

Melting point: 227-228°C.

1H-NMR spectrum (400 MHz, CDCl3+CD3OD) δ ppm:

to 7.61 (1H, DD, J=9 Hz, 5 Hz), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,07-6,97 (1H, m)6,91 (1H, s), is 4.93 (1H, DD, J=6 Hz, 4 Hz), to 4.81 (1H, DD, J=6 Hz, 4 Hz), 4,39 (1H, d, J=5 Hz), 4.26 deaths-of 4.05 (3H, m), 4,01 (1H, d, J=11 Hz), 3,51-to 3.41 (2H, m), 2,54-of 2.34 (2H, m), 2,20-2,07 (1H, m), 1,90-to 1.79 (1H, m), 1,25 (3H, t, J=7 Hz).

Example 128

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,2,3,3-tetramethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), 2,3-dimethyl-2,3-bis[(trimethylsilyl)oxy]butane was used instead of 1,4-di-About-benzoyl-2,3-di-O -trimethylsilyl-D-threitol, obtaining specified in the title compounds as a pale yellow oil (yield: 10%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=8,8 Hz, 5.6 Hz), 7,16 (1H, DD, J=7,8 Hz, 2.7 Hz),? 7.04 baby mortality-7,03 (1H, m), 6.89 in (1H, s), 4,37 (1H, d, J=4.0 Hz), 4,25-4,10 (2H, m), of 2.51 is 2.43 (2H, m), 2,24 with 2.14 (1H, m), 1,94-1,89 (1H, m), 1,31-1,23 (15H, m).

Example 129

Ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,2,3-triethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), 3-ethyl-3,4-bis[(trimethylsilyl)oxy]hexane, obtained in reference example 22 was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compound as a white powder (yield: 88%).

Melting point: 124-126°C.

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-7,66 (1H, m), 7,17-to 7.15 (1H, m),? 7.04 baby mortality-7,00 (2H, m), 6,88-6,69 (1H, m), 4,40-4,39 (1H, m), 4,28-4,10 (2H, m), 3,90-3,68 (1H, m), 2,54-2,31 (2H, m), 2,25-2,12 (1H, m), 1.85 to 1,37 (7H, m), 1,29-1,24 (3H, m), 1,08 is 0.84 (9H, m).

Example 130

Ethyl (3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,2,3-triphenyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), (R)-1,2-bis[(trimethylsilyl)oxy]-1,1,2-triphenyltin obtained in reference example 23 was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, is obtaining specified in the title compounds as colorless oil (yield: 30%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,22-6,91 (20H, m), 5,99-USD 5.76 (1H, m), 4,54-4,32 (1H, m), 4,34-4,08 (2H, m), 2,87-of 1.97 (4H, m), 1,36-to 1.14 (3H, m).

Example 131

Ethyl (2R,3R)-8-[N-(2-chlorophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-206)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-chlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 54 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 31%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,71-to 7.67 (1H, m), 7,41-7,38 (1H, m), 7,32-7,26 (1H, m), 7,14-7,06 (2H, m), 6.90 to (0,5H, t, J=1 Hz), 6,84 (0,5H, t, J=1 Hz), 4,47 (1H, DD, J=6 Hz, 2 Hz), 4.26 deaths-4,07 (3,5H, m), 4,05-4,00 (0,5H, m), 3,94-of 3.80 (2H, m), of 3.77-to 3.67 (2H, m), 2,64-2,47 (2H, m), 2,27-to 1.87 (4H, m), 1,27-1,22 (3H, m).

Example 132

Ethyl (2R,3R)-8-[N-(2-bromophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1392)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-bromophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 5, used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 28%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,71-to 7.67 (1H, m), 7,56 (1H, d, J=8 Hz), 7,35-7,31 (1H, m), 7,07-6,98 (2H, m), 6.90 to (0,5H, C)6,84 (0,5H, s), 4,48 (1H, d, J=5 Hz), 4,25-4,08 (3,5H, m), 4,06-4,01 (0,5H, m), 3,94-of 3.80 (2H, m), 3,76-3,68 (2H, m), 2,65-2,48 (2H, m), 2,23-to 1.87 (4H, m), 1,27-1,22 (3H, m).

Example 133

Ethyl (2R,3R)-2,3-bis(hydroxymethyl)-8-[N-(2-itfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2226)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-itfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 56 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 26%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,80 (1H, d, J=8 Hz), 7.68 per-7,63 (1H, m), 7,38-7,33 (1H, m), 6.90 to-6,83 (3H, m), 4,50-to 4.46 (1H, m), 4,27-4.09 to (3,5H, m), 4,06-was 4.02 (0,5H, m), 3,94-of 3.80 (2H, m), of 3.77-3,68 (2H, m), 3,53 (1H, users), 2,66-of 2.56 (1H m), by 2.55-2.49 USD (1H, m), 2,24 with 2.14 (1H, m), 2.00 in of 1.85 (2H, m), 1,27-of 1.23 (3H, m).

Example 134

Ethyl (2R,3R)-8-[N-(2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro]Oct-6-ene-7-carboxylate (example compound No. 1-734)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 4 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a colourless oil (yield: 28%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,54 is 7.50 (1H, m), 7.23 percent-7,17 (2H, m), 7,15-to 7.09 (1H, m), 6,94-6,91 (0,5H, m), 6,88-6,85 (0,5H, m)6,70 (0,5H, s), 6,65 (0,5H, s), 4,48-4,43 (1H, m), 4,28-4,08 (3,5H, m), 4,06-4,00 (0,5H, m), 3,93-of 3.80 (2H, m), 3,76-3,68 (2H, m), 2,70-2,61 (2H, m), 2,55-to 2.41 (2H, m), 2.21 are 2,07 (1H, m), 1,96 is 1.75 (3H, m), 1,64-of 1.52 (2H, m), 1,42 is 1.23 (9H, m), 0,91-of 0.85 (3H, m).

Example 135

Ethyl (2R,3R)-8-[N-(2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-910)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 5 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a colourless oil (yield: 33%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,54-7,50 (1, m), 7.23 percent-to 7.18 (2H, m), 7,14-to 7.09 (1H, m), 6,94-6,91 (0,5H, m), 6,88-6,85 (0,5H, m)6,70 (0,5H, s), 6,65 (0,5H, s), 4,47-4,43 (1H, m), 4,28-4,08 (3,5H, m), 4,06-4,00 (0,5H, m), 3,93-of 3.80 (2H, m), 3,76-3,68 (2H, m), 2,70-2,61 (2H, m), 2,54-to 2.41 (2H, m), 2,20-of 2.08 (1H, m), 1,96-of 1.74 (3H, m), 1,64-of 1.53 (2H, m), 1.41 to 1,22 (11H, m)to 0.88 (3H, t, J=7 Hz).

Example 136

Ethyl (2R,3R)-8-[N-(2-chloro-4-were)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-470)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-chloro-4-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 108 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 50%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,56 (1H, DD, J=8 Hz, 2 Hz), 7.23 percent-7,21 (1H, m), 7,11-7,07 (1H, m), 7,01 (1H, users), 6,90 (0,5H, t, J=1 Hz), 6,84-6,82 (0,5H, m), of 4.44 (1H, DD, J=6 Hz, 2 Hz), 4,27-4,08 (3,5H, m), 4,05-4,00 (0,5H, m), 3,93-of 3.80 (2H, m), of 3.77-3,68 (2H, m), 2,63 is 2.44 (2H, m), 2,31 (3H, s), 2,22-of 1.62 (4H, m), 1,29 is 1.23 (3H, m).

Example 137

Ethyl (2R,3R)-8-[N-(2,4-dichlorophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2499)

In accordance with the process described in examples 7, (16A) and 17 (al is ernationa procedure), ethyl 8-[N-(2,4-dichlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 106 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 22%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.64 (1H, DD, J=9 Hz, 2 Hz), 7,41 (1H, d, J=2 Hz), 7,28-of 7.25 (1H, m), 7,07 (1H, users), 6,91 (0,5H, t, J=1 Hz), 6,85 (0,5H, t, J=1 Hz), 4,43 (1H, DD, J=6 Hz, 2 Hz), 4.26 deaths-4.09 to (3,5H, m), 4,07-was 4.02 (0,5H, m), 3,94-3,81 (2H, m), of 3.77-3,68 (2H, m), 2,60-2,47 (2H, m), 2,24-of 1.85 (4H, m), 1,29-1,24 (3H, m).

Example 138

Ethyl (2R,3R)-8-[N-(2-bromo-4-chlorophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2408)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-bromo-4-chlorophenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 93 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 10%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

to 7.64 (1H, DD, J=9 Hz, 3 Hz), EUR 7.57 (1H, d, J=2 Hz), 7,31 (1H, DD, J=9 Hz, 2 Hz), 7,01 (1H, users), 6,91 (0,5H, s), 6,85 (0,5H, C)of 4.45 (1H, d, J=4 Hz), 4.26 deaths-4,10 (3,5H, m), 4,06-was 4.02 (0,5H, m), 3,94-3,82 (2H, m), of 3.77-3,69 (2, m), 2,61-2,48 (2H, m), 2,24-to 2.15 (1H, m), 2,02-of 1.85 (3H, m), 1,29-1,24 (3H, m).

Example 139

Ethyl (2R,3R)-8-[N-(2-chloro-6-were)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1480)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 112 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 45%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,28 (1H, DD, J=8 Hz, 1 Hz), 7.23 percent-7,07 (3H, m), 6,93-6,91 (0,5H, m), 6,86-6,85 (0,5H, m), 4,80 was 4.76 (1H, m), 4,30-4,17 (3H, m), 4,11-4,07 (0,5H, m), Android 4.04-4.00 points (0,5H, m), 3,92-3,81 (2H, m), 3.75 to at 3.69 (2H,, m), 2,59-2,48 (3H, m), 2,42 is 2.33 (1H, m), 2.26 and-to 2.15 (1H, m)2,07 (1H, users), 1,94-of 1.85 (1H, m), and 1.63 (1H, users), 1,29-1,24 (3H, m).

Example 140

Ethyl (2R,3R)-8-[N-(3-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2366)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(3-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 80, using the Ali instead of ethyl 8-[ N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 47%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,47 (1H, DD, J=6 Hz, 3 Hz), 7,29-of 7.25 (1H, m), 7,17-7,06 (2H, m), 6,97 (0,5H, t, J=1 Hz), 6,93-6,92 (0,5H, m), 4,33-4.09 to (4,5H, m), 4,06-was 4.02 (0,5H, m), 3,94-3,82 (2H, m), of 3.77-3,68 (2H, m), 2,48-is 2.40 (1H, m), 2,34-of 2.24 (1H, m), 2,12 is 2.01 (2H, m), 1,97-1,89 (2H, m)of 1.35 (3H, t, J=7 Hz).

Example 141

Ethyl (2R,3R)-8-[N-(2-chloro-4,6-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2548)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-chloro-4,6-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 115 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 35%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,07-6,85 (4H, m), of 4.67 (1H, DD, J=10 Hz, 6 Hz), 4,32-4,19 (3H, m), 4,14-was 4.02 (1H, m), 3,93-3,82 (2H, m), 3,76-3,70 (2H, m), 2,66 is 2.55 (1H, m), 2,43-of 2.34 (1H, m), 2,28-2,17 (1H, m), 2.06 to a 1.88 (3H, m), 1,33-1,29 (3H, m).

Example 142

Ethyl (2R,3R)-8-[N-(2,6-dichloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (Pref the Albanian example compound No. 1-2555)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2,6-dichloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 116 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 25%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,26-7,05 (3H, m), 6,97-6,95 (0,5H, m), 6.90 to-6,89 (0,5H, m), 4,85-4,80 (1H, m), 4,33-4,19 (3H, m), 4,13-4,08 (0,5H, m), 4,06-was 4.02 (0,5H, m), 3,93-3,82 (2H, m), 3,76-3,70 (2H, m), 2,72-of 2.56 (1H, m), 2,39-of 2.20 (2H, m), 2.05 is-to 1.59 (3H, m), 1,35-of 1.30 (3H, m).

Example 143

Ethyl (2R,3R)-8-[N-(2-bromo-6-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2562)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-bromo-6-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 117 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 29%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

of 7.36-7,31 (1H, m), 7.23 percent-7,19 (1H, m), 7,16 (1H, users), 6,95(0,5H, s), 6.90 to-6,88 (0,5H, m), 4,91-is 4.85 (1H, m), 4,33-4,17 (3H, m), 4,15-4,00 (1H, m), 3,94-of 3.80 (2H, m), 3,76-3,70 (2H, m), 3,55 (1H, users), 2,70-to 2.57 (1H, m), 2,38-of 2.16 (2H, m), 1,96-to 1.87 (2H, m), 1,35-of 1.30 (3H, m).

Example 144

Ethyl (2R,3R)-8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-294)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2,4-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 77 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 35%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,63-7,56 (1H, m), 7,07 (1H, users), 6,94-6,85 (3H, m), of 4.38-4,34 (1H, m), 4,30-4,08 (3,5H, m), 4,06-4,00 (0,5H, m), 3,93-3,81 (2H, m), 3,78-3,68 (2H, m), 2,53-to 2.40 (2H, m), 2,38-to 1.87 (4H, m), 1,31-of 1.27 (3H, m).

Example 145

Ethyl (2S,3S)-8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-294)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(2,4-differenl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 77 was used instead of E. the Il 8-[ N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 58%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

a 7.62 EUR 7.57 (1H, m), 6,93-6,86 (3H, m), 4,37-4,34 (1H, m), 4,29-4,18 (3H, m), 4,13-4.09 to (0,5H, m), 4,06-4,01 (0,5H, m), 3,94-3,82 (2H, m), 3,76 at 3.69 (2H, m), 2,53-2,39 (2H, m), 2.21 are a 1.50 (4H, m), 1,32-of 1.27 (3H, m).

