Antagonist npy y5

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with applying pharmaceutical composition as an antagonist of NPY Y5 receptor that contains the compound of formula I

, moreover, it deals with compounds of formula I and method for treating obesity and suppressing food intake, as well.

EFFECT: higher efficiency of therapy.

18 cl, 13 ex, 6 tbl

 

The technical field to which the invention relates.

The present invention relates to a pharmaceutical composition for use as an antagonist of the receptor NPY Y5, particularly to a tool against obesity and new compounds with activity against obesity.

Background of invention

Neuropeptide Y (hereinafter referred to as NPY) is a peptide consisting of 36 amino acid residues isolated from porcine brain in 1982. NPY is widely distributed in the Central nervous system and peripheral tissues of humans and animals.

It is reported that NPY has activity, stimulating food intake, activity against attacks, activity, promoting training, activity against anxiety, anti-stress activity, etc. in the Central nervous system and can dramatically be involved in diseases of the Central nervous system such as Alzheimer's and Parkinson's disease. I believe that NPY is associated with cardiovascular diseases, as it induces contraction of smooth muscles, such as muscle, blood vessels or heart, and in peripheral tissues. In addition, it is also known that NPY is involved in diseases associated with metabolism, such as obesity, diabetes, and hormonal disorders (General provisions in Pharmacological Sciences, Vol.15, and 153 (1994)). is that suppose the NPY receptor antagonist will be a therapeutic agent for the prevention or treatment of various diseases involving NPY receptor.

Now for NPY receptor identified subtypes Y1, Y2, Y3, Y4, Y5 and Y6 (General provisions in Pharmacological Sciences, Vol.18, and 372 (1997)). Assume that the NPY receptor at least involved in feeding behavior, and it is expected that his antagonist will become a tool against obesity (Peptides, Vol.18, and 445 (1997)).

In WO 97/20820, WO 97/20821, WO 97/20823 etc. describes hintline having a structure similar to the structure of the compounds of the present invention, and detecting antagonistic activity against NPY receptor. In addition, in WO 99/64349 describes derivatives of urea, containing sulfonamidnuyu group, and amide derivatives containing sulfonyloxy group, and in EP 1010691-And benzylmaleimide derivative having NPY-antagonist activity.

Compounds having the structure similar to the structure of the compounds of the present invention, are described in JP59-16871-A and WO 97/15567. Their activity is completely different from the compounds of the present invention, and these documents are not relevant to the present invention.

Description of the invention

The aim of the present invention is excellent pharmaceutical composition for use as an antagonist of the receptor NPY Y5 and new with the organisations, possessing such activity.

The present invention relates to

1) a pharmaceutical composition for use as an antagonist of the receptor NPY Y5 containing the compound of formula (I):

where R1represents optionally substituted lower alkyl,

optionally substituted cycloalkyl or optionally substituted aryl,

R2represents hydrogen or lower alkyl, and R1and R2taken together may form lower alkylene,

n is 1 or 2,

X is optionally substituted lower alkylene,

optionally substituted lower albaniles,

optionally substituted-CO-(lower alkylene),

optionally substituted-CO-(lower albaniles) or

where R3, R4, R5and R6represent, each independently, hydrogen or lower alkyl,

is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted bicycloalkyl, optionally substituted, Allen or optionally substituted heterocyclyl, and p and q each independently 0 or 1, -NR2-X may be a

where

is PIP ridinger, piperazinyl, pyridinyl, pyrazinyl, pyrrolidinyl or pyrrolidinyl, and U represents a simple bond, a lower alkylene or lower albaniles,

Y represents OCONR7, CONR7, CSNR7, NR7CO or NR7CS,

R7represents hydrogen or lower alkyl,

Z represents optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted amino, optionally substituted lower alkoxy, optionally substituted carbocyclic or optionally substituted heterocyclyl,

its prodrug, pharmaceutically acceptable salt or MES,

2) the pharmaceutical composition for use as an antagonist of the receptor NPY Y5 described in (1), where R2represents hydrogen or lower alkyl, Z represents optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted carbocyclic, optionally substituted heterocyclyl or optionally substituted amino, provided that R1is optionally substituted (C3-C10) alkyl when Z represents optionally substituted amino,

3) the pharmaceutical composition for use as an antagonist of the receptor NPY Y5 described in (1), where R1represents optionally substituted n is SSI alkyl or optionally substituted cycloalkyl, X is optionally substituted lower alkylene, optionally substituted lower albaniles or

where

has the values set in (1), and Z represents optionally substituted lower alkyl, optionally substituted carbocyclic or optionally substituted heterocyclyl,

4) the pharmaceutical composition for use as an antagonist of the receptor NPY Y5 described in any of (1)to(3), where R1is optionally substituted (C3-C10) alkyl,

5) the pharmaceutical composition for use as an antagonist of the receptor NPY Y5 described in any of (1)to(4), which is a tool against obesity

6) the pharmaceutical composition for use as an antagonist of the receptor NPY Y5 described in any of (1)to(4), which is a tool that reduces appetite,

7) the method of treatment and/or prevention of obesity, including the introduction of effective doses of the antagonist receptor NPY Y5 described in any of(1)-(4),

8) the method of suppressing food intake, including the introduction of effective doses of the antagonist receptor NPY Y5 described in any of(1)-(4),

9) the use of an antagonist of the receptor NPY Y5 described in any of (1)to(4), for the manufacture of a therapeutic agent for the treatment and/or prevention airen is I,

10) the use of an antagonist of the receptor NPY Y5 described in any of (1)to(4), for the manufacture of a therapeutic agent for suppressing food intake,

11) to the compound of formula (I):

where X represents a (C2-C6)alkylene or (C3-C6) albaniles, R1is optionally substituted (C3-C10)alkyl or optionally substituted (C5-C6)cycloalkyl, and other symbols have the meanings specified in (1), provided that Z is not lower alkylenediamine, hydroxy(lower) alkylenediamine, allterrain, when Y represents NR7CO.,

its prodrug, pharmaceutically acceptable salt or MES,

12) the compound described in (11), where Z is optionally substituted lower alkyl or optionally substituted phenyl,

its prodrug, pharmaceutically acceptable salt or MES,

13) the compound of formula (I):

where X represents

is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted bicycloalkyl or optionally substituted piperidinyl, R1is optionally substituted (C3-C10)alkyl or optional is tion substituted (C 5-C6)cycloalkyl, and other symbols have the meanings specified in (1),

its prodrug, pharmaceutically acceptable salt or MES,

14) the compound described in [13], where

is optionally substituted cyclohexyl or optionally substituted piperidinyl, and p and q are simultaneously equal to 0

its prodrug, pharmaceutically acceptable salt or MES,

15) the compound described in (13) or (14), where Y is CONH, its prodrug, pharmaceutically acceptable salt or MES,

16) the compound described in any of (13)-(15)where Z is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted pyridyl or optionally substituted benzopyranyl,

its prodrug, pharmaceutically acceptable salt or MES,

17) to the compound of formula (I):

where X represents

R1is optionally substituted (C3-C10)alkyl or optionally substituted (C5-C6)cycloalkyl, Z is n-(lower)alkylphenyl, and other symbols have the meanings specified in (1), provided that Z is not p-h-butylphenyl, when R1represents isopropyl,

its prodrug, pharmaceutically praml is my salt or MES,

18) the compound of formula (I):

where X represents

is heteroaryl, R1is optionally substituted (C3-C10)alkyl or optionally substituted (C5-C6)cycloalkyl, and other symbols have the meanings specified in (1),

its prodrug, pharmaceutically acceptable salt or MES,

19) the compound described in (18), where

is theoffender or furandi,

its prodrug, pharmaceutically acceptable salt or MES,

20) a pharmaceutical composition containing a compound described in any of(11)-(19),

its prodrug, pharmaceutically acceptable salt or MES.

The best way of carrying out the invention

In the present description, the term "halogen" includes fluorine, chlorine, bromine and iodine. Preferred fluorine or chlorine.

The term "protective group" in the case of the "optionally protected hydroxy" and "optionally protected hydroxy(lower)alkyl" includes all of the commonly used protective group for hydroxy. For example, such groups are acyl, such as acetyl, trichloroacetyl and benzoyl, lower alkoxycarbonyl, such as tert-butoxycarbonyl, lower alkylsulfonyl, such as means Lionel, lower alkoxy(lower)alkyl, such as methoxymethyl, trialkylsilyl, such as tert-butyldimethylsilyl.

Tramin "lower alkyl" includes linear or branched alkyl, C1-C10. Examples of "lower alkyl" are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl and n-decyl.

"Lower alkyl"represented by R1preferably represents (C3-C10) alkyl, preferably (C3-C6) alkyl and most preferably isopropyl or tert-butyl.

In other cases, a "lower alkyl" is preferably (C1-C6)alkyl and preferably (C1-C4)alkyl.

Examples of substituents of "optionally substituted lower alkyl"represented by Z, are

(1) halogen;

(2) cyano;

(3) the following groups (i)to(xvi), optionally substituted by one or more substituents selected from the group of substituents β", the values of which are listed below:

(i) hydroxy, (ii) lower alkoxy, (iii) mercapto, (iv) lower alkylthio, (v) acyl, (vi) acyloxy, (vii) carboxy, (viii) lower alkoxycarbonyl, (ix) imino, (x) carbarnoyl, (xi) thiocarbamoyl, (xii) lower allylcarbamate, (xiii) lower alkylthiomethyl, (xiv) amino, (xv) lower alkylamino or (xvi) heterotic ylcarbonyl;

or

(4) a group of the formula:

where R10and R11represent, each independently, hydrogen or lower alkyl, and when such a group contains two or more R10and/or two or more R11all R10and/or all R11can be different,

W represents a simple bond, O, S or NR12,

R12represents hydrogen, lower alkyl or phenyl,

is cycloalkyl, bicycloalkyl, cycloalkenyl, aryl or heterocyclyl, each of which is optionally substituted by one or more substituents selected from the group of substituents α", the values of which are listed below, and s is an integer from 0 to 4.

In the present description "the group of substituents and is a group consisting of (1) halogen; (2) oxo; (3) cyano; (4) nitro; (5) imino, optionally substituted lower alkyl or hydroxy;

(6) the following groups (i)to(xxi), optionally substituted by one or more substituents selected from the group of substituents β:

(i) hydroxy, (ii) lower alkyl, (iii) lower alkenyl, (iv) lower alkoxy, (v) carboxy, (vi) lower alkoxycarbonyl, (vii) acyl, (viii) acyloxy, (ix) imino, (x) mercapto, (xi) lower alkylthio, (xii) carbarnoyl, (xiii) lower allylcarbamate, (xiv) cycloalkylcarbonyl, (xv) thiocarbamoyl, (xvi) lower allylthiourea is l, (xvii) lower alkylsulfonyl, (xviii) lower alkylsulfonyl, (xix) sulfamoyl, (XX) the lowest alkylsulfonyl and (xxi) cycloalkylcarbonyl;

(7) the following groups (i)to(v), optionally substituted by substituents of the group β, lowest akilam, lower alkoxy(lower)alkyl, optionally protected hydroxy(lower)alkyl, halo(lower)alkyl, lower alkylsulfonyl and/or arylsulfonyl:

(i) cycloalkyl, (ii) cycloalkenyl, (iii) cycloalkane,

(iv) amino and (v) alkylenedioxy;

and

(8) the following groups (i)to(xii), optionally substituted by substituents of the group β, lowest akilam, halogen (lower) alkyl and/or oxo:

(i) phenyl, (ii) naphthyl, (iii) phenoxy, (iv) phenyl(lower)alkyl, (v) phenylthio, (vi) phenyl(lower) alkylthio, (vii) phenylazo, (viii) heterocyclyl, (ix) heterocyclic, (x), heterocyclic, (xi) heterocalixarenes and (xii) heterocyclizations.

Preferred examples of the group of substituents α as the substituents for ring b are halogen; nitro; hydroxy;

optionally substituted lower alkyl, where the substituents are halogen, cyano, phenyl, carboxy and/or lower alkoxycarbonyl;

lower alkenyl; lower alkoxycarbonyl(lower)alkenyl;

optionally substituted lower alkoxy, where the substituents are halogen, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkilani is about and/or cyano;

acyl; hydroxyimino; lower alkylthio; lower alkylsulfonyl; sulfamoyl;

optionally substituted amino where the substituents are lower alkyl, optionally protected hydroxy(lower)alkyl, phenyl and/or acyl;

alkylenedioxy; cyanophenyl; heterocyclimamines; biphenylyl; phenoxy; phenylazo, optionally substituted lower alkyl;

or

optionally substituted heterocyclyl, where the substituents are optionally protected hydroxy, mercapto, halogen, lower alkyl, cycloalkyl, lower alkoxycarbonyl, amino, lower alkoxycarbonyl, carbarnoyl, oxo, phenyl, lower alkoxyphenyl or heterocyclyl.

More preferred examples are halogen, lower alkyl, optionally substituted with halogen, or lower alkoxy, optionally substituted with halogen.

"The group of substituents β" represents the group consisting of halogen, optionally protected hydroxy, mercapto, lower alkoxy, lower alkenyl, amino, lower alkylamino, lower alkoxycarbonyl, lower alkylthio, acyl, carboxy, lower alkoxycarbonyl, carbamoyl, cyano, cycloalkyl, phenyl, phenoxy, lower alkylphenyl, lower alkoxyphenyl, halogenfree, naphthyl and heterocyclyl.

Examples of substituents for "optionally substituted lower alkyl"represented any other the group, in addition to Z (for example, R1are one or more substituents selected from the group of substituents β. The lower alkyl may be substituted by these substituents at any possible positions.

The lower alkyl part of "lower alkoxy", "lower alkoxycarbonyl", "lower alkoxycarbonyl(lower)alkyl", "lower alkylphenyl", "lower alkoxyphenyl", "lower alkylcarboxylic", "lower alkyldiethanolamine", "lower alkylamino", "halo(lower)alkyl", "hydroxy(lower) alkyl", "phenyl(lower)alkoxy", "lower alkylthio", "phenyl(lower)alkylthio", "lower alkoxycarbonyl", "lower alkoxycarbonyl(lower)alkenyl", "lower alkylsulfonyl", "lower alkylsulfonyl", "aryl(lower)alkoxycarbonyl", "lower alkylbenzene" and "lower alkoxybenzyl" has the values specified above for "lower alkyl".

Examples of substituents for "optionally substituted lower alkoxy" are one or more substituents selected from the group of substituents β. Preferred examples are phenyl, lower alkylphenyl, lower alkoxyphenyl, naphthyl and heterocyclyl.

The term "cycloalkyl" includes (C3-C8)cyclic alkyl, and preferably (C5-C6)cyclic alkyl. Examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

Examples is amestitelj for "optionally substituted cycloalkyl" are one or more substituents, selected from the group of substituents αand cycloalkyl may be substituted by these substituents at any possible positions.

The term "bicycloalkyl" includes a group formed by excluding one hydrogen from (C5-C6)aliphatic cycle containing two rings with two or more common atoms. Examples are bicyclo[2.1.0]pentyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2] octyl and bicyclo[3.2.1]octyl.

The term "lower alkenyl" includes linear or branched alkenyl2-C10preferably2-C8and preferably With3-C6containing one or more double bonds in all possible positions. Examples are vinyl, propenyl, Isopropenyl, butenyl, Isobutanol, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexanol, hexadienyl, heptenyl, octenyl, nonanal and decanal.

"Lower Alchemilla part of the" in "lower alkoxycarbonyl(lower)alkenyl" has the values specified above for "lower alkenyl".

Examples of substituents for "optionally substituted lower alkenyl" are halogen, lower alkoxy, lower alkenyl, amino, lower alkylamino, lower alkoxycarbonyl, lower alkylthio, acyl, carboxy, lower alkoxycarbonyl, carbarnoyl, cyano, cycloalkyl, phenyl, lower alkylphenyl, lower alkoxide the sludge, naphthyl and/or heterocyclyl.

The term "acyl" includes (1) a linear or branched alkylaryl or alkenylboronic C1-C10preferably C1-C6and preferably C1-C4(2) cycloalkylcarbonyl4-C9and preferably4-C7and (3) (C7-C11) arylcarbamoyl. Examples are formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, pivaloyl, hexanoyl, acryloyl, propionyl, methacryloyl, crotonoyl, cyclopropanecarbonyl, cyclohexylcarbonyl, cyclooctylmethyl and benzoyl.

"Acyl" part in "acyloxy" has the values listed above.

The term "cycloalkenyl" includes a group containing at least one double bond at any possible position in the above cycloalkyl. Examples are cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl and cyclohexadienyl.

Examples of substituents for "optionally substituted cycloalkenyl" are one or more substituents selected from the group of substituents β.

Examples of substituents for "optionally substituted amino" are substituents of the group β, optionally substituted benzoyl and/or optionally substituted heterocalixarenes, where the substituents are hydroxy, lower alkyl, lower alkoxy and/or lower alkylthio.

The term "aryl" in the cancel monocyclic or polycyclic aromatic carbocyclic group, and examples include phenyl, naphthyl, antril and tenantry. "Aryl" includes aryl condensed with other non-aromatic carbocyclic group, for example of indanyl, indenyl, biphenylyl, acenaphthyl, tetrahydronaphthyl and fluorenyl. Preferred is phenyl.

Aryl part of "aryl(lower)alkoxycarbonyl" has the values listed above.

The terms "optionally substituted aryl" and "optionally substituted phenyl", when Z represents include the above "aryl" and "phenyl", respectively, which may be substituted by substituents of the group α or lower alkyl which may be substituted by one or more groups selected from the substituents group α.

Examples of substituents for "optionally substituted aryl" and "optionally substituted phenyl", other than Z, are one or more groups selected from the substituents group β.

The term "carbocycle" includes the above "cycloalkyl", "cycloalkenyl", "bicycloalkyl" and "aryl".

The term "non-aromatic carbocycle" includes the above "cycloalkyl", "cycloalkenyl and bicycloalkyl".

The term "optionally substituted carbocycle" includes the above "optionally substituted cycloalkyl", "optionally substituted cycloalkenyl", "optionally substituted bicycloalkyl" and "optionally substituted aryl".

The term "hetero CLIL" includes a heterocyclic group, containing at least one heteroatom, optionally selected from C, S and N. Examples include 5 - or 6-membered heteroaryl, such as pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, oxazolyl, oxadiazolyl, isothiazolin, thiazolyl, thiadiazolyl, furyl and thienyl; condensed heterocyclyl consisting of two cycles, such as indolyl, isoindolyl, indazoles, indolizinyl, indolinyl, isoindolyl, hinely, ethanolic, cinnoline, phthalazine, hintline, naphthyridine, honokalani, purinol, pteridinyl, benzopyranyl, benzimidazolyl, benzisoxazole, benzoxazole, benzoxadiazole, benzisothiazole, benzothiazolyl, benzotriazolyl, benzofuran, isobenzofuran, benzothiazyl, benzotriazolyl, imidazopyridine, triazolopyridine, imidazothiazoles, pyrazinamidase, dihydropyridin, tetrahydroquinolin and tetrahydrobenzene; condensed heterocyclyl consisting of three rings, such as carbazolyl, acridines, xantener, phenothiazinyl, phenoxathiin, phenoxazines and dibenzofuran; and non-aromatic heterocyclyl, such as dioxane, thiiranes, oxiranyl, oxathiolane, azetidine, tiani, pyrrolidinyl, pyrrolyl, imidazolidinyl, imidazolyl, pyrazolidine, pyrazoline, piperidyl, piperazinil, morpholinyl, morpholino, thiomorpholine, thiomorpholine, dihydropyridin, tetrahydrofuryl those whom rehydration, tetrahydrofuryl and tetrahydrocortisol.

"Condensed heterocyclyl", condensed with other than a heterocycle, ring (for example, benzothiazolyl)may join in any possible position.

The substituents for "optionally substituted heterocyclyl" have the values specified above for the "optionally substituted aryl".

Heterocyclyl part in the "heterocalixarenes", "heterocyclic", "heterocyclic" and "heterocyclization the phenyl have the values specified above for "heterocyclyl".

The term "lower alkylene" includes a divalent group containing 1 to 6 methylene groups, preferably 2 to 6 methylene groups and preferably 3-6 methylene groups. For example, these include methylene, ethylene, trimethylene, tetramethylene, pentamethylene and hexamethylene. Preferred tetramethylene.

The statement "R1and R2taken together may form lower alkylene" includes the case where

is

.

Preferred examples are

and.

Lower Allenova part in the "lower alkylenedioxy" has the values specified above for "lower alkylene". Preferred is methylendioxy or Ethylenedioxy.

Term is n "lowest albaniles" includes a bivalent group, containing 2 to 6 methylene groups, preferably 3-6 methylene groups and preferably 4-5 methylene groups, and comprising at least one double bond.

The term "cycloalkyl" includes a divalent group formed by eliminating one hydrogen of the above "cycloalkyl". A preferred example of cycloalkyl represented by X is 1,4-cyclohexanediyl.

The term "cycloalkenyl" includes a group containing at least one double bond in the above cycloalkene.

The term "bicycloalkyl" includes a group formed by eliminating one hydrogen of the above "bicycloalkyl". Examples are bicyclo[2.1.0] pentalen, bicyclo[2.2.1]heptylene, bicyclo[2.2.2]octile and bicyclo[3.2.1]octile.

The term "heterocyclyl" includes a divalent group formed by eliminating one hydrogen of the above "heterocyclyl". Preferred are piperidinyl, piperazinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrrolidinyl or pyrrolidinyl and more preferred piperidinyl.

The term "Allen" includes a divalent group formed by eliminating one hydrogen of the above "aryl". Preferred is phenylene.

The term "heteroaryl" includes aromatic group of numbers is shown above in the definition of "heterocyclyl". Examples are pyrrolidinyl, imidazolidinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazolyl, triazinyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolin, thiazolyl, thiadiazolyl, purandar and theoffender.

One or more groups selected from the group of substituents βare examples of substituents for "optionally substituted lower alkylene", "optionally substituted lower Alcanena", "optionally substituted cycloalkyl", "optionally substituted cyclohexene", "optionally substituted bicycloalkyl", "optionally substituted cycloalkenyl", "optionally substituted phenylene", "optionally substituted heterocyclyl" and "optionally substituted piperidinyl". Preferred are halogen, hydroxy, lower alkyl, halo(lower)alkyl, lower alkoxy, amino, lower alkylamino, acyl, carboxy or lower alkoxycarbonyl. These substituents may join in any possible position.

When-NR2-X represents

,

U preferably represents a simple bond or methylene.

Preferred

is

Compounds of the present invention include any and pharmaceutically acceptable salts. Examples of "pharmaceutically acceptable salts are salts with mineral acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid; salts with organic acids such as para-toluensulfonate acid, methanesulfonate acid, oxalic acid and citric acid; salts with organic bases, such as salts of ammonium, trimethylammonium and triethylamine; salts of alkaline metals such as sodium and potassium; salts of alkaline earth metals such as calcium and magnesium.

Compounds of the present invention include their solvate. It is preferable hydrate, and with the connection of the present invention may be coordinated by an arbitrary number of water molecules.

Compounds of the present invention include prodrugs. The prodrugs include derivatives of compounds of the present invention, which contain the group, biodegradable chemically or metabolically, and can turn into a pharmaceutically active compound of the present invention in vivo by solvolysis or under the influence of physiological conditions. Methods of selecting and obtaining the appropriate prodrugs are described in Design of Prodrugs, Elsevier, Amsterdam 1985.

When soy is inania (I) of the present invention contains carboxypropyl, examples of prodrugs are ester derivatives and amide derivatives which can be obtained by reaction of the compound (I)containing carboxypropyl, with a suitable alcohol or a suitable amine, respectively.

When the compound (I) of the present invention contains a hydroxy-group, examples of prodrugs is allocryptopine, which can be synthesized by the interaction of the compound (I)containing a hydroxy-group, with a suitable galogenangidridy or a suitable acid anhydride.

When the compound (I) of the present invention contains an amino group, examples of prodrugs is an amide derivative, which can be synthesized by the interaction of the compound (I)containing an amino group, with a suitable galogenangidridy or a suitable mixed anhydride of the acid.

When the compound (I) of the present invention contains an asymmetric carbon atom, it includes the racemates, all enantiomers and all stereoisomers, such as diastereoisomer, epimere and enantiomer.

When the compound (I) of the present invention containing one or more double bonds, forms the E-isomer or Z-isomer, compound (I) includes both isomers. When X represents cycloalkyl, the compound (I) includes both the CIS-isomer and TRANS-isomer.

For example, the compound (I) of the present invention can be synthesized following the existing methods.

(Connection, where Y=CONR7)

In the above formulas Hal represents halogen, Q represents a group protecting the amino and the other symbols have the meanings specified above.

Stage And

Connection 1 is introduced into the reaction aminoguanidinium 2 containing the desired substituents Z and R7, in a suitable solvent at 0°S-50°over time from several minutes to several hours. As solvents can be used tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile, water, mixtures thereof and the like If necessary, you can use the activator, such as thionyl chloride, halogenmethyl, the anhydride of the acid and the activated ester.

Stage

From junction 3 remove the protective group in the usual way and enter it into reaction with sulphonylchloride 4 containing the desired substituent R1, in a suitable solvent at 0°S-50°over time from several minutes to several hours, obtaining the compound (I-A), where n is equal to 2. The solvent can be used tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, n is ntan, heptane, dioxane, acetone, acetonitrile, water, mixtures thereof and the like

Stage

The compound (I-B), where n is 1 can be synthesized by the reaction of compound 3 with sulphonylchloride 5 containing substituent R1. Reaction conditions are the same as above, for phase C.

Stage D

The compound (I-B)obtained in stage C are oxidized in the usual way and get the compound (I-A), where n is equal to 2. As an oxidizer, you can use m-chloroperbenzoic acid, peracetic acid, hydrogen peroxide, cryptocercus acid, periodate sodium, sodium hypochlorite, potassium permanganate, etc. and the reaction can be carried out at 0°S-50°C. Examples of the solvent are tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile, water, methanol, ethanol, isopropanol mixtures thereof.

In the case when X is heterocyclyl containing at least one N atom and the N atom is attached to CONR7Z in the compound (I), you can use the reaction, described later, to obtain the compound (I-A') or (I-B'). Stage D can be performed immediately after stage C or stage that is

In the above formulas R represents lower alkyl or aryl, and L is removed the th group.

Stage

Compound 5 is introduced into reaction with the compound 6 is the same as the above-described method for the stage With obtaining compound 7.

Stage E

Thus obtained compound 7 is treated with a base in a suitable solvent and receive connection 8. As a basis you can use, for example, barium hydroxide, sodium hydroxide, potassium hydroxide, hydrazine or propandiol lithium. The solvent can be used tetrahydrofuran, dimethylformamide, dioxane, acetone, acetonitrile, methanol, ethanol, propanol, water, mixtures thereof or the like. The interaction can be performed at 0°S-100°over time from several minutes to several tens hours.

Stage F

Compound 8 reacts in a suitable solvent with compound 9 containing the group that you want and need a substitute, in the presence or in the absence of a base at 0°S-100°over time from several minutes to several days, to obtain the compound (I-B'). Examples of the deleted group are phenoxy, chlorine, trichloromethyl. Examples of the base include triethylamine, pyridine, diisopropylethylamine, sodium hydroxide, potassium carbonate and sodium bicarbonate. Examples of the solvent are tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, Huck is an, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile, methane, ethanol and mixtures thereof.

Stage D

The compound (I-B') is injected into the reaction similar to the above method for stage D with obtaining the compound (I-A').

(Connection, where Y=NR7CO)

In the above formulas, each character has the values listed above.

Stage G stage and In

Compound 10 is reacted with compound 11 under the same conditions as in stage C. the thus Obtained compound 12 is introduced into a reaction similar to the above method for the stage In obtaining the compound (I-C), where n=2.

Stage C and stage D

In order to synthesize the compound (I-D), compound 12 obtained in stage G, can be introduced into the reaction by methods similar to those described above for phase C and phase D.

(Connection, where Y=OCONR7)

In the above formulas, each character has the values listed above.

Stage N

The connection 13 is reacting in a suitable solvent with isocyanate 14, Deputy containing Z, in the presence or in the absence of a suitable catalyst, at 0°S-100°over time from several minutes to several days to obtain compound 15. Examples of the solvent are tetrahydrofuran, dimethylformamide, diethyl ether, di is Loretan, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile and mixtures thereof.

Stage C and stage D

Thus obtained compound 15 is introduced into the reaction by methods similar to those described in stage C and stage D, and obtain the compound (I-E) of the present invention. (Connection, where Y=CSNR7or NR7CS)

The compound (I)where Y represents the CSNR7or NR7CS, can be synthesized by the reaction of the compound (I)where Y represents CONR7or NR7CO., synthesized by any of the methods described above, with a reagent of Losona or pentasulfide phosphorus in a suitable solvent at 30°S-100°over time from several minutes to several hours. Examples of the solvent are tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile and mixtures thereof.

The amino group can be protected with suitable protective group conventional manner on a suitable stage. For example, as a protective group can be used phthalimid, lower alkoxycarbonyl, lower alkenylacyl, halogenosilanes, aryl(lower)alkoxycarbonyl, trialkylsilyl, lower alkylsulfonyl, halogen(lower) alkylsulfonyl, ar is sulfonyl, lowest alkylsulphonyl and arylcarbamoyl.

After protection of the amino compound is subjected to the above reactions and the compounds obtained are removing the protective group by treatment with an acid or base in a suitable solvent at a suitable stage. Examples of the solvent are tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile and mixtures thereof. Examples of the base are hydrazine, pyridine, sodium hydroxide and potassium hydroxide, and examples of acids are hydrochloric acid, triperoxonane acid and hydrofluoric acid.

All compounds of the present invention have an antagonistic activity against NPY Y5, and among the compounds of formula (I) are particularly preferred are: connection, where R1represents optionally substituted lower alkyl or optionally substituted cycloalkyl (hereinafter referring to that "R1is R1-1"), the compound wherein R1is (C3-C10)alkyl or (C5-C6)cycloalkyl, each of which is optionally substituted with halogen (hereinafter referring to that "R1is R1-2"), a compound where R1is (C3-C10)alkyl, optionally substituted the first halogen (hereinafter mean that "R1is R1-3"), a compound where R1is isopropyl or tert-butyl (hereinafter referring to that "R1is R1-4"), a compound where R2represents hydrogen or (C1-C3) alkyl (hereinafter referred to mean that "R2is R2-1"), the compound wherein R2is hydrogen (hereinafter referred to mean that "R2is R2-2"), a compound where X is optionally substituted lower alkylene, optionally substituted lower albaniles or

,

where

is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted bicycloalkyl, optionally substituted phenylene or optionally substituted heterocyclyl (hereinafter referred to mean that "X is X-1," connection, where X is (C2-C6) alkylene, (C3-C8) albaniles or

,

where

is optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted bicycloalkyl, optionally substituted phenylene, optionally substituted piperidinyl, optionally substituted theoffender or optionally substituted forand the sludge (hereinafter mean that "X is X-2",

connection, where X is (C2-C6) alkylen or

,

where

is optionally substituted cycloalkyl, optionally substituted phenylene, optionally substituted piperidinyl, optionally substituted theoffender or optionally substituted purandar (hereinafter referred to mean that "X is X-3"),

connection, where X is (i) (C2-C6)alkylene or (ii) cycloalkyl or phenylene, each of which is optionally substituted with halogen, hydroxy, lower alkyl or halo(lower)alkyl (hereinafter referred to mean that "X is X-4"),

connection, where X represents a C2-C6) alkylene or (C5-C6)cycloalkyl (hereinafter referred to mean that "X is X-5"),

connection, where X is (C3-C6) alkylen or 1,4-cyclohexene (hereinafter referred to mean that "X is X-6"),

connection, where Y is CONR7, CSNR7HR7CO or NR7CS and R7represents hydrogen or (C1-C3)alkyl (hereinafter referred to mean that "Y is Y-1"),

connection, where Y is CONR, CSNR, or NHCO (hereinafter mean that "Y is Y-2")

connection, where Y is CONH (hereinafter mean that "Y is Y-3"),

connection, where Z is optionally substituted lower alkyl, optionally substituted lower carbocyclic or optionally substituted heterocyclyl (hereinafter mean that "Z is Z-1"),

connection, where Z is -(CR8R9)r-W-(CR10R11)s-V, where R8, R9, R10and R11each independently represent hydrogen or lower alkyl and, when Z contains two or more R8two or more R9two or more R10and/or two or more R11all R8, R9, R10and R11may be different, W represents a simple bond, O, S or NR12, R12represents hydrogen, lower alkyl or phenyl, V is hydrogen, optionally substituted cycloalkyl, optionally substituted bicycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, g is an integer from 1 to 4 and s is an integer from 0 to 4 (hereinafter referred to mean that "Z is Z-2"),

connection, where Z represents -(CH2)r-W-(CH2)s-V, where W represents a simple bond, O, S or NR12, R12represents hydrogen or lower alkyl, V is optionally substituted aryl or optionally substituted heterocyclyl, where the substituents are halogen, hydroxy, lower lcil, halogen(lower)alkyl, lower alkoxy, lower alkenyl, amino, lower alkylamino, acyl, carboxy, lower alkoxycarbonyl, phenyl or monocyclic heteroaryl, g is an integer from 1 to 4 and s is an integer from 0 to 4 (hereinafter referred to mean that "Z is Z-3"),

connection, where Z is (CH2)r-W-(CH2)s-V, where W represents a simple bond O, S, NH or NMe, V is optionally substituted phenyl or optionally substituted heteroaryl, where the substituents are halogen, lower alkyl, halo(lower)alkyl, lower alkoxy, amino or lower alkylamino, r is an integer from 1 to 3, and s is 0 or 1 (hereinafter mean that "Z is Z-4"),

connection, where Z represents optionally substituted carbocyclic,

where the substituents are halogen; hydroxy;

optionally substituted lower alkyl, where the substituents are halogen, hydroxy, carboxy, lower alkoxycarbonyl, cyano and/or phenyl;

lower alkenyl, optionally substituted lower alkoxycarbonyl;

optionally substituted lower alkoxy, where the substituents are halogen, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkylamino, cycloalkyl, cyano and/or heterocyclyl;

cycloalkyl; cycloalkane; acyl; lower alkylthio; carbarnoyl; lower allylcarbamate; sianoa kilcarbery; hydroxyimino;

optionally substituted amino where the substituents are lower alkyl, optionally protected hydroxy(lower) alkyl, lower alkoxy(lower)alkyl, acyl, lower alkylsulfonyl, arylsulfonyl and/or phenyl;

phenyl, optionally substituted with halogen, cyano, phenyl and/or heterocyclyl;

lowest alkylsulfonyl; lower alkylsulfonyl; cycloalkylcarbonyl;

nitro; cyano; alkylenedioxy; phenylazo, optionally substituted lower alkyl; phenoxy; oxo;

optionally substituted heterocyclyl, where the substituents are optionally protected hydroxy, mercapto, halogen, lower alkyl, cycloalkyl, lower alkoxycarbonyl, acyl, amino, lower alkoxycarbonyl, carbarnoyl, oxo, phenyl, lower alkoxyphenyl, halogenarenes, heterocyclyl and/or oxo;

heterocyclisation, optionally substituted lower alkyl; heterocyclic; heterocalixarenes, optionally substituted lower alkyl (hereinafter referred to mean that "Z is Z-5"),

connection, where Z represents optionally substituted phenyl,

where the substituents are halogen; hydroxy; lower alkyl, optionally substituted with halogen, hydroxy, lower alkoxycarbonyl, cyano and/or phenyl; lower alkoxycarbonyl(lower)alkenyl; lower alkoxy, optionally substituted with halogen, nor the PWM alkoxy, lowest alkoxycarbonyl, cycloalkyl and/or heterocyclyl;

cycloalkyl; cycloalkane; acyl; lower alkylthio;

carbarnoyl; lower allylcarbamate; amino, optionally substituted lower alkyl, hydroxy(lower)alkyl, acyl, lower alkylsulfonyl and/or phenyl; phenyl, optionally substituted with halogen, cyano, phenyl and/or heterocyclyl;

lowest alkylsulfonyl; cycloalkylcarbonyl; nitro; alkylenedioxy; phenylazo, optionally substituted lower alkyl; phenoxy; oxo;

heterocyclyl, optionally substituted hydroxy, halogen, lower alkyl, lower alkylaminocarbonyl, amino, carbamoyl, phenyl, halogenfree, heterocyclyl and/or oxo;

heterocyclics and/or heterocyclisation, optionally substituted lower alkyl (hereinafter referred to mean that "Z is Z-6"),

connection, where Z represents optionally substituted phenyl,

where the substituents are halogen; lower alkyl, optionally substituted with halogen, hydroxy, lower alkoxycarbonyl and/or phenyl; lower alkoxy, optionally substituted with halogen and/or cycloalkyl; cycloalkyl; cycloalkane; acyl; lower alkylthio; lower allylcarbamate; amino, optionally substituted lower alkyl, hydroxy(lower)alkyl, acyl and/or phenyl; phenyl, optionally substituted piperidyl is m; cycloalkylcarbonyl; alkylenedioxy; phenoxy;

morpholinyl or morpholino, each of which is optionally substituted lower alkyl; piperidyl, optionally substituted by hydroxy, lower alkyl, lower alkoxycarbonyl, phenyl, halogenfree and/or oxo; pyrrolidinyl, optionally substituted hydroxy, carbamoyl and/or oxo;

piperazinil, optionally substituted phenyl or pyrimidinyl; dihydropyridin; pyrrolyl; pyrrolidyl; imidazolyl, optionally substituted with halogen and/or lower alkyl; pyrazolyl; thienyl; thiadiazolyl; furyl; oxazolyl; isoxazolyl; tetrazolyl, optionally substituted lower alkyl and/or phenyl; indolinyl; indolyl; tetrahydropyranyl; benzothiazolyl, optionally substituted lower alkyl; tetrahydrocortisol, optionally substituted by oxo; benzopyranyl, optionally substituted by oxo; tetrahydropyranyloxy; tetrahydropyranyloxy; morpholinomethyl, optionally substituted lower alkyl; and/or piperidinemethanol, optionally substituted lower alkyl (hereinafter referred to mean that "Z is Z-7"),

connection, where Z represents optionally substituted phenyl,

where the substituents are halogen, lower alkyl, halo(lower)alkyl, lower alkoxy, cycloalkane lowest allylcarbamate, phenyl, (lower alkyl)morpholino and/or tetrahedra is enyloxy (hereinafter mean that "Z is Z-8"),

connection, where Z represents optionally substituted heterocyclyl,

where the substituents are halogen, hydroxy, lower alkyl, halo(lower)alkyl, lower alkoxy, mercapto, lower alkylthio, acyl, carboxy, lower alkoxycarbonyl, amino, lower alkylamino, phenyl, naphthyl, phenylthio, optionally substituted with halogen, phenoxy, optionally substituted with halogen, oxo and/or heterocyclyl, optionally substituted lower alkyl (hereinafter referred to mean that "Z is Z-9"),

connection, where Z represents thienyl, pyrazolyl, thiazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, isoindolyl, indolinyl, isoindolyl, indazoles, benzopyranyl, benzoxazolyl, benzothiazyl, benzothiazolyl, benzotriazolyl, benzothiazolyl, hinely, ethanolic, dihydrobenzofuran, carbazolyl, acridines or dibenzofuran, each of which is optionally substituted by substituents selected from the group consisting of lower alkyl; halogen(lower)alkyl; lower alkoxy; lower alkoxycarbonyl; acyl; lower alkoxycarbonyl(lower) alkyl; mercapto; phenyl, naphthyl, or phenylthio phenoxy, each of which is optionally substituted with halogen; furil; nitro; oxo, morpholino, optionally substituted lower alkyl (hereinafter referred to mean that "Z is Z-10"),

with the unity, where Z represents thienyl, thiazolyl, thiadiazolyl, pyridyl, pyrazinyl, indolyl, isoindolyl, benzopyranyl, hinely, carbazolyl, dibenzofuran, benzothiazyl or benzothiazolyl, each of which is optionally substituted by one or more substituents selected from the group consisting of lower alkyl, halo(lower)alkyl, lower alkoxy, lower alkoxycarbonyl, acyl, phenyl, naphthyl, phenylthio, lower alkylamino and oxo (hereinafter mean that "Z is Z-11"),

connection, where R1is R1-2, R2is R2-2, n is 2, and the combination of X, Y and Z, i.e. the (X, Y, Z) is any of the following:

(X, Y, Z)=(X-3, Y-2, Z-1), (X-3, Y-2, Z-2), (X-3, Y-2, Z-3), (X-3, Y-2, Z-4), (X-3, Y-2, Z-5), (X-3, Y-2, Z-6), (X-3, Y-2 Z-7), (X-3, Y-2, Z-8), (X-3, Y-2, Z-9), (X-3, Y-2, Z-10), (X-3, Y-2, Z-11),

(X-3, Y-3, Z-1), (X-3, Y-3, Z-2), (X-3, Y-3, Z-3), (X-3, Y-3, Z-4), (X-3, Y-3, Z-5), (X-3, Y-3, Z-6), (X-3, Y-3, Z-7), (X-3, Y-3, Z-8), (X-3, Y-3, Z-9), (X-3, Y-3, Z-10), (X-3, Y-3, Z-11),

(X-4, Y-2, Z-1), (X-4, Y-2, Z-2) (X-4, Y-2, Z-3) (X-4, Y-2, Z-4) (X-4, Y-2, Z-5) (X-4, Y-2, Z-6) (X-4, Y-2, Z-7), (X-4, Y-2, Z-8) (X-4, Y-2, Z-9) (X-4, Y-2, Z-10), (X-4, Y-2, Z-11),

(X-4, Y-3, Z-1), (X-4, Y-3, Z-2) (X-4, Y-3, Z-3) (X-4, Y-3, Z-4) (X-4, Y-3, Z-5) (X-4, Y-3, Z-6) (X-4, Y-3, Z-7), (X-4, Y-3, Z-8) (X-4, Y-3, Z-9) (X-4, Y-3, Z-10), (X-4, Y-3, Z-11),

(X-5, Y-2, Z-1), (X-5, Y-2, Z-2) (X-5, Y-2, Z-3) (X-5, Y-2, Z-4) (X-5, Y-2, Z-5) (X-5, Y-2, Z-6) (X-5, Y-2, Z-7), (X-5, Y-2, Z-8) (X-5, Y-2, Z-9) (X-5, Y-2, Z-10), (X-5, Y-2, Z-11),

(X-5, Y-3, Z-1), (X-5, Y-3, Z-2) (X-5, Y-3, Z-3) (X-5, Y-3, Z-4) (X-5, Y-3, Z-5) (X-5, Y-3, Z-6) (X-5, Y-3, Z-7), (X-5, Y-3, Z-8) (X-5, Y-3, Z-9) (X-5, Y-3, Z-10) or (X-5, Y-3, Z-11),

they are supplied with the Ki acceptable salt, the solvate or prodrug.

Receptor antagonist NPY Y5 of the present invention is effective in all diseases involving NPY Y5, and is particularly useful for preventing and/or treating obesity and suppression of food intake. In addition, the antagonist is effective for preventing and/or treating diseases in which obesity acts as a risk factor, such as diabetes, hypertension, hyperlipemia, atherosclerosis and acute coronary syndrome.

In addition, receptor antagonist NPY Y5 of the present invention has a low affinity for NPY receptors Y1 and Y2, and has high selectivity for receptor NPY Y5. NPY causes prolonged constriction of peripheral blood vessels, and the specified action is carried out mainly via the Y1 receptor. As the Y5 receptor not involved in this action, receptor antagonist NPY Y5 has a low risk of inducing side effects, based on the constriction of peripheral blood vessels, and it is assumed that it is suitable for use as a safe drug.

Receptor antagonist NPY Y5 detects action against obesity by suppressing food intake. Therefore, one of the features is that this antagonist does not cause side effects, such as dyspepsia caused by remedy about what Irene, inhibiting digestion and absorption, and the main side effects, such as antidepressiva caused by the inhibitor of the transport of serotonin, showing action against obesity.

The compound of the present invention can be administered orally or parenterally as an anti-obesity or means for reducing the appetite. In the case of oral administration, it can be in normal form, such as tablets, granules, powders, capsules, pills, solutions, syrups, buccal tablets and sublingual tablets. When the compound is administered parenterally, preferably any form, such as injections (e.g., intravenous, intramuscular), suppositories, percutaneous means and means for inhalation. Oral administration is particularly preferred, since the compounds of the present invention show high oral absorption capacity.

The pharmaceutical composition can be obtained by mixing an effective amount of the compounds of the present invention with various pharmaceutical additives, suitable for injection, such as excipients, binders, moisturizing agents, disintegrators, lubricants and diluents. When the composition is injection, the active ingredient together with a suitable carrier can be sterilized and get farm is tsevtichesky composition.

Examples of excipients include lactose, sucrose, glucose, starch, calcium carbonate, and crystalline cellulose. Examples of disintegrators include methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, gelatin and polyvinylpyrrolidone. Examples of disintegrators include carboxymethyl cellulose, sodium carboxymethyl cellulose, starch, sodium alginate, agar, and sodium lauryl sulfate. Examples of lubricants include talc, magnesium stearate and macrogol. Cocoa butter, macrogol, methylcellulose and the like can be used as bases for suppositories. When the composition was prepared in the form of solutions, injection, emulsion or injection suspensions, you can add accelerators dissolution, suspendresume tools, emulsifiers, stabilizers, preservatives, isotonic tools, etc. In the case of oral administration in a song you can also add podslushivala, corrigentov etc.

Although the dosage of the compounds of the present invention as anti-obesity, or a means of reducing appetite, should be determined with consideration of the age and body weight of the patient, the type and severity of the disease, the route of administration and the like, the usual oral dosage for adults is 0.05-100 mg/kg/day and preferably 0.1 to 10 mg/kg/day. In the case of parenteral administration the usual dosage, although it is man who is depending on the method of administration, ranges from 0.005 to 10 mg/kg/day, preferably 0.01 to 1 mg/kg/day. Assigned dose can be administered one to several times per day.

Further, the present invention is illustrated examples and experiments, which are not intended to limit the scope of the present invention.

Examples

Example 1. Synthesis of compound (I-7)

Stage 1

Sodium carbonate (995 mg, 9,38 mmol) dissolved in 30 ml of water and to the solution is added to the original amino acid (1.0 g, 8,53 mmol) and N-carbamaxepine (2,49 g of 11.4 mmol). The mixture is stirred at room temperature overnight. Bring the pH of the mixture to 1 by adding conc. hydrochloric acid. Precipitated precipitated crystalline substance is washed with water and dried, obtaining the desired compound (1,72 g, yield 82%).

1H-NMR (CD3OD) δ ppm: 1,59-to 1.77 (m, 4H), of 2.34 (t, 2H, J=6.3 Hz), of 3.69 (t, 2H, J=6.6 Hz), 7,78-7,87 (m, 4H).

Stage 2

The compound obtained in stage 1 (1.0 g, 4.0 mmol)at room temperature was dissolved in 5 ml dichloromethane. To the mixture while cooling with ice add oxalicacid (0,459 ml, 5.2 mmol) and trace amounts of DMF and conduct the reaction while cooling the mixture with ice and at room temperature for 30 minutes After removal of the solvent under reduced pressure, add 5 ml of dichloromethane. To the resulting mixture at ohlazhdeniya add 4-butylaniline (664 mg, 4.4 mmol) and triethylamine (0,564 ml, 4.4 mmol) and conducting the reaction for 30 min at room temperature. The reaction mixture was poured into water and extracted with chloroform. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, the residue is purified by chromatography on silica gel, obtaining the desired compound (1,49 g, yield 97%).

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,27-of 1.39 (m, 2H), 1,51-of 1.62 (m, 2H), 1,72-of 1.84 (m, 4H), 2.40 a is 2.46 (m, 2H), has 2.56 (t, 2H, J=7.5 Hz), 3,76 (t, 1H, J=5.7 Hz), 7,12 (d, 2H, J=7.8 Hz), 7,33 (s, 1H), 7,42 (d, 2H, J=8.1 Hz), 7,71-7,73 (m, 2H), 7,83-7,86 (m, 2H).

Stage 3

After dissolution of the compound obtained in stage 2 (1,49 g, 3.9 mmol)in 30 ml of ethanol is added hydrazine monohydrate (0,591 mg of 11.8 mmol) and conducting the reaction at 50°C for 3 hours. The solvent is removed, add 1 mol/l aqueous solution of NaOH and the solution extracted with ethyl acetate. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, obtaining the desired compound (808 mg, yield 83%).

1H-NMR (CD3OD) δ ppm: of 0.93 (t, 3H, J=7.2 Hz), 1,28-of 1.40 (m, 2H), 1,50-of 1.62 (m, 4H), 1,67-to 1.77 (m, 2H), is 2.37 (t, 2H, J=7.5 Hz), of 2.56 (t, 2H, J=7.8 Hz), 2,68 (t, 2H, J=7,2 Hz), 7,11 (d, 2H, J=8.1 Hz), 7,42 (d, 2H, J=8,4 Hz).

Stage 4

The connection obtained by CT the Hai 3 (808 mg, 3.25 mmol), while cooling with ice suspended in 5 ml of dichloromethane and add isopropylacetanilide (696 mg, 4.9 mmol) and triethylamine (494 mg, 4.9 mmol). After the reaction mixture for one hour under ice cooling, the reaction mixture was poured into water and extracted with chloroform. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure and the residue purified by chromatography on silica gel, receiving the desired compound in quantitative yield.

1H-NMR (CDCI3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,27-of 1.40 (m, 2H), 1,36 (d, 6N, J=6,6 Hz)and 1.51-1.69 in (m, 4H), 1.77 in is 1.86 (m, 2H), of 2.38 (t, 2H, J=7,2 Hz), of 2.56 (t, 2H, J=7.5 Hz), 3,12-is 3.21 (m, 3H), of 4.38 (t, 1H, J=5,7 Hz), 7,11 (d, 2H, J=8,4 Hz), of 7.36-7,41 (m, 3H).

Example 2. Synthesis of compound (I-10)

The desired compound is synthesized analogously to the method of stage 4 of example 1, except that the compound obtained in stage 3 of example 1, add tert-butylsulfonyl (689 mg, 4.9 mmol) and triethylamine (494 mg, 4.9 mmol).

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,22 (s, N), of 1.30 to 1.37 (m, 2H), 1,51 by 1.68 (m, 4H), 1,76 is 1.86 (m, 2H), 2,31-to 2.40 (m, 2H), has 2.56 (t, 2H, J=7.5 Hz), 3,15-3,26 (m, 3H), 7,11 (t, 2H, J=8.7 Hz), 7,42 (d, 2H, J=8.1 Hz), 7,54 (s, 1H).

Example 3. Synthesis of compound (I-11)

The compound obtained in example 2 (352 mg, 1.0 mmol), while cooling l the house is dissolved in 5 ml of dichloromethane and to the solution was added mCPBA (259 mg, 1.5 mmol). The reaction solution is carried out at room temperature for one hour and the insoluble matter is filtered off. The filtrate is successively washed with 1 mol/l NaOH, Na2S205and water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure and the residue purified by chromatography on silica gel, obtaining the desired compound (338 mg, yield 92%).

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,29-of 1.39 (m, 2H), 1.39 in (C, N), 1,51, by 1.68 (m, 4H), 1,76-of 1.84 (m, 2H), is 2.37 (t, 2H, J=7.5 Hz), of 2.56 (t, 2H, J=7.8 Hz), 3,19-3,26 (m, 2H), 4,20 (t, 1H, J=5.7 Hz), 7,11 (t, 2H, J=8.1 Hz), 7,42 (d, 2H, J=8.7 Hz), 7,46 (s, 1H).

Example 4. Synthesis of compound (I-72)

Stage 1

The original amino acid (mixture of CIS-isomer and TRANS-isomer) (1.0 g, 8,53 mmol) dissolved in 7.5 ml of methanol. While cooling with ice to the mixture is added thionyl chloride (1.0 ml, 13.7 mmol) and the mixture is stirred at room temperature overnight. After concentrating the mixture under reduced pressure, add diethyl ether and filtered phase precipitate crystals. The crystals are washed with diethyl ether and dried, obtaining the desired compound (1.25 g, yield 93%).

1H-NMR (CDCl3) δ ppm: 1,50-2,60 (m, N), is 3.08-to 3.36 (m, 1H), to 3.67 (s, 3H, CO2Me CIS-isomer), 3,71 (s, 3H, CO2IU TRANS-isomer), 8,15-8,55 (m, 3H).

Stage 2

Treb is Amy the sulfonamide (mixture of CIS-isomer and TRANS-isomer) are synthesized from the original methyl ester analogously to the method of stage 3 of example 1 and example 2.

CIS-isomer

1H-NMR (CDCl3) δ ppm: 1,39 (s, N), 1,52 of 1.99 (m, 8H), 2,43 of $ 2.53 (m, 1H), 3,42-3,55 (m, 1H), 3,69 (s, 3H), 3,85 (d, 1H, J=9.0 Hz).

Stage 3

Source sulfonamide (19,4 g, 70,0 mmol, mixture of CIS isomer and TRANS-isomer) is dissolved in 30 ml of methanol. To the mixture is added a 28% solution of sodium methoxide (284 ml, 140,0 mmol) and the mixture is stirred under ice cooling to form phlegmy. The residue after removal of the solvent was diluted with chloroform and with stirring and ice cooling was added 1 mol/l HCl up until the pH of the aqueous layer reaches 3. The aqueous layer was extracted with chloroform and the organic layer washed with water and dried over anhydrous magnesium sulfate. The crude crystalline material is recrystallized from hexane and ethyl acetate, obtaining the desired sulfonamide (TRANS-isomer of 7.75 g, yield 40%) .

The TRANS-isomer

1H-NMR (CD3OD) δ ppm: 1,16-of 1.32 (m, 2H), 1.39 in (C, N), 1,44-of 1.52 (m, 2H), 1,98-of 2.09 (m, 2H), 2,14-to 2.29 (m, 3H), 3,18-3,37 (m, 1H), 3,63 (d, 1H, J=9.0 Hz), to 3.67 (s, 3H).

Stage 4

The original methyl ether (4.77 g, and 17.2 mmol) dissolved in 95 ml of methanol and, while stirring and cooling with ice add 1 mol/l NaOH (43 ml, 43,0 mmol). The mixture is stirred at room temperature overnight and concentrated under reduced pressure. Then with stirring, and Oh is Adeney ice add 1 mol/l HCl as long while the pH of the mixture reaches 3, precipitated precipitated crystalline substance is filtered off, washed with water and dried. The crude crystalline material is recrystallized from hexane and ethyl acetate, obtaining the desired carboxylic acid (4,20 g, yield 93%).

1H-NMR (COCl3) δ ppm: 1.18 to about 1.35 (m, 2H), 1.39 in (C, N), 1,46-to 1.63 (m, 2H), 2,01 with 2.14 (m, 2H), 2,14 of-2.32 (m, 3H), 3,18-to 3.35 (m, 1H), 3,80 (d, 1H, J=9.6 Hz).

Stage 5

The original carboxylic acid (5,86 g of 22.3 mmol) was dissolved in 88 ml of dichloromethane at room temperature. To the mixture while cooling with ice add oxalicacid (2,34 ml, or 26.7 mmol) and catalytic amount of DMF and the mixture is stirred at room temperature for one hour. After removal of the solvent under reduced pressure, add dichloromethane (115 ml), substituted aniline (of 5.05 g, 24.5 mmol) and triethylamine (4,65 ml, 33.4 mmol). The mixture is stirred at room temperature for 2.5 hours, poured water into it, chilled with ice, and the mixture is extracted with chloroform. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure and to the residue is added ethyl acetate and hexane. Precipitated precipitated crystalline substance is filtered off, getting the desired amide (7,00 g, yield 70%).

1H-NMR (CDCl3) δ ppm: 1,25 (d, 6N, J=6.3 Hz), 117-1,42 (m, 2H), 1,40 (s, N), 1,60-of 1.78 (m, 2H), 1,98 is 2.43 (m, 7H), 3,20-of 3.43 (m, 3H), to 3.67 (d, 1H, J=9.6 Hz), 3,74-3,86 (m, 2H), 6,86 (d, 2H, J=9.0 Hz),? 7.04 baby mortality (s, 1H), 7,38 (d, 2H, J=9.0 Hz).

Example 5. Synthesis of compound (I-2)

Stage 1

After the suspension of the original diamine (461 mg, 2.5 mmol) in dichloromethane while cooling with ice add the acid chloride of acid (500 mg, 2.5 mmol) and triethylamine (773 mg, 7.5 mmol) and conducting the reaction for 30 minutes To the reaction mixture are added water and dichloromethane and the insoluble matter is filtered off. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, obtaining the desired compound in the form of sludge (100 mg, yield 15%).

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=1.2 Hz), 1.30 and of 1.42 (m, 2H), 1,57-to 1.67 (m, 2H), 2,66 (t, 2H, J=7.8 Hz), 3,50 (Ushs, 1H), to 6.57 (s, 1H), of 6.68 (d, 2H, J=8.7 Hz), 7,26 (d, 2H, J=8,4 Hz), 7,39 (d, 2H, J=8.7 Hz), 7.68 per (s, 1H), of 7.75 (d, 2H, J=8.1 Hz).

Stage 2

The desired compound is synthesized analogously to the method of stage 4 of example 1.

1H-NMR (CDCl3) δ ppm: to 0.94 (t, 3H, J=7.5 Hz), 1,34-of 1.44 (m, 2H), 1,40 (d, 6N, J=6.6 Hz), 1,59 by 1.68 (m, 2H), 2,69 (t, 2H, J=7.8 Hz), 3,24-to 3.35 (m, 1H), of 6.49 (s, 1H), 7.23 percent-to 7.32 (m, 4H), and 7.6 (d, 2H, J=8.7 Hz), 7,79 (d, 2H, J=8.1 Hz), the 7.85 (s, 1H).

Example 6. Synthesis of compound (I-31)

Stage 1

Source diamine (of 8.37 g, 73,3 mmol) at room temperature RAS is varaut in 30 ml of dioxane and add a solution of Boc 2O (2 g, 9.2 mmol) in dioxane (30 ml). Conduct the reaction at room temperature for 3 days and remove the solvent. To the residue water is added and the mixture extracted with chloroform. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, obtaining the desired compound in the form of sludge (1.8 g, yield 92% with respect to the Boc2O).

1H-NMR (CDCl3) δ ppm: 1,07-of 1.26 (m, 6N), the 1.44 (s, N), 1,84 is 2.00 (m, 4H), 2,58-to 2.67 (m, 1H), 3,37 (Ushs, 1H), 4,43 (Ushs, 1H).

Stage 2

The desired compound is synthesized analogously to the method of stage 1 of example 5.

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.2 Hz), 1.26 in-1.42 are (m, 6N), 1,45 (s, N), 1,54 by 1.68 (m, 2H), 1,99-2,12 (m, 4H), of 2.64 (t, 2H, J=7.8 Hz), 3.43 points (Ushs, 1H), 3,90-4,00 (m, 1H), 4,48 (d, 1H, J=5.7 Hz), 5,95 (d, 1H, J=8,4 Hz), 7,21 (d, 2H, J=8,4 Hz), the 7.65 (d, 2H, J=8,4 Hz).

Stage 3

The original Boc-compound (2,08 g, 5,55 mmol) under ice cooling was dissolved in 20 ml of ethyl acetate and add 20 ml of 4 mol/l HCl/AcOEt. Conduct the reaction at room temperature for one hour and remove the solvent under reduced pressure, obtaining the desired compound in the form of sludge (1.7 g, yield 98%).

1H-NMR (CD3OD) δ ppm: of 0.93 (t, 3H, J=7.2 Hz), 1,29-of 1.41 (m, 2H), 1,50-of 1.66 (m, 6N), 2,02-to 2.18 (m, 4H), to 2.66 (t, 2H, J=7.8 Hz), 3,13 (Ushs, 1H), 3,82-of 3.94 (m, 1H), 7,26 (d, 2H, J=8.7 Hz), 7,72 (d, 2H, J=8,4 Hz).

Study the 4

The desired compound is synthesized analogously to the method of stage 4 of example 1.

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.5 Hz), 1,21 (s, N), 1,28-of 1.62 (m, 8H), 2,07 with 2.14 (m, 4H), of 2.64 (t, 2H, J=7.8 Hz), 3,11 (d, 1H, J=5,1 Hz), 3,20 (Ushs, 1H), 3,90-Android 4.04 (m, 1H), 6,06-6,14 (m, 1H), 7,21 (t, 2H, J=8.1 Hz), to 7.67 (t, 2H, J=8,4 Hz).

Example 7. Synthesis of compound (I-32)

The desired compound synthesized from the compound obtained in example 6, similar to the method of example 3.

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.2 Hz), 1,27-of 1.65 (m, 8H), of 1.40 (s, N), 2,10-of 2.23 (m, 4H), to 2.65 (t, 2H, J=7.5 Hz), 3,23-to 3.35 (m, 1H), 3,49 (s, 1H), 3,88-was 4.02 (m, 1H), of 5.84-of 5.92 (m, 1H), 7,13 (t, 2H, J=8,4 Hz), the 7.65 (d, 2H, J=8.1 Hz).

Example 8. Synthesis of compound (I-5)

Stage 1

The desired compound is synthesized analogously to the method of step 2 of example 1.

1H-NMR (CDCl3) δ ppm: to 0.94 (t, 3H, J=7.5 Hz), 1.30 and of 1.42 (m, 2H), 1,50-of 1.65 (m, 2H), 2,61 (t, 2H, J=7.8 Hz), 7,20 (d, 2H, J=7,2 Hz), of 7.48-7,51 (m, 3H), 7,72 (s, 1H), 7,88-of 7.90 (m, 1H).

Stage 2

To a mixture of the original nitro compounds (593 mg, of 1.95 mmol) and tin (358 mg, 3.0 mmol) is added 30 ml of 6 mol/l HCl and 6 ml of THF and conducting the reaction at 50°C for 3 hours. After cooling remove the solvent, the residue is neutralized with 10% NaOH solution and extracted with chloroform. The organic layer is washed with water and dried over betwedn the m magnesium sulfate. The solvent is removed under reduced pressure and the residue purified by chromatography on silica gel, obtaining the desired compound (110 mg, yield 21%).

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,26-of 1.39 (m, 2H), 1,49-to 1.59 (m, 2H), 2,50 (t, 2H, J=7.8 Hz), 4,37 (s, 1H), 6,65 (d, 2H, J=8,4 Hz), 6,97 (d, 2H, J=8,4 Hz), 7,14 (d, 1H, J=8,4 Hz), the 7.43 (D, 1H, J=8,7 Hz).

Stage 3

The desired compound is synthesized analogously to the method of stage 4 of example 1.

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.2 Hz), 1,28-of 1.41 (m, 2H), 1,46 (d, 6N, J=6.9 Hz), 1,53-to 1.63 (m, 2H), 2,59 (t, 2H, J=7.8 Hz), 3,35-3,44 (m, 1H), 7,15 (d, 2H, J=8.7 Hz), 7,38 (s, 1H), 7,45 (d, 2H, J=8.7 Hz), EUR 7.57 (s, 1H).

Example 9. Synthesis of compound (I-4)

Stage 1

The desired compound is synthesized analogously to the method of stage 4 of example 1.

1H-NMR (CDCl3) δ ppm: 1,44 (d, 6N, J=6.9 Hz), 3.33 and-of 3.43 (m, 1H), 3,88 (s, N), 6,24-of 6.26 (m, 1H), 7,11-7,14 (m, 2H).

Stage 2

The desired compound is synthesized analogously to the method of stage 4 of example 4.

1H-NMR (CDCl3) δ ppm: 1,44 (d, 6N, J=6.3 Hz), 3.33 and is-3.45 (m, 1H), 6,25-6,28 (m, 1H), 7,27-7,28 (m, 1H), 7,51 (s, 1H).

Stage 3

The desired compound is synthesized analogously to the method of step 2 of example 1.

1H-NMR (CD3OD) δ ppm: to 0.92 (t, 3H, J=6.9 Hz), 1,28-of 1.41 (m, 2H), 1,46 (d, 6N, J=6.3 Hz), 1,53-to 1.63 (m, 2H), 2,58 (t, 2H, J=7.8 Hz), 3.33 and-of 3.43 (m, 1H), 6,27-of 6.29 (m, 1H), 7,14-7,16 (m, 3H), 7,50 (d, 2H, J=8,4 Hz), of 7.90 (s, 1H).

Example 10. Synthesis of compound (I-28)

Stage 1

The desired compound is synthesized analogously to the method of stage 1 of example 1.

1H-NMR (CDCl3) δ ppm: 1,37-of 1.52 (m, 3H), 1,74-to 1.79 (m, 2H), 2,07 and 2.13 (m, 2H), 2,28-to 2.42 (m, 2H), 3.72 points-3,81 (m, 1H), 4.09 to-4,20 (m, 1H), 7.68 per-7,73 (m, 2H), 7,81-a 7.85 (m, 2H).

Stage 2

In 30 ml of THF was dissolved 4-butylferrocene (2.85 g, 16.3 mmol) and add original alcohol (1.0 g, 4,08 mmol) and the oxide bis-anti - (972 mg, and 1.63 mmol). After stirring the mixture overnight to remove the solvent, water is added and the solution extracted with chloroform. The organic layer is washed with water and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure and the residue purified by chromatography on silica gel, obtaining the desired compound (332 mg, yield 19%).

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=6.9 Hz), 1,30-1,40 (m, 2H), 1,48-of 1.62 (m, 4H), 1,79 of-1.83 (m, 2H), 2.21 are of 2.25 (m, 2H), 2,37-of 2.50 (m, 2H), 2.57 m (t, 2H, J=7.8 Hz), 4,11-4,22 (m, 1H), 4,77-to 4.87 (m, 1H), of 6.49 (s, 1H), 7,11 (d, 2H, J=8.7 Hz), 7,28 (d, 2H, J=8.7 Hz), 7,69-7,73 (m, 2H), 7,80-to 7.84 (m, 2H).

Stage 3

The desired compound is synthesized analogously to the method of stage 3 of example 1 and example 2.

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,21 (s, N), 1,30-of 1.62 (m, 8H), 2,08 (d, 4H, J=11,1 Hz), of 2.56 (t, 2H, J=78 Hz), 3.04 from (d, 1H, J=4,8 Hz), 3,20-3,30 (m, 1H), 4,65 was 4.76 (m, 1H), to 6.57 (s, 1H), 7,10 (d, 2H, J=8.7 Hz), 7,26 (d, 2H, J == 8,1 Hz).

Example 11. Synthesis of compound (I-29)

The desired compound is synthesized analogously to the method of example 3.

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=1.2 Hz), 1,23-of 1.62 (m, 8H), of 1.40 (s, N), 2,12 (d, 4H, J=14.4 Hz), of 2.56 (t, 2H, J=7.8 Hz), 3,28 is 3.40 (m, 1H), 3,90 (s, 1H), 4,60-to 4.73 (m, 1H), to 6.57 (s, 1H), 7,10 (d, 2H, J=8.4 and Hz), 7,25 (d, 2H, J=8,4 Hz).

Example 12. Synthesis of compound (I-114)

To a solution of 100 mg of compound (I-110)synthesized similarly to the method of example 1, in toluene (2.7 ml) is added a reagent Losson [2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphate-2,4-disulfide] (132 mg) and the mixture was stirred at 80°C for 3 hours. The reaction mixture was concentrated under reduced pressure and the residue purified by chromatography on silica gel (ethyl acetate:n-hexane=1:1)to give pale-yellow crystalline substance (82,3 mg, 79%). Crystalline substance is recrystallized from a mixture of methylene chloride/diisopropyl ether, obtaining the desired compound in the form of colorless needle-like crystals (50.5 mg, 48%).

Example 13. Synthesis of compound (I-120)

Stage 1

In 5 ml of dichloromethane was dissolved ethyl 4-amino-1˜ piperidinecarboxylate (300 mg) and triethylamine (258 mg). To the mixture is added 2 ml solution of tert-butylsulfide is chloride (222 mg) in dichloromethane and the mixture is stirred at room temperature for 4 hours. The solution is treated with an aqueous solution of potassium hydrosulfate and ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure and the residue purified by chromatography on silica gel, getting 378 mg 4-tert-butylmethylamine-1-ethoxycarbonylpyrimidine.

Stage 2

In a mixture of 5 ml of 2-propanol and 5 ml of water is suspended 378 mg 4-tert-butylmethylamine-1-ethoxycarbonylpyrimidine and add to 1.77 g of barium hydroxide. The mixture is refluxed with stirring for 4 hours. The mixture is diluted with methanol and the insoluble matter is filtered off. The solvent is removed under reduced pressure, obtaining 4-tert-butyl-sulfonilmorpholid. The resulting material without purification was dissolved in 5 ml of THF, add 984 mg N-phenoxycarbonyl-4-butylaniline and 236 mg of diisopropylethylamine and then the mixture is stirred at room temperature overnight. To this mixture an aqueous solution of potassium hydrosulfate and the mixture is extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure and the residue purified by chromatography on silica gel, getting 291 mg (4-tert-butylphenyl)amide 4-tert-butylmethylamine-1-carboxylic acid./p>

1H-NMR (CDCl3) δ ppm: to 0.89 (t, 3H, J=7,3 Hz), 1,19 (s, N), 1,25-to 1.38 (m, 4H), 1,40-1,60 (m, 4H), 1,89-2,03 (m, 3H), 2,52 (t, 2H, J=7,7 Hz), 2,89 totaling 3.04 (m, 2H), 3,14 (d, 1H, J=5,2 Hz), 3,37 (m, 1H), 3.96 points (m, 2H), to 6.67 (s, N), 7,05 (d, 2H, J=8.5 Hz), 7,22 (d, 2H, J=8.5 Hz).

Stage 3

In a mixture of 2 ml of methanol and 2 ml of methylene chloride is dissolved 291 mg (4-tert-butylphenyl)amide 4-tert-butylmethylamine-1-carboxylic acid. To the mixture is added 570 mg 80% MRR (uranyl monoperoxyphthalate magnesium) and the mixture is stirred at room temperature for 2 hours. The solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure, and the residue purified by chromatography on silica gel, receiving 130 mg (4-tert-butylphenyl)amide 4-tert-butylmethylamine-1-carboxylic acid (I-120).

Such methods synthesize other compounds (I). Structure and physical properties of compounds (I) below.

I-2

1H-NMR (CDCl3) δ ppm: to 0.94 (t, 3H, J=7.5 Hz), 1,34-of 1.44 (m, 2H), 1,40 (d, 6N, J=6.6 Hz), 1,59 by 1.68 (m, 2H), 269 (t, 2H, J=7.8 Hz), 3,24-to 3.35 (m, 1H), of 6.49 (s, 1H), 7.23 percent-to 7.32 (m, 4H), and 7.6 (d, 2H, J=8.7 Hz), 7,79 (d, 2H, J=8.1 Hz), the 7.85 (s, 1H).

I-3

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.2 Hz), 1.30 and 1.39 in (m, 2H), 1,37 (d, 6N, J=6.9 Hz), of 1.57 (Quint, 2H, J=7.5 Hz), a 1.96 (Quint, 2H, J=6.6 Hz), 2.49 USD (t, 2H, J=6.6 Hz), 2.57 m (t, 2H, J=7.8 Hz), 3,16-3,26 (m, 3H), 4,62 (Ushs, 1H), 7,12 (d, 2H, J=8.1 Hz), the 7.43 (d, 2H, J=8,4 Hz), to 7.64 (s, 1H).

I-4

1H-NMR (CD3OD) δ ppm: to 0.92 (t, 3H, J=6.9 Hz), 1,28-of 1.41 (m, 2H), 1,46 (d, 6N, J=6.3 Hz), 1,53-to 1.63 (m, 2H), 2,58 (t, 2H, J=7.8 Hz), 3.33 and-of 3.43 (m, 1H), 6,27-of 6.29 (m, 1H), 7,14-7,16 (m, 3H), 7,50 (d, 2H, J=8,4 Hz), of 7.90 (s, 1H).

I-5

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.2 Hz), 1,28-of 1.41 (m, 2H), 1,46 (d, 6N, J=6.9 Hz), 1,53-to 1.63 (m, 2H), 2,59 (t, 2H, J=7.8 Hz), 3,35-3,44 (m, 1H), 7,15 (d, 2H, J=8.7 Hz), 7,38 (s, 1H), 7,45 (d, 2H, J=8.7 Hz), EUR 7.57 (s, 1H).

I-6

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,29-of 1.39 (m, 2H), 1,37 (d, 6N, J=6,9 Hz)of 1.55 (Quint, 2H, J=7.5 Hz), to 2.55 (t, 2H, J=5,1 Hz), 3,18-of 3.27 (m, 1H), 3,92 (d, 2H, J=6.0 Hz), the 5.51 (t, 1H, J=5.7 Hz), 7,10 (d, 2H, J=8,4 Hz), 7,39 (d, 2H, J=8,4 Hz), 8,23 (s, 1H).

I-7

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,28-to 1.38 (m, 2H), 1,37 (d, 6N, J=6.9 Hz), 1,51-to 1.67 (m, 4H), 1,78-of 1.88 (m, 2H), 2,39 (t, 2H, J=7,2 Hz), 2.57 m (t, 2H, J=7.5 Hz), 3,12-up 3.22 (m, 3H), 4,30-4,37 (m, 1H), for 7.12 (d, 2H, J=8,4 Hz), of 7.36-7,42 (m, 3H).

I-8

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), to 1.21 to 1.47 (m, 4H), of 1.35 (d, 6N, J=6.6 Hz), 1,51-to 1.63 (m, 4H), 1,67-to 1.77 (m, 2H), 2,34 (t, 2H, J=7.5 Hz), to 2.55 (t, 2H, J=7.8 Hz), is 3.08-3,17 (m, 3H), 4,71 (t, 1H, J=6,0 Hz), to 7.09 (d, 2H, J=8.1 Hz), the 7.43 (d, 2H, J=8,4 Hz), 7,74 (s, 1H).

I-9

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,29-of 1.39 (m, 2H), of 1.35 (d, 6N, J=6.9 Hz), 1,50-1,60 (m, 2H), 2,54 (t, 2H, J=7,8 Hz)of 2.64 (t, 2H, J=5.7 Hz), 3,14 is 3.23 (m, 1H), 3,41-3,47 (m, 2H), from 5.29 (t, 1H, J=6.3 Hz), 7,10 (d, 2H, J=8,4 Hz), 7,39 (d, 2H, J=8,4 Hz), to $ 7.91 (s, 1H).

I-10

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,22 (s, N), of 1.30 to 1.37 (m, 2H), 1,51 by 1.68 (m, 4H), 1,76 is 1.86 (m, 2H), 2,31-to 2.40 (m, 2H), has 2.56 (t, 2H, J=7.5 Hz), 3,15-3,26 (m, 3H), 7,11 (t, 2H, J=8.7 Hz), 7.42 (d, 2H, J=8.1 Hz), 7,54 (s, 1H).

I-11

TPL: 128-129°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,29-of 1.39 (m, 2H), 1.39 in (C, N), 1,51 by 1.68 (m, 4H), 1,76-of 1.84 (m, 2H), is 2.37 (t, 2H, J=7.5 Hz), of 2.56 (t, 2H, J=7.8 Hz), 3,19-3,26 (m, 2H), 4,20 (t, 1H, J=5.7 Hz), 7,11 (d, 2H, J=8.1 Hz), 7,42 (d, 2H, J=8.7 Hz), 7,46 (s, 1H).

I-12

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), of 1.28 to 1.37 (m, 2H), 1,47 by 1.68 (m, 6N), of 2.23 (t, 2H, J=7,2 Hz), of 2.56 (t, 2H, J= 7.5 Hz), 2,90-of 2.97 (m, 2H), 5,10 (Ushs, 1H), 7,11 (d, 2H, J=8,4 Hz), was 7.36 (d, 2H, J=8,1 Hz), 7,50-to 7.68 (m, 3H), of 7.93 (d, 1H, J=8.1 Hz), of 8.06 (d, 1H, J=8,4 Hz), 8,24 (d, 1H, J=7.5 Hz), 8,66 (d, 1H, J=8.7 Hz).

I-13

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,28-of 1.40 (m, 2H), 1,45-of 1.73 (m, 6N), of 2.23 (t, 2H, J=7.5 Hz), of 2.56 (t, 2H, J=7.8 Hz), 2,88 (C, 6N), 2,88-2,95 (m, 2H), 5,04 (Ushs, 1H), 7,10 (d, 2H, J=8.1 Hz), 7,17 (d, 1H, J=7,2 Hz), 7,37 (d, 2H, J=8,4 Hz), of 7.48-rate of 7.54 (m, 2H), 8,23 (d, 1H, J=7,2 Hz), 8,30 (d, 1H, J=8.7 Hz), 8,53 (d, 1H, J=8,4 Hz).

I-14

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1.30 and USD 1.43 (m, 6N), of 1.36 (d, 6N, J=6.6 Hz), 1,51-of 1.62 (m, 4H), 1,67-of 1.78 (m, 2H), 2,34 (t, 2H, J=7.5 Hz), of 2.56 (t, 2H, J=7.8 Hz), 3,09-3,20 (m, 3H), 4,34 (Ushs, 1H), 7,10 (d, 2H, J=8,4 Hz), 7,41-7,44 (m, 3H).

I-15

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,23 (s, N), 1.27mm and 1.80 (m, N), 2,30-of 2.38 (m, 2H), 2,56(t, 2H, J=7.5 Hz), 3.15 in (Ushs, 2H), 7,11 (d, 2H, J=7.8 Hz), the 7.43 (d, 2H, J=7.8 Hz), to 7.59 (s, 1H).