Example 146

Ethyl (2R,3R)-8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1568)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 78 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 33%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,69-to 7.64 (1H, m), 7,33 (1H, DD, J=7 Hz, 3 Hz), 7,10-7,05 (1H, m), 6,93 (1H, users), 6,93 (0,5H, C)6,84 (0,5H, C)of 4.44 (1H, d, J=4 Hz), 4,27-4.09 to (3,5H, m), 4,06-4,01 (0,5H, m), 3,94-of 3.80 (2H, m), of 3.77-3,68 (2H, m), of 3.54 (1H, users), 2,61 is 2.46 (2H, m), 2,23 with 2.14 (1H, m), 2,02-of 1.85 (2H, m), 1,29-1,24 (3H, m).

Example 147

Ethyl (2S,3S)-8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (at the Eden connection example No. 1-1568)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 78 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a white amorphous substance (yield: 49%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-the 7.65 (1H, m), 7,33 (1H, DD, J=8 Hz, 3 Hz), 7,10-7,06 (1H, m), of 6.99 (1H, users), 6,91 (0,5H, s), 6,83 (0,5H, C)of 4.44 (1H, d, J=4 Hz), 4,24-to 3.73 (8H, m), 2,61-2,48 (2H, m), 2,61-2,48 (1H, m), 1,96-1,87 (1H, m)of 1.26 (3H, t, J=6 Hz).

Example 148

Ethyl (2R,3R)-8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-646)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 85 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a pale red amorphous substance (yield: 40%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,51 was 7.45 (1H, m), 6,97-6,85 (3H, m), 6,65 (0,5H, s), 59 (0,5H, C), 4,43 is 4.36 (1H, m), 4,29-4,16 (3H, m), 4,13-4,08 (0,5H, m), 4,07-4,01 (0,5H, m), 3.95 to of 3.80 (2H, m), of 3.77-3,68 (2H, m), 2,78-2,62 (2H, m), 2,53 to 2.35 (2H, m), 2,19-of 1.84 (4H, m), 1,65-1,49 (2H, m), 1,44-1,35 (2H, m), 1,33-of 1.27 (3H, m)of 0.95 (3H, t, J=7 Hz).

Example 149

Ethyl (2S,3S)-8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-646)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 85 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a pale red amorphous substance (yield: 14%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,50-7,44 (1H, m), 6,98-6,86 (3H, m), 6.73 x (0,4H, C), 6,68 (0,6H, s), 4,43-4,37 (1H, m), 4.26 deaths-of 4.16 (3H, m), 4,11-4,07 (0,4H, m), 4,05-3,99 (0,6H, m), 3,90-of 3.80 (2H, m), 3,78-3,68 (2H, m), 2.77-to 2,62 (2H, m), 2,53-of 2.23 (3H, m), 2,20-2,07 (2H, m), 1,96 is 1.86 (1H, m), 1,63-of 1.53 (2H, m), 1,44 is 1.34 (2H, m), 1,32-of 1.26 (3H, m)of 0.95 (3H, t, J=7 Hz).

Example 150

Ethyl (2R,3R)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1744)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure is), ethyl 8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 86 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a pale red amorphous substance (yield: 33%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,50-the 7.43 (1H, m), 6,97-6,85 (3H, m), 6,67 (0,5H, s), 6,61 (0,5H, s), 4,42-4,37 (1H, m), 4,30-4,17 (3H, m), 4,12-4,08 (0,5H, m), 4,05-4,01 (0,5H, m), 3,93-3,82 (2H, m), 3,76-3,68 (2H, m), 2.77-to 2,61 (2H, m), 2,53 to 2.35 (2H, m), 2,19 and 1.80 (4H, m), 1,66 of 1.50 (2H, m), 1,40-1,22 (7H, m), 0,95-of 0.87 (3H, m).

Example 151

Ethyl (2S,3S)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1744)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 86 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a pale red amorphous substance (yield: 30%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,50-7,42 (1H, m), 6,97-6,84 (3H, m), 6,77 (0,5H, s), 6,72 (0,5H, s), 4,42 is 4.36 (1H, m), 4,30-to 4.14 (3H, m), 4,12-4,05 (0,5H, m), 4.04 the-3,98 (0,5H, m), 3,91-of 3.77 (2H, m), 3,76-to 3.67 (2H, m),was 2.76 at 2.59 (2H, m), 2,53-of 2.20 (4H, m), 2,20-to 2.06 (1H, m), 1,97-of 1.84 (1H, m), 1,66-of 1.52 (2H, m), 1.41 to 1,22 (7H, m), 0,95-to 0.88 (3H, m).

Example 152

Ethyl (2R,3R)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-822)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 87 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 54%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,50 was 7.45 (1H, m), of 6.96-6,86 (3H, m), 6,67 (0,5H, s), 6,61 (0,5H, C)to 4.41-4,37 (1H, m), 4,30-4,16 (3H, m), 4,13-4,08 (0,5H, m), 4,06-4,01 (0,5H, m), 3,93-3,81 (2H, m), 3,76 at 3.69 (2H, m), was 2.76-2,61 (2H, m), 2,52-of 2.36 (2H, m), 2,20-of 1.50 (6H, m), 1.41 to of 1.26 (9H, m), 0,91 is 0.86 (3H, m).

Example 153

Ethyl (2S,3S)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-822)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 87 was used instead of E. the Il 8-[ N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 54%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,50-7,44 (1H, m), of 6.96-6,86 (3H, m), 6,70-6,67 (0,5H, m), 6,64-6,61 (0,5H, m), to 4.41-4,37 (1H, m), 4,29-to 4.15 (3H, m), 4,12-4,07 (0,5H, m), 4,05-4,00 (0,5H, m), 3,93-of 3.80 (2H, m), 3,76-3,68 (2H, m), was 2.76-2,61 (2H, m), 2,52 to 2.35 (2H, m), 2,31-is 1.51 (6H, m), 1,40-of 1.26 (9H, m), 0,91 is 0.86 (3H, m).

Example 154

Ethyl (2R,3R)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-998)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 88 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 41%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, m), of 6.96-6.87 in (3H, m), 6,68 (0,5H, s), 6,61 (0,5H, C)to 4.41-and 4.40 (1H, m), 4,30-3,71 (8H, m), 2,72-to 2.65 (2H, m), 2,48-2,39 (2H, m), 2,14 is 2.10 (2H, m), 1,95-to 1.87 (2H, m), 1,37-1,22 (11H, m)to 0.88 (3H, t, J=7 Hz).

Example 155

Ethyl (2S,3S)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (see the example compound No. 1-998)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 88 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a white amorphous substance (yield: 70%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,50-of 7.48 (1H, m), 6,97-to 6.88 (3H, m), 6,70 (0,5H, C)6,70 (0,5H, C)to 4.41-4,39 (1H, m), 4,28-3,71 (8H, m), of 2,75 2,63 (2H, m), of 2.51-is 2.37 (2H, m), 2,19 is 2.10 (2H, m), 1,95-of 1.88 (2H, m), 1,35-1,23 (11H, m), 0.88 to (3H, t, J=7 Hz).

Example 156

Ethyl (2R,3R)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1920)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 89 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 47%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,51-7,47 (1H, m), 6,97-to 6.88 (3H, m), of 6.71 (0,5H, s), 6,64 (0,5H, C)to 4.41-4,39 (1H, m), 4,28-3,72 (H, m), was 2.76-2,62 (2H, m), of 2.51-is 2.37 (2H, m), 2,18-1,89 (4H, m), 1,37-1.27mm (13H, m)to 0.88 (3H, t, J=7 Hz).

Example 157

Ethyl (2S,3S)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1920)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 89 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 51%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), 6,97-to 6.88 (3H, m), 6,69 (0,5H, s), 6,63 (0,5H, C)to 4.41-4,39 (1H, m), or 4.31-3,70 (8H, m), 2,72-of 2.66 (2H, m), 2,52-is 2.37 (2H, m), 2,19-of 1.88 (4H, m), 1,37-1.27mm (13H, m)to 0.88 (3H, t, J=7 Hz).

Example 158

Ethyl (2R,3R)-8-[N-(4-fluoro-2-nonylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2604)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(4-fluoro-2-nonylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 90 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-di is suspiro[4.5]Dec-6-ene-7-carboxylate, obtaining specified in the title compound as an amorphous substance (yield: 48%). This compound was separated into two optical isomers in accordance with the following HPLC conditions.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd. Inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 4,43 minutes
high-polar compound (second peak) 4,73 minutes

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,50 was 7.45 (1H, m), 6,97-6,86 (3H, m), 6,66 (0,5H, s), 6,60 (0,5H, s), 4,42-4,37 (1H, m), 4,28-4,18 (3H, m), 4,13-4,08 (0,5H, m), 4,06-4,01 (0,5H, m), 3.95 to 3,81 (2H, m), 3,76 at 3.69 (2H, m), 2.77-to 2,61 (2H, m), 2,53 to 2.35 (2H, m), 2,19 of 1.99 (2H, m), 1,96 is 1.86 (2H, m), 1,64-of 1.52 (2H, m), 1,40-1,18 (15H, m), 0,91-of 0.85 (3H, m).

Example 159

Ethyl (2S,3S)-8-[N-(4-fluoro-2-nonylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxyl the t (example compound No. 1-2604)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(4-fluoro-2-nonylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 90 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 54%). This compound was separated into two optical isomers in accordance with the following HPLC conditions.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 6.7 minutes
high-polar compound (second peak) 10.1 minutes

1H-NMR spectrum (400 MHz, CDCl3) δ m is.:

7,50 was 7.45 (1H, m), 6,97-6,86 (3H, m), of 6.71 (0,5H, s), 6,65 (0,5H, s), 4,42-4,37 (1H, m), 4,30-4,16 (3H, m), 4,13-4,08 (0,5H, m), 4,05-4,00 (0,5H, m), 3,93-of 3.80 (2H, m), of 3.77 at 3.69 (2H, m), was 2.76-2,61 (2H, m), 2,52 is 2.01 (5H, m), 1,95 is 1.86 (1H, m), 1,64-of 1.52 (2H, m), 1.41 to 1,22 (15H, m)to 0.88 (3H, t, J=7 Hz).

Example 160

Ethyl (2R,3R)-8-[N-(2-decyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2618)

In accordance with the process described in examples 7, (16A) and 17 (alternative procedure), ethyl 8-[N-(2-decyl-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 91 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 35%). This compound was separated into two optical isomers in accordance with the following HPLC conditions.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
So the temperature value: 40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 4,30 minutes
high-polar compound (second peak) 4,55 minutes

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,51 was 7.45 (1H, m), 6,97-6,86 (3H, m), 6,67 (0,5H, s), 6,61 (0,5H, s), 4,42 is 4.36 (1H, m), 4,30-4,17 (3H, m), 4,13-4,08 (0,5H, m), 4,06-4,01 (0,5H, m), 3,94-of 3.80 (2H, m), 3,76 at 3.69 (2H, m), was 2.76-2,61 (2H, m), 2,53 to 2.35 (2H, m), 2,19 is 2.00 (2H, m), 1,99-to 1.86 (2H, m), 1,65-is 1.51 (2H, m), 1,40-1,18 (17H, m), 0,91-of 0.85 (3H, m).

Example 161

Ethyl (2S,3S)-8-[N-(2-decyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2618)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(2-decyl-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 91 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 56%). This compound was separated into two optical isomers in accordance with the following HPLC conditions.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 6.4 minutes
high-polar compound (second peak) of 9.1 minutes

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

7,50 was 7.45 (1H, m), 6,97-6,87 (3H, m), 6,70 (0,5H, s), 6,64 (0,5H, s), 4,42-to 4.38 (1H, m), 4,30-4,17 (3H, m), 4,12-4,08 (0,5H, m), 4,05-4,01 (0,5H, m), 3,93-3,81 (2H, m), 3,78 at 3.69 (2H, m), was 2.76-2,62 (2H, m), 2,52-is 2.37 (2H, m), 2,33-of 2.09 (2H, m), 2.06 to to 1.87 (2H, m), 1,63-of 1.52 (2H, m), 1,40-1,22 (17H, m)to 0.88 (3H, t, J=7 Hz).

Example 162

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak) (high-polar compound, second peak) (example compound No. 1-382)

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in CA is re 17, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 12.0 minutes
high-polar compound (second peak) 16.5 minutes

(Iskopaemoe compound, first peak)

Optical ROTC is I (cyclic shift) [α] D+86,7 (C = 2.0, Meon)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,07-6,98 (2H, m)6,91 (1H, s), 4,42 (1H, DD, J=6 Hz, 2 Hz), 4,28-4,08 (4H, m), 3,91 (1H, DD, J=12 Hz, 4 Hz), a-3.84 (1H, DD, J=12 Hz, 4 Hz), of 3.77-3,68 (2H, m), 2,60 is 2.43 (2H, m), 2.26 and-2,11 (1H, m), 1,99-to 1.87 (1H, m), 1,58 (2H, users), of 1.27 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,07-6,98 (2H, m), at 6.84 (1H, s), 4,42 (1H, d, J=5 Hz), 4,28-4,08 (3H, m), 4,07-4,01 (1H, m), 3,93-3,82 (2H, m), of 3.77-3,68 (2H, m), 2,61 is 2.46 (2H, m), 2,24-2,11 (1H, m), 1,95-to 1.87 (1H, m), of 1.57 (2H, users), of 1.27 (3H, t, J=7 Hz).

Example 163

Ethyl (2S,3S)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak) (high-polar compound, second peak) (example compound No. 1-382)

Ethyl (2S,3S)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 18 was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white amorphous substance. With the according to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 11.4 minutes
high-polar compound (second peak) 27,4 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9 Hz, 5 Hz), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,06-7,00 (1H, m), 6,98 (1H, s), at 6.84 (1H, s), 4,42 (1H, d, J=5 Hz), 4,27-4.09 to (3H, m), 4,07-4,00 (1H, m), 3,93-a 3.83 (2H, m), 3,76-3,68 (2H, m), 2,60-2,47 (2H, m), 2,24-2,12 (1H, m), 1,95-to 1.60 (3H, m)of 1.27 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,06-6,99 (2H, m), 6.90 to (1H, s), of 4.44-to 4.41 (1H, m), 4,27-4.09 to (4H, m), 3,91 (1H, DD, J=12 Hz, 4 Hz), a-3.84 (1H, DD, =12 Hz, 4 Hz), of 3.77-3,68 (2H, m), 2,60 at 2.45 (2H, m), 2,24-2,12 (1H, m), 2.00 in of 1.65 (3H, m)of 1.27 (3H, t, J=7 Hz).