I-16

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,29-of 1.44 (m, 6N), of 1.39 (s, N)and 1.51-of 1.61 (m, 4H), 1,68-of 1.78 (m, 2H), 2,35 (t, 2H, J=7.5 Hz), of 2.56 (t, 2H, J=8.1 Hz), 3.15 and 3.21-in (m, 2H), 4,14-to 4.23 (m, 1H), 7,11 (d, 2H, J=7.8 Hz), of 7.36-7,44 (m, 3H).

I-19

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.5 Hz), 1,21 (s, N), 1,30-1,40 (m, 2H), 1,55-1,72 (m, 6N), of 2.64 (t, 2H, J=7.8 Hz), is 3.08-of 3.33 (m, 3H), 3,42-to 3.50 (m, 2H), to 6.39 (s, 1H), 7,22 (d, 2H, J=8,4 Hz), 7,69 (d, 2H, J=8,1 Hz).

I-20

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.2 Hz), 1,31-of 1.39 (m, 2H), 1.39 in (C, N), 1,55-1,72 (m, 6N), of 2.64 (t, 2H, J=7.8 Hz), 3,24 (quart, 2H, J=6.6 Hz), 3,48 (quart, 2H, J=6.6 Hz), is 4.21 (t, 1H, J=6.3 Hz), of 6.29 (s, 1H), 7,22 (d, 2H, J=7.8 Hz), to 7.67 (d, 2H, J=8.1 Hz).

I-21

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,23 (s, N), 1,30-of 1.42 (m, 2H), 1,50-2,02 (m, 10 H), 2,30-to 2.42 (m, 1H), 2.57 m (t, 2H, J=8.1 Hz), 3,10 (Ushs, 1H), 3,57 (Ushs, 1H), 7,12 (d, 2H, J=8,4 Hz), 7,41 (d, 2H, J=7,8 Hz).

I-22

TPL: 78-79°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,30-1,40 (m, 2H), 1,40 (s, N), 1,50-of 1.65 (m, 4H), 1.70 to to 1.98 (m, 8H), 2,30-to 2.40 (m, 1H), 2.57 m (t, 2H, J=7.5 Hz), to 3.58-3,70 (m, 1H), 4.16 the (d, 1H, J=9.3 Hz), 7,11-7,15 (m, 3H), 7,40 (d, 2H, J=8.1 Hz).

I-23

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,21 (s, N), 1,21-of 1.41 (m, 4H), 1,51-of 1.64 (m, 4H), 1,86 is 2.01 (m, 4H), 2,12 was 2.25 (m, 1H), has 2.56 (t, 2H, J=7.5 Hz), 2,87-2,96 (m, 1H), 3.00 and-of 3.12 (m, 1H), 3,23-to 3.34 (m, 1H), 3,67 of 3.75 (m, 1H), 7,11 (d, 2H, J=8.1 Hz), 7,40 (d, 2H, J=8,4 Hz).

I-24

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,25-to 1.37 (m, 2H), 1,40 (s, N), 1,48-of 1.65 (m, 6N), 1,90 (d, 2H, J=11.7 Hz), 2,02 (d 2H, J=11.7 Hz), 2,12-of 2.24 (m, 1H), has 2.56 (t, 2H, J=7.5 Hz), 3.04 from (t, 2H, J=6.3 Hz), or 4.31 (t, 1H, J=5.7 Hz), 7,11 (d, 2H, J=8.1 Hz), 7,42 (d, 2H, J=8,4 Hz).

I-25

TPL: 232-233°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,23-of 1.40 (m, 4H), of 1.40 (s, N)and 1.51 to 1.76 (m, 4H), 2,01,2,26 (m, 5H), of 2.56 (t, 2H, J=7.5 Hz), 3,22-to 3.38 (m, 1H), 3,79 (d, 1H, J=9.3 Hz), 7,11 (d, 2H, J=8.7 Hz), 7,17 (s, 1H), 7,40 (d, 2H, J=8,4 Hz).

I-26

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,22 (s, N), 1,28-of 1.40 (m, 2H), 1,52-of 1.62 (m, 2H), 1.85 to a 1.96 (m, 1H), 2.00 in and 2.14 (m, 1H), 2,38 of $ 2.53 (m, 2H), has 2.56 (t, 2H, J=7.5 Hz), 3,22-3,37 (m, 3H), 7,11 (d, 2H, J=and 8.4 Hz), was 7.45 (d, 2H, J=8,4 Hz), 8,19 (s, 1H).

I-27

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,30-1,40 (m, 2H), 1,40 (s, N), 1,52-to 1.61 (m, 2H), 1,95 (Quint, 2H, J=6.3 Hz), 2,50 (t, 2H, J=6.9 Hz), of 2.56 (t, 2H, J=7,8 Hz)and 3.31 (quart, 2H, J=6.0 Hz), 4,30 is 4.36 (m, 1H), for 7.12 (d, 2H, J=8,4 Hz), the 7.43 (d, 2H, J=8,4 Hz), the 7.65 (s, 1H).

I-28

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,21 (s, N), 1,30-of 1.62 (m, 8H), 2,08 (d, 4H, J=11,1 Hz), of 2.56 (t, 2H, J=7.8 Hz), 3.04 from (d, 1H, J=4,8 Hz), 3,20-3,30 (m, 1H), 4,65 was 4.76 (m, 1H), to 6.57 (s, 1H), 7,10 (d, 2H, J=8.7 Hz), 7,26 (d, 2H, J=8.1 Hz).

I-29

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.2 Hz), 1,23-of 1.62 (m, 8H), of 1.40 (s, N), 2,12 (d, 4H, J=14.4 Hz), of 2.56 (t, 2H, J=7.8 Hz), 3,28 is 3.40 (m, 1H), 3,90 (s, 1H), 4,60-to 4.73 (m, 1H), to 6.57 (s, 1H), 7,10 (d, 2H, J=8.4 and Hz), 7,25 (d, 2H, J=8,4 Hz).

I-30

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,26-of 1.39 (m, 2H), 1,51-of 1.64 (m, 4H), 1,72-of 1.81 (m, 2H), 2,34 (t, 2H, J=6.9 Hz), of 2.56 (t, 2H, J=7.8 Hz), 2.95 and-a 3.01 (m, 2H), 4,84 (t, 1H, J=5.7 Hz), 6,99 for 7.12 (m, 6N), 7,19-7,24 (m, 1H), 7,30 (s, 1H), 7,38-the 7.43 (m, 4H), 7,79 (d, 2H, J=8.7 Hz).

I-31

1H is the Mr (CDCl 3) δ ppm: to 0.92 (t, 3H, J=7.5 Hz), 1,21 (s, N), 1,28-of 1.62 (m, 8H), 2,07 with 2.14 (m, 4H), of 2.64 (t, 2H, J=7.8 Hz), 3,11 (d, 1H, J=5,1 Hz), 3,20 (Ushs, 1H), 3,90-Android 4.04 (m, 1H), 6,06-6,14 (m, 1H), 7,21 (t, 2H, J=8.1 Hz), to 7.67 (t, 2H, J=8,4 Hz).

I-32

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.2 Hz), 1,27-of 1.65 (m, 8H), of 1.40 (s, N), 2,10-of 2.23 (m, 4H), to 2.65 (t, 2H, J=7.5 Hz), 3,23-to 3.35 (m, 1H), 3,49 (s, 1H), 3,88-was 4.02 (m, 1H), of 5.84-of 5.92 (m, 1H), 7,13 (t, 2H, J=8,4 Hz), the 7.65 (d, 2H, J=8.1 Hz).

I-33

1H-NMR (CDCl3) δ ppm: to 0.94 (t, 3H, J=7.2 Hz), 1.30 and of 1.42 (m, 2H), 1,32 (s, N), 1,57-of 1.66 (m, 2H), to 2.67 (t, 2H, J=7.8 Hz), 5,61 (s, 1H), 6,93 (d, 2H, J=8.7 Hz), 7,25 (d, 2H, J=8,4 Hz), 7,49 (d, 2H, J=9.0 Hz), 7,80 (d, 2H, J=8.1 Hz), by 8.22 (s, 1H).

I-34

1H-NMR (CD3OD) δ ppm: of 0.95 (t, 3H, J=7.5 Hz), of 1.35 (s, N), 1,35-of 1.44 (m, 2H), 1,57 was 1.69 (m, 2H), 2,69 (t, 2H, J=7.5 Hz), 7,28-7,33 (m, 4H), 7,56 (d, 2H, J=9.0 Hz), 7,83 (d, 2H, J=8,4 Hz).

I-36

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.5 Hz), 1,31 is 1.70 (m, 11N), of 1.39 (s, N), a 1.75-of 1.85 (m, 1H), 2,65 (t, 2H, J=8.1 Hz), of 3.13 (t, 2H, J=6.6 Hz), 3,40 (t, 2H, J=7,2 Hz), 4,10 (t, 1H, J=5.7 Hz), 6,21 (t, 1H, J=5.7 Hz), of 7.23 (d, 2H, J=8.1 Hz), to 7.67 (d, 2H, J=8,4 Hz).

I-37

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.5 Hz), 0,95-1,10 (m, 2H), 1,31-of 1.40 (m, 2H), 1.39 in (C, N), 1,55-to 1.63 (m, 4H), 1,80-of 1.92 (m, 4H), to 2.65 (t, 2H, J=7.8 Hz), 3,03 (t, 2H, J=6,6 Hz)and 3.31 (t, 2H, J=6.6 Hz), 4,06 (t, 1H, J=6.0 Hz), to 6.22 (t, 1H, J=6.0 Hz), of 7.23 (d, 2H, J=8,4 Hz), to 7.67 (d, 2H, J=8.1 Hz).

I-39

1H-NMR (CDCl3) δ ppm: of 1.13 (t, 3H, J=7.2 Hz), 1.39 in (C, N), 1,69-of 1.97 (m, 8H), 2,27-of 2.38 (m, 1H), 3,29-to 3.35 (m, 4H), 3,60-3,70 (m, 1H), to 4.52 (d, 1H, J=9.3 Hz), only 6.64 (d, 2H, J=8,4 Hz), 7,22 (s, 1H), 7,31 (d, 2H, J=9,0 Hz).

I-40

1H-NMR (CDCl3) δ to 1.38 ppm (s, N), 1,68 is 1.96 (m, 8H), 2,30-to 2.40 (m, 1H), 3,11 (t, 4H, J=4,8 Hz), 3,60-and 3.72 (m, 1H), 3,86 (t, 4H, J=4,8 Hz), 4,51 (Ushs, 1H), 6.89 in (d, 2H, J=9.0 Hz), 7,42 (d, 2H, J=8.7 Hz).

I-41

TPL: >278°C (decomp.)

1H-NMR (CDCl3) δ M. D.: 1,18-of 1.40 (m, 2H), 1,40 (S, N), of 1.62 and 1.75 (m, 2H), 2,01-of 2.27 (m, 5H), 3,10-3,13 (m, 4H), 3,22-to 3.38 (m, 1H), and 3.72 (d, 1H, J=9.3 Hz), 3,85-3,88 (m, 4H), 6.87 in (d, 2H, J=9.0 Hz), 7,10 (s, 1H), 7,40 (d, 2H, J=9.0 Hz).

I-42

1H-NMR (CDCl3) δ ppm: 1,40 (s, N), 1,61-of 1.97 (m, 8H), of 2.16 (s, 3H), 2,33 is 2.43 (m, 1H), 3,60-3,70 (m, 1H), 4,66 (Ushs, 1H), 7,12 (d, 1H, J=8.7 Hz), 7,46 is 7.50 (m, 1H), 7.62mm (C, H), 7,75 for 7.78 (m, 1H), 7,86-to $ 7.91 (m, 2H).

I-43

1H-NMR (CDCl3) δ ppm: 1,40 (s, N), 1,62 is 2.00 (m, 8H), to 1.87 (s, 3H), 2,36-2,47 (m, 1H), 3,24 (s, 3H), 3,64-3,74 (m, 1H), 4,87 (Ushs, 1H), 7,13 (d, 2H, J=9.0 Hz), to 7.64 (d, 2H, J=8,4 Hz), 7,81 (C, H).

I-44

TPL: 235-236°

1H-NMR (CDCl3) δ ppm: 1,13 (t, 6N, J=6.9 Hz), of 1.18 and 1.33 (m, 2H), 1,40 (s, N), 1,60-to 1.77 (m, 2H), 2.00 in of 2.26 (m, 5H), 3,28-to 3.35 (m, 4H), to 3.73 (d, 1H, J=9.3 Hz), 6,60-6,70 (m, 2H), 7,03 (Ushs, 1H), 7,31 (d, 2H, J=7,8 Hz).

I-45

TPL: >268°C (decomp.)

1H-NMR (CDCl3) δ ppm: of 1.20 to 1.34 (m, 2H), 1,40 (s, N), and 1.56 to 1.76 (m, 8H), 2.00 in of 2.26 (m, 5H), 3,06-3,14 (m, 4H), 3,24-to 3.36 (m, 1H), and 3.72 (d, 1H, J=9.3 Hz), 6.90 to (d, 2H, J=8.7 Hz), to 7.09 (s, 1H), was 7.36 (d, 2H, J=8.7 Hz).

I-46

TPL: >272°C (decomp.)

1H-NMR (DMSO-d6) δ ppm: 1.28 (in C, N), 1,31-to 1.59 (m, 7H), 1,87 is 2.00 (m, 4H), 2,23-of 2.34 (m, 1H), 3.00 and-and 3.16 (m, 1H), 4,35 is 4.45 (m, 2H), for 6.81 (d, 1H, J=9.0 Hz), 7,16 (t, 1H, J=7,2 Hz), the 7.43 (t, 1H, J=8,4 Hz), 7,52-7,58 (m, 3H), of 8.04 (d, 1H, J=7.8 Hz), 8,43 (s, 1H).

I-47

1H-NMR (CDCl3) δ ppm: 1,20-of 1.36 (m, 2H), 1,40 (s, N), 1,62 to 1.7 (m, 2H), 1,98 of-2.32 (m, 5H), 3,31 is 3.40 (m, 1H), 3,62 (d, 1H, J=9.0 Hz), was 7.08 (s, 1H), 7,29 (d, 2H, J=9.0 Hz), to 7.61 (d, 2H, J=9.0 Hz).

I-48

1H-NMR (CDCl3) δ ppm: 1,22-of 1.36 (m, 2H), 1,40 (s, N), of 1.62-1.77 in (m, 2H), 2.00 in 2,31 (m, 5H), 3,24 is 3.40 (m, 1H), 3,62 (d, 1H, J=10,2 Hz), 7,01 (t, 2H, J=8.7 Hz), to 7.09 (s, 1H), 7,42-to 7.50 (m, 2H).

I-49

TPL: 270°C (decomp.)

1H-NMR (CDCl3) δ ppm: 1,20-of 1.36 (m, 2H), 1,40 (s, N), 1,61-to 1.77 (m, 2H), 1,95-2,30 (m, N), 3,17-to 3.38 (m, 5H), to 3.67 (d, 1H, J=9.3 Hz), 6,50 (d, 2H, J=9.0 Hz), 6,97 (s, 1H), 7,30 (d, 2H, J=9.0 Hz).

I-50

TPL: 252-253°

1H-NMR (CDCl3) δ ppm: to 1.21 to 1.37 (m, 2H), 1,40 (s, N), 1,62-of 1.78 (m, 2H), 1,98 of-2.32 (m, 5H), 3,26 is 3.40 (m, 1H), 3,68 (d, 1H, J=9.6 Hz), 6,94-7,02 (m, 4H), was 7.08 (t, 1H, J=7.5 Hz), 7,13 (s, 1H), 7,31 (t, 2H, J=7.5 Hz,), 7,46 (d, 2H, J=9.0 Hz).

I-51

TPL: 278-279°

1H-NMR (CDCl3) δ ppm: 1,02 (d, 6N, J=6,9 Hz)of 1.35 (s, N), 1,39-1,71 (m, 6N), 1,90-of 2.09 (m, 2H), 3,16-3,30 (m, 1H), 3.46 in (d, 1H, J=9.0 Hz), 4.92 in-5,01 (m, 1H), 6,91-to 6.95 (m, 2H), 7,00-7,07 (m, 3H), 7,13-7,16 (m, 2H), 7,30 and 7.36 (m, 2H).

I-52

TPL: 276-277°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.36 (m, 2H), 1,40 (s, N), 1,60-of 1.78 (m, 2H), 1,98-of 2.30 (m, 5H), a 2.36 (s, 3H), 2,58 (t, 4H, J=4.5 Hz), 3,17 (t, 4H, J=4.5 Hz), 3,21 is 3.40 (m, 1H), 3,64 (d, 1H, J=9.0 Hz), to 6.88 (d, 2H, J=9,0 Hz), 7,01 (s, 1H), 7,37 (d, 2H, J=9.0 Hz).

I-53

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1,20-and 1.54 (m, 4H), 1.27mm (s, N), 1,73-of 1.88 (m, 2H), 1,89 is 2.01 (m, 2H), 2.13 and was 2.25 (m, 1H), 2,98-of 3.12 (m, 1H), 3,15-of 3.31 (m, 8H), 6,76-6,84 (m, 2H), 6,93 (d, 2H, J=9.0 Hz), of 6.99 (d, 2H, J=8,1 Hz), from 7.24 (d, 2H, J=8.1 Hz), 7,46 (d, 2H, J=9.0 Hz), a 9.60 (S, 1H).

I-54

TPL: >215°C (decomp.)

1H-NMR (DMSO-d6 ) δ ppm: 1,27 (s, N), 1,27-2,00 (m, N), 2,14-of 2.26 (m, 1H), 2,53-2,84 (m, 4H), 2,86-3,30 (m, 2H), 3.46 in-3,54 (m, 1H), 3,62-3,74 (m, 2H), 6,78 (d, 1H, J=8.7 Hz), 6.87 in (d, 2H, J=7.8 Hz), 7,42 (d, 2H, J=to 8.7 Hz), 9,58 (s, 1H).

I-55

TPL: >290°C (decomp.)

1H-NMR (CDCl3) δ ppm: 1,23-of 1.40 (m, 2H), 1,40 (s, N), 1,60 to 1.76 (m, 2H), 2,02-of 2.27 (m, 5H), 3,20 (t, 4H, J=5.4 Hz), 3,21-of 3.32 (m, 1H), to 3.67 (d, 1H, J=9.3 Hz), 3,98 (t, 4H, J =4,8 Hz), of 6.52 (t, 1H, J=4,8 Hz), 6,93 (d, 2H, J=8,4 Hz), 7,06 (s, 1H), 7,41 (d, 2H, J=8.7 Hz), with 8.33 (d, 2H, J=4,8 Hz).

I-56

TPL: >232°C (decomp.)

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), of 1.27 to 1.48 (m, 4H), 1,80-1,99 (m, 4H), 2,14 was 2.25 (m, 1H), 3.04 from-3,24 (m, 8H), 3,68 (s, 3H), 3,76 (s, 3H), 6,44-6,47 (m, 1H), 6,66 (s, 1H), 6,76-6,84 (m, 2H), 6,92 (d, 2H, J=8,4 Hz), 7,46 (d, 2H, J=8,4 Hz), being 9.61 (s, 1H).

I-57

TPL: 284-285°C (decomp.)

1H-NMR (CDCl3) δ ppm: of 1.27 (t, 3H, J=7.2 Hz), 1,40 (s, N), 1,61-of 2.24 (m, N), 2,35-2,49 (m, 1H), was 2.76 (t, 2H, J=10,2 Hz), 3.04 from is 3.15 (m, 2H), 3,20-to 3.36 (m, 1H), 3,55-3,59 (m, 2H), a 3.87 (d, 1H, J=9.6 Hz), 4,12-4,19 (m, 2H), 6.90 to (d, 2H, J=8.7 Hz), and 2.79 (s, 1H), 7,40 (d, 2H, J=8.7 Hz).

I-58

TPL: >299°C (decomp.)

1H-NMR (CDCl3) δ ppm: 1,26-of 1.33 (m, 2H), 1,40 (s, M), 1.56 to to 2.42 (m, N), 2,73-of 2.81 (m, 4H), 3,16-3,26 (m, 4H), to 3.64 (d, 1H, J=9.6 Hz), 6.87 in (d, 2H, J=8.7 Hz),? 7.04 baby mortality (s, 1H), 7,37 (d, 2H, J=9.0 Hz).

I-59

TPL: >270°C (decomp.)

1H-NMR (CDCl3) δ ppm: 1.26 in to 1.47 (m, 2H), 1,47 (s, N), 1,60-1,80 (m, 4H), 2,01 of-2.32 (m, 5H), 3,28 is 3.40 (m, 3H), 3,62-3,74 (m, 3H), 5,74-5,96 (ra, 2H), 6,92 (d, 2H, J=8.7 Hz), 7,13 (s, 1H), 7,39 (d, 2H, J=9.0 Hz).

I-60

TPL: 247-250°C (decomp.)

1H-NMR (CDCl3) δ ppm: of 1.20 to 1.37 (m, 2H), 1,40 (s, N), 1,60-of 1.78 (m,2H), 1,98 is 2.33 (m, 5H), 2,93-3,03 (m, 2H), 3,22 is 3.40 (m, 1H), 3,52 (t, 2H, J=6.0 Hz), 3,62 (d, 1H, J=8,4 Hz), 4,36 (s, 2H), 6,93 (d, 2H, J=8.7 Hz), 7,00 (s, 1H), 7,11-7,22 (m, 4H), 7,39 (d, 2H, J=8.7 Hz).

I-61

TPL: 280-281°

1H-NMR (CDCl3) δ ppm: 1,21-to 1.38 (m, 2H), 1,41 (s, N), 1,64 and 1.80 (m, 2H), 2,02 is 2.33 (m, 5H), 3,24 is 3.40 (m, 1H), 3,61 (d, 1H, J=9.0 Hz), 6,33 (t, 2H, J=2.1 Hz),? 7.04 baby mortality (t, 2H, J=2.1 Hz), 7,14 (a, 1H), 7,34 (d, 2H, J=9,0 Hz), 7,56 (d, 2H, J=9.0 Hz).

I-62

TPL: 260-262°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.39 (m, 2H), 1,41 (s, N), 1,64-to 1.82 (m, 2H), 2,02-of 2.36 (m, 5H), 3,24 is 3.40 (m, 1H), 3,62 (d, 1H, J=9.6 Hz), 7,31 (d, 2H, J=9.0 Hz), 7,51 (s, 1H), 7,69 (d, 2H, J=9.0 Hz).

I-63

TPL: 248°

1H-NMR (CDCl3) δ ppm: 1,20-to 1.38 (m, 2H), 1,40 (s, N), 1,61-of 1.78 (m, 2H), 1,98 of-2.32 (m, 5H), 3,22 is-3.45 (m, 1H), 3,64 (d, 1H, J=9.3 Hz), 7,11 (s, 1H), 7,37-7,46 (m, 4H).

I-64

TPL: 272-275°C (decomp.)

1H-NMR (DMSO-d6) δ ppm: 1,20-of 1.53 (m, 4H), 1.27mm (s, N), a 1.75-of 1.88 (m, 2H), 1,88 is 2.00 (m, 2H), 2,11-of 2.24 (m, 1H), 2,96-of 3.12 (m, 1H), 5,96 (s, 2H), 6,77 (d, 1H, J=8.7 Hz), PC 6.82 (d, 1H, J=8,4 Hz), to 6.95 (DD, 1H, J=1,8, and 8.4 Hz), 7,29 (d, 1H, J=1.8 Hz), to 9.70 (s, 1H).

I-65

TPL: 293-296°C (decomp.)

1H-NMR (DMSO-d6) δ ppm: 1,20-1,70 (m, 10H), 1.27mm (s, N), 1,79-2,038 (m, 4H), 2,18 is 2.33 (m, 1H), 2,98-3,30 (m, 5H), 6,79 (d, 1H, J=9.0 Hz), 6,97 (d, 2H, J=8.1 Hz), 7,43-EUR 7.57 (m, 4H), a 7.62 (d, 2H, J=8.1 Hz), 9,82 (s, 1H).

I-66

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,27-of 1.53 (m, 4H), 1,86 of 1.99 (m, 4H), 2,22-of 2.34 (m, 1H), 2,39 (s, 3H), 3.00 and-3,14 (m, 1H), and 6.25 (s, 1H), 6,79 (d, 1H, J=9.0 Hz), 7,47-to 7.50 (m, 1H), 7,69-7,76 (m, 1H), 10,27 (s, 1H).

I-67

TPL: 248-249°

1H-YAM who (DMSO-d 6) δ ppm: 1,20-and 1.54 (m, 4H), 1.27mm (s, N), 1,77-1,90 (m, 2H), 1,90-2,02 (m, 2H), 2,02 (s, 3H), 2,17 of-2.32 (m, 1H), 2,96-3,13 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 7,12-7,30 (m, 3H), 7,89 (s, 1H), 9,79 (s, 1H), 9,88 (s, 1H).

I-68

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1,20-and 1.54 (m, 4H), 1.27mm (s, N), 1,77-1,89 (m, 2H), 1,89-2,03 (m, 2H), from 2.00 (s, 3H), 2,14-of 2.28 (m, 1H), 2.95 and-3,13 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 7,40-rate of 7.54 (m, 4H), 9,72 (s, 1H), 9,83 (s, 1H).

I-69

TPL: 199-201°

1H-NMR (DMSO-d6) δ ppm: 1,21-of 1.53 (m, 4H), 1.27mm (s, N), 1,76-1,89 (m, 2H), 1,89-2,02 (m, 2H), 2,13-of 2.30 (m, 1H), 2,85 (C, 6N), 2,94-3,14 (m, 1H), 6,40 (DD, 1H, J=2,4, and 8.4 Hz), 6,78 (d, 1H, J=8.7 Hz), 6.90 to (d, 1H, J=and 8.4 Hz), 7,05 (t, 2H, J=8,4 Hz), a 9.60 (s, 1H).

I-70

TPL: 227-230°

1H-NMR (DMSO-d6) δ ppm: 1,22-of 1.52 (m, 4H), 1.27mm (s, N), 1,72-to 1.87 (m, 2H), 1,87 is 2.01 (m, 2H), 2,12-to 2.29 (m, 1H), 2,96-of 3.12 (m, 1H), 5,00 (s, 2H), from 6.22 (d, 1H, J=7.5 Hz), of 6.66 (d, 1H, J=7.5 Hz), 6,78 (d, 1H, J=9,0 Hz), 6,86 (d, 1H, J=7.5 Hz), 6.89 in-to 6.95 (m, 1H), 9,46 (s, 1H).

I-71

TPL: 270-272°

1H-NMR (DMSO-d6) δ ppm: 1,22-of 1.52 (m, 4H), 1.26 in (C, N), 1,73 is 1.86 (m, 2H), 1,88 is 2.00 (m, 2H), 2,08-2,22 (m, 1H), 2.95 and-3,11 (m, 1H), 4,80 (s, 2H), 6,47 (d, 2H, J=8,4 Hz), 6,77 (d, 1H, J=8,4 Hz), 7,20 (d, 2H, J=8,4 Hz), a 9.35 (s, 1H).

I-72

TPL: 262-263°

1H-NMR (CDCl3) δ ppm: 1,25 (d, 6N, J=6.3 Hz), 1,17-of 1.42 (m, 2H), 1,40 (s, N), 1,60-of 1.78 (m, 2H), 1,98 is 2.43 (m, 7H), 3,20-of 3.43 (m, 3H), to 3.67 (d, 1H, J=9.6 Hz), 3,74-3,86 (m, 2H), 6,86 (d, 2H, J=9.0 Hz),? 7.04 baby mortality (s, 1H), 7,38 (d, 2H, J=9.0 Hz).

I-73

TPL: 218-219°

1H-NMR (CD3OD) δ ppm: 1,36 (s, N), 1,36 was 1.69 (m, 4H), 1,45 (s, N), 1,88-2,02 (m, 3H), 2.06 to 2,30 (m, 4H), 3,05-3,44 (m, 3H), 3.46 in of 3.56 (m, 1 is), of 4.16-4.26 deaths (m, 1H), 6,51 (d, 2H, J=9.0 Hz), 7,30 (d, 2H, J=8.7 Hz).

I-74

TPL: 295-296°C (decomp.)

1H-NMR (CD3OD) δ ppm: 1,36 (s, N), 1,36-to 1.67 (m, 4H), 1,92 and 2.13 (m, 4H), and 2.26-2.40 a (m, 2H), 2,62 is 2.75 (m, 1H), 3,16-of 3.25 (m, 1H), to 3.58-3,98 (m, 4H), 4,16-of 4.25 (m, 1H), 7,20-7,30 (m, 2H), a 7.62 (d, 2H, J=9.0 Hz).

I-75

TPL: 250-251°

1H-NMR (DMSO-d6) δ ppm: 1,23-of 1.55 (m, 4H), 1.27mm (s, N), of 1.78-1.90 (m, 2H), 1,90-2,02 (m, 2H), 2,15-of 2.28 (m, 1H), 2,98-3,14 (m, 1H), 3,06 (t, 2H, J=8,4 Hz), a 3.87 (t, 2H, J=8,4 Hz), to 6.67 (DD, 1H, J=1,5, 7,2 Hz), 6,80 (d, 1H, J=8,4 Hz), 6,94-7,05 (m, 2H), 7,12-7,19 (m, 1H), 7,16 (d, 2H, J=9,3 Hz), EUR 7.57 (d, 2H, J=9,3 Hz), 9,73 (s, 1H).

I-76

TPL: 265-266°

1H-NMR (DMSO-d6) δ ppm: 1,23 is 1.58 (m, 4H), 1.28 (in C, N)and 1.83-2,04 (m, 4H), 2,20-of 2.36 (m, 1H), 2,97-and 3.16 (m, 1H), to 6.67 (d, 1H, J=3.0 Hz), PC 6.82 (d, 1H, J=8,4 Hz), 7,07-7,22 (m, 2H), 7,47-7,53 (m, 1H), 7,50 (d, 2H, J=9.0 Hz), 7,58 (d, 1H, J=3.0 Hz), to 7.64 (d, 1H, J=7.5 Hz), 7,79 (d, 2H, J=9.0 Hz), 10,02 (s, 1H).

I-77

TPL: 281°

1H-NMR (DMSO-d6) δ ppm: 1,21-of 1.56 (m, 4H), 1.27mm (s, N), 1,80-2,03 (m, 4H), 2,18-2,31 (m, 1H), 2,97-3,14 (m, 1H), 6,51 (DD, 1H, J=2,1, 2.7 GHz), for 6.81 (d, 1H, J=9.0 Hz), to 7.67 for 7.78 (m, 5H), to 8.41 (d, 1H, J=2.1 Hz), 9,96 (, 1H).

I-78

TPL: >300°C (decomp.)

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,27-of 1.52 (m, 4H), 1,74-2,04 (m, 7H), 2,10-of 2.25 (m, 2H), 2,96-3,20 (m, 2H), 3,48-to 3.58 (m, 1H), 3.75 to-a-3.84 (m, 1H), 6,39 (d, 2H, J=8,4 Hz), 6,79 (d, 1H, J=8,4 Hz), 7,02 (s, 1H), 7,30 (s, 1H), was 7.36 (d, 2H, J=8.1 Hz), 9,48 (s, 1H).

I-79

TPL: 248-250°C (decomp.)

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,27-and 1.54 (m, 4H), 1.85 to 1,99 (m, 4H), 2,24 is 2.33 (m, 1H), 3.00 and-3,14 (m, 1H), PC 6.82 (d, 1H, J=8.7 Hz), to 7.77 (d, 2H, J=84 Hz), 8,07 (d, 2H, J=8,4 Hz).

I-80

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1,22 is 1.58 (m, 4H), 1.27mm (s, N), 1,80-2,03 (m, 4H), 2,18 of-2.32 (m, 1H), 2,98-3,14 (m, 1H), 6,80 (d, 1H, J=8.7 Hz), 7,35 is 7.50 (m, 2H), to 7.99 (s, 1H), 8,11 (s, 1H), 9,79 (s, 1H), 12,94 (s, 1H).

I-81

TPL: 261-262°

1H-NMR (DMSO-d6) δ ppm: 1,21-of 1.57 (m, 4H), 1.27mm (s, N), 1,78-2,02 (m, 4H), 2,17-of 2.30 (m, 1H), 2,96-and 3.16 (m, 1H), 6,34 (s, 1H), 6,80 (d, 1H, J=8.7 Hz), 7,14-to 7.32 (m, 3H), a 7.85 (s, 1H), 9,58 (s, 1H), 10,95 (s, 1H).

I-82

1H-NMR (CDCl3) δ ppm: 0,86 (s, N), of 1.24 to 1.37 (m, 2H), 1,37 (s, M), 1.56 to around 1.74 (m, 2H), 1,95-2,19 (m, 5H), 3,18-of 3.32 (m, 1H), 3,44 (t, 4H, J=6.3 Hz), 3,70 (t, 4H, J=6.3 Hz), 4,39 (d, 1H, J=9.0 Hz), 6,59 (d, 2H, J=9,0 Hz), 7,31 (d, 2H, J=8.7 Hz), the 7.43 (s, 1H).

I-83

TPL: 264-265°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,27-of 1.52 (m, 4H), 1,78-of 1.88 (m, 2H), 1,90-2,00 (m, 2H), 2,14-of 2.26 (m, 1H), 2,96-3,14 (m, 1H), 6,72-PC 6.82 (m, 2H), 6,99 (t, 4H, J=7.8 Hz), 7,18 (t, 2H, J=7.5 Hz), 7,46 (d, 2H, J=9.0 Hz), 8,00 (s, 1H), 9,65 (s, 1H).

I-84

TPL: 257°C (decomp.)

1H-NMR (DMSO-d6) δ ppm: 1,23-of 1.57 (m, 4H), 1.27mm (s, N)and 1.83-2,03 (m, 4H), 2,23 to 2.35 (m, 1H), 2,98 is 3.15 (m, 1H), 6,80 (d, 1H, J=8.1 Hz), 7,87 (d, 2H, J=9.0 Hz), a 8.34 (d, 2H, J=9.0 Hz), of 9.21 (s, 1H), and 10.20 (s, 1H).

I-85

TPL: 256-258°

1H-NMR (DMSO-d6) δ ppm: 1,22-of 1.53 (m, 4H), 1.26 in (C, N), 1,79 is 2.01 (m, 4H), of 2.25 (s, 3H), 2,28-to 2.42 (m, 1H), 2,97-to 3.02 (m, 1H), of 6.71 (d, 1H, J=0.9 Hz), to 6.80 (d, 1H, J=8.1 Hz), 11,91 (s, 1H).

I-86

TPL: 228-230°

1H-NMR (CD3OD) δ ppm: 1,36 (s, N), 1,36 is 1.48 (m, 2H), 1,55-1,70 (m, 2H), 1,87-to 1.98 (m, 2H), 2,08-2,17 (m, 2H), 2,20 of-2.32 (m, 1H), 3,15-of 3.27 (m, 1H), 3,50 (t, 4H, J=5.7 G is), of 3.69 (t, 4H, J=5.7 Hz), 6,72 (d, 2H, J=9.0 Hz), 7,29-7,33 (m, 2H).

I-87

TPL: 183-184°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), of 1.27 to 1.48 (m, 4H), 1,73-1,89 (m, 4H), 1,90-2,00 (m, 2H), 2,16-of 2.28 (m, 1H), 2,28 (t, 2H, J=7.5 Hz), of 2.51-of 2.54 (m, 2H), 2,97-3,13 (m, 1H), to 3.58 (s, 3H), 6,79 (d, 1H, J=8.7 Hz), 7,08 (d, 2H, J=8.7 Hz), 7,49 (d, 2H, J=8,4 Hz), 9,73 (s, 1H).

I-88

TPL: 217-218°

1H-NMR (CD3OD) δ ppm: 1,36 (s, N), 1,36 of 1.46 (m, 2H), 1,55 was 1.69 (m, 2H), 1,83 is 2.00 (m, 4H), 2,07-to 2.18 (m, 2H), 2.26 and-a 2.36 (m, 3H), 2,61 (t, 2H, J=7.5 Hz), 3,14-3,26 (m, 1H), 7,13 (d, 2H, J=8.1 Hz), 7,44 (d, 2H, J=8,1 Hz).

I-89

1H-NMR (CDCl3) δ ppm: 0,08 (d, 6N, J=3.3 Hz), 0.88 to (C, N), 1,21-of 1.36 (m, 2H), 1.39 in (C, N), 1,61-of 1.74 (m, 2H), 1,88-of 2.23 (m, 6N), 3,06-3,11 (m, 1H), 3,24-3,74 (m, 4H), 3,92 (d, 1H, J=9.6 Hz), 4,48-4,56 (m, 1H), 6,47 (d, 2H, J=9.0 Hz), 7,17 (s, 1H), 7,32 (d, 2H, J=9.0 Hz).

I-90

TPL: amorphous

1H-NMR (CD3OD) δ ppm: 1,36 (S, N), of 1.36 to 1.47 (m, 2H), 1.56 to to 1.70 (m, 3H), 1,88-2,30 (m, 6N), 3,05-to 3.49 (m, 5H), 4,50 (Ushs, 1H), 6,50 (d, 2H, J=9.0 Hz), 7,29 (d, 2H, J=9.0 Hz).

I-91

TPL: 105-106°

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7,3 Hz), 1,25-of 1.27 (m, 2H), 1,36 (d, 6N, J=6.9 Hz), 1,51-to 1.59 (m, 2H), has 2.56 (t, 2H, J=7.8 Hz), 3.27 to (Sept, 1H, J=6.9 Hz), 7,12 (d, 2H, J=8.6 Hz), 7,32 (t, 1H, J=7.8 Hz), 7,45 (USD, 1H, J=7.8 Hz), 7,53 (d, 2H, J=8.6 Hz), 7,58 (d, 1H, J=7.8 Hz), 7,71-7,72 (m, 2H), of 8.27 (s, 1H).

I-92

TPL: 163-164°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1.32 to 1.39 in (m, 2H), 1,55-1,65 (m, 2H), 1,87 (s, 3H), of 1.95 (s, 3H), 2,60 (t, 2H, J=7,6 Hz), 7,07 (d, 2H, J=8,4 Hz), 7,18 (d, 2H, J=8.5 Hz), 7,54 (d, 2H, J=8.5 Hz), to $ 7.91 (Ushs, 1H), 8,18 (d, 2H, J=8,4 Hz), 8,77 (s, 1H).

I-93

TPL: 173°the

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,32-of 1.40 (m, 2H), 1.39 in (d, 6N, J=6.9 Hz), 1,55-of 1.62 (m, 2H), 2,60 (t, 2H, J=7.8 Hz), of 3.13 (Sept, 1H, J=6.9 Hz), 4,39 (d, 2H, J=6.3 Hz), of 4.45 (t, 1H, J=6.3 Hz), 7,18 (d, 2H, J=8.7 Hz), 7,46 (d, 2H, J=8.7 Hz), 7,54 (d, 2H, J=8.7 Hz), 7,80 (s, 1H), a 7.85 (d, 2H, J=8.7 Hz).

I-94

TPL: 159-160°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1.32 to 1.39 in (m, 2H), 1,54 and 1.80 (m, 2H), 1,79 (s, 3H), of 1.80 (s, 3H), 2,60 (t, 2H, J=7,7 Hz), 3,18 (s, 3H), 7,18 (d, 2H, J=8.5 Hz), 7,30 (d, 2H, J=8,8 Hz), 7,52 (d, 2H, J=8.5 Hz), 7,70 (Ushs, 1H), to 7.84 (d, 2H, J=8,8 Hz), 8,77 (s, 1H).

I-95

TPL: 177-178°

1H-NMR (CDCl3) δ ppm: to 0.94 (t, 3H, J=7.2 Hz), is 1.31 to 1.48 (m, 8H), 1,54-of 1.66 (m, 2H), by 2.55 (s, 3H), 2,62 (t, 2H, J=7,6 Hz), 3,92 (Sept, 1H, J=6.6 Hz), 7,20 (d, 2H, J=to 8.45 Hz), 7,74 (d, 2H, J=8.5 Hz), 9,01 (Ushs, 1H), 9,17 (s, 1H).

I-96

TPL: 220-223°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,28-of 1.42 (m, 2H), 1,50 (d, 6N, J=6,8 Hz), 1,54-of 1.65 (m, 2H), 2,62 (t, 2H, J=7,6 Hz), 4,08 (Sept, 1H, J=7,1 Hz), 7,20 (d, 2H, J=8.5 Hz), of 7.48 (d, 2H, J=8.5 Hz), 7,71 (Ushs, 1H), 8,51 (Ushs, 1H), of 8.95 (s, 1H).

I-97

TPL: 195-197°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7,6 Hz)to 0.94 (t, 3H, J=7,3 Hz), 1.32 to the 1.44 (m, 6N), and 1.54-of 1.64 (m, 2H), 1,66-of 1.78 (m, 2H), 2,62 (t, 2H, J=7,7 Hz), 2,86 (Ushs, 2H), 3,98 (Sept, 1H, J=7,1 Hz), 7,19 (d, 2H, J=8.5 Hz), 7,63 (d, 2H, J=8,4 Hz), 8,72 (Ushs, 1H), 8,81 (Ushs, 1H).

I-98

TPL: 216-218°

1H-NMR (CDCl3+CD3OD) δ ppm: of 0.93 (t, 3H, J=7.4 Hz), 1,29-of 1.40 (m, 2H), USD 1.43 (d, 2H, J=6.9 Hz), 1,51-to 1.63 (m, 2H), 2,60 (t, 2H, J=7.8 Hz), 3,65 (Sept, 1H, J=6.9 Hz), 7,18 (d, 2H, J=8.5 Hz), 7,22 (d, 1H, J=8,8 Hz), 7,55 (d, 2H, J=8.5 Hz), 8,18 (DD, 1H, J=8,8 2,4 Hz), 8,63 (d, 1H, J=2.4 Hz).

I-99

TPL: 201-202°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,22-of 1.40 (m, 2H), 1,49 (d, 2H, J=7,1 Hz), 1,51-to 1.63 (m, 2H), 2,59 (t, 2H, J=7,7 Hz), 4,22 (Sept, 1H, J=7,1 Hz), 7,16 (d, 2H, J=8,4 Hz), 7,41 (Ushs, 1H), 7,52 (d, 2H, J=and 8.4 Hz), 8,10 (Ushs, 1H), 8,13 (d, 1H, J=2.2 Hz), 8,61 (Ushs, 1H).

I-100

TPL: 160-162°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,22-of 1.42 (m, 2H), 1,45 (d, 2H, J=6.9 Hz), 1,51-to 1.63 (m, 2H), 2,61 (t, 2H, J=7.8 Hz), 3,37 (Sept, 1H, J=6.9 Hz), 6.89 in (Ushs, 1H), 7,19 (d, 2H, J=8,4 Hz), the 7.65 (d, 2H, J=and 8.4 Hz), 7,80 (DD, 1H, J=8,4, 2.4 Hz), of 8.27 (d, 1H, J=8,4 Hz), to 8.45 (d, 1H, J=2.4 Hz), 9,75 (Ushs, 1H).

I-101, I-214

TPL: 192-194°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,27-of 1.41 (m, 2H), 1,35 (s, N), 1,50-of 1.66 (m, 2H), 2,60 (t, 2H, J=7,6 Hz), 5,58 (Ushs, 1H), 7,07 (d, 2H, J=8.5 Hz), 7,17 (d, 2H, J=8.5 Hz), 7,52 (d, 2H, J=8.5 Hz), 7,71 (Ushs, 1H), 7,79 (d, 2H, J=8.5 Hz).

I-102

TPL: 216-217°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,26-of 1.42 (m, 2H), 1,45 (s, N), 1,70 of-1.83 (m, 2H), 2,60 (t, 2H, J=7,7 Hz), 6.42 per (Ushs, 1H), 7,18 (d, 2H, J=8.5 Hz), 7,35 (d, 2H, J=8.5 Hz), 7,51 (d, 2H, J=8.5 Hz), 7.68 per (Ushs, 1H), 7,82 (d, 2H, J=8.5 Hz).

I-103

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7,3 Hz), 1,28-of 1.36 (m, 2H), 1,32 (d, 6N, J=6.9 Hz), 1,49-to 1.59 (m, 2H), 2,54 (t, 2H, J=7,7 Hz), 3,23 (Sept, 1H, J=6.9 Hz), 3.46 in (s, 3H), 6,76 (Ushs, 1H), 6,91 (d, 2H, J=8,2 Hz), 6,99 (d, 2H, J=8,8 Hz), 7,03 (d, 2H, J=8,2 Hz), 7,25 (d, 2H, J=8,8 Hz).

I-104

TPL: 182-183°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,28-of 1.40 (m, 2H), 1,51-to 1.63 (m, 2H), 1,64-of 1.88 (m, 4H), 1,90-of 2.23 (m, 4H), 2,60 (t, 2H, J=7,6 Hz), 3,39 (m, 1H), 6,16 (Ushs, 1H), 7,07 (d, 2 is, J=8.5 Hz), 7,16 (d, 2H, J=8.5 Hz), 7,52 (d, 2H, J=8.5 Hz), 7,74 (Ushs, 1H), to 7.77 (d, 2H, J=8.5 Hz).

I-105

TPL: 190-191°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,28-of 1.41 (m, 2H), 1,52 was 1.69 (m, 4H), 1,75-1,90 (m, 2H), 1,92-2,07 (m, 4H), 2,58 (t, 2H, J=7,6 Hz)and 3.59 (m, 1H), 6,53 (Ushs, 1H), 7,18 (d, 2H, J=8.5 Hz), 7,31 (d, 2H, J=8,5 Hz), 7,52 (d, 2H, J=8.5 Hz), to 7.67 (Ushs, 1H), to 7.84 (d, 2H, J=8.5 Hz).

I-106

TPL: 194-197°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,22-of 1.41 (m, 2H), 1,53-of 1.65 (m, 2H), 1,90 (C, 6N), 2,60 (t, 2H, J=7.8 Hz), 6,86 (Ushs, 1H), 7,18 (d, 2H, J=8.5 Hz), the 7.43 (d, 2H, J=8.5 Hz), 7,51 (d, 2H, J=8.5 Hz), 7,71 (Ushs, 1H), to 7.84 (d, 2H, J=8.5 Hz).

I-107

TPL: 211-212°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz), 1,24-of 1.40 (m, 2H), 1,50-of 1.62 (m, 2H), 2,60 (t, 2H, J=7,6 Hz), to 6.19 (Ushs, 1H), 7,17 (d, 2H, J=8.5 Hz), 7,18 (d, 2H, J=8.5 Hz), 7,51 (d, 2H, J=8,5Hz), 7,66 (Ushs, 1H), 7,86 (d, 2H, J=8.5 Hz).

I-108

TPL: 298-300°

1H-NMR (DMSO-d6) δ ppm: of 0.90 (t, 3H, J=7,3 Hz), 1,22-of 1.39 (m, 2H), 1,48 is 1.60 (m, 2H), 2,54 (t, 2H, J=7,3 Hz),? 7.04 baby mortality (d, 2H, J=8,8 Hz), 7,12 (d, 2H, J=8.5 Hz), to 7.64 (d, 2H, J=8.5 Hz), 7,69 (d, 2H, J=8,8 Hz), 9,80 (, 1H).

I-109

TPL: 122-123°

1H-NMR (CDCl3) δ ppm: of 0.90 (t, 3H, J=7.4 Hz), of 0.97 (t, 3H, J=7,7 Hz), 1,26-to 1.38 (m, 2H), 1,30 (C, 6N), 1,50-of 1.66 (m, 4H), 1,72 of-1.83 (m, 4H), of 2.34 (t, 2H, J=7,1 Hz)to 2.55 (t, 2H, J=7,6 Hz), 3,19 (kV, 1H, J=6.0 Hz), 4,60 (Ushs, 1H), was 7.08 (d, 2H, J=8.5 Hz), 7,42 (d, 2H, J=8.5 Hz), the 7.85 (s, 1H).

I-110

TPL: 109-110°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.4 Hz), 1,10 (d, 6N, J=6,7 Hz), 1,29-to 1.38 (m, 2H), 1.55V (8, N), 1,60-1,70 (m, 2H), 1,78-1,89 (m, 2H), and 2.26 (m, 1H), 2,39 (t, 2H, J=7.0 Hz), 2.57 m (t, 2H, J=7,7 Hz), 2,90 (d, 2H, J=6.6 Hz), and 3.16 (Ushs, 1H), 4,24 (Ushs, 1H), 7,12 (d, 2H, J=8,5Hz), 7,40 (d, 2H, J=8.5 Hz).

I-111

TPL: 64-65°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7,3 Hz)of 1.02 (t, 3H, J=7.5 Hz), of 1.35 (d, 3H, J=6,7 Hz), 1,26-to 1.38 (m, 2H), 1,48 was 1.69 (m, 5H), 1,76-to 1.87 (m, 2H), 2,04 (m, 1H), of 2.38 (t, 2H, J=7,3 Hz), of 2.56 (t, 2H, J=7,6 Hz), only 2.91 (m, 1H), and 3.16 (Ushs, 2H), 4,42 (Ushs, 1H), 7,11 (d, 2H, J=8.5 Hz), 7,42 (d, 2H, J=8.5 Hz), 7,47 (Ushs, 1H).

I-112

TPL: 79-80°

1H-NMR (CDCl3) δ ppm: 1,36 (s, N), 1,52-of 1.62 (m, 2H), 1,67 to 1.76 (m, 2H), 2,22 (t, 2H, J=7,4 Hz), and 3.16 (q, 2H, J=6.3 Hz), of 3.78 (s, 3H), 4,33 (d, 2H, J=5.4 Hz), 4,62 (Ushs, 1H), 6,20 (Ushs, 1H), 6,85 (d, 2H, J=8,8 Hz), 7,19 (d, 2H, J=8,8 Hz).

I-113

TPL: 125-126°

1H-NMR (CDCl3) δ ppm: 1.38kg (with, IN), 1,62 is 1.70 (m, 2H), 1,76-of 1.88 (m, 2H), 2,46 (t, 2H, J=7.4 Hz), up 3.22 (q, 2H, J=6,1 Hz), 4,22 (t, 1H, J=6,1 Hz), 7,24 (DD, 1H, J=8,9, and 2.3 Hz), was 7.36 (d, 1H, J=2.3 Hz), 7,65 (Ushs, 1H), 8,29 (d, 1H, J=8,9 Hz).

I-114

TPL: 89-91°

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.0 Hz), 1.06 a (d, 6N, J=7,0 Hz)of 1.36 (m, 1H), 1,50-1,72 (m, 5H), 1,94-to 2.06 (m, 2H), and 2.26 (m, 1H), 2,60 (t, 2H, J=7,7 Hz), 2,84 (t, 2H, J=7,7 Hz), with 2.93 (d, 2H, J=6.3 Hz), 3,20 (t, 2H, J=6.6 Hz), 4,30 (Ushs, 1H), 7,19 (d, 2H, J=8.5 Hz), 7,63 (d, 2H, J=8.5 Hz), 9,15 (Ushs, 1H).

I-115

TPL: 94-95°

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.5 Hz), of 1.03 (t, 3H, J=7.5 Hz), 1,23-of 1.40 (m, 5H), 1,42-of 1.65 (m, 6N), a 1.75 (m, 1H), 2,02 (m, 1H), 2,24 (t, 2H, J=7,0 Hz)at 2.59 (t, 2H, J=8.0 Hz), 2,90 (m, 1H), 3,14 (q, 2H, J=6.6 Hz), 4,20 (m, 1H), and 4.40 (d, 2H, J=5.4 Hz), 5,70 (Ushs, 1H), 7,14 (d, 2H, J=8.1 Hz), 7,18 (d, 2H, J=8.1 Hz).

I-116

TPL: 89-91°

1H-NMR (CDCl3) δ ppm: to 0.97 (t, 3H, J=7,3 Hz)of 1.02 (t, H, J=7.5 Hz), of 1.35 (d, 3H, J=7.0 Hz), 1,40-1,90 (m, N), 2,04 (m, 1H), is 2.37 (t, 2H, J=7.0 Hz), 2,90 (m, 1H), 3,17 (q, 2H, J=6.6 Hz), 3,93 (t, 2H, J=6.6 Hz), 4,32 (m, 1H), at 6.84 (d, 2H, J=9.0 Hz), 7,31 (Ushs, 1H), 7,40 (d, 2H, J=9.0 Hz).

I-117

TPL: 110-111°

1H-NMR (CDCl3) δ ppm: 1,02 (t, 3H, J=7.5 Hz), of 1.34 (d, 3H, J=6.6 Hz), 1,45 is 1.70 (m, 3H), 1,75-of 1.85 (m, 2H), 2.05 is (m, 1H), a 2.36 (t, 2H, J=7.5 Hz), 2,90 (m, 1H), and 3.16 (q, 2H, J=6.6 Hz), of 3.78 (s, 3H), 4,50 (m, 1H), at 6.84 (d, 2H, J=6.8 Hz), 7,42 (d, 2H, J=6.8 Hz), of 7.48 (Ushs, 1H).

I-118

TPL: 113-115°

1H-NMR (CDCl3) δ ppm: to 0.92 (t, 3H, J=7.0 Hz), of 1.20 to 1.34 (m, 1H), 1,37 (d, 6N, J=7,0 Hz), 1,48 is 1.70 (m, 3H), 2,43 (q, 2H, J=6.6 Hz), 2,58 (t, 2H, J=7,7 Hz), 3,10-of 3.31 (m, 3H), and 4.75 (m, 1H), 6,04 (d, 1H, J=15,0 Hz), 6,77 (dt, 1H, J=7,7, 15,0 Hz), 7,14 (d, 2H, J=8,4 Hz), 7,55 (d, 2H, J=8,4 Hz), 7,85 (Ushs, 1H).

I-119

TPL: 139-140°

1H-NMR (CDCl3) δ ppm: 1,19 (s, N), of 1.47 (m, 2H), 1.61 of (m, 2H), 2,18 (t, 2H, J=7,6 Hz), 3,03 (q, 2H, J=6.3 Hz), 4.09 to (t, 1H, J=5,9 Hz), 6,85 (USD, 1H, J=8.0 Hz), 7,00 (t, 1H, J=8.0 Hz), 7,16 (USD, 1H, J=8.0 a), of 7.48 (Ushs, 1H), EUR 7.57 (Ushs, 1H).

1-120

TPL: 183°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7,3 Hz), 1,20-1,58 (m, 6N), of 1.40 (s, N), 2,07 (DD, 1H, J=12,9, 3.1 Hz), 2,52 (t, 2H, J=7,7 Hz), 2,95 (DD, 2H, J=11,5, 2,5 Hz), 3.46 in (m, 1H), 3,88-4,07 (m, 3H), 6,47 (s, 1H), 7,08 (d, 2H, J=8.5 Hz), 7,22 (d, 2H, J=8.5 Hz).

I-121

TPL: 163-166°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7,3 Hz), 1,32-of 1.62 (m, 6N), 1,45 (s, N), 1,95-2,07 (m, 3H), of 2.20 (m, 1H), 2,46 (TD, 1H, J=10,4, and 3.7 Hz), is 2.37 (t, 2H, J=7,6 Hz), 3.43 points (USD, 2H, J=10.4 Hz), 4,80 (s, 1H), 7,12 (d, 2H, J=8,4 Hz), 7,14 (s, 1H), 7,39 (d, 2H, J=8,4 Hz).

I-122

TPL: 188-189°

1H-I Is R (CDCl 3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,25-of 1.41 (m, 2H), 1,42 (s, N), 1,50-of 1.62 (m, 2H), 1,78-of 1.95 (m, 4H), 2.00 in of 2.20 (m, 6N), to 2.57 (t, 2H, J=7.5 Hz), 3,99 (Ushs, 1H), 7,10 (Ushs, 1H), 7,12 (d, 2H, J=6.5 Hz), 7,41 (d, 2H, J=6.5 Hz).

I-123

TPL: 197-198°

1H-NMR (CDCl3) δ ppm: of 0.91 (t, 3H, J=7.5 Hz), 1,24-of 1.40 (m, 2H), 1.39 in (C, N), 1,50-1,70 (m, 2H), 1,99 (Ushs, N), of 2.56 (t, 2H, J=7.5 Hz), 3,47 (Ushs, 1H), 7,10 (s, 1H), 7,11 (d, 2H, J=8.5 Hz), 7,38 (d, 2H, J=8.5 Hz).

I-124

TPL: 258-260°

1H-NMR (CDCl3) δ ppm: 1,20-1,40 (m, 2H), 1,41 (s, N), 1,62-of 1.81 (m, 2H), 2,03 to 2.35 (m, 5H), is 2.37 (s, 3H), 2,71 (s, 3H), of 3.32 (m, 1H), 3,64 (d, 1H, J=8,4 Hz), 7,08 (Ushs, 1H), 7,24 (m, 1H), 7,33 (m, 2H), 7,60 (d, 1H, J=8.1 Hz), to 7.77 (s, 1H), 7,80 (d, 1H, J=8,4 Hz), 8,14 (m, 1H).

I-125

TPL: 297-299°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,28-of 1.56 (m, 4H), 1,80 for 2.01 (m, 4H), 2,47 (m, 1H), was 2.76 (Ushs, 1H), 3,05 (m, 2H), 6,78 (d, 1H, J=9.0 Hz), 7.23 percent (d, 1H, J=9.0 Hz), 7,46 (DD, 1H, J=2,0, 9.0 Hz), 8,03 (d, 1H, J=2,0 Hz).

I-126

TPL: 198-199°

1H-NMR (CDCl3) δ ppm: 1.18 to 1.39 in (m, 2H), 1,40 (s, N), 1,60-to 1.79 (m, 2H), 1,98 to 2.35 (m, 5H), 3,30 (m, 1H), to 3.67 (d, 1H, J=9.6 Hz), of 5.89 (TT, 1H, J=3,0, 50.0 Hz), 6,97 (d, 1H, J=7.8 Hz), 7,21 (s, 1H), 7,30-7,40 (m, 2H), at 7.55 (s, 1H).

I-127

TPL: 262 to 264°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.39 (m, 2H), 1,41 (s, N), 1,60-1,80 (m, 2H), 2.00 in a 2.36 (m, 5H), to 2.57 (s, 3H), of 3.33 (m, 1H), 3,62 (d, 1H, J=8.7 Hz), 7,28 (Ushs, 1H), 7.62mm (d, 2H, J=8.7 Hz), 7,94 (d, 2H, J=8.7 Hz).

I-128

TPL: 252-254°

1H-NMR (CDCl3) δ ppm: 1.18 to 1.39 in (m, 2H), 1,40 (s, N), 1,58-to 1.79 (m, 2H), 1,99-of 2.30 (m, 5H), to 2.46 (s, 3H), of 3.32 (m, 1H), to 3.64 (m, 1H), 7,11 (Ushs, 1H), 7.23 percent (d, 2H, J=9.0 Hz), 7,44 (who, 2H, J=9.0 Hz).

I-129

TPL: >300°

1H-NMR (CDCl3+CD3OD) δ ppm : 1,30-1,45 (m, 2H), 1,42 (s, S), 1.70 to a 1.88 (m, 2H), 2,10-is 2.37 (m, 4H), 2,52 (m, 1H), 3,34 (m, 1H), 7,43-rate of 7.54 (m, 3H), of 7.82 (d, 1H, J=6,7 Hz), 7,88 (d, 1H, J=8.5 Hz), 7,98-8,07 (m, 2H), 8,44 (s, 1H), 8,46 (s, 1H).

I-130

TPL: 123-124°

1H-NMR (CDCl3) δ ppm: of 1.18 to 1.34 (m, 2H), 1,40 (s, N), of 1.62 and 1.75 (m, 2H), 2.00 in 2,28 (m, 5H), and 3.31 (m, 1H), 3,61 (d, 1H, J=9.5 Hz), 5,59 (s, 1H), 7,17 (s, 1H), 7,30-7,37 (m, 6N), 7,41 (d, 1H, J=8.5 Hz), to 7.84 (d, 1H, J=2.1 Hz).

I-131

TPL: 202-204°

1H-NMR (CDCl3) δ ppm: 1,27-to 1.38 (m, 2H), 1,38 (s, N), of 1.62 and 1.75 (m, 2H), 1,97-2,04 (m, 2H), 2,18-of 2.27 (m, 3H), 3,26 (m, 1H), 3,81 (s, 3H), to 4.62 (d, 1H, J=7.9 Hz), 7,12 (d, 1H, J=7.8 Hz), 7,40 (t, 1H, J=7.8 Hz), 7,51 (s, 3H), to 7.61 (d, 1H, J=7.8 Hz), 7,71 (s, 1H), 8,21 (Ushs, 1H).

I-132

TPL: 236-237°

1H-NMR (CDCl3) δ ppm: 1,23 was 1.43 (m, 2H), 1,41 (s, N), 1,66 and 1.80 (m, 2H), 2,08-2,12 (m, 2H), 2.23 to-2,31 (m, 3H), 3,34 (m, 1H), a 3.87 (d, 1H, J=9.5 Hz), was 4.02 (s, 3H), 7,30 (TD, 1H, J=7,3, 1.1 Hz), was 7.36 (s, 1H), 7,39 (TD, 1H, J=7,3, 1.5 Hz), 7,53 (USD, 1H, J=7,3 Hz), 7,84 (USD, 1H, J=7,3 Hz), with 8.05 (s, 1H), 8,73 (s, 1H).

I-133

TPL: 198-200°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7,3 Hz)to 0.97 (t, 3H, J=6,7 Hz), 1.18 to is 1.81 (m, 7H), 1.39 in (C, N), 1,98-2,05 (m, 2H), 2.21 are of 2.24 (m, 3H), 3,29 (m, 1H), 4,00 (DD, 1H, J=10,7, 6,7 Hz), 4.09 to (DD, 1H, J=10,7, 6,1 Hz), 4,27 (d, 1H, J=9.8 Hz), 6,37 (d, 1H, J=15,9 Hz), 7,47 (d, 2H, J=8.5 Hz), to 7.59 (d, 2H, J=8.5 Hz), a 7.62 (d, 1H, J=15,9 Hz), 7,83 (Ushs, 1H).

I-134

TPL: 212-213°

1H-NMR (CDCl3) δ ppm: 1,21-of 1.32 (m, 2H), 1.39 in (C, N), 1,59-of 1.73 (m, 2H), 1,99-2,04 (m, 2H), 2,10-of 2.26 (m, 3H), 3,26 (m, 1H), and 3.72 (d, 1H, J=9.6 Hz), 6,74 (m, 1H), 7,02 d, 2H, J=7.4 Hz), 7,11 (t, 1H, J=7.4 Hz), 7,13-7,19 (m, 2H), 7,22-7,26 (m, 2H), 7,34 (t, 2H, J=7,4 Hz).

I-135

TPL: 294-296°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,28-of 1.55 (m, 4H), 1,81-2,05 (m, 4H), and 2.26 (m, 1H), 2,98-3,20 (m, 2H), 6,78 (d, 1H, J=9.0 Hz), 7,31 (t, 1H, J=7.5 Hz), 7,54-7,72 (m, 5H), 7,94 (Ushs, 1H).

I-136

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1.28 (in C, N), 1,29 was 1.69 (m, 4H), 1,81-2,02 (m, 4H), and 2.27 (m, 1H), 3,06 (m, 1H), for 6.81 (d, 1H, J=8.7 Hz), 7,38 (t, 1H, J=7,2 Hz), of 7.48 (t, 2H, J=7,2 Hz), 7,62-7,81 (m, J), to 9.93 (Ushs, 1H).

I-137

TPL: 291-292°

1H-NMR (CDCl3) δ ppm: 1,25-of 1.39 (m, 2H), 1,41 (s, N), 1,61 and 1.80 (m, 2H), 2,01-of 2.36 (m, 5H), of 3.32 (m, 1H), 3,63 (d, 1H, J=9.3 Hz), 7,20 (Ushs, 1H), 7,53-7,74 (m, 8H).

I-138

TPL: 259-262°

1H-NMR (CD3OD) δ ppm: 1,40 (s, N), of 1.40 and 1.80 (m, 4H), 2,00-2,30 (m, 4H), of 2.45 (m, 1H), 3.00 and (s, 3H), 3,15-3,30 (m, 2H), of 7.90 (d, 1H, J=8,4 Hz)to 8.12 (d, 1H, J=9.0 Hz), 8,39 (d, 1H, J=9.0 Hz), 8,72 (s, 1H), 8,92 (d, 1H, J=8,4 Hz), 10,4 (s, 1H).

I-139

TPL: 265-268°

1H-NMR (CDCl3) δ ppm: 1,25-1,40 (m, 2H), 1,40 (s, N), 168-1,81 (m, 2H), 2.05 is is 2.10 (m, 2H), 2,23-is 2.37 (m, 3H), of 3.32 (m, 1H), 4,27 (d, 1H, J=9.1 Hz), 7,53 (t, 1H, J=7.9 Hz), 7,63 (TD, 1H, J=7,9, and 1.4 Hz), to 7.77 (d, 1H, J=7.9 Hz), 8,03 (d, 1H, J=7.9 Hz), of 8.37 (Ushs, 1H), cent to 8.85-8,86 (m, 2H).

I-140

TPL: 258-260°

1H-NMR (CDCl3) δ ppm: 1,20-1,40 (m, 2H), 1,41 (s, N), 1,52-of 1.85 (m, 2H), 2,03 to 2.35 (m, 5H), to 3.34 (m, 1H), 3,75 (m, 1H), 7,35-7,66 (m, 3H), with 8.05 (d, 1H, J=9.0 Hz), 8,11 (d, 1H, J=9.0 Hz), 8,40 (Ushs, 1H), 8,83 (s, 1H).

I-141

TPL: 205-206°

1H-NMR (CDCl3) δ ppm: of 1.20 to 1.37 (m, 2H), 1,40 (s, N), 1,43-of 1.62 (m, 2H), 1,90 for 2.01 (m, 2H), 2,02-of 2.23 (m, 3H), of 3.27 (m, 1H), 3,63 (d, 1H, J=9.6 Hz), 3,70 (s, 3H), only 6.64 (d, 1H, J=8,8 Hz), 7,28-7,41 (m, 5H), 7,45 (Ushs, 1H), compared to 8.26 (d, 1H, J=8,8 Hz).

I-142

TPL: 277-280°

1H-NMR (CDCl3) δ ppm: 0,23-0,34 (m, 2H), 1,34 (s, N), 1,34-of 1.55 (m, 5H), of 1.76 and 1.80 (m, 2H), 2,97 (ni, 1H), and 3.31 (d, 1H, J=9.6 Hz), 7,18 (s, 1H), 7,50-to 7.59 (m, 4H), to 7.77 (DD, 1H, J=7,4, 1.0 Hz), to $ 7.91-7,98 (m, 2H), 8,39 (DD, 1H, J=7,4, 1.9 Hz).

I-143

TPL: 202-203°

1H-NMR (CDCl3) δ ppm: 1,23-of 1.40 (m, 2H), 1,40 (s, N), 1,57-1,71 (m, 2H), 2.05 is is 2.10 (m, 2H), 2,18-of 2.28 (m, 3H), and 3.31 (m, 1H), 3,91 (s, 3H), 3,93 (s, 3H), of 4.05 (d, 1H, J=9.5 Hz), 8,15 (s, 1H), of 9.56 (s, 1H).

I-144

TPL: 177-178°

1H-NMR (CDCl3) δ ppm: 1,27-of 1.39 (m, 2H), 1,40 (s, N), 1,65-to 1.79 (m, 2H), 2,04-2,07 (m, 2H), 2,12-of 2.34 (m, 3H), up 3.22 (m, 1H), 3,93 (d, 1H, J=9.1 Hz), 6.90 to-7,03 (m, 3H), 7,25 (m, 1H), to 7.77 (DD, 1H, J=4,9) and 1.7 Hz), 7,81 (Ushs, 1H), 8,72 (DD, 1H, J=7,8, 1.5 Hz).

I-145

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1.30 on (C, N), 1,44 is 1.70 (m, 4H), 2.05 is-are 2.19 (m, 4H), 2,73 (m, 1H), 3,18 (m, 1H), 6,86 (d, 1H, J=8,8 Hz), a 7.62 (t, 2H, J=8.5 Hz), 7,86 (t, 2H, J=8.5 Hz), 7,89 (d, 2H, J=8.5 Hz), 8,16 (d, 2H, J=8,5 Hz).

I-146

TPL: 240-242°

1H-NMR (DMSO-d6) δ ppm: 1,26-of 1.53 (m, 4H), 1.27mm (s, N), 1,74 of-1.83 (m, 2H), 1,90-of 1.97 (m, 2H), and 2.26 (m, 1H), 3.04 from (m, 1H), 6,59 (Ushs, 1H), 6,74-6,79 (m, 3H), 7,74 (s, 1H), 10,32 (s, 1H), 12,80 (s, 1H).

I-147

TPL: 167-169°

1H-NMR (CDCl3) δ ppm: 1,05 of 1.28 (m, 2H), 1,38 (s, N), 1,47 is 1.70 (m, 2H), 1,80-2,00 (m, 3H), 2.13 and was 2.25 (m, 2H), 2,75 (t, 2H, J 6.9 Hz), 3,24 (m, 1H), 3,49 (dt, 2H, J=6,3 and 6.9 Hz), to 3.58 (d, 1H, J=8.7 Hz), a 3.87 (s, 6N), 5,40 (Ushs, 1H), of 6.71 (m, 2H), PC 6.82 (d, 1H, J=8.7 Hz).

I-148

TPL: 171-172°

sup> 1H-NMR (CDCl3) δ ppm: 1,16-to 1.38 (m, 2H), 1.39 in (C, N), 1,50-1,79 (m, 4H), 1.85 to 2,02 (m, 3H), 2,15-of 2.30 (m, 2H), 2,35-of 2.56 (m, 6N)at 3.25 (m, 1H), 3.33 and (q, 2H, J=6.0 Hz), 3,63 (d, 1H, J=9.0 Hz), and 3.72 (t, 4H, J=4,6 Hz), 6,77 (Ushs, 1H).

I-149

1H-NMR (CDCl3) δ ppm: 1,20-of 1.36 (m, 2H), 1.28 (in t, 3H, J=7.2 Hz), 1.39 in (C, N), 1,45 is 1.70 (m, 2H), 1.85 to 2,30 (m, 7H), 2,43 (s, 3H), 3,05-of 3.42 (m, 3H), 3.46 in-of 3.80 (m, 3H), 7,31 (d, 1H, J=7,2 Hz), 7,40-7,52 (m, 3H), 8,18 (Ushs, 1H).

I-150

TPL: 203-204°

1H-NMR (CDCl3) δ ppm: to 1.15 to 1.37 (m, 2H), 1.39 in (C, N), 1,42 is 1.70 (m, 2H), 1.85 to to 2.29 (m, 5H), was 2.76 (t, 2H, J=6.0 Hz), 3,26 (m, 1H), 3,49 (q, 2H, J=6.0 Hz), 3,61 (m, 1H), a 4.03 (s, 2H), 5,88 (Ushs, 1H), 7,15 (DD, 1H, J=7,0, 8,8 Hz), 7,30-7,35 (m, 2H).

I-151

TPL: 181-183°

1H-NMR (CDCl3) δ ppm: 1,15-1,30 (m, 2H), 1.39 in (C, N), 1,45-of 1.64 (m, 2H), 1,88-2,05 (m, 3H), 2,15 was 2.25 (m, 2H), 2,69 (t, 2H, J=6.0 Hz), or 3.28 (m, 1H), 3,47 (q, 2H, J=6.0 Hz), to 3.58 (d, 1H, J=9.9 Hz), a 3.87 (s, 2H), of 5.83 (Ushs, 1H), 7,00 (m, 1H), 7,20 (m, 2H).

I-152

TPL: 222-224°

1H-NMR (CDCl3) δ ppm: of 1.16 to 1.37 (m, 2H), 1.39 in (C, N), 1,49 is 1.70 (m, 2H), 1,90 was 2.25 (m, 5H), 3,26 (m, 1H), on 3.36 (t, 2H, J=6.4 Hz), 3,66 (dt, 3H, J=6,0, 6.4 Hz), by 5.87 (t, 1H, J=6.0 Hz), 7,58 (s, 1H), 7,68 (DD, 1H, J=7,0, 8.5 Hz), 7,83 (DD, 1H, J=7,0, 8.5 Hz), 8,19 (t, 2H, J=8.5 Hz).

I-153

TPL: 207-209°

1H-NMR (CDCl3) δ ppm: 1,05-1,25 (m, 2H), 1,38 (s, N), 1,40-2,03 (m, 10H), 2.05 is was 2.25 (m, 2H), 2,58 (s, 3H), was 2.76 (m, 1H), 3,05-to 3.35 (m, 2H), 3,97 (d, 1H, J=9.5 Hz), 4,94 (t, 1H, J=4.0 Hz), 8,42 (d, 1H, J=5.5 Hz), 8,97 (d, 1H, J=5,5 Hz).

I-154

TPL: 184-185°

1H-NMR (CDCl3) δ ppm: 1,05-1,25 (m, 2H), 1,37 (s, N), 1,50 was 1.69 (m, 2H), 1.85 to 2.05 is (m, 3H), 2,10-of 2.21 (m, 2H), 3,2 (m, 1H), to 3.64 (m, 1H), 4,87 (s, 1H), 4,88 (s, 1H), 5,67 (Ushs, 1H), 7,42 (d, 2H, J=5.5 Hz), 7,52 (m, 2H), 7,78 (m, 1H), 7,82 (m, 1H), 7,95 (d, 1H, J=7,0 Hz).

I-155

TPL: 208-210°

1H-NMR (DMSO-d6) δ ppm: 1.26 in (C, N), 1,27 of 1.50 (m, 4H), 1,75-2,00 (m, 4H), of 2.16 (m, 1H), 2,81 (s, 3H), to 3.02 (m, 1H), 6,79 (d, 1H, J=8.5 Hz), 10,00 (s, 1H), 10,66 (s, 1H).

I-156

TPL: 256-257°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.39 (m, 2H), 1,41 (s, N), 1,60-of 1.81 (m, 2H), 2,01 to 2.35 (m, 5H), 2,69 (t, 2H, J=6.0 Hz), 3,11 (t, 2H, J=6.0 Hz), 3,30 (m, 1H), 3,61 (d, 1H, J=9.3 Hz), 7,21 (d, 1H, J=8.0 Hz), 7,31 (s, 1H), of 7.70 (d, 1H, J=8.0 Hz), to 7.99 (s, 1H).

I-157

TPL: 269-271°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.45 (m, 2H), 1,41 (s, N), 1,70-1,90 (m, 2H), 2,10,2,45 (m, 5H), 3,37 (m, 1H), 3,68 (m, 1H), 7,45 (DD, 1H, J=4,0, 8.0 Hz), 7,53 (Ushs, 1H), 7,72 (t, 1H, J=8.0 Hz), 7,83 (d, 1H, J=8.0 Hz), 8,02 (d, 1H, J=8.0 Hz), 8,18 (d, 1H, J=8.0 Hz), 8,93 (d, 1H, J=4.0 Hz).

I-158

TPL: 253-255°

1H-NMR (CDCl3) δ ppm: 1,20-1,40 (m, 2H), 1,42 (s, N), 1,60-1,90 (m, 2H), 2.06 to 2,50 (m, 5H), of 2.72 (s, 3H), of 3.33 (m, 1H), 3,78 (d, 1H, J=9,2 Hz), 7,52 (t, 1H, J=7,0 Hz), 7,62-7,80 (m, 2H), 7,94 (Ushs, 1H), with 8.05 (d, 1H, J=8.5 Hz), to 8.20 (s, 1H).

I-159

TPL: 253-255°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.39 (m, 2H), 1,40 (s, N), 1,60-1,80 (m, 2H), 1,98-of 2.30 (m, 5H), 2,71 (s, 3H), and 3.31 (m, 1H), 3,68 (d, 1H, J=9.0 Hz), 7,41 (Ushs, 1H), to 7.61 (d, 2H, J=9.0 Hz), of 7.70 (d, 2H, J=9.0 Hz).

I-160

TPL: 211-212°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.32 (m, 2H), 1.39 in (t, 3H, J=7.0 Hz), 1,40 (s, N), 1,55-to 1.79 (m, 2H), 1,98 to 2.35 (m, 5H), and 3.31 (m, 1H), 3,65 (d, 1H, J=9.5 Hz), a 4.03 (q, 2H, J=7.0 Hz), only 6.64 (d, 1H, J=8.0 Hz), 6,92 (d, 1H, J=8.0 Hz), 7,10 (S, 1H), 7,19 (t, 1H, J=8.0 Hz), 7,3 (Ushs, 1H).

I-161

TPL: 202-203°

1H-NMR (CDCl3) δ ppm as 0.96 (t, 1H, J=7,3 Hz), 1,29-of 1.39 (m, 2H), 1,40 (s, N), 1,41 is 1.58 (m, 2H), 1,60-1,80 (m, 4H), 1,98-2,31 (m, 5H), and 3.31 (m, 1H), 3,66 (d, 1H, J=8.5 Hz), of 3.96 (t, 2H, J=6.4 Hz), only 6.64 (d, 1H, J=8.0 Hz), 6.90 to (d, 1H, J=8.0 Hz), 7,11 (s, 1H), 7,19 (t, 1H, J=8.0 Hz), 7,31 (Ushs, 1H).

I-162

TPL: 177-180°

1H-NMR (CDCl3) δ ppm: 1.18 to to 1.38 (m, 2H), 1.39 in (C, N), 1,59-of 1.78 (m, 2H), 1,95-2,05 (m, 2H), 2,07 was 2.25 (m, 3H), 3,26 (m, 1H), 3.46 in (s, 3H), 4,17 (d, 1H, J=9.5 Hz), further 5.15 (s, 2H), 6,7 (d, 1H, J=8.0 Hz), 7,10-of 7.23 (m, 2H), 7,34 (s, 1H), 7,58 (s, 1H).