Example 164

Ethyl (2R,3R)-8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak) (high-polar compound, second peak) (example compound No. 1-294)

Ethyl (2R,3R)-8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 144 was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of an amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 13.7 minutes
high-polar compound (second peak) of 15.9 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

a 7.62 EUR 7.57 (1H, m), 6,93-6,87 (3H, m), 4,36 (1H, square, J=3 Hz), 4,28-4,18 (3H, m), 4,15-4.09 to (1H, m), 3,91 (1H, DD, J=12 Hz, 4 Hz), a-3.84 (1H, DD, J=12 Hz, 4 Hz), 3.75 to 3,70 (2H, m), of 2.51-2.40 a (2H, m), 2,20-2,12 (1H, m), 1,96-1,90 (1H, m)to 1.61 (2H, users), of 1.29 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

a 7.62 EUR 7.57 (1H, m), 6,97 (1H, users), 6,93-6,86 (3H, m), 4,37 is 4.35 (1H, m), 4,29-4,17 (3H, m), 4,06-was 4.02 (1H, m), 3,91-a-3.84 (2H, m), 3,76 at 3.69 (2H, m), 2,53-to 2.41 (2H, m), 2,20-2,11 (1H, m), is 2.05 (1H, users), 1,94-of 1.88 (2H,, m)of 1.29 (3H, t, J=7 Hz).

Example 165

Ethyl (2S,3S)-8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-294)

Ethyl (2S,3S)-8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, according to the scientists in example 145, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of an amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 6.9 minutes
high-polar compound (second peak) of 10.7 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (500 M is C, CDCl3) δ ppm:

a 7.62 EUR 7.57 (1H, m), 6,93-6,86 (3H, m), 4,36 (1H, d, J=4 Hz), 4,29-4,18 (3H, m), 4,06-4,01 (1H, m), 3,91-a-3.84 (2H, m), 3.75 to 3,70 (2H, m), 2,52-to 2.42 (2H, m), 2,19 of 1.50 (4H, m)of 1.29 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

a 7.62 EUR 7.57 (1H, m), 6,93-6,87 (3H, m), 4,36 (1H, DD, J=6 Hz, 3 Hz), 4,29-4,18 (3H, m), 4,13-4.09 to (1H, m), 3,91 (1H, DD, J=12 Hz, 4 Hz), a-3.84 (1H, DD, J=12 Hz, 4 Hz), 3.75 to 3,70 (2H, m), of 2.51-2.40 a (2H, m), 2,20 of 1.50 (4H, m)of 1.29 (3H, t, J=7 Hz).

Example 166

Ethyl (2R,3R)-8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-1568)

Ethyl (2R,3R)-8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 146 was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of an amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions the Oia HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 6.8 minutes
high-polar compound (second peak) 8.8 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9,2 Hz and 5.2 Hz), 7,34 (1H, DD, J=7,6 Hz, 2.9 Hz), 7,11-7,06 (1H, m)6,91 (1H, s), of 4.44 (1H, DD, J=5,8 Hz, 2.0 Hz), 4,28-4,10 (4H, m), 3,93-3,70 (4H, m), 2,60-2,47 (2H, m), 2,24 with 2.14 (1H, m), 1,97-1,92 (1H, m)of 1.27 (3H, t, J=7,0 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9,2 Hz, 5.3 Hz), 7,34 (1H, DD, J=7,6 Hz, 2.9 Hz), 7,11-7,06 (1H, m), 6,85 (1H, s), of 4.44 (1H, d, J=5.0 Hz), 4,27-was 4.02 (4H, m), 3,92-a-3.84 (2H, m), 3,76-3,70 (2H, m), 2,61-2,48 (2H, m), 2,23-to 2.15 (1H, m), 1,92-of 1.88 (1H, m)of 1.27 (3H, t, J=7.2 Hz).

Example 167

Ethyl (2S,3S)-8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bi is(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe connection, the first peak), (high-polar compound, second peak) (example compound No. 1-1568)

Ethyl (2S,3S)-8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 147 was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of an amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

/tr>
Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 6.7 minutes
high-polar compound (second peak) 13.2 mins

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,33 (1H, DD, J=8 Hz, 3 Hz), 7,10-7,06 (1H, m), at 6.84 (1H, s), of 4.44 (1H, d, J=5 Hz), 4,24-3,70 (8H, m), 2,61-2,48 (2H, m), 2,24-to 1.87 (2H, m)of 1.26 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9 Hz, 5 Hz), 7,33 (1H, DD, J=8 Hz, 3 Hz), 7,10-7,05 (1H, m)6,91 (1H, s), of 4.44 (1H, d, J=6 Hz), 4,27 at 3.69 (8H, m), 2,59-2,48 (2H, m), 2,23 is 1.91 (2H, m)of 1.26 (3H, t, J=7 Hz).

Example 168

Ethyl (2R,3R)-8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-646)

Ethyl (2R,3R)-8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 148, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers were obtained iskopaemoe connection (first peak) and highly polar with the unity (the second peak), respectively, in the form of pale red amorphous substance and a white powder. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 5,02 minutes
high-polar compound (second peak) 5,24 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), 6,98-6,93 (2H, m), 6.90 to (1H, dt, J=8 Hz, 3 Hz), to 6.67 (1H, s), and 4.40 (1H, DD, J=6 Hz, 3 Hz), 4,29-4,19 (3H, m), 4,13-4,08 (1H, m)to 3.92 (1H, DD, J=12 Hz, 4 Hz), 3,85 (1H, DD, 12 Hz, 4 Hz), 3,76 at 3.69 (2H, m), 2,78-2,62 (2H, m), 2,53 to 2.35 (2H, m), 2,19 and 1.80 (4H, m), 1,65-1,49 (2H, m), 1,44 is 1.34 (2H, m)is 1.31 (3H, t, J=7 Hz), of 0.95 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3 ) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), to 6.95 (1H, DD, J=9 Hz, 3 Hz), 6,93-6,86 (2H, m), 6,62 (1H, s)to 4.41 (1H, d, J=4 Hz), 4,28-4,17 (3H, m), 4,05-4,01 (1H, m), 3,91-a 3.83 (2H, m), of 3.77 at 3.69 (2H, m), 2.77-to 2,62 (2H,, m), 2,53 to 2.35 (2H, m), 2,18 to 1.76 (4H, m), 1,65 of 1.50 (2H, m), of 1.44 and 1.35 (2H, m)of 1.30 (3H, t, J=7 Hz), of 0.95 (3H, t, J=7 Hz).

Example 169

Ethyl (2S,3S)-8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-646)

Ethyl (2S,3S)-8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 149, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white powder and pale red amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (production is a company Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 5.08 minutes
high-polar compound (second peak) 5,58 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,47 (1H, DD, J=9 Hz, 5 Hz), to 6.95 (1H, DD, J=9 Hz, 3 Hz), 6,93-6,86 (2H, m), is 6.61 (1H, s)to 4.41 (1H, d, J=4 Hz), 4.26 deaths-of 4.16 (3H, m), 4,05-to 3.99 (1H, m), 3,90-of 3.80 (2H, m), 3,78-3,68 (2H, m), 2.77-to 2,62 (2H,, m), 2,53-2,39 (2H, m), 2,33-of 2.05 (2H, m), 1,96 is 1.86 (1H, m), 1,80-of 1.65 (1H, m), 1,63-of 1.52 (2H, m), of 1.44 and 1.35 (2H, m)of 1.29 (3H, t, J=7 Hz), of 0.95 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), 6,99-6,86 (3H, m), 6,70 (1H, s), and 4.40 (1H, DD, J=6 Hz, 3 Hz), 4,29-4,17 (3H, m), 4,13-4,07 (1H, m), 3,90 (1H, DD, J=12 Hz, 4 Hz), a-3.84 (1H, DD, 12 Hz, 4 Hz), 3,76 at 3.69 (2H, m), 2,77-2,62 (2H, m), 2,53-of 2.23 (3H, m), 2,20-2,00 (2H, m), 1,96 is 1.86 (1H, m), 1,63-of 1.52 (2H, m), 1,44 is 1.34 (2H, m)of 1.30 (3H, t, J=7 Hz), of 0.95 (3H, t, J=7 Hz).

Example 170

Ethyl (2R,3R)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-is oxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe connection, the first peak), (high-polar compound, second peak) (example compound No. 1-1744)

Ethyl (2R,3R)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 150 was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a pale red amorphous substance and a white powder. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

254 nm (UV)
Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:
Retention time:iskopaemoe connection (first peak) of 4.83 minutes
high-polar compound (second peak) 5,01 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), 6,97-6,92 (2H, m), 6.90 to (1H, dt, J=8 Hz, 3 Hz), of 6.66 (1H, s), and 4.40 (1H, DD, J=6 Hz, 3 Hz), 4,28-4,18 (3H, m), 4,14-4,07 (1H, m)to 3.92 (1H, DD, J=12 Hz, 4 Hz), 3,85 (1H, DD, 12 Hz, 4 Hz), 3,76 at 3.69 (2H, m), was 2.76-2,61 (2H, m), 2,50 to 2.35 (2H, m), 2,19-of 2.08 (1H, m), 1,97-to 1.87 (1H, m), 1,81-1,49 (4H, m), 1,40-of 1.32 (4H, m)of 1.30 (3H, t, J=7 Hz), of 0.90 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), to 6.95 (1H, DD, J=9 Hz, 3 Hz), 6,93-6,86 (2H, m), 6,60 (1H, s)to 4.41 (1H, d, J=5 Hz), 4,29-4,17 (3H, m), 4,07-4,01 (1H, m), 3,93-a-3.84 (2H, m), 3,76 at 3.69 (2H, m), was 2.76-2,61 (2H, m), 2,54-of 2.36 (2H, m), 2,19-2,07 (1H, m), 2.06 to to 1.70 (3H, m), 1,66 of 1.50 (2H, m), 1,40-of 1.32 (4H, m)of 1.30 (3H, t, J=7 Hz), of 0.90 (3H, t, J=7 Hz).

Example 171

Ethyl (2S,3S)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-1744)

Ethyl (2S,3S)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 151 was subjected to high performance liquid x is omatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white powder and a pale red amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 4.90 minutes
high-polar compound (second peak) 6.18 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz, 6,97-6,85 (3H, m), 6,59 (1H, s), and 4.40 (1H, d, J=5 Hz), 4,29-4,17 (3H, m), 4,06-4,00 (1H, m), 3,91-a 3.83 (2H, m), 3,76 at 3.69 (2H, m), was 2.76 at 2.59 (2H, m), 2,53-of 2.36 (2H, m), 2,20-to 2.06 (1H, m), 1,94-of 1.85 (1H, m), 1,80 of 1.50 (4H, m), 1.41 to 1,22 (7H, m)of 0.91 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,47 (1H, DD, J=9 Hz, 5 Hz), 6,97-6,92 (2H, m), 6.89 in (1H, dt, J=8 Hz, 3 Hz), was 6.73 (1H, s), and 4.40 (1H, DD, J=6 Hz, 3 Hz), 4,28-4,17 (3H, m), 4,12-of 4.05 (1H, m)to 3.89 (1H, DD, J=12 Hz, 4 Hz), 3,82 (1H, DD, 12 Hz, 4 Hz), 3,76 at 3.69 (2H, m), was 2.76-2,61 (2H, m), of 2.51 to 2.35 (2H, m), 2.26 and is 2.01 (2H, m), 1,97 by 1.68 (2H, m), 1,66-and 1.54 (2H, m), 1.41 to to 1.31 (4H, m)of 1.29 (3H, t, J=7 Hz), of 0.90 (3H, t, J=7 Hz).

Example 172

Ethyl (2R,3R)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-822)

Ethyl (2R,3R)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 152, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of an amorphous substance. According to the results of HPLC analysis of two optical is somerow, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 9:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 25.2 minutes
high-polar compound (second peak) 29.3 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), 6,97-6,87 (3H, m), of 6.66 (1H, s), to 4.41-4,37 (1H, m), 4,29-4,19 (3H, m), 4,13-4.09 to (1H, m), 3.95 to 3,88 (1H, m), a 3.87-3,81 (1H, m), of 3.77 at 3.69 (2H, m), 2.77-to 2,62 (2H, m), of 2.51-of 2.36 (2H, m), 2,19-of 2.09 (2H, m), 1,95-1,89 (2H, m), 1,63-of 1.52 (2H, m), 1,40 of 1.28 (9H, m), 0,91 is 0.86 (3H, m).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,47 (1H, DD, J=9 Hz, 5 Hz), of 6.96-6,86 (3H, m), 6,63 (1H, s), 4,42-4,39 (1H, m), 4,30-4,16 (3H, m), 4,06-4,01 (1H, m), 3,91-a 3.83 (2H, m), of 3.77 at 3.69 (2H, m), was 2.76-2,61 (H, m), 2,53-is 2.37 (2H, m), 2,18-of 2.08 (2H, m), 2,03-to 1.98 (1H, m), 1.93 and is 1.86 (1H, m), 1,63-of 1.52 (2H, m), 1.41 to of 1.26 (9H, m), 0,91 is 0.86 (3H, m).