I-163

TPL: 175-178°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,28 of 1.50 (m, 4H), 1,78 is 2.00 (m, 4H), 2,22 (m, 1H), 2,96 is 3.15 (m, 2H), 6,67 (m, 1H), 6,79 (d, 1H, J=8.5 Hz), 7,18 (m, 2H), 7,38 (s, 1H), 9,81 (s, 1H).

I-164

TPL: 232-233°

1H-NMR (CDCl3) δ ppm: to 0.97 (t, 3H, J=7,3 Hz), 1,22-of 1.30 (m, 2H), 1,40 (s, N), 1,44-is 1.51 (m, 2H), 1,67-to 1.77 (m, 4H), 2,02-of 2.24 (m, 5H), up 3.22 (m, 1H), 3,62 (d, 1H, J=9.6 Hz), 4,25 (t, 2H, J=6.8 Hz), of 6.71 (d, 1H, J=8,4 Hz), 7,01 (Ushs, 1H), to $ 7.91 (DD, 1H, J=8,4, and 3.3 Hz), 8,08 (d, 1H, J=3.3 Hz).

I-165

TPL: 199-200°

1H-NMR (CDCl3) δ ppm as 0.96 (t, 3H, J=7.4 Hz), 1,24-1,50 (m, 4H), of 1.40 (s, N), 1,67 to 1.76 (m, 3H), 2,03,2,08 (m, 2H), 2,24 to 2.35 (m, 3H), 3,29 (m, 1H), 3,76 (d, 1H, J=9.1 Hz), 3,91 (t, 2H, J=6.6 Hz), 6,41 (DD, 1H, J=8,8 and 2.5 Hz), 6,55 (d, 1H, J=2.5 Hz), PC 6.82 (d, 1H, J=8,8 Hz), the 7.43 (s, 1H), of 8.95 (s, 1H).

I-166

TPL: 215-218°

1H-NMR (CDCl3+CD3OD) δ ppm: to 0.97 (t, 3H, J=7.4 Hz), 1,24-of 1.40 (m, 4H), 1.39 in (C, N), 1,42 of 1.50 (m, 2H), 1,54-1,72 (m, 2H), 1,76-to 1.82 (m, 2H), 1.91 a is 2.00 (m, 2H), 2.06 to 2,22 (m, 3H), 3,24 (m, 1H), 4.00 points (t, 2H, J=6.6 Hz), is 6.78 (d, 1H, J=8,8 Hz), 6,98 DD, 1H, J=8,8, 2,5 Hz), to 7.09 (d, 1H, J=8,8 Hz).

I-167

TPL: 212-213°

1H-NMR (CDCl3) δ ppm as 0.96 (t, 3H, J=7.5 Hz), of 1.26 to 1.34 (m, 2H), 1,40 (s, N), 1,45-1,50 (m, 2H), 1,68-to 1.77 (m, 4H), 2,03-of 2.08 (m, 2H), 2,17 (m, 1H), 2.26 and-to 2.29 (m, 2H), 3,29 (m, 1H), 3,60 (d, 1H, J=9.0 Hz), 4,25 (t, 2H, J=6.8 Hz), of 6.71 (d, 1H, J=8,4 Hz), 7,01 (Ushs, 1H), to $ 7.91 (DD, 1H, J=8,4, and 3.3 Hz), 8,08 (d, 1H, J=3.3 Hz).

I-168

TPL: 230-232°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.35 (m, 2H), 1,40 (s, N), and 1.63-1.77 in (m, 2H), 2,03-of 2.08 (m, 2H), 2,15-to 2.29 (m, 3H), and 3.31 (m, 1H), 3,63 (d, 1H, J=9.3 Hz), 6.89 in (d, 1H, J=9.4 Hz), 7,10 (USD, 2H, J=7.4 Hz), 7,12 (Ushs, 1H), to 7.18 (t, 1H, J=7.4 Hz), was 7.36 (Ust, 2H, J=7.4 Hz), 8,09-of 8.15 (m, 2H).

I-169

TPL: 159-160°

1H-NMR (CDCl3) δ ppm: to 0.97 (t, 3H, J=7,3 Hz)of 1.20 and 1.35 (m, 2H), 1,40 (s, N), 1,37-1,49 (m, 2H), 1,61-of 1.78 (m, 4H), 2.05 is-of 2.08 (m, 2H), 2,23-of 2.26 (m, 2H), a 2.36 (s, 3H), 2,97 (Ushs, 1H), 3,32 (m, 1H), 3,86 (Ushs, 1H), 4,30 (t, 2H, J=6.5 Hz), and 6.25 (s, 1H), 7,92 (Ushs, 1H).

I-170

TPL: 180-181°

1H-NMR (CDCl3) δ ppm: from 0.88 to 0.89 (m, 2H), 1.39 in (C, N), 1,42 is 1.60 (m, 2H), 1,86-1,90 (m, 2H), 2,04-of 2.09 (m, 2H), 2,42 (s, 3H), 2.91 in (m, 1H), 3,20 (m, 1H), 3,63 (d, 1H, J=9,2 Hz), 6,38 (s, 1H), 7,15 (m, 2H), 7,28 (m, 1H), 7,45 (m, 2H), 7,84 (Ushs, 1H).

I-171

TPL: 173-174°

1H-NMR (CDCl3) δ ppm: to 0.98 (t, 3H, J=7.5 Hz), 1,29-of 1.40 (m, 2H), 1,40 (s, N), of 1.55 (m, 2H), 1,62 of-1.83 (m, 4H), 2,09-2,12 (m, 2H), 2,24 of-2.32 (m, 3H), of 3.32 (m, 1H), 3,63 (d, 1H, J=9.5 Hz), 3,99 (t, 2H, J=6.4 Hz), 7,22 (DD, 1H, J=a 9.4, 2.7 Hz), 7,66 (d, 1H, J=2.7 Hz), 8,63 (d, 1H, J=9.4 Hz), 10,17 (s, 1H).

I-172

TPL: 238-242°

1H-NMR (CDCl3) δ ppm as 0.96 (t, 3H, J=7,3 Hz), 1,23-of 1.52 (m, 4H), of 1.40 (s, N), 1,61-of 1.78 (m, 4H), 2.05 is-of 2.28 (m, N), 3,30 (m, 1H), 3,66 (d, 1H, J=9.4 Hz), 3,84 (Ushs, 2H), 3,90 (t, 2H, J=6.4 Hz), 6,32 to 6.35 (m, 2H), of 6.96 (Ushs, 1H), 6,97 (d, 1H, J=9.4 Hz).

I-173

TPL: 165-166°

1H-NMR (CDCl3) δ ppm: 1,23-of 1.26 (m, 2H), 1,40 (s, N), 1,67-1,72 (m, 2H), 2,01-to 2.06 (m, 2H), 2,11-of 2.28 (m, 3H), and 3.31 (m, 1H), 3,60 (s, 2H), 3,69 (s, 3H), was 4.02 (Ushs, 1H), 7,01 (d, 1H, J=8.0 Hz), 7,25 (t, 1H, J=8.0 Hz,), the 7.43 (d, 1H, J=8.0 Hz), 7,49 (Ushs, 1H), 7,51 (Ushs, 1H).

I-174

TPL: 264-265°

1H-NMR (CDCl3+CD3OD) δ ppm: 1,26-of 1.29 (m, 2H), 1.39 in (C, N), 1,62 was 1.69 (m, 2H), 1,96 is 2.00 (m, 2H), 2,18-of 2.21 (m, 3H), of 3.25 (m, 1H), to 3.58 (s, 2H), 7,01 (d, 1H, J=7.5 Hz), 7,26 (t, 1H, J=7.5 Hz), 7,42 (Ushs, 1H), 7,50 (d, 1H, J=7.5 Hz).

I-175

TPL: 90-94°

1H-NMR (CDCl3) δ ppm: 1,16-of 1.23 (m, 2H), 1,37 (s, N), 1,44-of 1.56 (m, 2H), 1,73-of 1.85 (m, N), 2,11-of 2.15 (m, 2H), only 3.57 (t, 2H, J=6.4 Hz), 3,21 (m, 1H), to 3.58 (m, 2H), 3,84 (d, 1H, J=9.3 Hz), 5.56mm (Ushs, 1H), 7,01 (s, 1H), 7,11 (t, 1H, J=7.5 Hz), 7,21 (t, 1H, J=7.5 Hz), 7,38 (d, 1H, J=7.5 Hz), to 7.59 (d, 1H, J=7.5 Hz), 8,24 (Ushs, 1H).

I-176

TPL: 116-118°

1H-NMR (CDCl3) δ ppm: 1.18 to to 1.38 (m, 2H), 1,40 (s, N), 1,60-to 1.79 (m, 2H), 1,95-of 2.30 (m, 5H), 3,30 (m, 1H), 3,69 (m, 1H), 3,80 (s, 3H), with 4.64 (s, 2H), to 6.67 (d, 1H, J=8.0 Hz), 7,00 (d, 1H, J=8.5 Hz), 7,15-7,24 (m, 2H), 7,32 (Ushs, 1H).

I-177

TPL: 219-220°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,28 of 1.50 (m, 4H), 1.75 is for 2.01 (m, 4H), 2,18-of 2.30 (m, 1H), 2.95 and is 3.15 (m, 2H), br4.61 (s, 2H), 6,56 (m, 1H), 6,80 (d, 1H, J=8.5 Hz), 7,16 (m, 2H), 7,28 (Ushs, 1H), 9,87 (Ushs, 1H).

I-178

TPL: 170-173°

1H-NMR (CDCl3) δ ppm: 1.18 to 1.39 in (m, 2H), 1,40 (s, N), 1,50-1,80 (m, 2H), 1,90 is 2.33 (m, 5H), a 2.36 (s, 6N), a 2.75 (t, 2H, J=5.5 Hz), 3,30 (m, 1H), 3,70 (m, N), 4,08 (t, 2H, J=5.5 Hz), of 6.68 (d, 1H, J=8.0 Hz), 6,94 (d, 1H, J=7.5 Hz), 7,15-of 7.23 (m, 2H), 7,33 (Ushs, 1H).

I-179

TPL: 191-193°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.39 (m, 2H), 1,40 (s, N), 1,58 and 1.80 (m, 2H), 1,98 of-2.32 (m, 5H), 3,30 (m, 1H), 3,70 (d, 1H, J=9.5 Hz), of 4.77 (s, 2H), 6.73 x (d, 1H, J=8.0 Hz),? 7.04 baby mortality (d, 1H, J=8.0 Hz), 7,20-7,31 (m, 2H), of 7.48 (Ushs, 1H).

I-180

TPL: 174-176°

1H-NMR (CDCl3) δ ppm: 1,10-1,30 (m, 2H), 1,40 (s, N), 1,45-of 1.65 (m, 2H), 1,81-2,02 (m, 3H), 2,15-of 2.30 (m, 2H), 2,58 (t, 2H, J=6.5 Hz)at 3.25 (m, 1H), 3,37 (dt, 2H, J=5,5, 6,5 Hz), 3,60 (d, 1H, J=9.5 Hz), 3,71 (s, 2H), 5,73 (Ushs, 1H), 7,20-7,40 (m, 5H).

I-181

TPL: 176-178°

1H-NMR (CDCl3) δ ppm: 1,15-1,30 (m, 2H), 1.39 in (C, N), 1,45 is 1.70 (m, 6N), 1,85 for 2.01 (m, 3H), 2,15-of 2.28 (m, 2H), 2.63 in (t, 2H, J=7,0 Hz)at 3.25 (dt, 2H, J=6,0, 7,0 Hz), with 3.27 (m, 1H), 3,63 (m, 1H), 5,35 (Ushs, 1H), 7,17 (m, 3H), 7,29 (m, 2H).

I-182

TPL: 152-154°

1H-NMR (CDCl3) δ ppm: 1,15-1,30 (m, 2H), 1.39 in (C, N), 1,45-of 1.65 (m, 2H), 1.85 to 2.05 is (m, 3H), 2,09 was 2.25 (m, 2H), 3,25 (m, 1H), of 3.45 (dt, 2H, J=5.0 and 5.0 Hz), 3,55 (t, 2H, J=5.0 Hz), 3,60 (m, 1H), 4,51 (s, 2H), 5,81 (Ushs, 1H), 7,29-7,40 (m, 5H).

I-183

TPL: 208-211°

1H-NMR (CDCl3) δ ppm: of 1.20 to 1.31 (m, 2H), 1.39 in (C, N), 1,62 by 1.68 (m, 2H), 1,98 was 2.25 (m, 5H), 3,30 (m, 1H), 3,57 (d, 1H, J=9,2 Hz), 4,59 (d, 2H, J=5.8 Hz), 5,76 (Ushs, 1H), 7,37 (DD, 1H, J=8,4, 2.0 Hz), 7,46-7,52 (m, 2H), 7,69 (Ushs, 1H), 7,78-7,83 (m, 3H).

I-184

TPL: 180-182°

1H-NMR (CDCl3) δ ppm: 1,22-to 1.37 (m, 2H), 1,40 (s, N), 1,60 was 1.69 (m, 2H), 2.05 is-is 2.09 (m, 2H), 2.21 are of 2.27 (m, 3H), of 3.45 (m, 1H), 3,64 (d, 1H, J=9.6 Hz), of 4.77 (d, 2H, J=4,9 Hz), the 7.43 (d, 1H, J=8.6 Hz), 7,46 (Ushs, 1H), to 7.61 (t, 1H, J=7,7 Hz), 7,73 (t, 1H, J=7,7 Hz), 7,87 (who, 1H, J=7,7 Hz), to 8.20 (t, 1H, J=7,7 Hz), 8,24 (d, 1H, J=8.6 Hz).

I-185

TPL: 260-261°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.32 (m, 2H), 1.39 in (C, N), 1,60-1,70 (m, 2H), 1,97 is 2.01 (m, 2H), 2,11 (m, 1H), 2.21 are of 2.24 (m, 2H), 3,30 (m, 1H), 3,61 (d, 1H, J=9.3 Hz), of 4.95 (d, 2H, J=6.0 Hz), 5,85 (Ushs, 1H), 7,33 (d, 1H, J=4,8 Hz), a 7.62 (DD, 1H, J=8,4 and 6.9 Hz), of 7.75 (DD, 1H, J=8,1, 6.9 Hz), 8,00 (d, 1H, J=8.1 Hz), to 8.20 (d, 1H, J=8,4 Hz), 8,42 (d, 1H, J=4,8 Hz).

I-186

TPL: 231-233°

1H-NMR (CDCl3) δ ppm: 1,23-of 1.40 (m, 2H), 1,40 (s, N), 1,62 to 1.76 (m, 2H), 2,04 is 2.10 (m, 2H), 2,22 of-2.32 (m, 3H), 3,30 (m, 1H), 3,95 (d, 1H, J=9.3 Hz), 5,04 (d, 2H, J=4,1 Hz), to 7.61 (d, 1H, J=5.8 Hz), 7,63 (Ushs, 1H), the 7.65 (DD, 1H, J=8,2, 6.9 Hz), 7,73 (DD, 1H, J=8,5 and 6.9 Hz), 7,86 (d, 1H, J=8,2 Hz), 8,10 (d, 1H, J=8.5 Hz), 8,42 (d, 1H, J=5.8 Hz).

I-187

TPL: 184-187°

1H-NMR (CDCl3) δ ppm: to 0.97 (t, 3H, J=7,3 Hz), 1,18-of 1.30 (m, 2H), 1.39 in (C, N), 1,42-of 1.65 (m, 4H), 1,70-1,80 (m, 2H), 1,94-of 2.08 (m, 3H), 2,18-of 2.26 (m, 2H), 3,29 (m, 1H), 3,61 (d, 1H, J=9.5 Hz), 3,93 (t, 2H, J=6,4 Hz), 4,39 (d, 2H, J=5.5 Hz), 5,67 (Ushs, 1H), 6,79-6,83 (m, 3H), of 7.23 (t, 1H, J=7,6 Hz).

I-188

TPL: 224-226°

1H-NMR (CDCl3) δ ppm: ,16-1,31 (m, 2H), 1,38 (s, N), 1,55-1,70 (m, 2H), 1,92-2,07 (m, 3H), 2,17-2,23 (ni, 2H), 3,21 (m, 1H), 3,81 (s, 3H), 3,83 (C, 6N), of 4.05 (d, 1H, J=9.8 Hz), 4,34 (d, 2H, J=5.8 Hz), 5,96 (Ushs, 1H), 6,47 (s, 2H).

I-189

TPL: 217-218°

1H-NMR (CDCl3) δ ppm: 1,15-1,30 (m, 2H), 1,37 (s, N), 1,52-of 1.66 (m, 2H), 1,90 e 2.06 (m, 3H), 2,13-of 2.20 (m, 2H), 2,93 (C, 6N), 3,24 (m, 1H), 3,94 (d, 1H, J=9.5 Hz), 4,30 (d, 2H, J=5.5 Hz), 5,73 (Ushs, 1H), 6,69 (d, 2H, J=8,9 Hz), 7,12 (d, 2H, J=8,9 Hz).

I-190

TPL: solid amorphous substance

1H-NMR (CDCl3) δ MD.: 1,17-1,32 (m, 2H), 1.39 in (C, N), 1,54-1,72 (m, 2H), 1,96 and 2.13 (m, 3H), 2,18-of 2.27 (m, 2H), 3,30 (m, 1H), 3,63 (d, 1H, J=9,2 Hz), 4,51 (d, 2H, J=5.8 Hz), of 5.82 (Ushs, 1H), 7,40 (d, 2H, J=8.5 Hz), 8,02 (d, 2H, J=8.5 Hz), 8,64 (s, 1H).

I-191

TPL: 126-128°

1H-NMR (CDCI3) δ ppm: to 0.97 (t, 3H, J=7.4 Hz), 1,10-of 1.28 (m, 2H), 1,36 (s, N), 1,42 is 1.86 (m, N), 2.06 to to 2.18 (m, 2H), up 3.22 (m, 1H), 3,95 (t, 2H, J=4.5 Hz), 4,16 (Ushs, 1H), around 4.85 (s, 2H), 6,82-to 6.95 (m, 3H), 7,26 (t, 1H, J=7.8 Hz), 8,54 (Ushs, 1H).

I-192

TPL: 178-181°

1H-NMR (CDCl3) δ ppm as 0.96 (t, 3H, J=7,3 Hz), 1,18-of 1.52 (m, 4H), 1.39 in (C, N), was 1.58 to 1.76 (m, 4H), 1,92 is 2.00 (m, 2H), 2,02-to 2.29 (m, 3H), of 3.28 (m, 1H), 3,78 (d, 1H, J=9.5 Hz), with 3.89 (t, 2H, J=6.6 Hz), 6,00 (Ushs, 1H), is 6.78 (s, 4H), 7,35 (Ushs, 1H).

I-193

TPL: 187-188°

1H-NMR (CDCl3+CD3OD) δ ppm: 1,21-of 1.40 (m, 2H), 1,38 (s, N), 1,52 was 1.69 (m, 2H), 1,90-2,00 (m, 2H), 2,02-of 2.20 (m, 3H), up 3.22 (m, 1H), 3,75 (s, 3H), 6,79 (s, 4H).

I-194

TPL: 251-253°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,24-1,50 (m, 4H), 1,72 of-1.83 (m, 2H), 1,91 of 1.99 (m, 2H), 2,16 (m, 1H), to 3.02 (m, 1H), 3,82 (s, 3H), 6,79 (d, 1H, J=8,2 Hz), 7,01 (d, 2H, J=8,8 Hz), the 7.85 (d, 2H, J=8,8 Hz), 9,72 (Ushs, 1H), 8,64 (Ushs, 1H).

I-195

TPL: 183-185°

1H-NMR (CDCl3) δ ppm: 1,22-to 1.37 (m, 2H), 1,40 (s, N), 1,58-1,7? (m, 2H), 2.05 is is 2.10 (m, 2H), 2,20-of 2.30 (m, 3H), of 3.32 (m, 1H), 3,70 (s, 2H), of 3.73 (s, 3H), 6,79 (s, 1H), 8,83 (Ushs, 1H).

I-196

TPL: 185-187°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.39 (m, 2H), 1,40 (s, N), the 1.44 (t, 6N, J=7,0 Hz), 1,60-1,80 (m, 2H), of 1.95 to 2.35 (m, 5H), 3,30 (m, 1H), 3,62 (d, 1H, J=8,9 Hz)4,06 (q, 2H, J=7.0 Hz), 4.09 to (q, 2H, J=7.0 Hz), between 6.08 (s, 1H), 7,02 (s, 1H), was 7.36 (s, 1H).

I-197

TPL: 211-213°

1H-NMR (CDCl3) δ ppm: 1,20-1,40 (m, 2H), 1,41 (s, N), 1,60-1,80 (m, 2H), 2.00 in a 2.36 (m, 5H), 2,61 (s, 3H), of 3.32 (m, 1H), 3,64 (d, 1H, J=9,2 Hz), 7,28 (s, 1H), 7,43 (t, 1H, J=7.5 Hz), 7,69 (d, 1H, J=7.5 Hz), 7,85 (d, 1H, J=7.5 Hz), 8,02 (s, 1H).

I-198

TPL: 268-269°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.39 (m, 2H), 1,40 (s, N), 1,42 of-2.32 (m, 7H), 2,90-3,10 (m, 4H), 3,30 (m, 1H), 3,68 (d, 1H, J=8,8 Hz), 6,59 (s, 1H), 7,18 (d, 1H, J=8.7 Hz), to 7.59 (d, 1H, J=8.7 Hz), to 7.77 (Ushs, 1H).

I-199

TPL: 221-224°

I-200

TPL: 237-240°

I-201

TPL: 87-90°

I-202

TPL: 222-223°

I-203

TPL: 255-257°

I-204

TPL: 234-236°

I-205

TPL: 208-210°

I-206

TPL: 217-218°

I-207

TPL: 275-279°

I-208

TPL: 248-250°

I-209

TPL: 256-258°

I-210

TPL: 270-271°

I-211

TPL: 219-220°

I-212

TPL: 260-261°

I-213

TPL: >300°

I-214

TPL: 206-207°

1H-NMR (CDCl3) δ ppm: of 0.93 (t, 3H, J=7.4 Hz), 1.30 and of 1.42 (m, 2H), 1,49 (d, 6N, J=6.9 Hz), 1,53-of 1.65 (m, 2H), 2,61 (t, 2H, J=7,7 Hz), 4,15 (Sept, 1H, J=6.9 Hz),? 7.04 baby mortality (d, 1H, J=8,2 Hz), 7,20 (d, 2H, J=8,2 Hz), 7,51 (d, 2H, J=8,2 Hz), 7,89 (d, 1H, J=8,8 Hz), 8,18 (s, 1H), 10,55 (s, 1H).

I-215

1H-NMR (CDCl3) δ ppm,-0,93 (t, 3H, J=7,3 Hz), 1.30 and of 1.41 (m, 2H), 1,52-to 1.63 (m, 2H), 1,95 (C, 6N), 2,61 (t, 2H, J=7.8 Hz), 6,99 (Ushs, 1H), 7,20 (d, 2H, J=8.5 Hz), the 7.65 (d, 2H, J=8.5 Hz), to 7.93 (DD, 1H, J=8,5, 2,5 Hz), of 8.28 (d, 1H, J=8.5 Hz), 8,55 (d, 1H, J=2.5 Hz), 9,76 (Ushs, 1H).

Ia-1

TPL: 221-224°

1H-NMR (CDCl3) δ ppm: 1,19-to 1.38 (m, 2H), 1,40 (s, N), of 1.62-1.77 in (m, 2H), 2,002,31 (m, 5H), 3,18 (t, 4H, J=4,8 Hz), 3,21-to 3.38 (m, 1H), 3,85 (t, 4H, J=4,8 Hz), 6,64-6,32 (m, 2H), 7,11 (s, 1H), 7,20 (t, 1H, J=7.8 Hz), 7,45 (s, 1H).

Ia-3

TPL: 87-90°

1H-NMR (CDCl3) δ ppm: 1,25 (d, 6N, J=6.3 Hz), of 1.37 (d, 6N, J=6.9 Hz), 1,59 is 1.70 (m, 2H), 1,76-of 1.88 (m, 2H), 2,32-to 2.42 (m, 4H), 3,11-of 3.23 (m, 3H), 3,39 (d, 2H, J=10,8 Hz), 3,74-3,86 (m, 2H), 4,34 (t, 1H, J=9.0 Hz), 6,86 (d, 2H, J=9.0 Hz), 7,30 (s, 1H), 7,40 (d, 2H, J=9.0 Hz).

Ia-4

TPL: 233-234°

1H-NMR (CDCl3) δ ppm: 1,25 (d, 6N, J=6.3 Hz), 1,40 (s, N), of 1.26 to 1.37 (m, 2H), 1,62-of 1.78 (m, 2H), 2.00 in 2,22 (m, 5H), 2,42 (t, 2H, J=11.7 Hz), 3,20-3,40 (m, 1H), 3.46 in (d, 2H, J=10.5 Hz), to 3.67 (d, 1H, J=9.3 Hz), 3.72 points-a-3.84 (m, 2H), 6,62-6,76 (m, 2H), 7,10 (s, 1H), 7,18 (t, 1H, J=7.8 Hz), 7,42 (s, 1H).

Ia-5

TPL: 125-126°

1H-NMR (CDCl3) δ ppm: 1,25 (d, 6N, J=6.3 Hz), 1,40 (s, N), 1,59 is 1.70 (m, 2H), 1.77 in-of 1.84 (m, 2H), 2,30 is 2.46 (m, 4H), 3,24 (q, 2H, J=6.6 Hz), to 3.38 (d, 2H, J=11.7 Hz), 3,74-3,88 (m, 2H), 4,08 (t, 1H, J=5.7 Hz), 6.87 in (d, 2H, J=8.7 Hz), 7,30 (s, 1H), 7,41 (d, 2H, J=8.7 Hz).

Ia-6

TPL: 229-230°

1H-NMR (CDCl3) δ ppm: 1,25 (d, 6N, J=6.3 Hz), of 1.26 to 1.34 (m, 2H), 1.39 in (d, 6N, J=6.9 Hz), 1,61-to 1.77 (m, 2H), 1,98-of 1.26 (m, 5H), 2,32 is 2.46 (m, 2H), 3.15 in (quintet, 1H, J=6.6 Hz), 3,22-to 3.35 (m, 1H), 3,39 (d, 2H, J=11,4 Hz), 3,74-to 3.92 (m, 2H), 3,88 (d, 1H, J=8,4 Hz), of 6.96-of 6.71 (m, 2H), 7,05 (Ushs, 1H), 7,39 (d, 2H, J=9,3 Hz).

Ia-7

TPL: 253-254°

1H-NMR (DMSO) δ ppm: 1,24-to 1.60 (m, 4H), 1.27mm (s, N), 1,77-2,07 (m, 4H), 2,16-of 2.34 (m, 1H), 2,97 is 3.15 (m, 1H), 6,78 (d, 1H, J=7,2 Hz), 7,01 (t, 1H, J=6.0 Hz), 7,27 (t, 2H, J=6.6 Hz), 7,58 (d, 2H, J=7,5 Hz), 9,78 (s, 1H).

Ia-8

TPL: 257-258°

1H-NMR (DMSO) δ ppm: 1,22-and 1.54 (m, 4H), 1.27mm (s, N), 1,77-of 1.88 (m, 2H), 1,88 is 2.00 (m, 2H), 216-2,34 (m, 1H), of 2.23 (s, 3H), 2,92-3,14 (m, 1H), 6,77 (d, 1H, J=8,4 Hz), 7,07 (d, 2H, J=8,4 Hz), 7,46 (d, 2H, J=8.1 Hz), 9,68 (s, 1H).

Ia-9

TPL: 231-232°

1H-NMR (CDCl3) δ ppm: to 1.21 (t, 3H, J=7.5 Hz), 1,22-to 1.38 (m, 2H), 1,40 (s, N), 1,62-of 1.78 (m, 2H), 1,98-2,31 (m, 5H), 2,61 (q, 2H, J=7.5 Hz), 3,24-to 3.38 (m, 1H), 3,70 (d, 1H, J=9.9 Hz), 7,11 (s, 1H), 7,14 (d, 2H, J=8,7 Hz), 7,40 (d, 2H, J=8.7 Hz).

Ia-10

TPL: 233-234°

1H-NMR (CDCl3) δ ppm as 0.96 (t, 3H, J=7.2 Hz), of 1.20 to 1.37 (m, 2H), 1,40 (s, N), 1,56-of 1.78 (m, 4H), 1,98 of-2.32 (m, 5H), of 2.54 (t, 2H, J=7,2 Hz), 3,23-3,39 (m, 1H), 3,66 (d, 1H, J=9.6 Hz), was 7.08 (s, 1H), 7,12 (d, 2H, J=8,4 Hz), 7,39 (d, 2H, J=8,4 Hz).

Ia-11

TPL: 243-244°

1H-NMR (CDCl3) δ ppm: 1,22 (d, 6N, J=6,9), 1,22-to 1.77 (m, 4H), of 1.40 (s, N), 2,01-of 2.30 (m, 5H), 2,83 of 2.92 (m, 1H), 3,24 is 3.40 (m, 1H), 3,66 at 3.69 (m, 1H), to 7.09 (s, 1H), 7,17 (d, 2H, J=8,4 Hz), 7,41 (d, 2H, J=8,1 Hz).

Ia-12

TPL: 246-247°

1H-NMR (CDCl3) δ ppm: to 0.80 (t, 3H, J=7,5), of 1.20 (d, 3H, J=7,2), 1,26-to 1.77 (m, 6N), of 1.40 (s, N), 2,01-of 2.27 (m, 5H), of 2.51-2,60 (m, 1H), 3,20-to 3.38 (m, 1H), 3,64 at 3.69 (m, 1H), was 7.08 (s, 1H), 7,12 (d, 2H, J=8,4 Hz), 7,41 (d, 2H, J=8,4 Hz).

Ia-13

TPL: 278-279°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.52 (m, 4H), of 1.29 (s, N), of 1.40 (s, N), 1,61-to 1.77 (m, 2H), 2,02-of 2.30 (m, 5H), 3,20-to 3.38 (m, 1H), 3,66 at 3.69 (m, 1H), 7,10 (s, 1H), 7,33 (d, 2H, J=9.0 Hz), 7,42 (d, 2H, J=8.7 Hz).

Ia-14

TPL: 263-264°

1H-NMR (DMSO) δ ppm: 1,24-is 1.51 (m, 4H), 1.27mm (s, N), 1,82-1799 (m, 4H), 2,19-of 2.28 (m, 1H), 2,98-of 3.12 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 7,33 (d, 2H, J=8.7 Hz), to 7.61 (d, 2H, J=9.0 Hz), 9,94 (s, 1H).

Ia-15

TPL: 209-210°

1H-NMR (CDCl3) δ ppm: 1,25 (d, 6N, J=6.3 Hz), 1,40 (s, N) 1,70-to 1.98 (m, 8H), 2,19-of 2.38 (m, 3H), 3,39 (d, 2H, J=11.7 Hz), to 3.58-to 3.92 (m, 3H), 4,12-4.26 deaths (m, 1H), 6,82-of 6.96 (m, 2H), 7,10 (ush, 1H), 7,41 (d, 2H, J=8.1 Hz).

Ia-16

TPL: 238-240°

1H-NMR (DMSO) δ ppm: 1,22-of 1.52 (m, 4H), 1.27mm (s, N), 1,81-of 1.84 (m, 2H), 1.93 and-of 1.97 (m, 2H), 2,16-of 2.23 (m, 1H), 2.95 and-of 3.12 (m, 1H), 3,70 (s, 3H), 6,77 (d, 1H, J=8,4 Hz), 6,85 (d, 2H, J=9.0 Hz), of 7.48 (d, 2H, J=9,3 Hz), for 9.64 (s, 1H).

Ia-17

TPL: 245-246°

1H-NMR (DMSO) δ ppm: 1,22-of 1.52 (m, 4H), 1.27mm (s, N)and 1.83-to 1.87 (m, 2H), 1,94 of 1.99 (m, 2H), 2,20-of 2.28 (m, 1H), 2,98-of 3.12 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 7,28 (d, 2H, J=8.7 Hz), 7,69 (d, 2H, J=9.0 Hz), for 9.64 (s, 1H).

Ia-18

TPL: 240-241°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.78 (m, 4H), of 1.40 (s, N), 2,05 is 2.33 (m, 5H), 3,22-3,44 (m, 1H), 3,64-to 3.67 (m, 1H), is 6.61 (s, 1H), 6,69-6,77 (m, 2H).

Ia-19

TPL: 240-241°

1H-NMR (CDCl3) δ ppm: 1,24-to 1.77 (m, 4H), of 1.40 (s, N), 2,05-of 2.30 (m, 5H), 3,22-to 3.38 (m, 1H), 3,70-3,74 (m, 1H), 7,00-to 7.15 (m, 3H), of 7.36 (s, 1H), 8,29-to 8.34 (m, 1H).

Ia-20

TPL: 239-240°

1H-NMR (CDCl3) δ ppm: 1,24-of 1.78 (m, 4H), of 1.40 (s, N), 2,02-of 2.30 (m, 5H), 3,22 is 3.40 (m, 1H), 3,63-3,66 (m, 1H), 6.89 in-6,84 (m, 1H), 7,10-7,17 (m, 2H), 7,22-7,34 (m, 1H), of 7.48-7,51 (m, 1H).

Ia-21

TPL: 259-260°

1H-NMR (CDCl3/DMSO) δ ppm: 1,21 (d, 6N, J=6, 0 Hz), 1,22-of 1.44 (m, 2H), 1,40 (s, N), 1,60-of 1.78 (m, 2H), 1,87-2,03 (m, 2H), 2,08-to 2.29 (m, 3H), 2,39 (t, 2H, J=10,2 Hz), 3,14-of 3.32 (m, 1H), 3,19 (d, 2H, J=11.4 in Hz)of 3.77-3,93 (m, 2H), 5,33 (d, 1H, J=9.0 Hz), at 6.84 (DD, 1H, JFH, NN=8,1, 8.1 Hz), 7,20 (d, 1H, J=7.8 Hz), 7,49 (d, 1H, JFH=14,7 Hz), 8,86 (s, 1H).

Ia-22

TPL: 234-235°

1H-NMR (CDCl3) δ ppm: 1,20 (d, 6N, J=5.7 Hz), 1,22-of 1.44 (m, 2H), 1,38 (s, N), and 1.54 to 1.76 (m, 2H), 194-2,32 (m, 5H), and 2.27 (s, 3H), 2,39 (t, 2H, J=10,8 Hz), 2,87 (d, 2H, J=11,4 Hz), 3,20-3,40 (m, 1H), 3,76-to 3.92 (m, 2H), 3,91 (d, 1H, J=9.3 Hz), 6,93 (d, 1H, J=8.1 Hz), 7,21 (Ushs, 1H), 7,27 (Usha, 1H), was 7.36 (Ushs, 1H).

Ia-23

TPL: 195-196°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.44 (m, 4H), of 1.41 (s, N), 1,59 to 1.76 (m, 2H), 2,03 with 2.14 (m, 2H), 2,15 is 2.33 (m, 3H), 3,20-3,40 (m, 1H), 3,64 (s, 1H, J=9.0 Hz), 7,19-7,24 (m, 1H), 7,44 (Ushs, 1H), 7,52-7,63 (m, 2H), 8,17 (d, 1H, J=8.7 Hz).

Ia-24

TPL: 209-210°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.39 (m, 2H), and 1.56 (s, N), 1,61-of 1.78 (m, 2H), 2.00 in a 2.12 (m, 2H), 2,17 is 2.33 (m, 3H), 3,24-3,39 (m, 1H), to 3.67 (d, 1H, J=9.6 Hz), 6.90 to-7,01 (m, 1H), 7,21 (s, 1H), 7.95 is-of 8.06 (m, 1H).

Ia-25

TPL: 278-281°

1H-NMR (DMSO-d6) δ ppm: 1,10 (d, 6N, J=6.3 Hz), 1.27mm (s, N), 1,28-of 1.55 (m, 4H), 1,78 is 2.00 (m, 4H), 2,11-of 2.26 (m, 1H), 2,31 (t, 2H, J=11,1 Hz), 3.00 and-3,10 (m, 1H), is 3.08 (d, 1H, J=10,8 Hz), 3,67-of 3.80 (m, 2H), 6,78 (d, 1H, J=8.7 Hz), was 7.08 (d, 1H, J=9.0 Hz), 7,41 (DD, 1H, J=2,4, and 8.7 Hz), 7,78 (d, 1H, J=8.7 Hz), 9,85 (s, 1H).

Ia-26

TPL: 253-255°

1H-NMR (DMSO-d6) δ ppm: 1,13 (d, 6N, J=6.0 Hz), 1.27mm (s, N), 1,28-of 1.52 (m, 4H), 1,78 is 2.00 (m, 4H), of 2.21 (t, 2H, J=11,1 Hz), 2.26 and-a 2.36 (m, 1H), 2,96-3,10 (m, 1H), 3,56 (d, 1H, J=12.3 Hz), 3,60-and 3.72 (m, 2H), 6,66-6,84 (m, 4H), 7,47 (t, 1H, J=9.3 Hz), 9.28 are (s, 1H).

Ia-27

TPL: 223-226°

1H-NMR (DMSO-d6) δ ppm: 1,09 (d, 6N, J=6.3 Hz), 1.27mm (s, N), 1,28-and 1.54 (m, 4H), 1.77 in for 2.01 (m, 4H), 2,32 (t, 2H, J=11,1 Hz), 2,32-to 2.42 (m, 1H), 2,90 (d, 1H, J=11,4 Hz), 2,96-of 3.12 (m, 1H), 3,76-to 3.92 (m, 2H), 6,78-6,98 (m, 3H), 7,68 (DD, 1H, J=3.3, which is 8.7 Hz), 8,84 (s, 1H).

Ia-28

TPL: 237-238°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.44 (m, 2H), 1,25 (d, 6N, J=6.3 Hz), 1,40 (s, N), 1,61-to 1.79 (m,2H), 2,05 of-2.32 (m, 5H), of 2.21 (s, 3H), of 2.38 (t, 2H, J=10,2 Hz), 3,22-of 3.42 (m, 1H), 3,40 (d, 2H, J=11,1 Hz), the 3.65 (d, 1H, J=9.3 Hz), 3.72 points-3,90 (m, 2H), 6,70-of 6.78 (m, 2H), for 6.81 (Ushs, 1H), 7,50 (d, 1H, J=9.6 Hz).

Ia-29

TPL: 208-209°

1H-NMR (CDCl3) δ ppm: 1,22 (d, 6N, J=6.0 Hz), 1,23-of 1.40 (m, 2H), 1,40 (s, N), 1,60-of 1.78 (m, 2H), 2.00 in of 2.16 (m, 2H), 2,14 is 2.33 (m, 3H), of 2.45 (t, 2H, J=11,1 Hz), 3,21 (d, 2H, J=10,8 Hz), 3,24-to 3.38 (m, 1H), 3,63 (d, 1H, J=9,3 Hz), 3,80-of 3.94 (m, 2H), 5,33 (d, 1H, J=9.0 Hz), of 6.66 (DD, 1H, JFH, LV=and 6.6, and 6.6 Hz), 7,16 (Ushs, 1H), 7,89 (DD, 1H, JFH, NN=9,0, 9,0 Hz).

Ia-30

TPL: 284-287°

1H-NMR (DMSO-d6) δ ppm: 1,08 (d, 6N, J=6.0 Hz), 1.26 in (C, N), 1,28-of 1.53 (m, 4H), 1,82-2,22 (m, 4H), 2,25-2,39 (m, 1H), 2,78 (t, 2H, J=10.5 Hz), 2,97-3,14 (m, 1H), 3,18 (d, 2H, J=11,4 Hz), 3,65 is 3.76 (m, 2H), 6,79 (d, 1H, J=8.7 Hz), of 9.75 (s, 1H).

Ia-31

TPL: 200-201°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.40 (m, 2H), 1,40 (s, N), 1,62 to 1.76 (m, 2H), 2,04 of-2.32 (m, 5H), 3,22 is 3.40 (m, 1H), 3,62-3,66 (m, 1H), 7,22-7,24 (m, 1H), 7,38-7,38 (m, 1H), 7,60 (s, 1H), 8,33-at 8.36 (m, 1H).

Ia-32

TPL: 260-261°

1H-NMR (CDCl3/DMSO) δ ppm: 1,25-of 1.42 (m, 2H), 1,38 (s, N), 1,64 (q, 2H, J=13.5 Hz), 1,95 (d, 2H, J=12.3 Hz), 2,16 (d, 2H, J=10.5 Hz), 2,18 of-2.32 (m, 1H), 3,14-3,30 (m, 1H), of 5.53 (d, 1H, J=9.0 Hz), 7,31 (d, 1H, J=8,7 Hz), 7,46 (DD, 1H, J=2,4, and 8.7 Hz), of 7.90 (d, 1H, J=2.1 Hz), a 9.35 (s, 1H).

Ia-33

TPL: 227°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,30-of 1.56 (m, 4H), 1,78 is 2.01 (m, 2H), 2,12-of 2.36 (m, 2H), 2,96-3,13 (m, 1H), 3,70 (s, 3H), 3,71 (s, 3H), 6,77 (d, 1H, J=8.7 Hz), 6,85 (d, 1H, J=8.7 Hz), 7,06 (DD, 1H, J=2,4, 8,7 Hz), 7,33 (d, 1H, J=2.4 Hz), 9,65 (s, 1H).

Ia-35

TPL: 214-216°

1H-NMR (CDCl3) δ ppm: 1,23-1,38 (who, 2H), 1,40 (s, N), 1,60 to 1.76 (m, 2H), 2.00 in a 2.12 (m, 2H), 2,20 of-2.32 (m, 3H), 3,24-3,39 (m, 1H), 3,68 (d, 1H, J=9.0 Hz), 6,77 (d, 1H, J=8.7 Hz), 7,00 (DD, 1H, J=2,4, and 8.7 Hz), to 7.77 (s, 1H), 8,45 (d, 1H, J=2,4 Hz).

Ia-36

TPL: 241-242°

1H-NMR (CDCl3/DMSO) δ ppm: 1,25-of 1.42 (m, 2H), 1,37 (s, N), of 1.62 (q, 2H, J=11.7 Hz), 1.93 and (d, 2H, J=12.0 Hz), 2,12 (d, 2H, J=10,8 Hz), 2,16-of 2.30 (m, 1H), 3,12 of 3.28 (m, 1H), 3,84 (s, 3H), 6,07 (d, 1H, J=8,4 Hz), 6.89 in (DD, 1H, JFH, LV=to 9.3, 9.3 Hz), 7,24 (d, 1H, J=8.7 Hz), 7,55 (d, 1H, JFH=13.5 Hz), to 9.32 (s, 1H).

Ia-37

TPL: 248-249°

1H-NMR (CDCl3) δ ppm: 0,60-0,73 (m, 1H), of 0.91 (d, 6N, J=6,6), 1,12-of 1.40 (m, 2H), 1,40 (s, N), 1,54-of 1.88 (m, 5H), 1,98-to 2.29 (m, 7H), 3,22-3,37 (m, 1H), 3,51-of 3.54 (m, 2H), and 3.72 (d, 1H, J=9,6), to 6.88 (d, 1H, J=8,7), 7,06 (s, 1H), 7,35 (d, 1H, J=9,0).

Ia-38

TPL: 237-238°

1H-NMR (CDCI3) δ ppm: 1,01 (d, 6N, J=6,6), 1,20-1,40 (m, 2H), 1,40 (s, N), 1,60-of 1.74 (m, 4H), 1,99-of 2.28 (m, 7H), 2,69-2,82 (m, 2H), 3,02-3,14 (m, 2H), 3,20-to 3.38 (m, 1H), 3,80-3,90 (m, 1H), 6,83-6,86 (m, 2H), 7,14 (, 1H), 7,34 (d, 1H, J=8,4).

Ia-39

TPL: 234-235°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.36 (m, 2H), 1,40 (S, N), 1,60-to 1.77 (m, 2H), 1,90 of-2.32 (m, 5H), 3,21-3,39 (m, 1H), 3,65 (d, 1H, J=9.6 Hz), 6.87 in (d, 1H, J=8.7 Hz),? 7.04 baby mortality (s, 1H), 7,37 (DD, 1H, J=2.7, and 8.7 Hz), 7,56 (d, 1H, J=2.7 Hz).

Ia-40

TPL: 257-258°

1H-NMR (DMSO-d6) δ ppm: 1.14 in (d, 6N, J=6.0 Hz), 1.27mm (s, N), 1,28-of 1.53 (m, 4H), 1,78 is 2.00 (m, 4H), 2,13-2,256 (m, 1H), 2,30 (t, 2H, J=11.7 Hz), 2,97-of 3.12 (m, 1H), 3,53-to 3.67 (m, 2H), 4,01 (d, 1H, J=12.3 Hz), to 6.80 (DD, 1H, J=3,0, 9.0 Hz), 7,79 (d, 1H, J=9.0 Hz), of 8.27 (s, 1H), to 9.66 (s, 1H).

Ia-41

TPL: 245-246°

1H-NMR (CDCl3/DMSO) δ ppm: 1,25-of 1.42 (m, 2H), 1,37 (s, N), 1,62 (to whom, 2H, J=12,6 Hz), was 1.94 (d, 2H, J=11,1 Hz), 2,13 (d, 2H, J=11,1 Hz), 2,18 to 2.35 (m, 1H), 3,11-3,29 (m, 1H), 6,07 (d, 1H, J=8.1 Hz), 6,95-7,06 (m, 1H), 7,14-7,27 (m, 1H), 7,44 (d, 1H, J=7,2 Hz), 7,79 (s, 1H), 9,48 (s, 1H).

Ia-43

TPL: 294-295°

1H-NMR (DMSO-d6) δ ppm: 1.26 in (C, N), 1,28-of 1.53 (m, 4H), 1,76-to 1.87 (m, 2H), 1,89 is 2.00 (m, 2H), 2.13 and was 2.25 (m, 1H), 2,96-3,10 (m, 5H), 3,52-of 3.60 (m, 4H), 6,78 (d, 1H, J=9.0 Hz), to 6.88 (d, 2H, J=9.0 Hz), 7,44 (d, 2H, J=9.0 Hz), 9,59 (s, 1H).

Ia-44

TPL: 250-252°

1H-NMR (CDCI3) δ ppm: 1,13 (d, 6N, J=6.3 Hz), 1,21-to 1.38 (m, 2H), 1,41 (s, N), 1,63 and 1.80 (m, 2H), 1.93 and (t, 2H, J=10,8 Hz), 2,00-2,10 (m, 2H), 2,16 of-2.32 (m, 3H), 3,24-3,39 (m, 1H), 3,54 (d, 2H, J=10,2 Hz), 3,64-of 3.78 (m, 3H), 7,47 (s, 1H), 7,69 (d, 2H, J=9.0 Hz), 7,73 (d, 2H, J=9.0 Hz).

Ia-45

TPL: 193°

1H-NMR (DMSO-d6) δ ppm: 1,10 (t, 6N, J=7,2 Hz), 1.26 in (C, N), 1,28-of 1.52 (m, 4H), 1,75 is 1.86 (m, 2H), 1,89 is 2.01 (m, 2H), 2,10-2,22 (m, 1H), 2,96-3,10 (m, 1H), 3,30-to 3.52 (m, N), 6,60 (d, 2H, J=9.0 Hz), to 6.80 (d, 1H, J=9.0 Hz), 7,33 (d, 2H, J=9.0 Hz), 9,46 (s, 1H).

Ia-46

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1.28 (in C, N), 1,28 is 1.58 (m, 4H), 1,83-2,04 (m, 4H), 2,23-of 2.36 (m, 1H), 2,46 (s, 3H), 3.00 and-3,14 (m, 1H), 6,79 (d, 1H, J=8.7 Hz), 7,34 (d, 1H, J=8.7 Hz), 7,78 (d, 2H, J=8.7 Hz), 7,89 (d, 1H, J=8,4 Hz), to $ 7.91 (s, 1H), 8,00 (d, 2H, J=8.7 Hz), 10,13 (s, 1H).

Ia-47

TPL: 236-237°

1H-NMR (CDCl3) δ ppm: 0,97 (d, 6N, J=6.6 Hz), 1,01 (d, 6N, J=6.6 Hz), of 1.20 to 1.37 (m, 2H), 1,40 (s, N), 1,60-of 1.84 (m, 3H), 1,97-2,31 (m, 5H), 2,50 (t, 1H, J=10,8 Hz), 2,78 (dt, 1H, J=3.3, which is 11.4 Hz), 3.25 to to 3.38 (m, 1H), of 3.45 (d, 1H, J=11,4 Hz in), 3.75 (dt, 1H, J=2,4, and 11.4 Hz), was 4.02 (dt, 1H, J=2,4, and 11.4 Hz), to 6.88 (d, 2H, J=9.0 Hz), 7,05 (s, 1H), 7,39 (d, 2H, J=9.0 Hz).

Ia-48

TPL: 228-29° With

1H-NMR (CDCl3) δ ppm: 0,88 (t, 6N, J=7,2 Hz), 1,19-of 1.45 (m, 4H), of 1.40 (s, N), 1,45 to 1.76 (m, 4H), 1,76-of 1.92 (m, 1H), 1,96-of 2.30 (m, 5H), 2,66-3,20 (m, 3H), 3,20-3,40 (m, 1H), 3,78 (d, 1H, J=9.3 Hz), 3,82 (s, 1H), 6,62-6,98 (m, 2H), 7,09 (Ushs, 1H), 7,37 (d, 2H, J=7,8 Hz).

Ia-49

TPL: 262-263°

1H-NMR (CDCl3/DMSO) δ ppm: 1,21 (d, 6N, J=5.7 Hz), of 1.26 to 1.34 (m, 2H), 1,37 (d, 6N, J=5.4 Hz), of 1.52 to 1.76 (m, 2H), 1.85 to 2,03 (m, 2H), 2,03-of 2.30 (m, 3H), 2,30 of $ 2.53 (m, 2H), 3,02-to 3.33 (m, 4H), 3.75 to 3,98 (m, 2H), 5,70 (Ushs, 1H), 6.73 x-6,98 (m, 1H), 7,14-7,25 (m, 1H), 7,52 (d, 1H, JFH=13.5 Hz), 8,86 (Ushs, 1H).

Ia-50

TPL: 232-233°

1H-NMR (CDCl3) δ ppm: 1,21 (d, 6N, J=6.3 Hz), to 1.22 to 1.37 (m, 2H), 1,38 (d, 6N, J=6.9 Hz), 1,68 (q, 2H, J=12,6 Hz), 1,98-of 2.26 (m, 5H), to 2.29 (s, 3H), 2,41 (t, 2H, J=10,2 Hz), is 2.88 (d, 2H, J=11,1 Hz), 3.15 in (septet, 1H, J=and 6.6 Hz), 3,21-3,37 (m, 1H), of 3.77-to 3.92 (m, 2H), a 3.87 (d, 1H, J=7.8 Hz), 6,88-7,06 (m, 3H), 7,35 (s, 1H).

Ia-51

TPL: 211-212°

1H-NMR (CDCl3) δ ppm: 1,20-of 1.42 (m, 2H), 1.26 in (d, 6N, J=6.3 Hz), 1,38 (d, 6N, J=6.9 Hz), 1,62-of 1.78 (m, 2H), 1,99-of 2.28 (m, 5H), 2.49 USD (DD, 2H, J=a 10.5, 10.5 Hz), 3,17 (Quint, 1H, J=6.9 Hz), 3,20-to 3.38 (m, 1H), 3,66-to 3.99 (m, 2H), 3,90-4,01 (m, 3H), 6,62 (d, 1H, J=9.0 Hz), 7,06 (s, 1H), of 7.90 (DD, 1H, J=2,4, and 9.0 Hz), of 8.09 (d, 1H, J=2.4 Hz).

Ia-52

TPL: 247-249°

1H-NMR (CDCl3) δ ppm: 1,21-of 1.36 (m, 2H), 1,40 (s, N) 1,62-of 1.78 (m, 2H), 1,98 of-2.32 (m, 5H), to 2.55 (t, 4H, J=6.0 Hz), 3,23-to 3.38 (m, 1H), 3,55 (t, 4H, J=6.0 Hz), and 3.72 (d, 1H, J=9.6 Hz), 6,94 (d, 2H, J=9.0 Hz), 7,10 (, 1H), 7 42 (d, 1H, J=9.0 Hz).

Ia-53

TPL: 234-235°

1H-NMR (CDCl3) δ ppm: 1,22-to 1.38 (m, 2H), 1,41 (s, N) 1,64 and 1.80 (m, 2H), 2.00 in 2,32 (m, 5H), 3.25 to 3.40 in (m, 1H), of 3.73 (d, 1H, J=9.3 Hz), the 7.43 (s, 1H), of 7.48 (who, 2H, J=7.5 Hz), 7,55-7,66 (m, 3H), 7.68 per-7,89 (m, 4H).

Ia-54

TPL: 235-236°

1H-NMR (CDCl3) δ ppm: 1,24-of 1.39 (m, 2H), 1,25 (d, 6N, J=6.3 Hz), 1.39 in (d, 6N, J=6.9 Hz), 1,60-1,80 (m, 2H), 2.00 in 2,28 (m, 5H), of 2.21 (s, 3H), of 2.38 (t, 2H, J=10,8 Hz), 3.15 in (septet, 1H, J=6.3 Hz), 3,23-to 3.38 (m, 1H), 3,40 (d, 2H, J=11.7 Hz), 3.72 points, 3,88 (m, 2H), a 3.87 (d, 1H, J=9.3 Hz), 6,78-6,86 (m, 3H), 7,50 (d, 1H, J=9.6 Hz).

Ia-55

TPL: 185-186°

1H-NMR (CDCl3) δ ppm: 1.14 in (d, 6N, J=6.3 Hz), 1,22-to 1.38 (m, 2H), 1,41 (s, N), 1,62-of 1.78 (m, 2H), 2,02 (t, 2H, J=10.5 Hz), 2,02 is 2.10 (m, 2H), 2,16-2,31 (m, 3H), 3,24-3,39 (m, 1H), of 3.56 (d, 2H, J=9,3 Hz), 3,63-of 3.80 (m, 3H), 7,46 (DD, 1H, J=1.5 and 8.1 Hz), 7,51 (t, 1H, J=8.1 Hz), 7,63 (s, 1H), 7,81 (t, 1H, J=1.8 Hz), 7,98 (dt, 1H, J=1,8, 8,1 Hz).

Ia-56

TPL: 229-230°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,28-and 1.54 (m, 4H), to 1.38 (s, 6N), 1,78-of 1.84 (m, 2H), 1,90-2,00 (m, 2H), 2,15-of 2.30 (m, 1H), 2,97-3,13 (m, 1H), 4,90 (s, 1H), 6,79 (d, 1H, J=9.0 Hz), 7,34 (d, 2H, J=8.7 Hz), of 7.48 (d, 2H, J=8,4 Hz), 9,72 (s, 1H).

Ia-57

TPL: 211-212°

1H-NMR (CDCl3/DMSO) δ ppm: 1,24-of 1.40 (m, 2H), 1,38 (s, N), 1,57-of 1.74 (m, 2H), 1.91 a (s, 3H), 1,92 is 2.01 (m, 2H), 2,12-of 2.24 (m, 2H), of 2.51 (Ushs, 1H), 3,18-to 3.33 (m, 1H), 4,96 (d, 1H, J=9.3 Hz), 7,16-7,53 (m, N), 7,41 (s, 1H).

Ia-58

TPL: 298-299°

1H-NMR (DMSO-d6) δ ppm: 1,24 (s, N), 1.27mm (s, N), 1,28-and 1.54 (m, 4H), 1,75-2,02 (m, 4H), 2,14-of 2.28 (m, 1H), 2,97-3,11 (m, 1H), 6,78 (d, 1H, J=8,4 Hz), 7,18 (d, 2H, J=9.0 Hz), of 7.48 (d, 2H, J=9.0 Hz), 9,46 (s, 1H), 9,76 (s, 1H).

Ia-59

TPL: 253-254°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.40 (m, 2H), 1,41 (s, N), 1,65-of 1.81 (m, 2H), 2,04-of 2.16 (m, 2H), 2,22-of 2.36 (m, 2H), 3,24-to 3.41 (m, 1H), 3,74 (d, 1H, J=9.6 Hz), 7,40-rate of 7.54 (m, 3H), 7,88 shed 8.01 (m, 3H), 8,66 (l, 1 is, J=1.5 Hz), to 9.57 (d, 1H, J=1.2 Hz).

Ia-60

TPL: 213-214°

1H-NMR (DMSO) δ ppm: 1.32 to 1,50 (m, 2H), 1,35 (s, N), 1,52 is 1.70 (m, 2H), 1,88 is 2.00 (m, 2H), 2,04-of 2.16 (m, 2H), 2,22-of 2.38 (m, 1H), 2,65 (s, 3H), 2,99 is 3.15 (m, 1H), 6,46 (d, 1H, J=9.3 Hz), 7,28 (d, 1H, J=9.0 Hz), 7,81 (s, 1H), to 8.20 (s, 1H), of 8.47 (s, 1H), of 9.89 (s, 1H).

Ia-61

TPL: 274-275°

1H-NMR (DMSO) ppm: 1,27 (s, 1H), 1,28 is 1.58 (m, 4H), 1,84-of 2.08 (m, 4H), 2,22-to 2.40 (m, 1H), 2,99 is 3.15 (m, 1H), 3,01 (s, 3H), for 6.81 (d, 1H, J=8.1 Hz), 7,78 (d, 2H, J=7.8 Hz), to 7.84 (d, 2H, J=8,4 Hz), 8,18 (s, 1H), 10,43 (s, 1H).

Ia-62

TPL: 235-236°

1H-NMR (CDCl3) δ ppm: 1,22-of 1.39 (m, 2H), 1,41 (s, 3H), 1,66 and 1.80 (m, 2H), 2,01-2,12 (m, 2H), 2,14-2,22 (m, 1H), 2,23-of 2.34 (m, 2H), 3,24-of 3.42 (m, 1H), 3,69 (d, 1H, J=9.5 Hz), 6,44 (d, 1H, J=9.3 Hz), 7,27 (Ushs, 1H), 7,28 (d, 1H, J=9.3 Hz), 7,37 (DD, 1H, J=2,4, and 9.0 Hz), to 7.68 (d, 1H, J=9.6 Hz), of 8.04 (d, 1H, J=2.4 Hz).

Ia-63

TPL: 277-279°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,28-and 1.54 (m, 4H), 1.77 in-2,02 (m, 4H), 2,15-to 2.29 (m, 1H), 2,90 (s, 3H), 2,96-3,13 (m, 1H), 6,79 (d, 1H, J=8.7 Hz), 7,12 (d, 2H, J=9.0 Hz), 7,54 (d, 2H, J=9.0 Hz), 9,50 (s, 1H), 9,81 (s, 1H).

Ia-64

TPL: 259-260°

1H-NMR (DMSO-d6) δ ppm: 1.26 in (C, N), 1,26 of 1.50 (m, 4H), 1,74 of 1.99 (m, 4H), 2,10-of 2.25 (m, 1H), 2.95 and-3,10 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 6,97 (d, 2H, J=9.0 Hz), 7,42 (d, 2H, J=9.0 Hz), 7,50-7,71 (m, 5H), 9,73 (s, 1H), of 10.05 (s, 1H).

Ia-65

TPL: 292-293°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,28-and 1.54 (m, 4H), 1,62-1,72 (m, 2H), 1.77 in-to 1.87 (m, 2H), 1,91 is 2.10 (m, 4H), 2.13 and was 2.25 (m, 1H), 2,98-of 3.12 (m, 1H), 3,41-to 3.52 (m, 2H), 5,09 (s, 1H), 6,79 (d, 1H, J=9.0 Hz), 6,91 (d, 2H, J=9.0 Hz), 7,37 (d, 2H, J=9.0 Hz), 7,42 (d, 2H, J=9.0 Hz), 7,51 (d, 2H, J=9.0 Hz), of 9.56 (s,1H).

Ia-66

TPL: >300°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,28 is 1.58 (m, 4H), 1.85 to 2,02 (m, 4H), 2.40 a-2,52 (m, 1H), 3.00 and-and 3.16 (m, 1H), for 6.81 (d, 1H, J=9.0 Hz), 7,50-7,58 (m, 3H), of 7.90-of 7.97 (m, 2H), 12,58 (s, 1H).

Ia-67

TPL: 199-200°

1H-NMR (DMSO-d6) δ ppm: 1.14 in (d, 6N, J=6.3 Hz), 1.28 (in C, N), is 1.31 to 1.48 (m, 4H), 1,76-of 1.88 (m, 2H), 2,17 (t, 2H, J=11,1 Hz), 2,82 (t, 2H, J=11.7 Hz), 3.46 in (d, 2H, J=11,4 Hz), 3,20-to 3.36 (m, 1H), 3,62-3,74 (m, 2H), was 4.02 (d, 2H, J=12.9 Hz), 6,83 (d, 2H, J=9.0 Hz), 6.89 in (d, 1H, J=8.7 Hz), 7,28 (d, 2H, J=9.0 Hz), of 8.27 (s, 1H).

Ia-68

TPL: 237-239°

1H-NMR (CDCl3/DMSO) δ ppm: 1,40 (s, N), 1,49-of 1.65 (m, 2H), 1,99 is 2.10 (m, 2H), 2.95 and (t, 2H, J=11,1 Hz), 3,36-to 3.52 (m, 1H), 4,17 (d, 1H, J=12.9 Hz), of 5.84 (d, 1H, J=8.7 Hz), to 6.39 (d, 1H, J=9.6 Hz), 7,21 (d, 1H, J=9,3 Hz), 7,51 (DD, 1H, J=2,4, and 9.3 Hz), 7,72 (d, 1H, J=9.9 Hz), the 7.85 (d, 1H, J=2.7 Hz), of 8.04 (s, 1H).

Ia-69

TPL: 259-260°

1H-NMR (DMSO) δ ppm: 1,25-of 1.55 (m, 4H), 1.27mm (s, N), 1,82-2,05 (m, 4H), 2,22-of 2.36 (m, 1H), 2,98-3,17 (m, 1H), 4.16 the (s, 3H), to 6.80 (d, 1H, J=8,4 Hz), to 7.77-7,87 (m, 4H), 10,16 (s, 1H).

Ia-70

TPL: 259-260°

1H-NMR (DMSO) δ ppm: 1.28 (in C, N), 1,36-of 1.56 (m, 2H), 1,80-of 1.92 (m, 2H), 2,86-to 3.02 (m, 2H), 3,36-to 3.52 (m, 1H), 4.04 the-4,20 (m, 2H), 6,92 (d, 1H, J=7.5 Hz), 7,38-7,58 (m, 3H), 8,00-to 8.14 (m, 2H), of 8.90 (s, 1H), remaining 9.08 (s, 1H), 9,63 (s, 1H).

Ia-71

TPL: 228-229°

1H-NMR (CDCl3/DMSO) δ ppm: 1,27-of 1.42 (m, 2H), 1,38 (s, N), 1,57 is 1.75 (m, 2H), 1,90-2,02 (m, 2H), 2,12-of 2.34 (m, 3H), 3,14-of 3.32 (m, 1H), lower than the 5.37 (d, 1H, J=9.3 Hz), 7,38-the 7.43 (m, 3H), 7,46 (d, 2H, J=8.7 Hz), 7,51-of 7.60 (m, 2H), 7,68 (d, 2H, J=9.0 Hz), was 9.33 (s, 1H).

Ia-75

TPL: 169-170°

1H-NMR (CDCl3) δ ppm: from 0.5 to 0.72 (m, 1H), 0,80 (d, 3H, J=6.6 Hz), were 0.94 (d, 3H, J=6.0 Hz), 1,14-of 1.35 (m, 3H), 1.39 in (C, N), 1,48-of 1.66 (m, 2H), 1,74-to 2.06 (m, 5H), 2.06 to 2,44 (m, 6N), 3,18-to 3.35 (m, 1H), 3,64-3,74 (m, 1H), 4,46-4,60 (m, 1H), 6,98-7,38 (m, 5H).

Ia-76

TPL: 236-237°

1H-NMR (CDCl3/DMSO) δ ppm: 1,27-of 1.42 (m, 2H), 1,38 (d, 6N, J=6.6 Hz), 1.60-to of 1.78 (m, 2H), 1,94-to 2.06 (m, 2H), 2,12-of 2.30 (m, 3H), 3,06-to 3.34 (m, 2H), 5,10 (Ushs, 1H), 6,41 (d, 1H, J=9.9 Hz), 7,25 (d, 1H, J=8,4 Hz), of 7.48 (DD, 1H, J=2,4, and 8.7 Hz), to 7.68 (d, 1H, J=9.9 Hz), to 8.12 (d, 1H, J=2.4 Hz), 8,88 (Ushs, 1H).

Ia-77

TPL: 117-118°

1H-NMR (CDCl3) δ ppm: 1,38 (d, 6N, J=6, 9 Hz), of 1.65 (quintet, 2H, J=5.4 Hz), 1,75 is 1.91 (m, 2H), 2,42 (t, 2H, J=7.4 Hz), 3,10-3,24 (m, 3H), 4,77 (Ushs, 1H), 6,41 (d, 1H, J=9.6 Hz), 7.18 in-7,26 (m, 1H), of 7.48 (DD, 1H, J=1,8, and 8.7 Hz), to 7.67 (d, 1H, J=9.9 Hz), 8,01 (s, 1H), 8,23 (Ushs, 1H).

Ia-78

TPL: 138-139°

1H-NMR (CDCl3) δ ppm: 1,41 (s, N), of 1.64 (quintet, 2H, J=6.6 Hz), of 1.84 (quintet, 2H, J=7,3 Hz), 2,42 (t, 2H, J=7.5 Hz), 3,26 (q, 2H, J=6.5 Hz), 4,59 (Ushs, 1H), 6,41 (d, 1H, J=9.3 Hz), of 7.23 (d, 1H, J=8.7 Hz), 7,49 (DD, 1H, J=to 2.4, 9.0 Hz), to 7.67 (d, 1H, J=9.9 Hz), 8,03 (d, 1H, J=2.4 Hz), 8,28 (Ushs, 1H).

Ia-79

TPL: 289-290°

1H-NMR (DMSO) δ ppm: 1,24-to 1.63 (m, 4H), 1.28 (in C, N), 1,84-of 2.08 (m, 4H), 2,24-to 2.41 (m, 1H), 3.00 and-and 3.16 (m, 1H), PC 6.82 (d, 1H, J=8.1 Hz), of 7.36-of 7.60 (m, 5H), 7,86-to 7.99 (m, 2H), 8,28 (s, 1H), 10,50 (s, 1H).

Ia-80

TPL: 239-240°

1H-NMR (DMSO) δ ppm: 1,22 (d, 1H, J=6.6 Hz), 1,23-of 1.40 (m, 2H), 1,40-to 1.59 (m, 2H), 1,83-2,04 (m, 4H), 2.23 to-2,39 (m, 1H), 2,98 is 3.23 (m, 2H), 7,00 (d, 1H, J=7.8 Hz), of 7.36-to 7.59 (m, 5H), the 7.85-of 7.97 (m, 2H), 8,29 (s, 1H), 10,50 (s, 1H).

Ia-81

TPL: 205-206°

1H-NMR (CDCl3/DMSO) δ ppm: 1,40 (s, N), 1,66 (WinTec, 2H, J=7.0 Hz), of 1.85 (quintet, 2H, J=7,2 Hz), a 2.45 (t, 2H, J=7.5 Hz), 3,24 (t, 2H, J=6.5 Hz), 5,17 (Ushs, 1H), was 7.36-rate of 7.54 (m, 5H), the 7.85 (d, 1H, J=8,4 Hz), 8,07 (DD, 1H, J=1,8, 8.1 Hz), 8,23 (d, 1H, J=1.8 Hz), being 9.61 (s, 1H).

Ia-82

TPL: 216-217°

1H-NMR (DMSO-d6) δ ppm: 1.14 in (d, 6N, J=6.3 Hz), 1,22 (d, 6N, J=6.9 Hz), 1,22-of 1.53 (m, 4H), 1,76-to 1.98 (m, 2H), of 2.21 (t, 2H, J=10,8 Hz), 2,22-of 2.36 (m, 1H), 2,96-3,20 (m, 2H), 3,57 (d, 2H, J=12.0 Hz), 3,60-3,74 (m, 1H), 6,66-6,85 (m, 2H), 6,98 (d, 1H, J=7.8 Hz), 7,47 (d, 1H, J=8.7 Hz), of 9.30 (s, 1H).

Ia-83

TPL: 118-119°

1H-NMR (DMSO-d6) δ ppm: 1,41 (d, 6N, J=6.3 Hz), 1.26 in (C, N), 1,40-to 1.67 (m, 4H), 2,17-of 2.36 (m, 3H), 2,97-3,10 (m, 2H), 3,57 (d, 2H, J=12.0 Hz), 3,6T-3,74 (m, 1H), 6,67-6,92 (m, 3H), of 7.48 (t, 1H, J=9.0 Hz), 9,37 (, 1H).

Ia-84

TPL: 265-267°

1H-NMR (DMSO-d6) δ ppm: 1,21 (d, 6N, J=6.6 Hz), 1,20-of 1.57 (m, 4H), 1.60-to 2,30 (m, N), 2,99-3,20 (m, 4H), 3,40-to 3.52 (m, 2H), 5,09 (s, 1H), 6,91 (d, 2H, J=8.7 Hz), 6,98 (d, 1H, J=7.5 Hz), 7,37 (d, 2H, J=8.7 Hz), 7,42 (d, 2H, J=8.7 Hz), 7,51 (d, 2H, J=8.7 Hz), of 9.56 (s, 1H).

Ia-85

TPL: 185-186°

1H-NMR (DMSO-d6) δ ppm: 1.26 in (C, N), 1,42-1,72 (m, 6N), 1,96 is 2.10 (m, 2H), and 2.26 (t, 2H, J=6.9 Hz), 2,96-of 3.12 (m, 4H), 3,41-to 3.52 (m, 2H), 5,09 (s, 1H), to 6.88 (d, 1H, J=8.7 Hz), 6,92 (d, 2H, J=9.0 Hz), 7,37 (d, 2H, J=8,7 Hz), the 7.43 (d, 2H, J=9.0 Hz), 7,52 (d, 2H, J=8.7 Hz), 9,63 (s, 1H).

Ia-86

TPL: 162-164°

1H-NMR (DMSO-d6) δ ppm: 1,21 (d, 6N, J=6.6 Hz), 1.41 to at 1.73 (m, 6N), 1,96 is 2.10 (m, 2H), and 2.26 (t, 2H, J=7.2 Hz), 2.91 in-3,20 (m, 5H), 3,42-to 3.52 (m, 2H), 5,09 (s, 1H), 6,92 (d, 2H, J=9,3 Hz), of 6.99 (t, 1H, J=6.0 Hz), 7,37 (d, 2H, J=8.7 Hz), the 7.43 (d, 2H, J=9,3 Hz), 7,52 (d, 2H, J=8.7 Hz), for 9.64 (s, 1H).

Ia-87

TPL: 245-247°

1H-NMR (DMSO-d 6) δ ppm: 1,22 (d, 6N, J=6, 6 Hz), 1,22 is 1.58 (m, 4H), 1,81-2,02 (m, 4H), 2,22-of 2.36 (m, 1H), 3,00-3,20 (m, 2H), 3,01 (s, 3H), of 6.99 (d, 1H, J=8,4 Hz), 7,75-7,88 (m, 2H), 8,19 (d, 1H, J=1.2 Hz), 10,43 (, 1H).

Ia-88

TPL: 208-209°

1H-NMR (DMSO-d6) δ ppm: 1,22 (d, 6N, J=6.9 Hz), 1,22-1.55V (n, 4N), a 1.75-to 1.98 (m, 4H), 2,11-of 2.24 (m, 1H), 2,98-3,20 (m, 2H), 5,96 (s, 2H), PC 6.82 (d, 1H, J=8,4 Hz), 6,91-7,03 (m, 2H), 7,30 (d, 1H, J=1.8 Hz), 9,72 (s, 1H).

Ia-89

TPL: 142-143°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,40-of 1.66 (m, 4H), and 2.26 (t, 2H, J=7.5 Hz), to 3.02 (q, 2H, J=6.6 Hz), 5,96 (s, 2H), PC 6.82 (d, 1H, J=8,4 Hz), to 6.88 (t, 1H, J=8,4 Hz)6,94 (DD, 1H, J=1,8, and 8.4 Hz), 7,30 (d, 1H, J=1,8 Hz), 9,78 (s, 1H).

Ia-90

TPL: 100°

1H-NMR (DMSO-d6) δ ppm: 1,20 (d, 6N, J=6.9 Hz), 1,40-of 1.66 (m, 4H), and 2.26 (t, 2H, J=7.5 Hz), 2,89-to 2.99 (m, 2H), 3,13 (Quint, 1H, J=6.6 Hz), 5,96 (s, 2H), 6,83 (d, 1H, J=8.1 Hz), 6,91-7,02 (m, 2H), 7,30 (d, 1H, J=1.8 Hz), 9,78 (s, 1H).

Ia-91

TPL: 189-190°

1H-NMR (DMSO-d6) δ ppm: 1.26 in (C, N), 1,43-1,71 (m, 4H), 2.40 a (t, 2H, J=7.5 Hz), 2,97-to 3.09 (m, 2H), 3,01 (s, 3H), 6,85-6,93 (m, 1H), 7,76-7,88 (m, 2H), to 8.20 (d, 1H, J=1.2 Hz), 10,49 (s, 1H).

Ia-104

TPL: 238-241°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), of 2.50 (m, 1H), 3,05 (m, 1H), 6,55 (ush s, 1H), 6,79 (d, 1H, J=8,2), to 7.15 (t, 1H, J=4,8), 8,64 (d, 2H, J=4,8).

Ia-105

TPL: 232-234°

1H-NMR (DMSO) δ ppm: 1.26 in (C, N), 1,2-1,5, (m, 4H), 1,8-2,0 (m, 4H), to 2.55 (m, 1H), 3,05 (m, 1H), 6,77 (d, 1H, J=8,7), 9,92 (s, 2H), of 10.93 (s, 1H).

Ia-106

TPL: 226-228°

1H-NMR (DMSO) δ ppm: 1.28 (in C, N), 1,22 is 1.58 (m, 4H), 1,82-2,04 (m, 4H), to 2.29 (m, 1H), of 3.07 (m, 1H), 6,9 (d, 1H, J=8.7 Hz), 7,6 1 (DD, 1H, J=1.8 Hz, 8.7 Hz), of 8.04 (d, 1H, J=8.7 Hz), 8,48 (d, 1H, 2.1 Hz), a 9.35 (s, 1H), of 10.05 (s, 1H).

Ia-107

TPL: 282-283°

1H-NMR (DMSO) δ ppm: 1,22-of 1.57 (m, 4H), 1.27mm (s, N), 1,80-2,04 (m, 4H), and 2.27 (m, 1H), 3,06 (m, 1H), for 6.81 (d, 1H, J=8.7 Hz), 7,32 (m, 1H), 7,44 (t, 2H, J=7.5 Hz), EUR 7.57-7,72 (m, 6N), to 9.91 (s, 1H).

Ia-108

TPL: 191-192°

1H-NMR (DMSO) δ ppm: 1,24 is 1.58 (m, 4H), 1.28 (in C, N), 1,86-2,04 (m, 4H), 2,70 (m, 1H), is 3.08 (m, 1H), 6,83 (d, 1H, J=8.7 Hz), 7,63-7,79 (m, 2H), 8,31 (d, 1H, J=7,2 Hz), 10,27 (s, 1H).

Ia-109

TPL: 283-285°

1H-NMR (DMSO) δ ppm: 1,24-to 1.60 (m, 4H), 1.28 (in C, N), 1,87-2,04 (m, 4H), 2,42 (m, 1H), 3,09 (m, 1H), a 3.87 (s, 2H), PC 6.82 (d, 1H, J=8.7 Hz), 7,28-the 7.43 (m, 3H), 7,60 (d, 2H, J=7.8 Hz), to 7.68 (d, 1H, J=7,2 Hz), 7,89 (d, 1H, J=7.5 Hz), 9,48 (s, 1H).

Ia-110

TPL: 263-265°

1H-NMR (DMSO) δ ppm: 1,24-and 1.54 (m, 4H), 1.27mm (s, N), 1,76-to 1.87 (m, 2H), 1,89 is 2.01 (m, 2H), 2,17 (m, 1H), 3.04 from (m, 1H), 4,01 (s, 4H), 6,01 (s, 2H), 6,44 (d, 2H, J=8.7 Hz), 6,77 (d, 1H, J=8.7 Hz), 7,39 (d, 2H, J=9.0 Hz), 9,44 (s, 1H).

la-111

TPL: 239-241°

1H-NMR (DMSO) δ ppm: 1,24-and 1.54 (m, 4H), 1.27mm (s, N), 1,62 to 1.76 (m, 4H), 1,80-2,02 (m, 4H), 2,30 (m, 1H), 2,47 at 2.59 (m, 2H), 2,66 was 2.76 (m, 2H), between 6.08 (m, 1H), 6,79 (d, 1H, J=9.0 Hz), to 6.88 (d, 1H, J=6,9 Hz), 7,02 (t, 1H, J=7.5 Hz), 7,13 (d, 1H, J=7.5 Hz), 8,98 (s, 1H).

Ia-124

TPL: 247-249°

1H-NMR (DMSO) δ ppm: 1,15 (d, 6N, J=6.3 Hz), of 1.30 (s, N), 2,15-of 2.26 (m, 2H), 3,48 is 3.57 (m, 2H), 3,63 is 3.76 (m, 2H), 6,92 (d, 2H, J 8.7 Hz), to 7.59 (d, 2H, J=9.0 Hz), 7,38 (d, 2H, J=9.0 Hz), 7,87 (d, 2H, J=8,7 Hz), 9,92 (Ushs, 1H), 9,98 (Ushs, 1H).