Example 173

Ethyl (2S,3S)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-822)

Ethyl (2S,3S)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 153, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of an amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1/td>
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 7.6 minutes
high-polar compound (second peak) 10.6 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), to 6.95 (1H, DD, J=9 Hz, 3 Hz), 6,92-6,87 (2H, m), is 6.61 (1H, s), and 4.40 (1H, d, J=4 Hz), 4,29-4,17 (3H, m), 4,06-was 4.02 (1H, m), 3,91-a-3.84 (2H, m), 3,76-3,70 (2H, m), 2,75-2,62 (2H, m), 2,52 is 2.46 (1H, m), 2,42 (1H, TD, J=14 Hz, 3 Hz), 2,17-of 2.09 (1H, m), is 2.05 (1H, DD, J=8 Hz, 5 Hz), 1,96-to 1.87 (2H, m), 1,64-of 1.53 (2H, m), 1,40-of 1.27 (9H, m), 0,91-0,87 (3H, m).

(High-polar compound, second peak)

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), of 6.96-6,93 (2H, m), 6.90 to (1H, TD, J=8 Hz, 3 Hz), to 6.67 (1H, m), 4,39 (1H, DD, J=6 Hz, 4 Hz), 4,30-4,19 (3H, m), 4,13-4.09 to (1H, m), 3,91 (1H, dt, J=12 Hz, 4 Hz), a-3.84 (1H, dt, J=12 Hz, 4 Hz), 3,76 at 3.69 (2H, m), was 2.76 2.63 in (2H, m), 2,50 is 2.44 (1H, m), is 2.40 (1H, TD, J=13 Hz, 3 Hz), 2,18 is 2.10 (2H, m), 1,95-1,89 (2H, m), 1,63-of 1.53 (2H, m), 1,40 of 1.28 (9H, m), 0,91-0,87 (3H, m).

Example 174

Ethyl (2R,3R)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, W is Roy peak) (example compound No. 1-998)

Ethyl (2R,3R)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 154, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 9:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:low is alamae connection (first peak) 23.9 minutes
high-polar compound (second peak) 27.4 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=8 Hz, 5 Hz), of 6.96-to 6.88 (3H, m), to 6.67 (1H, s), 4,40-to 4.38 (1H, m), 4,27 at 3.69 (8H, m), 2,72-2,62 (2H, m), 2,49-1,89 (6H, m), 1,34-1,25 (11H, m)to 0.88 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,47 (1H, DD, J=9 Hz, 5 Hz), of 6.96-6.87 in (3H, m), only 6.64 (1H, users), and 4.40 (1H, d, J=4 Hz), 4,29-3,71 (8H, m), 2,75-2,61 (2H, m), of 2.51-is 2.37 (2H, m), 2,17 is 1.86 (4H, m), 1,42-1,22 (11H, m)to 0.88 (3H, t, J=7 Hz).

Example 175

Ethyl (2S,3S)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-998)

Ethyl (2S,3S)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 155 was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white powder and white amorphous substance. According to the results of HPLC analysis of the Vuh optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 4.8 minutes
high-polar compound (second peak) 6.3 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), 6,97-to 6.88 (3H, m), only 6.64 (1H, s)to 4.41 (1H, d, J=4 Hz), 4,27-and 3.72 (8H, m), 2,75-2,62 (2H, m), of 2.51-of 2.38 (2H, m), 2,18-to 1.38 (4H, m), 1,38 of 1.28 (11H, m)to 0.88 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 5 Hz), 6,97-to 6.88 (3H, m), 6,69 (1H, s), to 4.41-4,39 (1H, m), 4,29-3,71 (8H, m), 2.77-to 2,62 (2H, m), 2,49-1,90 (6H, m), 1,38-1,29 (11H, m)to 0.89 (3H, t, J=7 Hz).

Example 176

Ethyl (2R,3R)-8-[N-(4-f the PR-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe connection, the first peak), (high-polar compound, second peak) (example compound No. 1-1920)

Ethyl (2R,3R)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 156, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 9:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 n is (UV)
Retention time:iskopaemoe connection (first peak) 22.9 minutes
high-polar compound (second peak) 25.8 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), of 6.96-to 6.88 (3H, m), of 6.68 (1H, s), 6,68-and 4.40 (1H, m), 4,28-3,70 (8H, m), 4,28-3,70 (2H, m), 2,52-1,89 (6H, m), 1,36-1,19 (13H, m)to 0.88 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,46 (1H, DD, J=9 Hz, 5 Hz), 6,95-6,87 (3H, m), and 4.40 (1H, d, J=5 Hz), 4,28-3,71 (8H, m), 2,73-2,60 (2H, m), 2,50-to 1.87 (6H, m), 1,31-1,25 (13H, m)to 0.89 (3H, t, J=7 Hz).

Example 177

Ethyl (2S,3S)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe compound, first peak), (high-polar compound, second peak) (example compound No. 1-1920)

Ethyl (2S,3S)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 157, was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and highly polar compounds is their (the second peak) in the form of a white powder and colorless oil. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively > 99% ee.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) 4.7 minutes
high-polar compound (second peak) of 6.1 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.48 (1H, DD, J=9 Hz, 5 Hz), 6,97-to 6.88 (3H, m), 6,63 (1H, s)to 4.41 (1H, d, J=5 Hz), 4,28-3,71 (8H, m), 2,75-2,62 (2H, m), of 2.51-of 1.88 (6H, m), 1,38-1.27mm (13H, m)to 0.88 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=9 Hz, 6 Hz), 6,97-to 6.88 (3H, m), 6,97-to 6.88 (1H, m), to 4.41-to 4.38 (1H, m), or 4.31-3,71 (8H, m), 2.77-to 2,63 (2H, m), 2,50-1,90 (6H, m), 2,50-1,90 (13H, m)to 0.88 (3H, t, J=7 G is).

Example 178

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(methoxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), 1,4-di-About-methyl-2,3-di-About-trimethylsilyl-D-threitol used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compounds as colorless oil (yield: 89%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,68-to 7.64 (1H, m), 7,16 (1H, DD, J=8,1 Hz, 3.0 Hz), 7,17-7,16 (3H, m), 4,39 (1H, d, J=3.5 Hz), 4,24-3,98 (4H, m), 3.43 points-of 3.42 (4H, m), 3.43 points (1,5H, s), 3.42 points (1,5H, s), 3,39 (1,5H, s), 3,38 (1,5H, s), 2.57 m at 2.45 (2H, m), 2.57 m at 2.45 (1H, m), 1,96 is 1.86 (1H, m)of 1.27 (3H, dt, J=6,9 Hz, 2.1 Hz).

Example 179

Ethyl (2S,3S)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(methoxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), 1,4-di-About-methyl-2,3-di-About-trimethylsilyl-L-threitol used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compounds as colorless oil (yield: 91%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,68-to 7.64 (1H, m), 7,16 (1H, DD, J=7.8 and 2.4 Hz),? 7.04 baby mortality-7,00 (2H, m), 6.89 in (1H, s), 4,40-4,39 (1H, m), 4,23-of 3.97 (4H, m), 3,62-3,47 (4H, m), 3.43 points (1,5H, s), 3,41 (1,5H, s), 3,39 (1,5H, s), 3,38 (1,5H, ), 2,58 at 2.45 (2H, m), 2.26 and-of 2.16 (1H, m), 1,96 is 1.86 (1H, m), 1,2 (3H, dt, J=7.0 and 3.5 Hz).

Example 180

Ethyl (2S,3S)-2,3-bis(benzoyloxymethyl)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), 1,4-di-About-benzyl-2,3-di-About-trimethylsilyl-L-threitol used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compounds as colorless oil (yield: 94%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-to 7.64 (1H, m), 7,37-7,26 (10H, m), 7,16 (1H, DD, J=7,8 Hz, 2.8 Hz),? 7.04 baby mortality-of 6.90 (3H, m), with 4.64-4,51 (4H, m), and 4.40 (1H, t, J=4.5 Hz), 4,30-of 4.05 (4H, m), 3,68 is 3.57 (4H, m), 2,58 at 2.45 (2H, m), 2,25-2,17 (1H, m), 1,96 is 1.86 (1H, m)to 1.21 (3H, dt, J=7,0 Hz, 3.5 Hz).

Example 181

Ethyl (2R,3R)-2,3-bis(acetoxymethyl)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate

In accordance with the process described in example (17A), 1,4-di-About-acetyl-2,3-di-About-trimethylsilyl-D-threitol obtained in reference example 24 was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compound as a white amorphous substance (yield: 50%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.67 (1H, DD, J=9,2 Hz, 5.3 Hz), 7,17 (1H, DD, J=7.9 Hz, 2.8 Hz), 7,05-7,00 (2H, m), 6.90 to-6,76 (1H, m)to 4.41 (1H, d, J=4,7 Hz), 4,37-4,37 (8H, m), 2,60 is 2.46 (2H, m), 2,23-,04 (8H, m)of 1.26 (3H, t, J=7,0 Hz).

Example 182

Ethyl (2S,3S)-2,3-bis(acetamidomethyl)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-410)

218 mg (1.07 mmol)ofN-(4-acetylamino-2R,3R-dihydroxybutyl)ndimethylacetamide and 0.57 ml (3,20 mmol) of isopropoxytitanium was dissolved in 3 ml of nitromethane and consistently added 13 μl (0,071 mmol) trimethylsilyltrifluoromethane and 300 mg (0,711 mmol) ethyl 6-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-dimethoxy-1-cyclohexen-1-carboxylate obtained in example (16A), under stirring with ice cooling, followed by stirring at the same temperature for 3 hours and then at room temperature for 116 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: ethyl acetate:methanol = 9:1), with 203 mg specified in the title compound as an amorphous substance (yield: 51%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,68-7,63 (1H, m), 7,20-to 7.15 (1H, m), 7,08-7,00 (2H, m), 6,78-of 6.73 (1H, m), 6,46-6,38 (1H, m) 6,34-of 6.26 (1H, m), 4,42-4,39 (1H, m), 4,29-to 4.14 (2H, m), 3.96 points-3,85 (1,5H, m), 3.75 to 3,69 (0,5H, m), 3,61-of 3.42 (4H, m), 2,55 is 2.43 (2H, m), 2.21 are 2,01 (7H, m), 1,90-of 1.78 (1H, m), 1,31-1,25 (3H, m).

Example 183

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis((R)-1-hydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2163)

In accordance with the process described in example 17 (alternative procedure), (1R,2R,3R,4R)-4-benzoyloxy-1-methyl-2,3-bis[(trimethylsilyl)oxy]pentylbenzoic obtained in reference example 25 was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compound as a white amorphous substance (yield: 33%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,66 (1H, DD, J=9.0 and 5.0 Hz), 7,17 (1H, DD, J=7,8 and 2.7 Hz), to 7.09 (1H, d, J=9.0 Hz), 7,05-7,00 (1H, m), 6,80 (0,5H, C)6,76 (0,5H, s), 4,39 (1H, d, J=5.4 Hz), 4,27-4.09 to (2H, m), 3,88 of 3.56 (4H, m), 2,50-2,42 (2H, m), 2,19-2,11 (1H, m), 1.85 to to 1.79 (1H, m)of 1.33 (3H, t, J=5.3 Hz), of 1.27 (6H, t, J=7,0 Hz).

Example 184

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis((R)-1-hydroxypropyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2164)

In accordance with the process described in example 17 (alternative procedure), (1R,2R,3R,4R)-4-benzoyloxy-1-ethyl-2,3-bis[(trimethylsilyl)oxy]hexylbenzoate, p is obtained in reference example 26, used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compound as a white amorphous substance (yield: 21%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 7.68 (1H, DD, J=9,2 Hz and 5.2 Hz), 7,18 (1H, DD, J=7,4 Hz, 2.4 Hz), 7,06-7,01 (2H, m), for 6.81 (0,5H, s), 6,78 (0,5H, s), and 4.40 (1H, d, J=5,1 Hz), 4,29-4,12 (2H, m), 3,88-3,55 (4H, m), 3,03 (1H, users), of 2.92 (1H, users), of 2.51-to 2.41 (2H, m), 2.21 are to 2.13 (2H, m), 1,90-of 1.73 (1H, m), 1,55 was 1.43 (3H, m)of 1.29 (3H, t, J=7.2 Hz), of 1.05 to 0.97 (6H, m).

Example 185

Ethyl (3A'R6A'R,6'R)-4-[N-(2-chloro-4-forfinal)sulfamoyl]-6'-hydroxymethyl-4'-oxo-3A',4',6',6A'-tetrahydrofuro[cyclohex-2-ene-1,2'-furo[3,4-d][1.3]dioxol]-3-carboxylate (example compound No. 1-2165)

In accordance with the process described in example (17A), (3R,4R,5R)-3,4-bis[(trimethylsilyl)oxy]-5-[(trimethylsilyl)oxy]methyldihydro-2-he was used instead of 1,4-di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol, obtaining specified in the title compound as a white amorphous substance (yield: 25%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,69-to 7.64 (1H, m), 7,20-7,16 (1H, m), 7,06-of 6.96 (2H, m), 6,82 of 6.68 (1H, m), 5,04-to 4.62 (3H, m), of 4.44-and 4.40 (1H, m), 4.26 deaths-to 4.14 (2H, m), 4,05-3,98 (1H, m), 3,90-3,81 (1H, m), 2,74 is 2.46 (2H, m), 2,24-2,12 (1H, m), 1,97 of-1.83 (2H, m), 1.30 and 1.26 in (3H, m).

Example 186

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis((1R)-1,2-dihydroxyethyl)-14-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (iskopaemoe connection, the first peak), (high-polar compound, second peak) (example compound No. 1-386)

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis((1R)-1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 23 was subjected to high performance liquid chromatography (column: CHIRALPAK AD-H, size: inner diameter 2 cm, length 25 cm, solvent: hexane:2-propanol) for separation and purification of two optical isomers, respectively, were obtained iskopaemoe connection (first peak) and high-polar compound (second peak) in the form of a white amorphous substance. According to the results of HPLC analysis of two optical isomers, obtained under the conditions shown below, their optical purity were respectively >99% e.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection: 254 nm (UV)
Retention time:iskopaemoe connection (first peak) ,3 minutes
high-polar compound (second peak) ,9 minutes

(Iskopaemoe compound, first peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

the 7.65 (1H, DD, J=9 Hz, 5 Hz), 7,21 (1H, users), 7,17 (1H, DD, J=8 Hz, 3 Hz), 7,06-6,99 (1H, m), to 6.80 (1H, s), to 4.38 (1H, d, J=5 Hz), 4,27-4,12 (4H, m), 4,08 (2H, d, J=7 Hz), 3.95 to 3,88 (1H, m), a 3.87-of 3.64 (5H, m), 2,98 of 2.68 (2H, m), 2,54-to 2.42 (2H, m), 2,22-of 2.08 (1H, m), 1.91 a-1,82 (1H, m), 1,25 (3H, t, J=7 Hz).