Ia-125

TPL: 228-232°

1H-NMR (DMSO) δ ppm: 1.30 on (C, N), 1,95-of 2.08 (m, 2H), 2.77-to 2,89 (who, 4H), 7,17 (d, 1H, J=8,4 Hz), 7,39 (d, 2H, J=9.0 Hz), 7,42-of 7.48 (m, 1H), to 7.64 (Ushs, 1H), 7,87 (d, 2H, J=9.0 Hz), 9,99 (Ushs, 2H).

Ia-126

TPL: 244-246°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), 7,42 (d, 2H, J=8,4 Hz), 7,81 (DD, 1H, J=2.1 Hz, 8.7 Hz), to 7.93 (d, 2H, J=9.0 Hz), with 8.05 (d, 1H, J=9.0 Hz), 8,66 (d, 1H, J=2.1 Hz), 9,29 (s, 1H), of 10.05 (Ushs, 1H), accounted for 10.39 (Ushs, 1H).

Ia-127

TPL: 238-239°

1H-NMR (DMSO) δ ppm: 1.30 on (C, N), 4,18-4,27 (m, 4H), for 6.81 (d, 1H, J=8,4 Hz), 7,16 (DD, 1H, J=2.7 Hz, 9.0 Hz), 7,34-7,42 (m, 3H), a 7.85 (d, 2H, J=8,4 Hz), 9,94 (Ushs, 1H), 9,99 (Ushs, 1H).

Ia-128

TPL: 286 and 287°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), 7,41 (d, 2H, J=8.7 Hz), 7,71 (d, 2H, J=8,4 Hz), to $ 7.91 (d, 2H, J=8.7 Hz), to 7.99 (d, 2H, J=8.7 Hz), of 10.05 (Ushs, 1H), 10,44 (Ushs, 1H).

Ia-129

TPL: 232-234°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), OF 2.25 (1H, m), of 3.07 (m, 1H), 6,80 (d, 1H, J=9,0), 7,37 (d, 1H, J=8,1), 7,53 (t, 1H, J=8,1), of 7.75 (t, 1H, J=8,1 Hz)to 8.12 (s, 1H), 10,16 (s, 1H).

Ia-130

TPL: 274-277°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,23 is 1.58 (m, 4H), 1,81-2,03 (m, 4H), 2,28 (m, 1H), of 3.07 (m, 1H), 6,80 (d, 1H, J=8,4 Hz), was 7.36 (DD, 1H, J=0.9 Hz, 5.7 Hz), the 7.43 (DD, 1H, J=2.1 Hz, 8.7 Hz), 7,60 (d, 1H, J=5.4 Hz), 7,78 (d, 1H, J=8.7 Hz), 8,40 (d, 1H, 1.8 Hz), becomes 9.97 (Ushs, 1H).

Ia-131

TPL: 259-260°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), 7,40 (d, 1H, J=4,8 Hz), 7,41 (d, 2H, J=8.7 Hz), 7,66 (d, 1H, J=5,1 Hz), to 7.67 (DD, 1H, J=1.8 Hz, 8.7 Hz), to 7.84 (d, 1H, J=9.0 Hz), 7,92 (d, 2H, J=8.7 Hz), and 8.50 (s, 1H), there is a 10.03 (Ushs, 1H), 10,27 (Ushs 1H).

Ia-132

TPL: 265-266°

1H-NMR (DMSO) δ ppm: 1,17 (d, 6N, J=6.6 Hz), 1,31 (s, N), 4,10 (m, 1H), 7,35-7,46 (m, 3H),7,54 (d, 1H, J=7.5 Hz) 7,87-of 7.97 (m, 3H), 8,15 (Ushs, 1H), to 8.20 (d, 1H, J=7.5 Hz), there is a 10.03 (Ushs, 1H), of 10.25 (Ushs, 1H).

Ia-133

TPL: 249-250°

1H-NMR (DMSO) ppm: 1,31 (s, N), 7,41 (d, 2H, J=8.7 Hz), was 7.45 (d, 1H, J=5.4 Hz), to 7.67 (DD, 1H, J=1.8 Hz, 8.7 Hz), 7,76 (d, 1H, J=5.4 Hz), 7,92 (d, 2H, J=8.7 Hz), 7,95 (d, 1H, J=8.1 Hz), 8,39 (d, 1H, J=1.8 Hz), 10,02 (Ushs, 1H), 10,23 (Ushs, 1H).

Ia-134

TPL: 305-306°

1H-NMR (DMSO) δ ppm: 1,25 (m, 2H), 1,25 (s, N), of 1.52 (m, 2H), equal to 1.82 (m, 2H,), was 1.94 (m, 2H), 2.13 in (m, 1H), 3.04 from (m, 1H), 6,00 (d, 1H, J=8.1 Hz), 6,74 (d, 1H, J=8,4 Hz), 7.3 to 7.5 (m, 6N), the 7.85 (d, 2H, J=7.5 Hz), 8,31 (d, 1H, J=8,4 Hz).

Ia-135

TPL: 220-222°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), is 2.37 (m, 1H), 3,03 (m, 1H), 6,80 (d, 1H, J=8.7 Hz),? 7.04 baby mortality (m, 1H), 7,29 (m, 1H), 7,79 (m, 1H), 9,60 (s, 1H).

Ia-136

TPL: 263-264°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), of 2.20 (m, 1H), 3,03 (m, 1H), 6,80 (d, 1H, J=8,4 Hz), 6.87 in (m, 1H), 7,31 (m, 2H), of 10.21 (s, 1H).

Ia-137

TPL: 260-262°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), 2,30 (m, 1H), 3,05 (m, 1H), 6,80 (d, 1H, J=8,4 Hz), 7,13 (t, 2H, J=8.1 Hz), 7,31 (m, 1H), 9,52 (s, 1H).

Ia-138

TPL: 270-273°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), 2,12 (m, 1H), 3,05 (m, 1H), 6,79 (d, 1H, J=9.0 Hz), 7,31 (m, 2H), 7,80 (m, 1H), of 10.05 (s, 1H).

Ia-139

TPL: 267-270°

1H-NMR (DMSO) δ ppm: 1.30 on (C, N), of 4.05 (s, 4H), 6,04 (s, 2H), 6,51 (d, 2H, J=8.7 Hz), 7,34 (d, 2H, J=8,4 Hz), 7,54 (d, 2H, J=8,4 Hz), 7,87 (d, 2H, J=8,4 Hz), 9,82 (Ushs, 1H), becomes 9.97 (Ushs, 1H).

Ia-140

TPL: 227-229°

1H-NMR (DMSO) δ ppm: 1,22 (d, 6N, J=6.6 Hz), 1.0 to of 1.57 (m, 4H), 1,80 for 2.01 (m, 4H), and 2.27 (m, 1H), 2,95-up 3.22 (m, 2H), 6,99 (d, 1H, J=7.8 Hz), the 7.65 (d, 2H, J=8.7 Hz), 7,80 (d, 2H, J=8,4 Hz), 10,18 (Ushs, 1H).

Ia-141

TPL: 205-207°

1H-NMR (DMSO) δ ppm: 1,22 (d, 6N, J=6.9 Hz), 1,20-of 1.55 (m, 4H), 1,75-2,05 (m, 6N), of 2.21 (m, 1H), 2,72-to 2.85 (m, 4H), 2,93-3,20 (m, 2H), 6,98 (d, 1H, J=8.1 Hz), 7,10 (d, 1H, J=8.1 Hz), 7,26 (DD, 1H, J=2.1 and Hz and 8.1 Hz), 7,51 (s, 1H), 9,67 (Ushs, 1H).

Ia-142

TPL: 295-296°

1H-NMR (DMSO) δ ppm: 1,15 (d, 6N, J=6,6), 1.27mm (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), and 2.27 (m, 1H), 3,05 (m, 1H), 4,07 (m, 1H), 6,80 (d, 1H, J=8.7 Hz), to 7.64 (d, 2H, J=8.7 Hz), 7,79 (d, 2H, J=8,7 Hz), of 8.06 (d, 1H, J=7.5 Hz), of 10.01 (s, 1H).

Ia-143

TPL: 146-147°

1H-NMR (DMSO) δ ppm: 1.26 in (C, N), of 1.5-1.7 (m, 4H), 2,36 (t, 6.3 Hz), 7,66 (d, 2H, J=8,4 Hz), 7,80 (d, 2H, J=8,4 Hz), of 10.25 (s, 1H).

Ia-144

TPL: 138-140°

1H-NMR (DMSO) δ ppm: 1,21 (d, 6N, J=6.0 Hz), 1,4-1,7 (m, 4H), is 2.37 (t, 2H, J=7.5 Hz), 2,96 (q, 2H, J=6.3 Hz), 3,14 (m, 1H), 6,99 (t, 1H, J=5.4 Hz), 7,66 (d, 2H, J=7.8 Hz), 7,81 (d, 2H, J=7.8 Hz), 10,26 (s, 1H).

Ia-145

TPL: 134-136°

1H-NMR (DMSO) δ ppm: 1.26 in (C, N), of 1.39 (m, 2H), 1,4-1,7 (m, 4H), 2,28 (t, 2H, J=7,2), and 2.79 (m, 4H), to 3.02 (q, 2H, J=7,2 Hz), to 6.88 (t, 1H, J=6.0 Hz), 7,10 (t, 1H, J=6.0 Hz), 7,51 (s, 1H), 9,73 (s, 1H).

Ia-146

TPL: 135-137°

1H-NMR (DMSO) δ ppm: 1,20 (d, 6N, J=6.6 Hz), 1,4-1,7 (m, 4H), of 1.99 (m, 2H), 2,28 (t, 2H, J=7,2 Hz), and 2.79 (m, 4H), to 2.94 (q, 2H, J=6.3 Hz), 3,13 (m, 1H), 6,98 (t, 1H, J=6.9 Hz), 7,10 (d, 2H, J=8,1 Hz), 7,26 (d, 2H, J=8.1 Hz), 7,51 (s, 1H), 9,73 (s, 1H).

Ia-147

TPL: 206-207°

1H-NMR (DMSO) δ ppm: 1,29 (s, N), of 4.54 (d, 2H, J=5.7 Hz), 7,35 (d, 2H, J=9.0 Hz), 7,52 (d, 2H, J=7.8 Hz), 7,69 d, 2H, J=8.1 Hz), 7,83 (d, 2H, J=8.7 Hz), 9,02 (t, 1H, J=5.7 Hz), becomes 9.97 (Ushs, 1H).

Ia-148

TPL: 250-251°

1H-NMR (DMSO) δ ppm: 1.30 on (C, N), 7,18 (t, 2H, J=9,3 Hz), 7,40 (d, 2H, J=8.7 Hz), 7,76 (DD, 2H, J=5,1 Hz and 9.3 Hz), 7,88 (d, 2H, J=9.0 Hz), 10,02 (Ushs, 1H), 10,17 (Ushs, 1H).

Ia-149

TPL: 220-222°

1H-NMR (DMSO) δ ppm: 1.30 on (C, N), 3,74 (s, 3H), 6,92 (d, 2H, J=9.0 Hz), 7,38 (d, 2H, J=9.0 Hz), to 7.64 (d, 2H, J=9.0 Hz), 7,87 (d, 2H, J=9.0 Hz), 9,99 (s, 2H).

Ia-150

TPL: 264-266°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), from 1.66 to 1.76 (m, 4H), 2.57 m)-2,66 (m, 2H), 2,71 is 2.80 (m, 2H), 6,98 (m, 1H), 7,06-7,16 (m, 2H), 7,38 (d, 2H, J=9.0 Hz), of 7.90 (d, 2H, J=8.7 Hz), a 9.60 (s, 1H), 9,99 (s, 1H).

Ia-151

TPL: 235-236°

1H-NMR (DMSO) δ ppm: 1,03-of 1.39 (m, 5H), 1.27mm (s, N), 1,55-to 1.87 (m, 5H), to 3.73 (m, 1H), 7,31 (d, 2H, J=8.7 Hz), 7,76 (d, 2H, J =8,4 Hz), 8,01 (d, 1H, J=7.8 Hz), for 9.90 (s, 1H).

Ia-152

TPL: 244-246°

1H-NMR (DMSO) δ ppm: from 0.50 to 0.72 (m, 4H), 1.27mm (s, N), of 2.81 (m, 1H), 7,31 (d, 2H, J=8.7 Hz), 7,73 (d, 2H, J=8.7 Hz), 8,30 (d, 1H, J=4, 2 Hz), to 9.91 (Ushs, 1H).

Ia-153

TPL: >300°

1H-NMR (DMSO) δ ppm: 1,06 (m, 6N), 1.27mm (s, N), 1.2 to 1.5 (m, 4H), 1,8-2,0 (m, 4H), of 2.25 (m, 1H), and 2.7 (m, 1H), 3,05 (m, 1H), 3,51 (m, 4H), 4,30 (m, 1H), 6,80 (d, 1H, J=8,4 Hz), 7,34 (d, 2H, J=8.4 and Hz), the 7.65 (d, 2H, J=8,4 Hz), of 10.01 (s, 1H).

Ia-154

TPL: 247-249°

1H-NMR (DMSO) δ ppm: 1,05 (m, 6N), 1.27mm (s, N), 1.2 to 1.5 (m, 4H), 1,8-2,0 (m, 4H), of 2.23 (m, 1H), 2,77 (m, 1H), 3,05 (m, 1H), 3,52 (m, 4H), to 4.33 (m, 1H), 6,80 (d, 1H, J=9.0 Hz), 7,03 (d, 1H, J=7,8 Hz), 7,35 (t, 1H, J=7.8 Hz), to 7.59 (d, 1H, J=7.8 Hz), 7,68 (s, 1H), 9,96 (s, 1H).

Ia-155

TPL: 258-259°

1H-NMR (DMSO) ; ppm: 1,25 (m, 2H), 1,50 (m, 2H), to 1.86 (m, 2H), 1,99 (m, 2H), 2,28 (m, 1H), 2,93 (s, 3H), 3,10 (m, 1H), 7,02 (d, 1H, J=7.5 Hz), the 7.65 (d, 2H, J=8,4 Hz), 7,80 (d, 2H, J=8,4 Hz), and 10.20 (s, 1H).

Ia-156

TPL: 250-253°

1H-NMR (DMSO) δ ppm: 1.28 (in m, 2H), 1,50 (m, 2H), equal to 1.82 (m, 2H), 2,00 (m, 4H), 2,22 (m, 1H), and 2.79 (m, 4H), of 2.92 (s, 3H), 3,11 (m, 1H), 7,01 (d, 1H, J=(a,1), 7,26 (d, 1H, J=8.1 Hz), 7,51 (s, 1H), 9,68 (s, 1H).

Ia-157

TPL: 259-262°

1H-NMR (DMSO) δ ppm: 1,13 (d, 6N, J=6,0), 1,25 (m, 2H), 1,50 (m, 2H), 1,80 (m, 2H), 1,95 (m, 2H), 2,17 (m, 3H), of 2.92 (s, 3H), 3,10 (m, 1H), 3,70 (m, 2H), 3,68 (m, 2H), 6,86 (d, 2H, J=9,3 Hz), 7,00 (d, 1H, J=7,2 Hz), the 7.43 (d, 2H, J=9,3 Hz), 9,58 (s, 1H).

Ia-158

TPL: 298-300°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), 7,30-to 7.50 (m, 5H), 7,63-7,71 (m, 4H), 7,87 (d, 2H, J=8.7 Hz), to $ 7.91 (d, 2H, J=9.0 Hz), there is a 10.03 (Ushs, 1H), 10,22 (Ushs, 1H).

Ia-159

TPL: 278-281°

1H-NMR (DMSO) δ ppm: 0,74-to 1.87 (m, 20N), of 1.29 (s, N), 3,76 (m, 1H), 7,32 (d, 2H, J=8,4 Hz), of 7.75 (d, 2H, J=8.7 Hz), of 7.75 (d, 1H, J=8.7 Hz), of 7.90 (Ushs, 1H).

Ia-160

TPL: 227-228°

1H-NMR (DMSO) δ ppm: 1,22-of 1.55 (m, 4H), 1.27mm (s, N), 1,80-2,02 (m, 4H), of 2.23 (m, 1H), 3,06 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), was 7.45 (t, 1H, J=9.9 Hz), 7,82 (m, 1H), 8,12 (DD, 1H, J=2.4 Hz, 6.3 Hz), 10,17 (Ushs, 1H).

Ia-161

TPL: 259-260°

1H-NMR (DMSO) δ ppm: 1,22-and 1.54 (m, 4H), 1.27mm (s, N), 1,78 is 2.01 (m, 4H), of 2.16 (s, 3H), of 2.21 (m, 1H), 3,05 (m, 1H), 6,77 (d, 1H, J=8,4 Hz), 7,12-7,21 (m, 2H), 7,53 (m, 1H), 9,90 (Ushs, 1H).

Ia-162

TPL: 222-226°

1H-NMR (DMSO) δ ppm: 1,15 (d, 6N, J=6.3 Hz), 1.26 in (d, 6N, J=6.9 Hz), 2,16-of 2.26 (m, 2H), and 3.31 (m, 1H), 3,48-to 3.58 (m, 2H), 3,63 is 3.76 (m, 2H), 6,92 (d, 2H, J=9.0 Hz), 7,32 (d, 2H, J=8.7 Hz, to 7.59 (d, 2H, 9.0 Hz), 7,89 (d, 2H, J=9.0 Hz), 9,92 (s, 1H), 10,13 (Ushs, 1H).

Ia-163

TPL: 197-200°

1H-NMR (DMSO) δ ppm: 1.26 in (d, 6N, J=6.3 Hz), 1,95-of 2.09 (m, 2H), 2.77-to 2,90 (m, 4H), of 3.32 (m, 1H), 7,17 (d, 1H, J=8.1 Hz), 7,32 (d, 2H, J=8.7 Hz), was 7.45 (DD, 1H, J=1.8 Hz, 8.1 Hz), to 7.64 (Ushs, 1H), of 7.90 (d, 2H, J=8.7 Hz), 9,99 (Ushs, 1H), 10,13 (Ushs, 1H).

Ia-164

TPL: 145-247°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,3-2,0 (m, N), 2,19 (m, 1H), 3,05 (m, 1H), 4,74 (m, 1H), 6,79 (d, 1H, J=9.0 Hz), to 6.80 (d, 2H, J=9.0 Hz), 7,47 (d, 2H, J=9.0 Hz), 9,63 (s, 1H).

Ia-165

TPL: >300°

1H-NMR (DMSO) δ ppm: 1,03-2,02 (m, N), 1.27mm (s, N), and 2.26 (m, 1H), 3,06 (m, 1H), to 3.73 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 7,63 (d, 2H, J=9.0 Hz), 7,78 (d, 2H, J=8.7 Hz), 8,02 (d, 1H, J=8.1 Hz), 10,00 (Ushs, 1H).

Ia-166

TPL: 200-201°

1H-NMR (DMSO) δ ppm: 1,03-2,02 (m, N), 1.27mm (s, N in), 2.25 (m, 1H), 3,06 (m, 1H), to 3.73 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 7,33 (t, 1H, J=8.1 Hz), 7,46 (d, 1H, J=8.1 Hz), 7,76 (m, 1H), 7,94 (m, 1H), 8,14 (d, 1H, J=8.1 Hz), 9,92 (Ushs, 1H).

Ia-167

TPL: 282-285°

1H-NMR (DMSO) δ ppm: 1,22-1/57 (m, 4H), 1.27mm (s, N), 1,87-2,03 (m, 4H), 2.49 USD (m, 1H), of 3.07 (m, 1H), 6,83 (d, 1H, J=8.7 Hz), 13,20 (Ushs, 1H).

Ia-168

TPL: 120-124°

1H-NMR (DMSO) δ ppm: 0,94-of 1.66 (m, 14N), 1.27mm (s, N), 1,80-2,04 (m, 4H), of 2.25 (m, 1H), 2,92 (m, 1H), 3,06 (m, 1H), 6,78 (d, 1H, J=8.7 Hz), 7,42-7,53 (m, 2H), 7,63 (d, 1H, J=7,2 Hz), 7,73 (m, 1H), 8,17 (m, 1H), 10,11 (Ushs, 1H).

Ia-169

TPL: 256-257°

1H-NMR (DMSO) δ ppm: 0,93-1,20 (m, 5H), 1,24-of 1.64 (m, N), 1.27mm (s, N), 1,80-2,02 (m, 4H), and 2.27 (m, 1H), 2,87 (m, 1H), 3,06 (m, 1H), 6,79 (d, 1H, J=9.0 Hz), of 7.48 (d, 1H, J=7,2 Hz), 7.68 per-7,79 (m, 4H), 10,17 (Ushs, 1H).

Ia-171

TPL: 242-244°

1H-NMR (DMSO) δ ppm: 1,27 (m, N), a 1.45 (m, 4H), 1,90 (m, 4H), of 2.25 (m, 1H), of 3.07 (m, 1H), to 3.67 (m, 2H), 6,77 (d, 1H, J=8.7 Hz), 6.90 to (d, 1H, J=7.8 Hz), 7,31 (t, 1H, J=7.5 Hz), 7,53 (d, 1H, J=7,8 Hz), to 7.59 (s, 1H), of 9.89 (s, 1H).

Ia-172

TPL: >310°

1H-NMR (DMSO) δ ppm: 1,27 (m, N), to 1.38 (m, 4H), of 1.84 (m, 2H), of 1.97 (m, 2H), 2,25 (m, 1H), of 3.07 (m, 1H), 3,66 (m, 2H), for 6.81 (d, 1H, J=8.7 Hz), 7,20 (d, 2H, J=6,7 Hz), to 7.61 (d, 2H, J=8.7 Hz), 9,94 (, 1H).

Ia-173

TPL: 279-281°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H)and 1.83 (m, 6N), of 1.93 (m, 2H), of 2.21 (m, 1H), a 2.36 (m, 2H), 3,05 (m, 1H), 3,54 (m, 2H), 6,79 (d, 1H, J=8.7 Hz), 7,16 (d, 2H, J=9.0 Hz), 7,56 (d, 2H, J=9.0 Hz), 9,83 (s, 1H).

Ia-174

TPL: 258-262°

1H-NMR (DMSO) δ ppm: 0,29 (m, 2H), 0,53 (m, 2H), 1,20 (m, 1H), 1.27mm (s, N), to 1.3-1.5 (m, 4H), 1,7-2,0 (m, 4H), of 2.20 (m, 1H), 3,05 (m, 1H), 3,75 (d, 2H, J=6.9 Hz), 6,79 (d, 1H, J=9.0 Hz), 6,83 (d, 2H, J=9.0 Hz), 7,46 (d, 2H, J=9.0 Hz), for 9.64 (s, 1H).

Ia-175

TPL: 246-248°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,3-2,0 (m, N), 2,19 (m, 1H), 3.04 from (m, 1H), 4,23 (m, 1H), 6,79 (d, 1H, J=8.7 Hz), at 6.84 (d, 2H, J=9.0 Hz), was 7.45 (d, 2H, J=9.0 Hz), for 9.64 (s, 1H).

Ia-176

TPL: 200-202°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,3-2,0 (m, N), of 2.21 (m, 1H), 3,05 (m, 1H), 4,23 (m, 1H), to 6.57 (d, 1H, J=6.9 Hz), to 6.80 (d, 1H, J=9.0 Hz), 7,0-7,2 (m, 2H), 7,28 (s, 1H), 9,74 (s, 1H).

Ia-177

TPL: 266-268°

1H-NMR (DMSO) δ ppm: 1,22-of 1.56 (m, 4H), 1.27mm (s, N), 1,79-2,02 (m, 4H), of 2.25 (m, 1H), 3,05 (m, 1H), 6,56 (m, 1H), 6,77-6,84 (m, 2H), 7,58-7,71 (m, 5H), 9,92 (Ushs, 1H).

Ia-178

TPL: p.223-224°

1H-NMR (DMSO) δ ppm: 1,26-and 1.54 (m, 4H), 1.27mm(s, N), 1,81-2,02 (m, 4H), of 2.45 (m, 1H), 3,06 (m, 1H), 6,80 (d, 1H, J=8.7 Hz), 8,15 (DD, 1H, J=2.4 Hz, 9.0 Hz), of 8.27 (d, 1H, J=9.0 Hz), to 8.70 (m, 1H), 10,85 (Ushs, 1H).

Ia-179

TPL: 224-227°

1H-NMR (DMSO) δ ppm: 1,24-of 1.56 (m, 4H), 1.27mm (s, N), 1,80-2,03 (m, 4H), and 2.27 (m, 1H), 3,06 (m, 1H), 6,80 (d, 1H, J=8.7 Hz), 6.90 to (d, 1H, J=1.8 Hz), 7,72-to 7.84 (m, 4H), at 8.60 (d, 1H, J=1.8 Hz), to 10.09 (Ushs, 1H).

Ia-180

TPL: 226-227 of the°

1H-NMR (DMSO) δ ppm: 0,92 (d, 6N, J=6, 6 Hz), 1,26-of 1.55 (m, 4H), 1.27mm (s, N), 1,80-2,03 (m, 4H), and 2.27 (m, 1H), 3,05 (m, 1H), 3,20 (m, 1H), 6,80 (d, 1H, J=8.7 Hz), 7,42 (d, 1H, J=7,2 Hz), to 7.67-7,79 (m, 4H), 10,19 (Ushs, 1H).

Ia-181

TPL: 191-192°

1H-NMR (DMSO) δ ppm: 0,95 (d, 6N, J=6.6 Hz), 1,26-of 1.55 (m, 4H), 1.27mm (s, N), 1,80-2,03 (m, 4H), of 2.25 (m, 1H), 3,06 (m, 1H), 3,23 (m, 1H), 6,80 (d, 1H, J=8,4 Hz), 7,41-7,53 (m, 2H), 7,58 (d, 1H, J=7,2 Hz), 7,73 (m, 1H), 8,18 (m, 1H), 10,13 (Ushs, 1H).

Ia-182

TPL: 192-193°

1H-NMR (DMSO) δ ppm: 0,30 (m, 2H), 0,55 (m, 2H), 1.2 to 1.5 (m, 5H), 1.27mm (s, 1H), 1,8-2,0 (m, 4H), of 2.20 (m, 1H), 3.04 from (m, 1H), 3,75 (d, 2H, J=6.9 Hz), to 6.58 (m, 1H), 6,79 (d, 1H, J=8.7 Hz), 7,0-7,2 (m, 2H), 7,31 (s, 1H), 9,76 (s, 1H).

Ia-183

TPL: >310°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), equal to 1.82 (m, 2H), of 1.97 (m, 2H), 2,04 (m, 2H), 2,39 (m, 1H), 2,46 (t, 2H, J=7.8 Hz), of 3.07 (m, 1H), 3,79 (t, 2H, J=7.5 Hz), 6,79 (d, 1H, J=8.7 Hz), 7,56 (m, 4H), 9,80 (s, 1H).

Ia-184

TPL: 281-283°

1H-NMR (DMSO) δ ppm: 1,24-of 1.57 (m, 4H), 1.27mm (s, N), 1,80-2,04 (m, 4H), and 2.27 (m, 1H), 3,06 (m, 1H), 6,80 (d, 1H, J=9.0 Hz), 7,33 (s, 1H), of 7.75 (d, 2H, J=9,3 Hz), to $ 7.91 (d, 2H, J=8.7 Hz), 8,16 (s, 1H), to 10.09 (Ushs, 1H).

Ia-185

TPL: 226-227 of the°

1H-NMR (DMSO) δ ppm: 1,24 is 1.58 (m, 10H), 1.27mm (N), 1,81-2,02 (m, 4H), 2,28 (m, 1H), 2,78-is 2.88 (m, 4H), 3,06 (m, 1H), 6,80 (d, 1H, J=8.7 Hz), to 7.64 (d, 2H, J=8.7 Hz), 7,82 (d, 2H, J=8.7 Hz), of 10.25 (Ushs, 1H).

Ia-186

TPL: 148-150°

1H-NMR (DMSO) δ M. D.: 1,25-to 1.60 (m, 10H), 1.27mm (s, N), 1,82-2,03 (m, 4H), 2,24 (m, 1H), 2,82 of 2.92 (m, 4H), 3,06 (m, 1H), 6,79 (d, 1H, J=8,4 Hz), was 7.36 (m, 1H), 7,55 (t, 1H, J=7.8 Hz), to 7.84 (m, 1H), 8,06 (m, 1H), 10,18 (Ushs, 1H).

Ia-187

TPL: >310°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), of 1.36 (s, N), USD 1.43 (m, 4H), of 1.85 (m, 2H), 1.93 and (m, 2H), and 2.27 (m, 1H), 3,06 (m, 1H), 6,80 (d, 1H, J=8.7 Hz), 7 58 (s, 1H), 7.62mm (d, 2H), of 7.75 (d, 2H, J=9.0 Hz), 10,00 (s, 1H).

Ia-188

TPL: 285-292°

1H-NMR (DMSO) δ ppm: of 0.85 (t, 3H, J=7.5 Hz), is 1.11 (d, 3H, J=6.3 Hz), 1.26 in (C, N), between 1.3-1.6 (m, 6N), of 1.85 (m, 2H), 1,95 (m, 2H), and 2.27 (m, 1H), 3,06 (m, 1H), 3,90 (m, 1H), 6,80 (d, 1H, J=8,4 Hz), of 7.64 (d, 2H, J=8.7 Hz), 7,79 (d, 2H, J=8.7 Hz), to 7.99 (d, 1H, J=8.1 Hz), 10,02 (s, 1H).

Ia-189

TPL: 278-281°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,2-2,0 (m, 17H), 2,03 (m, 2H), 3,03 (m, 1H), 6,79 (d, 1H, J=8,4 Hz), a 7.1 to 7.3 (m, 3H), 7,94 (s, 1H), 9,78 (m, 2H).

Ia-190

TPL: >310°

1H-NMR (DMSO) δ ppm: 1,1-2,0 (m, 17H), 1.27mm (s, N in), 2.25 (m, 2H), 3,03 (m, 1H), 6,79 (d, 1H, J=8.7 Hz), of 7.48 (m, 4H), 9,71 (m, 2H).

Ia-191

TPL: 275-277°

1H-NMR (DMSO) δ ppm: 1,16 (d, 6N, J=6.6 Hz), 1,31 (s, N), 4.09 to (m, 1H), 7,41 (d, 2H, J=8.7 Hz), to 7.84 (s, 4H), of 7.90 (d, 2H, J=9.0 Hz), 8,11 (d, 1H, J=7.5 Hz), 10,04 (Ushs, 1H), 10.30 a.m. (Ushs, 1H).

Ia-192

TPL: 204-205°

1H-NMR (DMSO) δ ppm: 1,15 (d, 6N, J=6.6 Hz), 1,20-of 1.56 (m, 4H), 1,22 (d, 6N, J=6.6 Hz), 1,78 is 2.00 (m, 4H), of 2.25 (m, 1H), 2,98-up 3.22 (m, 2H), 4,06 (m, 1H), 6,99 (d, 1H, J=8.1 Hz), 7,34 (t, 1H, J=8,1 Hz) 7,46 (d, 1H, J=7.8 Hz), to 7.75 (m, 1H), of 7.96 (m, 1H), 8,17 (d, 1H, J=8.7 Hz), 9,94 (Ushs, 1H).

Ia-193

TPL: 285-286°

1H-NMR (DMSO) δ ppm: 1,15 (d, 6N, J=6.6 Hz), 1,20-of 1.56 (m, 4H), 1,22 (d, 6N, J=6.9 Hz), 1,79 is 2.00 (m, 4H), and 2.26 (m, 1H), 2,97-3,20 (m, 2H), 4,07 (m, 1H), 6,99 (d, 1H, J=7.8 Hz), to 7.64 (d, 2H, J=8.7 Hz), 7,79 (d, 2H, J=8.7 Hz), of 8.06 (d, 1H, J=7.5 Hz), 10,02 (Ushs, 1H).

Ia-194

TPL: 248-250°

1H-NMR (DMSO) δ ppm: 1,22-of 1.57 (m, 4H), 1,22 (d, 6N, J=6.6 Hz), 1,78 is 2.00 (m, 4H), of 2.25 (m, 1H), 2,98-up 3.22 (m, 2H), 6,56 (m, 1H), PC 6.82 (d, 1H, J=3.3 Hz), of 6.99 (d, 1H, J=7.8 Hz), 7,58-7,71 (m, 5H), 9,92 (Ushs, 1H).

Ia-195

TPL: 271-275°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,28-of 1.56 (m, 4H), 1,80-2,02 (m, 4H), of 2.25 (m, 1H), 3,06 (m, 1H), 6,80 (d, 1H, J=9.0 Hz), EUR 7.57 (s, 1H), 7,62-7,74 (m, 4H), 8,39 (s, 1H), 9,99 (Ushs, 1H).

Ia-196

TPL: 226-228°

1H-NMR (CDCl3) δ ppm: 0,30 (m, 2H), 1,23 (d, 6N, J=6.9 Hz), 1,2-2,0 (m, 4H), of 2.20 (m, 1H), 3,10 (m, 2H), 3,76 (d, 2H, J=6.9 Hz), 6,83 (d, 2H, J=8.7 Hz), of 6.99 (d, 1H, J=8.1 Hz), 7,46 (d, 2H, J=8.7 Hz), 9,65 (, 1H).

Ia-197

TPL: 173-175°

1H-NMR (DMSO) δ ppm: 0,31 (m, 2H), 0,56 (m, 2H), 1,22 (d, 6N, J=6.6 Hz), 1.2 to 1.5 (m, 4H), 1,8-2,0 (m, 4H), 2,22 (m, 1H), 3,10 (m, 1H), 3,76 (d, 1H, J=7,2 Hz), to 6.58 (d, 1H, J=8.1 Hz), 7,0-7,2 (m, 2H), 7,32 (s, 1H), 9,78 (s, 1H).

Ia-198

TPL: 233-235°

1H-NMR (DMSO) δ ppm: 1,25 (d, 6N, J=6.9 Hz), 1,2-2,0 (m, N), 2,19 (m, 1H), 3,10 (m, 2H), 4,73 (m, 1H), 6,80 (d, 2H, J=8.7 Hz), 6,98 (d, 1H, J=7.8 Hz), was 7.45 (d, 2H, J=8.7 Hz), 9,63 (s, 1H).

Ia-199

TPL: 185-186°

1H-NMR (DMSO) δ ppm: 1,22 (d, 6N, J=6.9 Hz), 1,2-2,0 (m, N), 2,22 (m, 1H), 3,10 (m, 2H), 4,73 (m, 1H), 6,54 (m, 1H), 7,0-7,2 (m, 2H), and 7.3 (s, 1H), 9,75 (s, 1 is).

Ia-200

TPL: 235-237°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), between 1.3-1.6 (m, 6N), 1,8-2,0 (m, 6N), of 2.20 (m, 1H), 3,05 (m, 1H), of 3.45 (m, 2H), 3,82 (m, 2H), 4,47 (m, 1H), 6,79 (d, 1H, J=9.0 Hz), 6.89 in (d, 2H, J=9.0 Hz), 7,47 (d, 2H, J=9.0 Hz), to 9.66 (s, 1H).

Ia-201

TPL: 300-301°

1H-NMR (DMSO) δ ppm: 1,15 (d, 6N, J=6.6 Hz), 1,26-of 1.56 (m, 4H), 1.27mm (s, N), 1,82-2,03 (m, 4H), of 2.23 (s, 3H), is 2.37 (m, 1H), 3,06 (m, 1H), 4,07 (m, 1H), for 6.81 (d, 1H, J=8.7 Hz), 7,52 (d, 1H, J=8,4 Hz), a 7.62 (d, 1H, J=8,4 Hz), 7,68 (s, 1H), of 8.09 (d, 1H, J=7.5 Hz), which 9.22 (Ushs, 1H).

Ia-202

TPL: 269-270°

1H-NMR (DMSO) δ ppm: 1.25 and 1.26 in (m, 4H), 1.27mm (s, N), 1,80-2,03 (m, 4H), of 2.25 (m, 1H), of 3.07 (m, 1H), 6,80 (d, 1H, J=8,4 Hz), 7,11 (m, 1H), 7,42 (d, 1H, J=3.6 Hz), of 7.48 (m, 1H), 7,58 (d, 2H, J=8.7 Hz), to 7.64 (d, 2H, J=8,4 Hz), 9,92 (Ushs, 1H).

Ia-203

TPL: 271-273°

1H-NMR (DMSO) δ ppm: 1,14-and 1.54 (m, N), of 1.26 (s, N), 1,63-of 1.88 (m, 7H), 1,89 is 2.01 (m, 2H), of 2.21 (m, 1H), 2,42 (m, 1H), 3.04 from (m, 1H), 6,79 (d, 1H, J=9.0 Hz), 7,11 (d, 2H, J=8,4 Hz), 7,47 (d, 2H, J=8,1 Hz), 9,70 (Ushs, 1H).

Ia-204

TPL: 250-251°

1H-NMR (DMSO) δ ppm: 1,22-of 1.39 (m, 2H), 1,22 (d, 6N, J=6.6 Hz), 1,40-of 1.57 (m, 2H), 1,80 for 2.01 (m, 4H), 2,28 (m, 1H), 2,98-is 3.21 (m, 2H), 7,00 (d, 1H, J=7.8 Hz), 7,34 (s, 1H), of 7.75 (d, 2H, J=9.0 Hz), to $ 7.91 (d, 2H, J=8.7 Hz), 8,17 (s, 1H), 10,10 (Ushs, 1H).

Ia-205

TPL: 239-240°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1.2 to 1.5 (m, 4H), 1,8-2,0 (m, 5H), of 2.08 (m, 2H), 3,05 (m, 1H), 3,80 (m, 4H), of 4.95 (m, 1H), 6,79 (d, 1H, J=8.7 Hz), 6,83 (d, 2H, J=8.7 Hz), of 7.48 (d, 2H, J=8.7 Hz), to 9.66 (s, 1H).

Ia-206

TPL: 236-238°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1,2-1,7 (m, 8H), 1,8-2,0 (m, 6N), to 2.18 (m, 1H), 3.04 from (m, 1H), 3.3V, 3.6V (m, 2H), 3,85 (m, 3H) 6,80 (d, 1H, J=9.0 Hz), at 6.84 (d, 2H, J=9.0 Hz), 7,47 (d, 2H, J=9.0 Hz), 9,65 (s, 1H).

Ia-207

TPL: 224-226°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1.2 to 1.5 (m, 4H), 1,8-2,0 (m, 4H), 2,24 (m, 1H), 2,39 (m, 2H), 3,06 (m, 1H), 3,50 (t, 2H, J=7.5 Hz), 3,70 (t, 2H, J=6.3 Hz), 6,78 (d, 1H, J=6.6 Hz), 6,83 (m, 1H), 7,25 (m, 1H), 7,27 (m, 1H), 7,54 (s, 1H), being 9.61 (s, 1H).