(High-polar compound, second peak)

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,63 (1H, DD, J=9 Hz, 5 Hz), to 7.15 (1H, users), 7,12 (1H, DD, J=8 Hz, 3 Hz), 7,05-6,97 (1H, m), 6,76 (1H, s), 4,37 (1H, d, J=6 Hz), 4,27-4,01 (5H, m), 3,97-3,86 (2H, m), 3,85 is-3.45 (5H, m), 2.77-to to 2.57 (2H, m), 2,52-to 2.41 (2H, m), 2.21 are of 2.08 (1H, m), 1,89 and 1.80 (1H, m)of 1.26 (3H, t, J=7 Hz).

Example 187

Ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)-N-methylsulfanyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 2-15)

235 mg (0.49 mmol) of ethyl (2R,3R)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 17, was dissolved in 1.5 ml of acetone and consistently added 84 mg (0.59 mmol) of methyliodide and 138 mg (1.00 mmol) of potassium carbonate, followed by stirring at 50C for 3 hours. After the filtrowanie reaction solution, the filtrate was concentrated under reduced pressure and the residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 1:3), to obtain 175 mg specified in the title compound as a white amorphous substance (yield: 73%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

EUR 7.57 (1H, users), 7,22 (1H, DD, J=8 Hz, 3 Hz), 7,05-7,00 (1H, m), 6.87 in (0,5H, s), 6,79 (0,5H, s), 4,58 (1H, users), 4,28-to 3.73 (8H, m)of 3.25 (3H, s), 2,60 and 1.80 (6H, m)of 1.26 (3H, t, J=7 Hz).

Example 188

Ethyl 8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2077)

In accordance with the process described in example (1d), 4-fluoro-2-propylaniline obtained in reference example 27 was used instead of 2-chloro-4-foranyone, obtaining specified in the title compound as oil (yield: 84%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

8,09-8,07 (4H, m), to 7.59-of 7.55 (2H, m), 7,47-the 7.43 (4H, m), 7,47-the 7.43 (2H, m), of 3.96 (2H, s), 2.00 in to 1.79 (4H, m)of 1.02 (6H, t, J=7 Hz), 0,07 (18H, s).

Example 189

Ethyl (2S,3S)-8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2095)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 188 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carb is celata, obtaining specified in the title compound as a white amorphous substance (yield: 38%). This compound was separated into two optical isomers in accordance with the following HPLC conditions.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 9.6 minutes
high-polar compound (second peak) 14,1 minutes

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,51-7,47 (1H, m), 6,97-to 6.88 (3H, m), 6,70 (0,5H, s), 6,64 (0,5H, s), 4,42-4,39 (1H, m), 4,28-and 3.72 (8H, m), 2,75-2,61 (2H, m), 2,52-is 2.37 (2H, m), 2,19-to 1.87 (4H, m), 1,68-of 1.57 (2H, m), 1,32 of 1.28 (3H, m), 0,99 (3H, t, J=8 Hz).

Example 190

Ethyl (2R,3R)-2,3-bis((1R)-1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-1748)

In accordance with the process described in examples 7, (16A) and 23, ethyl 8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 86 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as a white powder (yield: 33%). This compound was separated into two optical isomers in accordance with the following HPLC conditions.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 7:3
Flow rate:1.0 ml/min
Temperature:40°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 5.29 minutes
high-polar compound (second peak) of 5.82 minutes

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49-7,44 (1H, m), 6,97-6,86 (2H, m), 6,84(0,5H, m), 6,82 (0,5H, m), 6.73 x (0,5H, s), 6,69 (0,5H, C)to 4.41 is 4.36 (1H, m), 4,27-4,17 (2H, m), 4,12-4,01 (1,5H, m), 3,97-3,88 (1,5H, m), 3,88-to 3.67 (5H, m), 2.77-to 2,60 (2H, m), 2,50-of 2.30 (2H, m), 2,20-1,40 (8H, m), 1,39-1,25 (7H, m), 0,93 is 0.86 (3H, m).

Example 191

Ethyl (2S,3S)-8-[N-(4-fluoro-2-were)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate (example compound No. 1-2359)

In accordance with the process described in examples 7, (16A) and 18 (alternative procedure), ethyl 8-[N-(4-fluoro-2-were)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate obtained in example 79 was used instead of ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate, to obtain the specified title compound as an amorphous substance (yield: 49%). This compound was separated into two optical isomers in accordance with the following HPLC conditions.

Conditions of HPLC

Column:CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd., inner diameter and 0.46 cm, length 25 cm)
Mobile phase:hexane:2-propanol = 4:1
Flow rate:1.0 ml/min
Temperature:4°C
Detection:254 nm (UV)
Retention time:iskopaemoe connection (first peak) of 13.5 minutes
high-polar compound (second peak) in 19.6 minutes

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,49 (1H, DD, J=8,8 Hz, 5.3 Hz), of 6.96-to 6.88 (3H, m), 6,70 (0,5H, users), 6,64 (0,5H, users), 4,40-4,37 (1H, m), 4,28-3,70 (8H, m), of 2.51 of-2.32 (5H, m), 2.21 are to 1.87 (2H, m), 1,31-of 1.27 (3H, m).

REFERENCE EXAMPLES

Reference example 1

1,4-Di-About-benzoyl-2,3-di-About- (trimethylsilyl)-meso-erythritol

300 mg (0.90 mmol) of 1,4-di-About-benzoyl-meso-erythritol (compounds described in J. Am. Chem. Soc., 82, 2585 (1960)), 0,28 ml (1,98 mmol) of triethylamine and 11 mg (0.09 mmol) of 4-dimethylaminopyridine was dissolved in 6 ml of dichloromethane and thereto were added to 0.24 ml (1,89 mmol) trimethylsilylpropyne, under stirring with ice cooling, followed by stirring at the same temperature for 2 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only ethyl acetate), obtaining 418 mg specified in the header is soedineniya in the form of a white powder (yield: 98%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 8.04 (4H, d, J=7 Hz), 7,55 (2H, t, J=7 Hz), 7,43 (4H, t, J=7 Hz), a 4.53 (2H, DD, J=12 Hz, J=3 Hz), 4,36 (2H, DD, J=12 Hz, 5 Hz), 4,13-4,08 (2H, m) 0,13 (18H, s).

Reference example 2

1,3,4,5,7-Penta-About- (trimethylsilyl)-D-arabitol

In accordance with the process described in referential example 1, D-arabitol used instead of 1,4-di-About-benzoyl-meso-erythritol, obtaining specified in the title compounds as colorless oil (yield: 26%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

3,84-of 3.80 (1H, m), 3,76-3,68 (3H, m), 3,63-of 3.54 (2H, m), 3,49 (1H, DD, J=10 Hz, J=7 Hz), 0,14-0,09 (45H, m).

Reference example 3

1,6-Di-About-benzoyl-2,3,4,5-Tetra-About- (trimethylsilyl)-D-mannitol

In accordance with the process described in referential example 1, 1,6-di-About-benzoyl-D-mannitol was used instead of 1,4-di-About-benzoyl-meso-erythritol, obtaining specified in the title compounds as a pale brown oil (yield: 98%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

with 8.05 (4H, d, J=7 Hz), 7,55 (2H, t, J=7 Hz), 7,43 (4H, t, J=7 Hz), 4,59 (2H, DD, J=12 Hz, 2 Hz), to 4.38-or 4.31 (2H, m), 4,24-4,20 (2H, m), 3,83 (2H, users), 0,17 (18H, s), 0,11 (18H, s).

Reference example 4

2 Trimethylsilyloxy-1-trimethylsilylacetamide adamantane-1-carboxylate

(4A) 2-Phenyl[1.3]dioxane-5-ol adamantane-1-carboxylate

to 1.00 g (5,55 mmol) 2-phenyl[1.3]dioxane-5-ol, of 1.16 ml (8,32 mmol) of triethylamine and 68 mg (0,56 mmol who) 4-dimethylaminopyridine was dissolved in 20 ml of dichloromethane and thereto was added 1.28 g (6,10 mmol) of 1-adamantanecarbonyl, under stirring with ice cooling, followed by stirring at the same temperature for 30 minutes and then at room temperature for 15 hours. Dichloromethane drove away under reduced pressure, to the residue was added saturated aqueous sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 9:1), to obtain 1.52 g specified in the title compounds as a pale yellow powder (yield: 80%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,52-of 7.48 (2H, m), 7,42-7,33 (3H, m)5,54 (1H, s), 4,68-of 4.66 (1H, m), 4.26 deaths-4,22 (2H, m), 4,18 is 4.13 (2H, m), 2,07 is 2.01 (3H, m), 2,01-of 1.97 (6H, m), 1.77 in was 1.69 (6H, m).

(4b) 2-Hydroxy-1-hydroxymethylation adamantane-1-carboxylate

400 mg (1,17 mmol) 2-phenyl[1.3]dioxane-5-yl adamantane-1-carboxylate obtained in (4A), was dissolved in 8 ml of ethyl acetate and thereto was added 400 mg of 20% palladium hydroxide on coal (water content: 50%), followed by stirring in an atmosphere of hydrogen at room temperature for 4 hours. After filtering off the catalyst, the filtrate was concentrated under reduced pressure, to obtain 294 mg specified in the title compound as a white powder (yield: 99%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,90-is 4.85 (1H, m), 3,84 is 3.76 (4H, m), 2,16 is 2.00 (5H, m), 1,94-to 1.87 (6H, m), 1,78-to 1.67 (6H, m).

(4C) 2-Trimethylsilyloxy-1-trimethylsilylacetamide adamantane-1-carboxylate

In accordance with the process described in referential example 1, 2-hydroxy-1-hydroxyethylacrylate-1-carboxylate obtained in (4b)was used instead of 1,4-di-About-benzoyl-meso-erythritol, obtaining specified in the title compounds as colorless oil (yield: 70%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,85-rate 4.79 (1H, m), 3.72 points-3,61 (4H, m), 2,04-of 1.97 (3H, m), 1,92 of-1.83 (6H, m), 1,76-of 1.65 (6H, m), 0,11 (18H, s).

Reference example 5

Diethyl 2,2-bis[(trimethylsilyl)oxy]methylmalonate

In accordance with the process described in referential example 1, diethyl 2,2-bis(hydroxymethyl)malonate used instead of 1,4-di-About-benzoyl-meso-erythritol, obtaining specified in the title compounds as colorless oil (yield: 75%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 4.17 (4H, square, J=7 Hz), Android 4.04 (4H, s)of 1.23 (6H, t, J=7 Hz), 0,07 (18H, s).

Reference example 6

2 Pencil-1H-pyrrol-1-ylamine

(6A) (2E)-4-Oxo-2-nonenal

2.0 g (14,47 mmol) of 2-pentylfuran was dissolved in 60 ml of dichloromethane and thereto is added dropwise under stirring with ice cooling was added of 3.84 g (14,47 mmol) 65%m-chloroperbenzoic acid, followed by stirring at the same pace is the temperature for 1 hour. To the reaction solution was added saturated aqueous solution of sodium carbonate and the mixture was extracted with dichloromethane. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure, obtaining of 1.62 g specified in the title compound as a yellow oil (yield: 73%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

10,23 (1H, d, J=7 Hz), to 6.95 (1H, d, J=12 Hz), 6,18 (1H, DD, J=12 Hz, 7 Hz), and 2.26 (2H, t, J=7 Hz), 1,73-to 1.61 (2H, m), 1,40-of 1.26 (4H, m)of 0.91 (3H, t, J=6 Hz).

(6b) 4-Axonemal

of 1.62 g (10.5 mmol) (2E)-4-oxo-2-nonenal obtained in (6A), was dissolved in 30 ml of ethyl acetate and thereto was added 160 mg of 10% palladium hydroxide on coal (water content: 50%), followed by stirring in an atmosphere of hydrogen at room temperature for 2 hours. After filtering off the catalyst, the filtrate was concentrated under reduced pressure, to obtain 1.50 g specified in the title compounds as a pale yellow oil (yield: 91%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

9,81 (1H, s), 2,81-to 2.67 (4H, m), 2,47 (2H, t, J=7 Hz), 1,67-of 1.53 (2H, m), 1,38-to 1.21 (4H, m)to 0.89 (3H, t, J=7 Hz).

(6C) Benzyl 2-pentyl-1H-pyrrol-1-ylcarbamate

1.50 g (a 9.60 mmol) 4-axonemal obtained in (6b), was dissolved in 45 ml of a mixture of ethanol-acetic acid (2:1), and thereto were added to 1.60 g (a 9.60 mmol) of benzylideneaniline, with subsequent displacement is ywaniem at 80 ° C for 1 hour. The reaction solution was concentrated under reduced pressure and the residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), obtaining 2,12 g specified in the title compound as a yellow oil (yield: 77%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 7.36 (5H, users), 7,21 (1H, DS), 6,63-6,59 (1H, m), 6,07 (1H, t, J=4 Hz), of 5.89 of 5.84 (1H, m), with 5.22 (2H, DS), 2,46-of 2.36 (2H, m), 1,63-1,49 (2H, m), 1,37-1,22 (4H, m)to 0.88 (3H, t, J=7 Hz).

(6d) 2 Pencil-1H-pyrrol-1-amine

1.0 g (3,49 mmol) benzyl 2-pentyl-1H-pyrrol-1-ylcarbamate obtained in (6C), was dissolved in 20 ml of ethanol and thereto was added 100 mg of 10% palladium on coal (water content: 50%), followed by stirring in an atmosphere of hydrogen at room temperature for 2 hours. After filtering off the catalyst, the filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 2:1), to obtain 430 mg specified in the title compound as a yellow oil (yield: 81%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 6.68 (1H, m), 5,97 (1H, t, J=3 Hz), of 5.82 is 5.77 (1H, m)to 4.52 (2H, s), 2,58 (2H, t, J=8 Hz), 1,69-of 1.57 (2H, m), 1,44 to 1.31 (4H, m)of 0.91 (3H, t, J=7 Hz).

Reference example 7

2-Hexyl-1H-pyrrol-1-ylamine

In accordance with the process described in referential example 6, 2-sexyporn used as source material BM is one hundred 2-pentylfuran, obtaining specified in the title compound as a yellow oil (yield: 29%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,67-6,63 (1H, m), 5,99-5,94 (1H, m), 5,81 is 5.77 (1H, m)to 4.52 (2H, users), 2,62 is 2.55 (2H, m), 1,67-of 1.56 (2H, m), 1,44-to 1.21 (6H, m)to 0.89 (3H, t, J=7 Hz).

Reference example 8

2-Heptyl-1H-pyrrol-1-ylamine

In accordance with the process described in referential example 6, 2-heptylphenol used as starting material instead of 2-pentylfuran, obtaining specified in the title compound as yellow solid (yield: 59%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,67-6,63 (1H, m), 5,99-5,94 (1H, m), 5,81 is 5.77 (1H, m)to 4.52 (2H, users), 2,62 is 2.55 (2H, m), 1,67-of 1.53 (2H, m), 1,44-to 1.21 (8H, m)to 0.89 (3H, t, J=7 Hz).

Reference example 9

2-Octyl-1H-pyrrol-1-ylamine

In accordance with the process described in referential example 6, 2-ockelford used as starting material instead of 2-pentylfuran, obtaining specified in the title compound as a yellow oil (yield: 11%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,65-of 6.61 (1H, m), 5,97-to 5.93 (1H, m), 5,78-of 5.75 (1H, m), 4,51 (2H, users), 2,60 is 2.55 (2H, m), 1,66-and 1.54 (2H, m), 1,42-1,21 (10H, m)to 0.88 (3H, t, J=7 Hz).

Reference example 10

2-Cyclopropyl-1H-pyrrol-1-ylamine

(10A) 4-Cyclopropyl-4-oxobutyl

230 mg (1,79 mmol) 1-cyclopropyl-4-hydroxy-1-butanone was dissolved in 7 ml of dichloromethane and thereto was added 580 mg (2.9 mmol) pyridylamine, followed by stirring at room temperature for 1 hour. To the reaction solution was added diethyl ether, the mixture was filtered using cellite and the filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: only diethyl ether)to obtain 176 mg specified in the title compounds as a pale yellow oil (yield: 78%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

9,78 (1H, s), only 2.91 (2H, t, J=7 Hz), 2,78-a 2.71 (2H, m), 2,01-of 1.93 (1H, m), 1,08-a 1.01 (2H, m), 0,96-0,88 (2H, m).

(10b) 2-Cyclopropyl-1H-pyrrol-1-ylamine

In accordance with the process described in the reference examples (6C) and (6d), 4-cyclopropyl-4-oxobutyl obtained in (10A)was used instead of 4-axonemal, obtaining specified in the title compounds as a pale yellow oil (yield: 45%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,70-only 6.64 (1H, m), 5,94-5,88 (1H, m), 5,71-5,64 (1H, m), 4,69 (2H, users)and 1.83-1,72 (1H, m), 0,91-0,83 (2H, m), 0,64-0,57 (2H, m).

Reference example 11

4-fluoro-2-heptylaniline

(11a) 4-fluoro-2-(hept-1-enyl)-1-nitrobenzene

3.0 g (7.0 mmol) of bromide hexyltrichlorosilane suspended in 30 ml of tetrahydrofuran, and thereto was added dropwise to 4.5 ml (7.0 mmol) of a solution (1,56 M) n-utility/hexane at-10C. After the reaction solution was stirred at the same temperature for 10 minutes, until alali 846 mg (5.0 mmol) 4-fluoro-2-nitrobenzaldehyde, and the reaction solution was then stirred for 1 hour. To the reaction solution was added 1 N. aqueous solution of potassium bisulfate and the mixture was extracted with ethyl acetate. The organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 19:1), obtaining 917 mg specified in the title compounds as a pale yellow oil (yield: 77%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

8,09 (1,7H, DD, J=9 Hz, 5 Hz), of 7.97 (1H, DD, J=9 Hz, 5 Hz), 7,26-6,99 (5,4H, m), 6.89 in (1H, d, J=16 Hz), 6,69 (1,7H, d, J=11 Hz), of 6.26 (1H, dt, J=16 Hz, 7 Hz), by 5.87 (1,7H, dt, J=12 Hz, 8 Hz), 2,28 (2H, square, J=7 Hz), 2,10 (3,4H, square, J=7 Hz), 1,52-1,23 (16,2H, m)of 0.91 (3H, m)0,86 (5,1H, m).

(11b) 4-fluoro-2-heptylaniline

910 mg (3.8 mmol) 4-fluoro-2-(hept-1-enyl)-1-nitrobenzene obtained in (11a), was dissolved in 5 ml of ethanol and thereto was added 100 mg of 10% palladium on coal (water content: 50%), followed by stirring in an atmosphere of hydrogen at room temperature for 2 hours. After filtering off the catalyst, the filtrate was concentrated under reduced pressure and the residue was subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate = 9:1), to obtain 730 mg specified in the title compounds as a pale yellow oil (yield: 91%).

1 H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,80-of 6.71 (2H, m), is 6.61 (1H, DD, J=9 Hz, 5 Hz), 3,47 (2H, users), a 2.45 (2H, t, J=7 Hz), 1,64 is 1.58 (2H, m), 1,42-of 1.24 (8H, m)to 0.89 (3H, t, J=6 Hz).

Reference example 12

2-Butyl-4-forfinally

In accordance with the process described in referential example 11, bromide propyltrichlorosilane used instead bromide hexyltrichlorosilane, obtaining specified in the title compound as a brown oil (yield: 78%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,80-6,69 (2H, m), 6,60 (1H, DD, J=9 Hz, 5 Hz), 3,51 (2H, users), the 2.46 (2H, t, J=8 Hz), 1,63-of 1.56 (2H, m), 1,45 to 1.37 (2H, m)to 0.96 (3H, t, J=7 Hz).

Reference example 13

4-fluoro-2-interphenylene

In accordance with the process described in referential example 11, bromide butyldiphenylsilyl used instead bromide hexyltrichlorosilane, obtaining specified in the title compound as a yellow oil (yield: 78%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,80-6,69 (2H, m), 6,60 (1H, DD, J=9 Hz, 5 Hz), 3,50 (2H, users), a 2.45 (2H, t, J=8 Hz), 1,64 is 1.58 (2H, m), 1,45-of 1.36 (4H, m)of 0.91 (3H, t, J=7 Hz).

Reference example 14

4-fluoro-2-hexylaniline

In accordance with the process described in referential example 11, bromide intelligentsia used instead bromide hexyltrichlorosilane, obtaining specified in the title compounds as a pale brown oil (yield: 63%).

1H-I Is R-spectrum (400 MHz, CDCl3) δ ppm:

for 6.81-of 6.71 (2H, m), of 6.66 (1H, DD, J=9 Hz, 5 Hz), 4,19 (2H, users), 2,48 (2H, t, J=8 Hz), 1,65-of 1.57 (2H, m), USD 1.43-1,25 (6H, m), 0,92-of 0.85 (3H, m).

Reference example 15

4-fluoro-2-octylaniline

In accordance with the process described in referential example 11, bromide reptilienfauna used instead bromide hexyltrichlorosilane, obtaining specified in the title compounds as a pale yellow oil (yield: 65%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,80-of 6.71 (2H, m), is 6.61 (1H, DD, J=9 Hz, 5 Hz), a 2.45 (2H, t, J=7 Hz), 1,64-of 1.56 (2H, m), 1,38-1,22 (10H, m)to 0.88 (3H, t, J=7 Hz).

Reference example 16

4-fluoro-2-nonylphenyl

In accordance with the process described in referential example 11, bromide octyltrichlorosilane used instead bromide hexyltrichlorosilane, obtaining specified in the title compounds as a pale brown oil (yield: 97%).

1H-NMR spectrum (500 MHz, CDCl3) δ ppm:

6,77 (1H, DD, J=10 Hz, 3 Hz), 6,72 (1H, TD, J=8 Hz, 3 Hz), 6,59 (1H, DD, J=9 Hz, 5 Hz), of 3.46 (2H, users), a 2.45 (2H, t, J=8 Hz), 1,64-of 1.56 (2H, m), 1,44-to 1.21 (12H, m)to 0.88 (3H, t, J=7 Hz).

Reference example 17

2-Decyl-4-forfinally

In accordance with the process described in referential example 11, bromide nortriptylene used instead bromide hexyltrichlorosilane, obtaining specified in the title compounds as a pale brown oil (yield: 67%).

1 H-NMR spectrum (500 MHz, CDCl3) δ ppm:

6,77 (1H, DD, J=10 Hz, 3 Hz), was 6.73 (1H, DD, J=8 Hz, 3 Hz), 6,60 (1H, DD, J=9 Hz, 5 Hz), 3,47 (2H, users), a 2.45 (2H, t, J=8 Hz), 1,64-of 1.56 (2H, m), USD 1.43-1,21 (14H, m)to 0.88 (3H, t, J=7 Hz).

Reference example 18

1,4-Di-About-benzoyl-2,3-di-About-trimethylsilyl-D-threitol

17,48 g (52,9 mmol) of 1,4-di-About-benzoyl-D-threitol and 10.8 g (159 mmol) of imidazole was dissolved in 250 ml of dichloromethane and thereto were added to 12.6 g (116 mmol) of chlorotrimethylsilane, under stirring with ice cooling, followed by stirring at room temperature for 1 hour. The reaction solution was directly subjected to column chromatography on silica gel (solvent: hexane:ethyl acetate= 20:1 - 5:1), obtaining 24,59 g specified in the title compound as a white powder (yield: 98%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 8.04 (4H, DD, J=8 Hz, J=1 Hz), EUR 7.57-7,52 (2H, m), 7,46-7,40 (4H, m), 4,50 (2H, DD, J=11 Hz, J=4 Hz), 4,48-to 4.33 (2H, m), 4,13-4,08 (2H, m)0,14 (18H, s).

Reference example 19

1,4-Di-About-benzoyl-2,3-di-About-trimethylsilyl-L-threitol

In accordance with the process described in referential example 18, 1,4-di-About-benzoyl-L-threitol used instead of 1,4-di-About-benzoyl-D-threitol, obtaining specified in the title compound as a white powder (yield: 98%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

of 8.04 (4H, DD, J=8 Hz, J=1 Hz), EUR 7.57-7,52 (2H, m), 7,46-7,40 (4H, m), 4,50 (2H, DD, J=11 Hz, J=4 Hz), 48-4,33 (2H, m), 4,13-4,08 (2H, m)0,14 (18H, s).

Reference example 20

Methyl (S)-3,4-bis[(trimethylsilyl)oxy]butyrate

In accordance with the process described in referential example 18, methyl (S)-3,4-dihydroxybutyl used instead of 1,4-di-About-benzoyl-D-threitol, obtaining specified in the title compound as oil (yield: 62%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,18-of 4.12 (1H, m)to 3.67 (3H, s), 3,52 (1H, DD, J=10 Hz, 6 Hz), 3,40 (1H, DD, J=10 Hz, 6 Hz), 2,59 (1H, DD, J=15 Hz, 5 Hz), is 2.37 (1H, DD, J=15 Hz, 7 Hz), 0,10 (18H, s).

Reference example 21

1,4-Anhydrous-2,3-di-About- (trimethylsilyl)-meso-erythritol

In accordance with the process described in referential example 1, 1,4-anhydromannitol used instead of 1,4-di-About-benzoyl-meso-erythritol, obtaining specified in the title compounds as colorless oil (yield: 21%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,15-4,10 (2H, m), 3,92-of 3.85 (2H, m), 3,68-3,62 (2H, m)0,14 (18H, s).

Reference example 22

3-Ethyl-3,4-bis[(trimethylsilyl)oxy]hexane

(22A) 3 Ethylhexan-3,4-diol

590 mg (5.0 mmol) of dimethyloxalate was dissolved in 20 ml of tetrahydrofuran was added 22 ml (22 mmol) of 1.0 M ethylmagnesium/tertrahydrofuran ring solution with stirring under ice cooling, followed by stirring for 2 hours at the same temperature. The reaction solution was acidified by addition of 1 N. hydrochloric acid and with whom ect was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to silicagel column chromatography (solvent: hexane:ethyl acetate = 3:1), to obtain 276 mg specified in the title compound as oil (yield: 38%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

3,45-to 3.41 (1H, m)to 1.87 (1H, d, J=6 Hz), a 1.75 (1H, s), 1.70 to to 1.31 (6H, m), was 1.04 (3H, t, J=7 Hz), to 0.89 (3H, t, J=8 Hz), to 0.89 (3H, t, J=8 Hz).

(22b) 3-Ethyl-3,4-bis[(trimethylsilyl)oxy]hexane

270 mg (of 1.85 mmol) 3-ethylhexan-3,4-diol obtained in (22A), was dissolved in 5 ml of pyridine and subsequently added 597 mg (3.7 mmol) of 1,1,1,3,3,3-hexamethyldisilazane and 1.20 g (11 mmol) of chlorotrimethylsilane, followed by stirring for 2 hours at the same temperature and additionally over night at room temperature. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue was subjected to silicagel column chromatography (solvent: hexane:ethyl acetate = 9:1), with 469 mg specified in the title compound as oil (yield: 88%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

to 3.38 (1H, DD, J=9,0 Hz, 3.0 Hz), 1,68 and 1.33 (6H, m)of 0.90 (3H, t, J=6.0 Hz), 0,92-0,90 (6H, m), 0,11-,08 (18H, m).