Ia-208

TPL: 275-277°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), to 1.3-1.5 (m, 4H), 1,8-2,0 (m, 4H), 2,22 (m, 1H), of 2.38 (m, 2H), of 3.07 (m, 1H), 3,47 (t, 2H, J=6.9 Hz), of 3.69 (t, 2H, J=6, 6 Hz), to 6.80 (d, 1H, J=8.7 Hz), 7,14 (d, 2H, J=8,4 Hz), 7,58 (d, 2H, J=8,4 Hz), 9,83 (s, 1H).

Ia-209

TPL: 214-215°

1H-NMR (DMSO) δ5 ppm: 1,26-of 1.56 (m, 4H), 1.27mm (s, N), 1,80-2,03 (m, 4H), of 2.25 (m, 1H), 3,06 (m, 1H), 6,59 (m, 1H), for 6.81 (d, 1H, J=8,4 Hz)6,86 (d, 1H, J=2.7 Hz), 7,28-7,40 (m, 2H), 7,47 (m, 1H), 7,75 (s, 1H), 8,01 (s, 1H), to 9.91 (Ushs, 1H).

Ia-210

TPL: 272-275°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), 6,59 (m, 1H), 6.87 in (d, 1H, J=3.3 Hz), 7,41 (d, 2H, J=8.7 Hz), to 7.68 (d, 2H, J=8.7 Hz), 7,72 (m, 1H), 7,83 (d, 2H, J=8.7 Hz), of 7.90 (d, 2H, J=8.7 Hz), there is a 10.03 (Ushs, 1H), 10,22 (Ushs, 1H).

Ia-211

TPL: 251-255°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), was 7.36 (s, 1H), 7,41 (d, 2H, J=8,4 Hz), to $ 7.91 (d, 2H, J=8,4 Hz), 7,92-of 8.00 (m, 4H), 8,19 (s, 1H), 10,06 (Ushs, 1H), 10,38 (Ushs, 1H).

Ia-212

TPL: 241-244°

1H-NMR (DMSO) δ ppm: 1.30 on (C, N), 1,50-of 1.78 (m, 6N), 1,81-of 1.97 (m, 2H), 4,78 (m, 1H), 6.87 in (d, 2H, J=9.0 Hz), 7,38 (d, 2H, J=8.7 Hz), to 7.61 (d, 2H, J=9.0 Hz), 7,87 (d, 2H, J=8.7 Hz), becomes 9.97 (Ushs, 1H), 9,99 (Ushs, 1H).

Ia-213

TPL: 283-286°

1H-NMR (DMSO) δ ppm: 1,31 (s, N), 7,12 (DD, 1H, J=3,6 Hz, 5.1 Hz), 7,41 (d, 2H, J=9.0 Hz), 7,46 (m, 1H), 7,50 (DD, 1H, J=1.2 G is, a 5.1 Hz), to 7.64 (d, 2H, J=8.7 Hz), 7,82 (d, 2H, J=8.7 Hz), of 7.90 (d, 2H, J=9,3 Hz), there is a 10.03 (Ushs, 1H), 10,22 (Ushs, 1H).

Ia-216

TPL: 224-225°

1H-NMR (CDCl3) δ ppm: 1,22 (d, 6N, J=6.9 Hz), 1.2 to 1.5 (m, 4H), 1,8-2,0 (m, 4H), of 2.45 (m, 1H), 3,12 (m, 2H), 6,99 (d, 1H, J=8.1 Hz), 8,15 (m, 1H), 8,27 (d, 1H, J=9.0 Hz), 8,69 (s, 1H), 10,86 (s, 1H).

Ia-219

TPL: 270-272°

1H-NMR (DMSO) δ ppm: 1.28 (in C, N), 1,34-is 1.51 (m, 2H), 1,80-of 1.92 (m, 2H), 2,83-of 2.97 (m, 2H), 3,32 (m, 1H), 3,99-4,12 (m, 2H), 6,92 (d, 1H, J=8.7 Hz), EUR 7.57 (d, 2H, J=8.7 Hz), to 7.68 (d, 2H, J=9.0 Hz), 8,90 (Ushs, 1H).

Ia-220

TPL: 187-189°

1H-NMR (DMSO) δ ppm: 1.28 (in C, N), 1,31-is 1.51 (m, 2H), of 1.78-1.90 (m, 2H), 2,78-of 2.93 (m, 2H), 3,30 (m, 1H), of 3.97-4.09 to (m, 2H), 6.90 to (d, 1H, J=8.7 Hz), 7,06 (t, 2H, J=9.0 Hz), 7,44 (DD, 2H, J=4,8 Hz, 9.0 Hz), 8,53 (Ushs, 1H).

Ia-221

TPL: 260-262°

1H-NMR (DMSO) δ ppm: 1,12-1,50 (m, 7H), of 1.28 (s, N), 1,63-1,90 (m, 7H), 2.40 a (m, 1H), was 2.76-2.91 in (m, 2H), or 3.28 (m, 1H), 3.96 points-4.09 to (m, 2H), 6.90 to (d, 1H, J=8.7 Hz), 7,06 (d, 2H, J=8,4 Hz), 7,32 (d, 2H, J=8,4 Hz), 8,40 (Ushs, 1H).

Ia-222

TPL: 265-267°

1H-NMR (DMSO) δ ppm: 1,23 (d, 6N, J=6.6 Hz), is 1.31 to 1.48 (m, 2H), 1.77 in-1,90 (m, 2H), 2,84 are 2.98 (m, 2H), and 3.16 (m, 1H), 3.33 and (m, 1H), 3.96 points-4,10 (m, 2H), 7,11 (d, 1H, J=7.8 Hz), EUR 7.57 (d, 2H, J=8.7 Hz), to 7.67 (d, 2H, J=8,4 Hz), 8,90 (Ushs, 1H).

Ia-223

TPL: 183-186°

1H-NMR (DMSO) δ ppm: 1,23 (d, 6N, J=6.9 Hz), of 1.28 to 1.47 (m, 2H), 1,76-of 1.88 (m, 2H), 2,80-and 3.16 (m, 2H), and 3.16 (m, 1H), 3,32 (m, 1H), 3,94-4,07 (m, 2H), 7,00-7,14 (m, 3H), 7,44 (DD, 2H, J=4,8 Hz, 9.0 Hz), 8,53 (Ushs, 1H).

Ia-224

TPL: 232-234°

1H-NMR (DMSO) δ ppm: 1,12-of 1.46 (m, 7H), of 1.23 (d, 6N, J=6.6 Hz), 1,63-to 1.87 (m, 7H), 2.40 a (m, 1H), 2,78-of 2.93 (m, 2H) 3.15 in (m, 1H), and 3.31 (m, 1H), 3,94-4,07 (m, 2H), 7,06 (d, 2H, J=8,4 Hz), to 7.09 (d, 1H, J=8.1 Hz), 7,32 (d, 2H, J=8,4 Hz), 8,39 (Ushs, 1H).

Ia-225

TPL: 222-224°

1H-NMR (DMSO) δ ppm: 1.28 (in C, N), 1,30-to 1.61 (m, 4H), 1.77 in-to 1.98 (m, 4H), 2,66-2,90 (m, 2H), or 3.28 (m, 1H), 3,40-to 3.50 (m, 2H), 3,79-3,88 (m, 2H), 3.96 points-4,08 (m, 2H), of 4.44 (m, 1H), 6,85 (d, 2H, J=9.0 Hz), 6,91 (d, 1H, J=9.0 Hz), 7,31 (d, 2H, J=9,3 Hz), 8.34 per (Ushs, 1H).

Ia-226

TPL: 194-195°

1H-NMR (CDCl3/DMSO) δ ppm: 1.39 in (d, 6N, J=7,2 Hz), of 1.66 (quintet, 2H, J=6, 8 Hz), to 1.87 (quintet, 2H, J=7,7 Hz), 2,47 (t, 2H, J=7.5 Hz), 3,11-up 3.22 (m, 1H), 3,21 (t, 2H, J=6.2 Hz), 5,00 (Ushs, 1H), 7,35-7,56 (m, 5H), 7,86 (d, 1H, J=8,4 Hz), with 8.05 (DD, 1H, J=1,8, 8.1 Hz), to 8.20 (d, 1H, J=1.8 Hz), 9,24 (s, 1H).

Ia-227

TPL: >300°

1H-NMR (DMSO) δ ppm: 1,22 (d, 6N, J=6.3 Hz), 1,20-1,40 (m, 4H), 1,74 is 2.10 (m, 4H), 2,20-2,40 (m, 1H), 2,39 (s, 3H), 3.00 and-3,30 (m, 2H), and 6.25 (s, 1H), 6,99 (Ushs, 1H), 7,43-EUR 7.57 (m, 1H), 7,71 (d, 1H, J=8,1 Hz), 7,76 (s, 1H), 10,27 (s, 1H).

Ia-228

TPL: 168-169°

1H-NMR (DMSO) δ ppm: 1.26 in (C, N), for 1.49 (quintet, 2H, J=7.5 Hz), of 1.64 (quintet, 2H, J=7.4 Hz), of 2.38 (t, 2H, J=7.2 Hz), 2.40 a (s, 3H), 3.04 from (q, 2H, J=6.5 Hz), and 6.25 (s, 1H), 6.89 in (t, 1H, J=6.0 Hz), of 7.48 (DD, 1H, J=1,8, and 8.4 Hz), 7,71 (d, 1H, J=8,4 Hz), to 7.77 (d, 1H, J=1.8 Hz), 10,33 (s, 1H).

Ia-229

TPL: 174-175°

1H-NMR (DMSO) δ ppm: 1,21 (d, 6N, J=6.6 Hz), 1,42-of 1.56 (m, 2H), 1.56 to to 1.70 (m, 2H), 2,33-to 2.42 (m, 2H), 2.40 a (s, 3H), 2,90-to 3.02 (m, 2H), 3,14 (septet, 1H, J=6.5 Hz), of 6.26 (s, 1H), 6,99 (Ushs, 1H), of 7.48 (d, 1H, J=8,4 Hz), 7,71 (d, 1H, J=8.7 Hz), to 7.77 (s, 1H), 10,33 (s, 1H).

Ia-230

TPL: 194-195°

1H-NMR (DMSO) δ ppm: 0,86 (d, 6N, J=6.9 Hz), 1,25-of 1.65 (m, 4H), 1.27mm (s, N), 1,81-2,05 (m, 5H), 2,232,35 (m, 1H), 2,99 is 3.15 (m, 1H), 3,36 (d, 2H, J=7,2 Hz), to 6.80 (d, 1H, J=8,4 Hz), 7,80 (d, 1H, J=8,4 Hz), 7,87 (d, 1H, J=8,4 Hz), 8,19 (s, 1H), 10,44 (s, 1H).

Ia-231

TPL: 221-222°

1H-NMR (DMSO) δ ppm: 0,86 (d, 6N, J=6.9 Hz), 1,22-of 1.40 (m, 2H), 1,23 (d, 6N, J=6.9 Hz), 1,40 is 1.58 (m, 2H), 1,82-2,04 (m, 5H), 2,22-is 2.37 (m, 1H), 3.00 and-and 3.16 (m, 1H), 3.15 in (septet, 1H, J=6.6 Hz), 3,36 (d, 2H, J=7.5 Hz), of 6.99 (d, 1H, J=7.5 Hz), 7,80 (d, 1H, J=8,4 Hz), 7,86 (d, 1H, J=8,4 Hz), 8,19 (s, 1H), 10,45 (s, 1H).

Ia-232

TPL: 196-197°

1H-NMR (CDCl3) δ ppm: 0,93 (d, 6N, J=6.6 Hz), 1,42 (s, 1H), 1,60-1,70 (m, 2H), of 1.88 (quintet, 2H, J=7.4 Hz), 2,02-of 2.20 (m, 1H), 2,46 (t, 2H, J=7,7 Hz), 3,29 (q, 2H, J=6,1 Hz), 3,48 (d, 2H, J=7.8 Hz), 4.26 deaths (t, 1H, J=6,0 Hz), 7,76 (d, 1H, J=8.1 Hz), of 7.90 (DD, 1H, J=1,8, 8.1 Hz), 8,07 (d, 1H, J=1.5 Hz), 8,39 (s, 1H).

Ia-233

TPL: 151-152°

1H-NMR (CDCl3) δ ppm: 0,93 (d, 6N, J=6, 6 Hz), 1,40 (d, 6N, J=6.6 Hz), 1,62 was 1.69 (m, 2H), of 1.88 (quintet, 2H, J=7,3 Hz), 2,03-of 2.16 (m, 1H), 2,47 (t, 2H, J=7.5 Hz), 3,21 (septet, 1H, J=6,8 Hz), 3,23 (q, 2H, J=6.3 Hz), 3,48 (d, 2H, J=7.5 Hz), 4,43 (t, 1H, J=6.0 Hz), 7,76 (d, 1H, J=8,4 Hz), to $ 7.91 (DD, 1H, J=1,8, and 8.4 Hz), of 8.06 (d, 1H, J=1.8 Hz), at 8.36 (s, 1H).

Ia-234

TPL: 219-220°

1H-NMR (DMSO-d6) δ ppm: 1.28 (in C, N), 1,30-1,50 (m, 2H), 1,74-of 1.88 (m, 2H), and 2.83 (t, 2H, J=11,1 Hz), 3,20-of 3.32 (m, 1H), 3,94-4,07 (m, 2H), 5,94 (s, 2H), 6,77 (d, 1H, J=8,8 Hz), PC 6.82 (DD, 1H, J=1,8, and 8.7 Hz), 6.89 in (d, 1H, J=8.7 Hz), 7,11 (d, 1H, J=1.8 Hz), scored 8.38 (s, 1H).

Ia-235

TPL: 280-282°

1H-NMR (DMSO-d6) δ ppm: 1,27 (s, N), 1,26-of 1.57 (m, 4H), 1,86-2,03 (m, 4H), 2,38-of 2.50 (m, 1H), 3.00 and-3,14 (m, 1H), for 6.81 (d, 1H, J=8,4 Hz), 7,29 (t, 1H, J=8,4 Hz), the 7.43 (t, 1H, J=7.5 Hz), 7,73 (d, 1H, J=8,4 Hz), of 7.96 (d, 1H, J=7.5 Hz), 12,27 (1H).

Ia-237

TPL: 204-205°

1H-NMR (DMSO) δ ppm: 1,23 (d, 6N, J=6.6 Hz), 1,29-to 1.61 (m, 4H), 1,75-to 1.98 (m, 4H), 2,78 of 2.92 (m, 2H), 3.15 in (m, 1H), 3,29 (m, 1H), 3,38-3,51 (m, 2H), 3,78-to 3.89 (m, 2H), 3,94-4,06 (m, 2H), of 4.44 (m, 1H), 6,85 (d, 2H, J=9.0 Hz), 7,10 (d, 1H, J=7.8 Hz), 7,31 (d, 2H, J=9,3 Hz), 8.34 per (Ushs, 1H).

Ia-238

TPL: 128-130°

1H-NMR (DMSO) δ ppm: 1.26 in (C, N), 1,41-of 1.53 (m, 2H), 1,55 by 1.68 (m, 2H), 2,44 (t, 2H, J=7,2 Hz), 2,98-of 3.07 (m, 2H), 6.90 to (t, 1H, J=6.0 Hz), 8,16 (DD, 1H, J=2.1 Hz, 8.7 Hz), 8,29 (d, 1H, J= 8.7 Hz), 8,70 (m, 1H), 10,91 (Ushs, 1H).

Ia-239

TPL: 256-258°

1H-NMR (DMSO) δ ppm: 1,26-of 1.53 (m, 4H), 1.26 in (C, N), 1,76 is 2.00 (m, 4H), of 2.23 (s, 3H), 2,39 (m, 1H), 3.04 from (m, 1H), 6,80 (d, 1H, J=8.7 Hz), EUR 7.57 (DD, 1H, J=2,4 Hz and 8.4 Hz), of 7.97 (d, 1H, J=8,4 Hz), 8,12 (m, 1H), 10,26 (Ushs, 1H).

Ia-240

TPL: 288-290°

1H-NMR (DMSO) δ ppm: 1,26-of 1.53 (m, 4H), 1.27mm (s, N), of 1.78-1.90 (m, 4H), 2.40 a (m, 1H), 3.04 from (m, 1H), for 6.81 (d, 1H, J=8.7 Hz), 7,07 (m, 1H), to 7.75 (m, 1H), 8,07 (d, 1H, J=8,4 Hz), 8,29 (m, 1H), 10,36 (Ushs, 1H).

Ia-241

TPL: 249-250°

1H-NMR (DMSO) δ ppm: 1.28 (in C, N), 1,34 of 1.50 (m, 2H), 1,79-1,90 (m, 2H), 2,74 are 2.98 (m, 2H), 3,32 (m, 1H), was 4.02-to 4.14 (m, 2H), 6,91 (d, 1H, J=8,4 Hz), 7,94 (d, 1H, J=9.0 Hz), of 8.04 (DD, 1H, J=2.1 Hz, 9.0 Hz), at 8.60 (s, 1H), 9,76 (Ushs, 1H).

Ia-242

TPL: 250-252°

1H-NMR (DMSO) δ ppm: 1,24 (s, N), 1.27mm (s, N), 1,24-and 1.54 (m, 4H), 1,76-of 1.88 (m, 2H), 1,90 for 2.01 (m, 2H), of 2.21 (m, 1H), 3,05 (m, 1H), 6,79 (d, 1H, J=8.7 Hz), to 6.88 (d, 2H, J=9.0 Hz), of 7.48 (d, 2H, J=9,0 Hz), 9,72 (Ushs, 1H).

136-0290

TPL: 250-252°

1H-NMR (DMSO) δ ppm: 1,15 (d, 6N, J=6.6 Hz), 1.28 (in C, N), 1,35-of 1.52 (m, 2H), 1,78-of 1.92 (m, 2H), measuring 2.20 (s, 3H), 2,81-2,96 (m, 2H), 3.33 and (m, 1H) 3.96 points-of 4.16 (m, 3H), 6,92 (d, 1H, J=8.7 Hz), 7,27 (d, 1H, J=8.1 Hz), 7,60 (m, 1H), 7,66 (m, 1H), of 8.06 (d, 1H, J=7.8 Hz), 8,14 (Ushs, 1H).

Ia-244

TPL: 211-213°

1H-NMR (DMSO) δ ppm: 1,29 (s, N), 1,35-of 1.52 (m, 2H), 1,81-of 1.93 (m, 2H), 2,83-of 2.97 (m, 2H), 3,32 (m, 1H), 4,03-to 4.14 (m, 2H), 6,93 (d, 1H, J=8.7 Hz), 7,55 (DD, 1H, J=2.1 Hz, 9.0 Hz), 7,94 (d, 1H, J=9.0 Hz), 8,29 (d, 1H, J=1.8 Hz), 8,78 (Ushs, 1H), 9,19 (s, 1H).

Ia-245

TPL: 196-197°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), of 1.2-1.6 (m, 6N), 1,8-2,0 (m, 6N), of 2.23 (m, 1H), 3,05 (m, 1H), to 3.73 (m, 4H), 4,99 (s, 1H), 6,79 (d, 1H, J=8.7 Hz), 7,13 (d, 1H, J=6,8 Hz), 7,22 (t, 1H, J=6,8 Hz), 7,49 (d, 1H, J=6,8 Hz), 7,72 (s, 1H), 9,78 (s, 1H).

Ia-246

TPL: 242-244°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), 1.2 to 1.5 (m, 4H), of 1.65 (m, 4H), 1,8-2,0 (m, 4H), of 2.23 (m, 1H), 2,71 (m, 1H), 3,06 (m, 1H), 3.43 points (m, 2H), 3,93 (m, 2H), 6,79 (d, 1H, J=8.7 Hz), 6,91 (d, 1H, J=8,7 Hz), 7,20 (t, 1H, J=7.5 Hz), 7,40 (d, 1H, J=7.5 Hz), 7,53 (s, 1H), 9,76 (s, 1H).

Ia-247

TPL: 242-245°

1H-NMR (DMSO) δ ppm: 1,27 (s, N), of 1.2-1.6 (m, 6N), 1,8-2,0 (m, 6N), of 2.23 (m, 1H), 3,05 (m, 1H), 3,74 (m, 4H), 4,94 (Ushs, 1H), 6,79 (d, 1H, J=8.7 Hz), 7,38 (d, 1H, J=8.7 Hz), 7,52 (d, 1H, 3=8.7 Hz), 9,76 (s, 1H).

Ia-248

TPL: 272-274°

1H-NMR (CDCl3) δ ppm: 1,27 (s, N), 1.2 to 1.5 (m, 4H), of 1.62 (m, 4H), 1,8-2,0 (m, 4H), 2,22 (m, 1H), 2,68 (m, 1H), 3,05 (m, 1H), 3,41 (m, 2H), 3,92 (m, 2H), 6,79 (d, 1H, J=9.0 Hz), to 7.15 (d, 2H, J=8.7 Hz), 7,50 (d, 2H, J=8.7 Hz), 9,73 (s, 1H).

Ia-249

TPL: 174-176°

Ia-250

TPL: 255-257°

Ia-252

TPL: 249-251°

Ia-253

TPL: 120-121°

Ia-254

TPL: 236-237°

Ia-255

TPL: 172-174°

Ia-256

TPL: 257-259°

Ia-257

Ia-258

TPL: 227-229°

Ia-259

TPL: 135-136°

Experiment 1. Means receptor NPY Y5

Sequence to the DNA encoding the receptor of the human NPY Y5 (WO 96/16542), clone in expressing vector pME18S (Takebe et al., Mol. Cell. Biol., 8, 8957). Received expressing vector transferout in cell owners SNO using the reagent Lipofect-AMINE (trademark, Gico BRL Co., Ltd.) according to the instructions on obtaining cells stably expressing the receptor for NPY Y5.

The membrane obtained from the above cells SNO expressing the receptor for NPY Y5, the compound of the present invention and 30000 Chim [125I] peptide YY (final concentration 60 PM, Amersham) and incubated in the buffer for analysis (20 mm HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25°C for 2 hours and then the mixture is filtered through a glass filter GF/C, treated with polyethylenimine. After washing the glass filter buffer Tris-HCl (50 mm, pH 7.4) measure the radioactivity on the filter using a counter gamma-quanta. Nonspecific binding detected in the presence of 200 nm of peptide YY. Calculate the concentration of the test compound for 50% inhibition of specific binding of peptide YY (value IC50) (Inui, A. et al.. Endocrinology, 131, 2090-2096 (1992)). The results are shown in tables 1 and 2.

Compounds of the present invention ingibiruyuscyeye peptide YY with receptors on NPY Y5. In other words, the compounds of the present invention show affinity to the receptor NPY Y5.

Experiment 2. Inhibitory activity against the production of camp in cells SNO.

After incubation of Cho-cells expressing the receptor for NPY Y5, in the presence of 2.5 mm isobutylmethylxanthine (SIGMA) at 37°C for 20 min add the compound of the present invention and are incubated for 5 minutes Then to cells add 50 nm NPY and 10 μm of Forskolin (SIGMA) and spend incubation for 30 minutes After stopping the reaction by adding 1 N. HCl measure the amount of camp in the upper layer of the liquid using EIA kit (Amersham LIFE SCIENCE). Inhibitory activity against NPY-stimulated Forskolin camp take over 100% and calculate the concentration of the compounds of the present invention, the inhibitory activity of NPY by 50% (the value of the IC50). The results are shown in tables 1-6.

Table 1
Connectionthe binding IC50(nm)CAMP IC50(HM)
I-27,572
I-73<10
I-111,35
I-184,429
I-20721
I-228,651
I-249,671
I-250,62,6
I-415,338,2
I-441,0the 13.4
I-451,227,9
I-460,810,5
I-470,614,9
I-490,48,1
I-500,38,4
I-534,121
I-559,040
I-574,847
I-590,835
I-600,6918
I-610,265,3
I-620,5816
I-631,350
I-642,280
I-651,872
I-661,530
I-67217
I-69the 3.813
I-722,32,1
I-75 0,553,4
I-760,615,5
I-771,828
I-790,5925
I-830,6129
I-841,325
I-863,4100
I-870,6621
I-902,850
I-92761
I-101a 3.938
I-1021,714
I-1066,429

Table 2
I-1091,23,2
I-1104,313,6
I-1111,86,1
I-114730
I-1161,211
I-1201,44,8
I-1231,8168
I-1260,613,2
I-1271,430,4
I-1281,3I-1292,1174
I-1301,142,5
I-1311,134,8
I-1322,230,4
I-1330,921,1
I-1340,510,0
I-1350,722,0
I-1362,8-
I-1371,468,2
I-1381,018,6
I-1390,417,6
I-1400,488,9
I-1410,427,4
I-1420,4928
I-1433,544
I-1443,452
I-1462,320
I-1477,163
I-1490,8315
I-1500,175,2
I-1510,172,6
I-1520,8846
I-1531,729
I-1541,1 11
I-1560,8117
I-1600,618,8
I-1610,493,1
I-1621,732
I-1632,383
I-1640,715,9
I-1650,4447
I-1660,37the 9.7
I-1670,7239
I-1682,132
I-1712,471
I-1720,9136
I-1870,5813
I-1911,111
I-1961,46,3
I-1976,739
I-1987,233
I-1994,831
I-2026,767
I-2041,06,3
I-2052,917
I-2065,954
I-2074,623
I-2101,113
I-2120,677,5
I-2130,444,0
Ia-14,831
Ia-39,2150
Ia-41,415
Ia-51,643
Ia-62,423
Ia-82,934
Ia-90,9411
Ia-100,472,7
Ia-110,647,2
Ia-120,945,5
Ia-131,53,3
Ia-144,828
Ia-160,1-
Ia-170,11,9
Ia-20a 4.9100

Table 3
Ia-213,435
Ia-223,138
Ia-245,274
Ia-251,118
Ia-261,927
Ia-28 5,2130
Ia-297,3
Ia-302,625
Ia-31the 3.811
Ia-320,526,7
Ia-331,864
Ia-351,8-
Ia-361,686
Ia-370,73the 3.8
Ia-3812,2
Ia-391,53,5
Ia-402,29,3
Ia-412,59
Ia-423,620
Ia-444,827
Ia-454,842
Ia-460,878,3
Ia-470,82the 3.8
Ia-481,26,1
Ia-492,683
Ia-501,724
Ia-511,33,4
Ia-521,922
Ia-530,228,1
Ia-540,44 9
Ia-551,127
Ia-562,396
Ia-570,9331
Ia-582,5110
Ia-590,7116
Ia-600,9510
Ia-610,6819
Ia-621,129
Ia-63a 3.9370
Ia-647,196
Ia-651,111
Ia-660,593,2
Ia-676,375
Ia-689,5150
Ia-692,733
Ia-701,531
Ia-711,3:2
Ia-762,2-
Ia-782150
Ia-790,82-
Ia-800,443,0
Ia-812,74,5
Ia-831,253
Ia-840,25 13
Ia-850,2214
Ia-860,7311
Ia-870,4961
Ia-880,6243
Ia-914150
Ia-1061,924
Ia-1070,141,3
Ia-1090,6a 3.9
Ia-1100,31,1
Ia-1115,128
Ia-1241,122
Ia-1254,146
Ia-1262,353
Ia-1276,1160
Ia-1291,326
Ia-1300,213
Ia-1311,317
Ia-1322,876
Ia-1331,78,8
Ia-1358,249
Ia-1361,613
Ia-1382,228
Ia-1391,925
Ia-1401
Ia-1411the 5.7
Ia-1420,675,5

Ia-182
Table 4
Ia-1437,839
Ia-1446,157
Ia-145786
Ia-1469,979
Ia-1580,711,7
Ia-1600,76140
Ia-1611,918
Ia-1637400
Ia-1640,38the 4.7
Ia-1680,9513
Ia-1691,988
Ia-1736,9140
Ia-1740,35of 5.4
Ia-1750,499,2
Ia-1760,635,1
Ia-1770,497,5
Ia-1784,616
Ia-1790,8919
Ia-1801,911
Ia-1817,725
0,242,1
Ia-1831,97,8
Ia-1840,38-
Ia-1850,944,4
Ia-1860,9312
Ia-1871,960
Ia-1880,7528
Ia-1893,595
Ia-1900,341000
Ia-1910,49220
Ia-1925,9200
Ia-1931,443
Ia-1940,228,1
Ia-1951,431
Ia-1960,391,3
Ia-1970,442,5
Ia-1980,232,6
Ia-1990,111,6
Ia-2001,418
Ia-2013,174
Ia-2020,373,4
Ia-2030,22,6
Ia-20416,3
Ia-2052,4460
Ia-2061,95,9
Ia-2070,555,9
Ia-2081,29
Ia-2090,55-
Ia-2102,899
Ia-2114,8240
Ia-2120,522,6
Ia-2130,9128
Ia-2192,528
Ia-2210,471,5
Ia-2223,718
Ia-2240,11,2
Ia-2253,420
Ia-2260,3721
Ia-2270,59-
Ia-2280,96-
Ia-2291,9-
Ia-2300,32-
Ia-2310,29-
Ia-2320,7-
Ia-2330,63-
Ia-2355,5-
Ia-2371,115
Ia-2411,9-
Ia-2431,3-
Ia-2460,2620
la-2470,7931
Ia-2480,2717
Ia-2501,9-
Ia-2521,2-
Ia-2530,53-
Ia-2542,0-
Ia-2553,2-
Ia-256the 5.7-
Ia-2578,6-
Ia-2581,8-

I-12
Table 5
ConnectionThe binding IC50(nm)ConnectionThe binding IC50(NM)
I-118,5I-8281
I-3the 17.3I-8815
I-825I-8913
I-914I-91696
I-1010I-93643
10I-98254
I-1337I-100198
I-I425I-104289
I-16145I-10527
I-1718I-11325
I-238,8I-11515
I-2616I-1178,9
I-2712I-11816
I-2S234I-119145
I-2529I-12281
I-30103I-124the 3.8
I-31400I-12518
I-32123I-15734
I-33369I-15817
I-3418I-1596,7
I-3586I-1731,9/td>
I-3629I-1756,1
I-37194I-1761,7
I-398,7I-1793,7
I-40283I-1800,43
I-43228I-1811,4
I-488,3I-18246
I-5656I-18312
I-6830I-18442
I-7054I-18512
I-789,3I-18623
I-8015I-1907,6
I-818,2I-19437
Table 6
ConnectionThe binding IC50(nm)ConnectionThe binding IC50(nm)
Ia-253Ia-14861
Ia-7 16Ia-14923
Ia-1539Ia-15366
Ia-1886Ia-15529
Ia-1920Ia-15654
Ia-7475Ia-15722
Ia-7515Ia-16241
Ia-7722Ia-16515
Ia-8256Ia-16620
Ia-8918Ia-16727
Ia-9067Ia-17119
Ia-10815Ia-17211
Ia-12816Ia-21619
Ia-13426Ia-22077
Ia-13746Ia-22390
Ia-14731

As can be seen from tables 1-6, the compounds of the present invention have an the agonistic activity against receptor NPY Y5.

Experiment 3

Using membranes obtained from cells expressing Y1 (human neuroblastoma, SK-N-MC), and membranes derived from cells expressing Y2 (human neuroblastoma, SMS-KAN), carry out an experiment similar to the method of experiment 1 to determine the affinity of the receptor for NPY Y1 and NPY receptor Y2.

The magnitude of the binding IC50with receptors on NPY Y1 and NPY Y2 compounds I-27, I-32, I-41, I-45, I-46, I-47, I-48, I-49, I-59, I-61, I-63, I-64, I-66, I-69, I-72, I-152, I-154, I-204, I-205, I-212, Ia-3, Ia-5, Ia-6, Ia-12, Ia-16 Ia-17, Ia-20, Ia-21, Ia-22, Ia-26, Ia-28 Ia-29, Ia-30, Ia-31, Ia-32, Ia-33, Ia-37, Ia-39, Ia-40, Cs-50, Cs-51, Cs-54, Ia-62, Ia-124, Ia-126, Ia-139, Ia-140, Ia-142, Ia-178, Ia-199 and Ia-120 is 100,000 nm or above, and each connection has activity against receptor NPY Y5.

Example composition 1. Tablets

The compound (I-1)15 mg
Starch15 mg
Lactose15 mg
Crystalline cellulose19 mg
Polyvinyl alcohol : 3 mg
Distilled water30 ml
Calcium stearate3 mg

After mixing all the above ingredients, except sterate calcium, until smooth mixture is crushed, granularit and dried, obtaining pellets of a suitable size is. After adding to the granules of calcium stearate get tablets direct compression.

Example composition 2. Capsules

The compound (I-2)10 mg
Magnesium stearate10 mg
Lactose80 mg

After mixing all the above ingredients to obtain powders or granules obtained powders or granules filled capsules.

Example of composition 3. Granules

The compound (I-3)30 mg
Lactose265 mg
Magnesium stearate5 mg

After mixing all the above ingredients until smooth and direct pressing the resulting material is shredded granularit and sift, obtaining pellets of a suitable size.

Industrial applicability

As can be seen from the above experiments, the compounds of the present invention have an antagonistic activity against receptor NPY Y5. Therefore, the compounds of the present invention are useful as anti-obesity and means of reducing the appetite.

1. Pharmaceutical composition for use as an antagonist of the receptor NPY Y5 containing Conn the General formula (I)

where R1represents optionally substituted lower alkyl, C5-C6cycloalkyl or optionally substituted phenyl or optionally substituted naphthyl,

R2represents hydrogen or lower alkyl and R1and R2taken together may form lower alkylene,

n is 1,

X represents a lower alkylene, lower albaniles, -CO- (lower alkylene) or

where R3, R4, R5and R6each independently represent hydrogen,

is3-C8cycloalkyl, bicycloalkyl, phenylene or optionally substituted heterocyclyl containing at least one heteroatom, optionally selected from O, N and S, where the heterocycle is 5 - or 6-membered heteroaryl, condensed heterocyclyl, consisting of two or three rings or non-aromatic heterocyclyl, and p and q are each independently 0 or 1,

-NR2-X - can imagine

where

is piperidinyl, piperazinyl, pyridinyl, pyrazinyl, pyrrolidinyl or pyrrolidinyl, and U represents a simple bond or a lower alkylene,

Y PR is dstanley OCONR 7, CONR7, CSNR7, NR7CO or NR7CS,

R7represents hydrogen or lower alkyl and

Z represents optionally substituted lower alkyl, optionally substituted amino, optionally substituted lower alkoxy, optionally substituted carbocyclic or optionally substituted heterocyclyl containing at least one heteroatom, optionally selected from O, N and S, where the heterocycle is 5 - or 6-membered heteroaryl, condensed heterocyclyl, consisting of two or three rings or non-aromatic heterocyclyl,

its prodrug, pharmaceutically acceptable salt or MES.

2. Pharmaceutical composition for use as an antagonist of the receptor NPY Y5 according to claim 1, where R2represents hydrogen or lower alkyl and Z is optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted carbocyclic, optionally substituted heterocyclyl containing at least one heteroatom, optionally selected from O, N and S, where the heterocycle is 5 - or 6-membered heteroaryl, condensed heterocyclyl, consisting of two or three rings or non-aromatic heterocyclyl or optionally substituted amino, provided that R1is optionally substituted (C3With 10)alkyl when Z is optionally substituted amino.

3. Pharmaceutical composition for use as an antagonist of the receptor NPY Y5 according to claim 1, where R1represents optionally substituted lower alkyl or C5-C6cycloalkyl, X represents a lower alkylene, lower albaniles orwherehas the values set in claim 1, and Z represents optionally substituted lower alkyl, optionally substituted carbocyclic or optionally substituted heterocyclyl containing at least one heteroatom, optionally selected from O, N and S, where the heterocycle is 5 - or 6-membered heteroaryl, condensed heterocyclyl, consisting of two or three rings or non-aromatic heterocyclyl.

4. Pharmaceutical composition for use as an antagonist of the receptor NPY Y5 according to any one of claims 1 to 3, where R1is optionally substituted (C3-C10)alkyl.

5. Pharmaceutical composition for use as an antagonist of the receptor NPY Y5 according to any one of claims 1 to 4, which is the tool against obesity.

6. Pharmaceutical composition for use as an antagonist of the receptor NPY Y5 according to any one of claims 1 to 4, which means reducing the appetite.

7. A method of treating and/or preventing the expectation is to be placed, including the introduction of effective doses of the antagonist receptor NPY Y5 according to any one of claims 1 to 4.

8. The method of suppressing food intake, including the introduction of effective doses of the antagonist receptor NPY Y5 according to any one of claims 1 to 4.

9. The compound of formula (I)

where X represents a C2-C6) alkylene or (C3-C6) albaniles, R1represents optionally substituted lower alkyl or (C5-C6) cycloalkyl, and other symbols have the meanings indicated in claim 1, provided that Z is not lower alkylenediamine, hydroxy (lower) alkylenediamine, allterrain, when Y represents NR7CO.,

its prodrug, pharmaceutically acceptable salt or MES.

10. The connection according to claim 9, where Z is optionally substituted lower alkyl or optionally substituted phenyl, its prodrug, pharmaceutically acceptable salt or MES.

11. The compound of formula (I)

where X represents

whereis3-C8cycloalkyl,3-C8cycloalkenyl, bicycloalkyl or optionally substituted piperidinyl, R1represents optionally substituted lower alkyl or long is correctly substituted (C 5-C6) cycloalkyl and other symbols have the meanings indicated in claim 1,

its prodrug, pharmaceutically acceptable salt or MES.

12. Connection to item 11, whereis cyclohexyl or piperidinyl, and p and q are simultaneously equal to 0, its prodrug, pharmaceutically acceptable salt or MES.

13. The connection according to item 11 or 12, where Y is CONH, its prodrug, pharmaceutically acceptable salt or MES.

14. The connection 11-13, where Z is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted pyridyl or optionally substituted benzopyranyl, its prodrug, pharmaceutically acceptable salt or MES.

15. The compound of formula (I)

where X represents

R1represents optionally substituted lower alkyl or (C5-C6)cycloalkyl, Z is n-(lower)alkylphenyl and other symbols have the meanings indicated in claim 1, provided that Z is not p-h-butylphenyl, when R1represents isopropyl, its prodrug, pharmaceutically acceptable salt or MES.

16. The compound of formula (I)

where X is

whereis heteroaryl, R1represents optionally substituted lower alkyl or (C5-C6)cycloalkyl and other symbols have the meanings indicated in claim 1,

its prodrug, pharmaceutically acceptable salt or MES.

17. Connection P16, whereis theoffender or furandi, its prodrug, pharmaceutically acceptable salt or MES.

18. Pharmaceutical composition for use as an antagonist of the receptor NPY Y5 containing compound according to any one of p-17, its prodrug, pharmaceutically acceptable salt or MES.

Priority signs:

R1and R2taken together may form lower alkylene; X represents-CO-(lower alkylene); -NR2-X - can imagineor lower alkylene; the term MES installed priority from 21.11.2000 according to the application PCT/J P00/08I97;

To connect

set the priority from 14.11.1999 according to the application Japan 11/353786;

All other signs of claims priority set from 26.11.1999 according to the application Japan 11-336469.



 

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