Reference example 23

(R)-1,2-Bis[(trimethylsilyl)oxy]-1,1,2-triphenyltin

Following the process described in referential example 18, (R)-1,1,2-triphenyl-1,2-ethanediol was used instead of 1,4-di-O-benzoyl-D-threitol, obtaining specified in the title compound as a powder (yield: 99%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

7,28-7,18 (15H, m), the 5.51 (1H, s)-0,05 (9H, s)-0,16 (9H, s).

Reference example 24

1,4-Di-About-acetyl-2,3-di-About-trimethylsilyl-D-threitol

According to the process described in referential example 18, 1,4-di-About-acetyl-D-threitol used instead of 1,4-di-O-benzoyl-D-threitol, obtaining specified in the title compound as oil (yield: 96%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

4,20 (2H, DD, J=11 Hz, 4 Hz)to 4.01 (2H, DD, J=11 Hz, 7 Hz), 3,88-a-3.84 (2H, m)to 2.06 (6H, s), 0,13 (18H, s).

Reference example 25

(1R,2R,3R,4R)-4-Benzoyloxy-1-methyl-2,3-bis[(trimethylsilyl)oxy]pentylbenzoic

According to the process described in referential example 18, instead of 1,4-di-O-benzoyl-D-threitol used (1R,2S,3S,4R)-4-benzoyloxy-2,3-dihydroxy-1-methylpentanoate, obtaining specified in the title compound as oil (yield: 86%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

8,06-8,04 (4H, m), EUR 7.57-rate of 7.54 (2H, m), 7,46-7,42 (4H, m), 5,31-a 5.25 (2H, m), 3,98-of 3.97 (2H, m)of 1.41 (6H, d, J=6 Hz), 0,12 (18H, s).

Reference the example 26

(1R,2R,3R,4R)-4-Benzoyloxy-1-ethyl-2,3-bis[(trimethylsilyl)oxy]hexylbenzoate

According to the process described in referential example 18, instead of 1,4-di-O-benzoyl-D-threitol used (1R,2S,3S,4R)-4-benzoyloxy-1-ethyl-2,3-dihydroxybenzoate, obtaining specified in the title compound as oil (yield: 82%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

8,09-8,07 (4H, m), to 7.59-of 7.55 (2H, m), 7,47-the 7.43 (4H, m), 7,47-the 7.43 (2H, m), of 3.96 (2H, s), 2.00 in to 1.79 (4H, m)of 1.02 (6H, t, J=7 Hz), 0,07 (18H, s).

Reference example 27

4-fluoro-2-propylaniline

According to the process described in referential example 11, instead of hexyltrichlorosilane used ethyltriphenylphosphonium, obtaining specified in the title compounds as a pale yellow oil (yield: 17%).

1H-NMR spectrum (400 MHz, CDCl3) δ ppm:

6,80-6,59 (3H, m), of 3.48 (2H, users), a 2.45 (2H, t, J=7 Hz), 1.70 to was 1.58 (2H, m), a 1.01 (3H, t, J=8 Hz).

EXAMPLES TEST

The test example 1. The effect of suppressing stimulated by endotoxin production of TNF-α in cells (in vitro)

We measured the degree of suppression of the compound according to the present invention, the production of TNF-α, when the cell line of human U937 monocytes stimulated by endotoxin. In particular, RPMI1640 medium containing 10% (vol.%), inactivated warmth of a newborn calf serum, was added 13-azet the t 12-O-tetradecanoylphorbol so, so that its final concentration was 30 ng/ml U937 Cells suspended in the medium and were placed on a 96-well plate for crops (Sumilon) so that the number of cells per volume was 2×104/0.1 ml, and then were cultured for 3 days at 37°C in deoxycholate incubator with 5% CO2and 100% humidity. After incubation, the culture supernatant was removed. To each well was added the compound according to the present invention in various concentrations and also added lipopolysaccharide (LPS) (E.cli 0111:B4, Sigma) so that its final concentration was 30 ng/ml After incubation the culture of the tablet in perodicticus the incubator for another 4.5 hours of culture supernatant was collected. Using 384-well black plate with half-edge (Greiner) and HTRF quantitative set of CIS Bio International was measured concentration of TNF-α in the culture supernatant in the form of time-resolved fluorescence using Discovery (Packard). According to the measured value in the absence of LPS (X), the measured value in the absence of the compounds according to the present invention (Y) and the measured value in the presence of compounds according to the present invention (Z) has received the degree of suppression of the production of TNF-α using the following calculation formula [I].

The degree of suppression of the production of TNF-α (%)=

{1-(Z-X)/(Y-X)}×100 [I]

Currently the test compound according to the present invention showed a superior effect of suppressing stimulated by endotoxin production of TNF-α in cells.

The test example 2. The effect of suppression of elevated concentrations of TNF-α in the blood (in vivo)

Evaluated the effect of suppressing compound according to the present invention increased concentrations of TNF-α in the blood. Test increasing concentrations of TNF-α in the blood was performed in accordance with the process Parant et al, which is described in the Journal of Leukocyte Biology, Vol. 47, 164 (1990).

In the test used 3-4 male rats Sprague Dawley (age 8-9 weeks) for each group.

4 hours prior to LPS injection in the tail vein injected with muramyldipeptide dissolved in physiological saline (1 mg/ml), in the amount of 1 ml/kg For 0.5 hours prior to LPS injection, rats were anestesiologi pentobarbital (40 mg/kg), and in the right femoral vein at a rate of 1 ml/kg was administered the compound according to the present invention, dissolved in a solution of 5% dimethylacetamide/95% polyethylene glycol 400. The control group in the amount of 1 ml/kg was injected a solution of 5% dimethylacetamide/95% polyethylene glycol 400. In the left femoral vein at a rate of 1 ml/kg was injected LPS dissolved in physiological saline solution (3 μg/ml). 2 hours after LPS injection, blood was collected using an anticoagulant to 3.8% (wt./about.) solution of sodium citrate and blood plasma was separated using a centrifuge (10000 g, 5 min, 4°C). The concentration of TNF-α in plasma was measured with the use of TNF-α quantitative kit (Bio-Source International, nc.). Concentration of TNF-α in the blood of the control group (X) and the concentration of TNF-α in blood group, which entered the compound according to the present invention (Y), calculated the degree of suppression of elevated concentrations of TNF-α using the computational formula [II].

The degree of suppression of elevated concentrations of TNF-α (%)=

{1-Y/X}×100 [II]

In this test, the compound according to the present invention showed excellent effects of suppressing elevated concentrations of TNF-α in the blood.

1. The connection represented by the General formula (I):

in which X and Y represent a group in which X and Y together with the carbon atom of the ring to which they are attached, form ring A, X and Y together represent Deputy ring, or X and Y each represents a hydrogen atom;
(1) when X and Y represent a group in which X and Y together with the carbon atom of the ring to which they are attached, form ring A:
the ring And is
3-7-membered heterocyclyl ring [heterocyclyl ring X and Y independently of one another represent any atom or group selected from a carbon atom, oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2, heterocyclyl ring may include unsaturated bond, may form condenser the data ring or spirocerca with a 3-7-membered heterocyclyl ring, and ring And including a condensed ring or a Spiro ring, may be substituted by same or different 1 to 4 groups selected from the group consisting of a carbonyl group, tocography, replacement group α, cyclopropyl C1-C6alkyl group,
C1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α];
(2) when X and Y together represent Deputy rings:
X and Y represent oxoprop;
1 and m independently from each other represent an integer from 0 to 3, and
1+m is 1-3;
n represents an integer of 0
R2represents a hydrogen atom,
C1-C6alkyl group which may be substituted with group(s)selected(s) from foster group β;
R3is
phenyl group which may be substituted with group(s),
the selected(s) from foster group ε, or
5 - or 6-membered heteroaryl group which may be substituted with group(s)selected(generated) from foster group ε (heteroaryl group comprises 1-3 heteroatoms selected from a nitrogen atom);
R5represents a hydrogen atom;
provided that when R3represents a phenyl group which may be substituted with group(s)selected(s) from foster group ε, X and Y represent the above-mentioned groups (1) or (2);
replacement group α represents
the hydroxy-group, halogen atom, With1-C6alkoxygroup, halogeno C1-C6alkoxygroup, carboxypropyl, C1-C6alkoxycarbonyl group;
and a group having the formula NR6R7and
R6and R7independently from each other represent a hydrogen atom, a C1-C6alkanoyloxy group or together with the nitrogen atom to which they are attached, form alkylpyridinium group;
replacement group β represents the
C1-C6alkoxygroup,1-C10alkoxycarbonyl group;
replacement group ε is
the hydroxy-group, a halogen atom, a C1-C14alkyl group, cyclopropyl1-C14alkyl group, halogeno1-C14alkyl group, a C1-C14alkoxygroup, halogeno C1-C14alkoxygroup, carboxypropyl, C1-C14alkanoyloxy group, C1-C14alkoxycarbonyl group, C1-C14allylthiourea, karbamoilnuyu group, C1-C14alkylcarboxylic group, a group having the formula NR6R7(R6and R7have the same meaning as R6and R7replacement group α), C6-C10aryl group and 5-membered heteroaryl group,
or its pharmacologically acceptable salt.

2. With the Association or its pharmacologically acceptable salt according to claim 1, in which 1 is 0 and m is an integer 1-3.

3. The compound or its pharmacologically acceptable salt according to claim 1, in which 1 is 0 and m is 2.

4. The compound or its pharmacologically acceptable salt according to claim 1, in which X and Y together with the carbon atom of the ring To form a ring a and ring a ' is
3-7-membered heterocyclyl ring
[heterocyclyl ring X and Y independently of one another represent any atom or group selected from a carbon atom, oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2, heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring has 1 or 2 oxygen atom and/or nitrogen as heteroatoms), and
ring And including a condensed ring or spirochaete may be substituted by same or different 1 to 4 groups selected from the group consisting of a carbonyl group, tocography,
replacement group α, cyclopropyl C1-C6alkyl groups and C1-C6alkyl group which may be substituted by 1 to 5 groups selected from foster group α].

5. The compound or its pharmacologically acceptable salt according to claim 1, in which
X and Y represent a group in which X and Y together with the carbon atom to which LCA To form a ring And, and the ring And is
3-7-membered heterocyclyl ring
[heterocyclyl ring X and Y independently of one another represent any atom or group selected from a carbon atom, oxygen atom, sulfur atom, a group having the formula SO, and a group having the formula SO2,
heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (heterocyclyl ring has 1 or 2 oxygen atom and/or nitrogen as heteroatoms), and
ring And including a condensed ring or spirochaete may be substituted by same or different 1 to 4 groups selected from the group consisting of a carbonyl group, tocography, replacement group α and C1-C6alkyl group which may be substituted by 1-4 groups selected from foster group α].

6. The compound or its pharmacologically acceptable salt according to claim 1, in which
X and Y represent a group in which X and Y together with the carbon atom of the ring To form a ring a and ring a ' is
3-7-membered heterocyclyl ring
[3-7-membered heterocyclyl ring is oxiran, oxolan, tetrahydrofuran, tetrahydropyran, 1,3-dioxolane, 1,3-dioxane, 1,3-dioxan, 1,3-ditiolan, 1,3-dition, 1,1,3,3-tetraoxo-1,3-ditiolan, 1,3-oxathiolane, 1,3-Ossetian or 1,3-exatape, data heterotic the ilen ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (5 - or 6-membered heterocyclyl ring represents tetrahydrofuran, tetrahydropyran, pyrrolidine, piperidine or 1,3-dioxane), and
ring And including a condensed ring and spirocerca may be substituted by 1 or 2 groups selected from the group consisting of a carbonyl group, tocography, replacement group α (replacement group α represents a hydroxy-group and a group having the formula NR6R7and R6and R7independently from each other represent a hydrogen atom or a C1-C6alkanoyloxy group, methyl group, ethyl group, and C1-C6alkyl group which is substituted by 1-4 hydroxy groups].

7. The compound or its pharmacologically acceptable salt according to claim 1, in which
X and Y represent a group in which X and Y together with the carbon atom of the ring To form a ring a and ring a represents a 3-6-membered heterocyclyl ring
{heterocyclyl ring is oxirane, tetrahydrofuran, 1,3-dioxolane, 1,3-dioxane, 1,3-ditiolan, 1,3-dition, 1,3-oxathiolan or 1,3-axation,
data heterocyclyl ring may form a condensed ring or spirocerca with a 5 - or 6-membered heterocyclyl ring (5 - or 6-membered heterocyclyl ring represents tetrahydrofuran, tetrahydropyran or 1,3-dioxane), and
ring And including a condensed ring or spirochaete may be substituted by 1 or 2 groups selected from the group consisting of the replacement group α [replacement group α represents a hydroxy-group and group, having the formula NR6R7(R6and R7independently from each other represent a hydrogen atom or acetyl group)], a methyl group, ethyl group, hydroxymethylene group, 1,2-dihydroxyethylene group, 1,2,3-trihydroxypropane group and 1,2,3,4-tetrahydroquinoline group}.

8. The compound or its pharmacologically acceptable salt according to claim 1, in which R2represents C1-C6alkyl group.

9. The compound or its pharmacologically acceptable salt according to claim 1, in which R2represents C1-C4alkyl group.

10. The compound or its pharmacologically acceptable salt according to claim 1, in which R2represents ethyl group.

11. The compound or its pharmacologically acceptable salt according to claim 1, in which
R3is
phenyl group which may be substituted with group(s)selected(s) from foster group ε, or
pyrrolidino group which may be substituted with group(s)selected(s) from foster group ε, and
replacement group ε represents a halogen atom, a C1-C14alkyl group, halogeno C1-C14alkyl group.

12. The compound or its pharmacologically acceptable salt according to claim 1, in which
R3is
phenyl group which may be substituted with group(s)selected(s) from somedays the th group ε, or
pyrrolidino group which may be substituted with group(s)selected(s) from foster group ε, and
replacement group ε represents a fluorine atom, a chlorine atom, a bromine atom, With3-C6alkyl group, halogeno C4-C8alkyl group.

13. The compound or its pharmacologically acceptable salt according to claim 1, in which
R3is
phenyl group which may be substituted with group(s)selected(s) from foster group ε, and
replacement group ε represents a fluorine atom, a chlorine atom and C3-C8alkyl group.

14. Join the next group selected from claim 1 or its pharmacologically acceptable salt:
ethyl 8-[N-(2-chlorophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chlorophenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2,4-differenl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-hydroxymethyl-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl is)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2,3-trihydroxypropane)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-4-forfinal)sulfamoyl]-2-(1,2,3,4-tetrahydroquinolin)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 2,3-bis(acetamidomethyl)-8-[N-(2-chloro-4-forfinal)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3-hydroxy-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,
ethyl 3-acetylamino-9-[N-(2-chloro-4-forfinal)sulfamoyl]-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,
ethyl 9-[N-(2-chloro-4-forfinal)sulfamoyl]-3,3-bis(hydroxymethyl)-1,5-dioxaspiro[5.5]undec-7-ene-8-carboxylate,
ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-butyl-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-hexylphenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-hexylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate
ethyl 8-[N-(2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-heptylphenol)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro [4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-heptylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-bromophenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-bromophenyl)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro [4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-chloro-6-were)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(2-bromo-4-forfinal)sulfamoyl]-2,3-bis(1,2-dihydroxyethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 2,3-bis(hydroxymethyl)-8-[N-(2-pentylphenol)sulfamoyl]-1,4-dioxaspiro [4.5]Dec-6-ene-7-carboxylate,
ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
e is Il 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-pentylphenol)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-octylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate,
ethyl 2,3-bis(1,2-dihydroxyethyl)-8-[N-(4-fluoro-2-propylphenyl)sulfamoyl]-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate and
ethyl 8-[N-(2-chloro-4-forfinal)-N-methylsulfonyl]-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]Dec-6-ene-7-carboxylate.

15. Drug, with overwhelming effect against intracellular signal transduction or cell activation induced by endotoxin, containing the compound or its pharmacologically acceptable salt according to any one of claims 1 to 14 as an active ingredient.

16. The drug is indicated in paragraph 15 for use in the inhibition of intracellular signal transduction or cell activation induced by endotoxin.

17. The drug is indicated in paragraph 15 for use in the suppression of the generation of inflammatory mediators due to intracellular signal transduction or cell activation induced by endotoxin.

18. The drug is indicated in paragraph 15 for use as a prophylactic or therapeutic agent against the disease, are the of egasa a consequence of intracellular signal transduction or cell activation, induced by endotoxin.

19. The drug is indicated in paragraph 15 for use as a prophylactic and/or therapeutic agent of diseases mediated inflammatory mediator generation which is induced by endotoxin.

20. The drug is indicated in paragraph 15 for use as a prophylactic and/or therapeutic agent of diseases mediated inflammatory mediator, which is generated due to intracellular signal transduction or cell activation induced by endotoxin.

21. The drug is indicated in paragraph 15 for use as a prophylactic and/or therapeutic agent from sepsis.



 

Same patents:

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention relates to compounds of formula I , wherein W is halogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C4-haloalkyl or C1-C4-haloalkoxy; X is hydrogen, halogen, C1-C6-alkyl; Y is hydrogen, halogen, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-haloalcoxy or cyano; Z is hydrogen, halogen, etc.; G is halogen or nitro; meanings of the other substituents are as defined in specification. Also disclosed are methods for production of said compounds by interaction compounds of formula II with halogenation agents in presence of solvent and optionally of radical initiator of with fumed nitric acid in presence of solvent.

EFFECT: new compounds with insecticide activity.

17 cl, 20 tbl, 114 ex

FIELD: color-forming compositions and recording material.

SUBSTANCE: claimed composition includes developer containing urea-urethane compound and colorless or light colored leuco dye. Recording material based on this composition also is proposed.

EFFECT: color-forming compositions with improved image conservation ability and increased image intensity.

21 cl, 14 tbl, 153 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound or its salt of formula 1: , where A, E, D, R0, R1-R4 and a assume values given in the formula of invention. The invention also relates to an antioxidant medicinal agent.

EFFECT: effectiveness during treatment of ischemic diseases of organs, during treatment of diseases caused by oxidation cell disorders and when inhibiting disorders of the retina.

4 cl, 1 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel 4-phenylpyrimidine-2-carbonitrile of formula

(values of R, R1, R2 are given in the formula of invention) or their pharmaceutically acceptable salts which have inhibition properties towards catepsin K and catepsin S. The invention also relates to use of derivatives of formula I for treating catepsin K and catepsin S related disorders, as well as to a pharmaceutical composition containing the said derivative.

EFFECT: improved properties of derivatives.

9 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: invention proposes 5-member heterocyclic inhibitors of kinase p38, including kinase p38α and kinase p38β, based on pyrazoles and imidazoles, with the general formula given below , in which ring B is phenyl, and C is a pyrazole or imidazole ring, and the rest of the symbols assume values given in paragraph 1 of the formula of invention.

EFFECT: there are described pharmaceutical compositions containing said compounds, as well as methods of using the compounds and compositions, including a method of treating, preventing or suppressing one or more symptoms of diseases and conditions mediated by kinase p38 which include, but not limited to, inflammatory diseases and conditions.

31 cl, 6 tbl, 175 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds with general formula (I), where W is oxygen or sulphur; X1 and X3 are independently hydrogen or C1-C6-alkoxy; X2 is hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy and X4 is hydrogen, Y is in position (N2) or (N3); when Y is in position (N2), Y is C1-C6-alkyl, C1-C6-fluoroalkyl, phenyl, pyridinyl or pyrazinyl; when Y is in position (N3), Y is phenyl, pyridinyl or pyrimidinyl, where phenyl is optionally substituted with one or more atoms or groups selected from halogen, C1-C5 alkyl, C1-C6-alkoxy; the bond in position C4-C5 is a single or double bond; R1 and R2 each independently represent phenyl and C1-C6-alkyl, where at least one of R1 and R2 represents C1-C6-alkyl; or R1 and R2 together with the nitrogen atom to which they are bonded form a cyclic group containing from 4 to 7 links and a nitrogen atom and possibly another heteroatom, such as nitrogen or oxygen, possibly substituted with one or more C1-C6-alkyl groups; or to their pharmaceutically acceptable salts. The invention also relates to methods of producing the proposed compounds with formula (I), and specifically to compounds with formulae (Ia) and (Ib), in which X1, X3, X3, X4 and Y are as described in general formula (I). The invention also relates to intermediate compounds of synthesis of formula (I) compounds - compounds with formulae (Va) and (Vb). In formula (Va) X1, X3 and X4 represent hydrogen; X2 is hydrogen, halogen or C1-C6-alkoxy and Y is C1-C6-alkyl, C1-C6-fluoroalkyl, phenyl, pyridinyl or pyrazinyl; where phenyl is possibly substituted with one or more atoms or groups selected from halogen, C1-C6-alkyl, C1-C6-alkoxy. In formula (Vb) X1 and X3 represent hydrogen or C1-C6-alkoxy; X2 is hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy, X4 is hydrogen; Y is phenyl, pyridinyl or pyrmidinyl; phenyl is possibly substituted with one or more atoms or groups selected from halogen, C1-C6-alkyl, C1-C6-alkoxy. The invention also relates to a medicinal agent based on a formula (I) compound or its pharmaceutically acceptable salt for preventing and treating pathologies where peripheral type benzodiazepine receptors take part. The invention also relates to use of formula (I) compounds in preparing the said medicinal agent and to a pharmaceutical composition for preventing and treating pathologies in which peripheral type benzodiazepine receptors take part.

EFFECT: new compounds have useful biological activity.

11 cl, 3 tbl, 6 ex

.

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula compounds, as well as their pharmaceutically acceptable salts, a pharmaceutical composition based on them, with inhibitory activity towards phosphorylation of protein Tau, and to methods of producing said compounds. In formula (I), R5 is aryl, aryl(C1-C6)alkyl; R6 is halogen; R3 is (C1-C6)alkyl, possibly substituted with substitutes selected from halogen, OH, NH2, azetidine; or monocyclic aryl or heteroaryl, such as thiophene or pyridine, possibly substituted with substitutes selected from NO2, CN, (C1-C6)alkoxy, (C1-C6)alkyl; or CONR1R2, SO2Ra, C(=NH)R1b, COOR1c; R1, R2 independently represent a hydrogen atom, possibly substituted with one halogen atom, (C1-C6)alkyl, moncyclic aryl or monocyclic 5- or 6-member heteroaryl containing 1 or 2 heteroatoms, such as S, O, N, possibly substituted with one or more substitutes selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxyl, trifluoromethyl, N(CH3)2; or R1 and R2 can form a 5- or 6-member ring which optionally contains a heteroatom such as N; R1a is aryl, possibly substituted with (C1-C6)alkoxy; R1b is (C1-C6)alkyl, possibly substituted aryl or 6-member heteroaryl, containing 1 or 2 N atoms, where the substitute is (C1-C6)alkoxyl; R1c is (C1-C6)alkyl, (C2-C6)alkenyl; and their pharmaceutically acceptable salts.

EFFECT: aminoindazole derivatives as kinase inhibitor.

8 cl, 44 ex

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of benzoindazole of formula I , where radicals A1, A2, A3, R1, R2, R3, R4 and n have values mentioned in formula of invention, and their pharmaceutically acceptable salts, and also to application of these compounds for production of medicinal agent intended for modulation of α2-subsort of GABA receptor, and pharmaceutical composition that contains it.

EFFECT: application of compounds for preparation of medicinal agent intended for treatment of depression, disorder in the form of anxiety, psychic disorder, disturbed ability to learning and cognition, sleep disturbance, disorder in the form of cramps or fits or pain.

16 cl, 5 tbl, 40 ex

FIELD: medicine.

SUBSTANCE: invention is related to compounds with common formulae I , III , IV and V , value of radicals such as given in formula of invention. Also suggested invention is related to pharmaceutical composition in the basis of above-mentioned compounds, to their use, and also to method of frequent urination treatment, enuresis and increased activity of urinary bladder.

EFFECT: increased efficiency of diseases treatment, in particular for treatment of frequent urination and enuresis, increased activity of urinary bladder and pain.

16 cl, 406 ex, 73 tbl

V:

FIELD: medicine.

SUBSTANCE: there are described derivatives of 1,3,4-oxadiazol-2-one of formula I and their pharmaceutically acceptable salts wherein ARYL represents phenyl which can have one substitute chosen from halogen; W represents chain or (CH2)m where m designates an integer 1 to 4; Z represents -O(CH2)n-, -(CH2)n-Y-(CH2)n- where Y designates O, n independently means an integer 1 to 5; X represents O or S; R1 represents C1-6 alkyl; R2 represents substituted phenyl where substitutes are chosen from the group including C1-6alkyl, C1-4perfluoralkyl. There are also described pharmaceutical composition, and method of treating a disease in mammal wherein said disease can be modulated by PPAR-delta receptor binding activity.

EFFECT: compounds possess agonist or antagonist activity with respect to PPAR-delta receptor.

9 cl, 2 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound or its salt of formula 1: , where A, E, D, R0, R1-R4 and a assume values given in the formula of invention. The invention also relates to an antioxidant medicinal agent.

EFFECT: effectiveness during treatment of ischemic diseases of organs, during treatment of diseases caused by oxidation cell disorders and when inhibiting disorders of the retina.

4 cl, 1 tbl, 6 ex

Triazole derivative // 2383536

FIELD: chemistry.

SUBSTANCE: described are novel triazole derivatives with general formula where values of radicals are given in the formula of invention, a pharmaceutical composition containing said derivatives, and a method of treating autoimmune diseases. Compounds with general formula (1) and their pharmaceutically acceptable salts have inhibition effect on S1P and its Edg-1 receptor (S1P1).

EFFECT: possibility of use as a pharmaceutical product.

43 cl, 10 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: chemistry.

SUBSTANCE: invention proposes 5-member heterocyclic inhibitors of kinase p38, including kinase p38α and kinase p38β, based on pyrazoles and imidazoles, with the general formula given below , in which ring B is phenyl, and C is a pyrazole or imidazole ring, and the rest of the symbols assume values given in paragraph 1 of the formula of invention.

EFFECT: there are described pharmaceutical compositions containing said compounds, as well as methods of using the compounds and compositions, including a method of treating, preventing or suppressing one or more symptoms of diseases and conditions mediated by kinase p38 which include, but not limited to, inflammatory diseases and conditions.

31 cl, 6 tbl, 175 ex

FIELD: chemistry.

SUBSTANCE: proposed phosphodiesterase 4 inhibitors are characterised by formulae II, III, V, VI, where X is CH or N; L is a single bond, -(CH2)nCONH-, -(CH2)nCON(CH2CH3)-, (CH2)nSO2, (CH2)nCO2 or alkylene, optionally substituted oxo or hydroxy; n assumes values from 0 to 3; R1 is optionally substituted alkyl; R3 - H, alkyl, cycloalkyl, alkoxyalkyl, optionally substituted phenyl, phenylalkyl, heterocyclyl, heterocyclylalkyl or cycloalkylalkyl; R4 and R5 represent alkyl; R6 - cycloalkyl, R7 is H; R8 is H, carboxy, alkoxycarbonyl, -CO-alkyl, optionally substituted alkyl.

EFFECT: new phosphodiesterase 4 inhibitors have improved properties.

55 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

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