Amide derivatives of 2,3,4,5-tetrahydrobenzo {f}-{1,4} oxazepine-5-carboxylic acid as inhibitor of y-secretase for treatment of alzheimer's disease

FIELD: chemistry.

SUBSTANCE: claim describes benzoxazepinone derivatives of formula : wherein R1 represents hydrogen, C1-C6 alkoxy, halogen or NR'R", n is 1 or 2, R', R" independently from each other represents hydrogen or C1-C6 alkyl; R2 represents hydrogen, C1-C6 alkyl -(CH2)m-C3-C7-cycloalkyl, -(CH2)m-phenyl or -(CH2)m-O-C1-C6 alkyl; m is 0.1 or 2; R3 represents C1-C6 alkyl,-(CH2)m-C(O)O-C1-C6 alkyl, C3-C7 cycloalkyl or -(CH2)m-phenyl which is unsubstituted or substituted by one or two substituents, selected from the group consisting of halogen, trifluoromethyl, -NR'R", nitro and -SO2NH2, or represents -C3-C7 -cycloalkyl, unsubstituted or substituted by phenyl, or is -(CR′R″)o-heterocyclyl, selected from the group consisting of tetrahydropyran-4-yl, pyridin-3-yl, indol-3-yl optionally substituted by halogen or C1-C6 alkoxy group, or thiophen-2-yl, furan-2-yl, NH-pyridin-2-yl optionally substituted by nitro group or benzoimidazol-2-yl, 2-oxo-tetrahydrofuran, and benzo[1,3]dioxol-5-yl and represents -tetrahydro-naphthalen-1-yl, -CHR′-naphthalen-2-yl, -fluoren-9-yl, -(CH2)o-S-lower alkyl, -(CH2)o-S-benzyl, -(CH2)o-C(O)NH2, -(CH2)oNR′R″, -CH[C(O)NH2]-(CH2)o-phenyl, -(CH2)o-CF3, or -(CH2)o-CR′R″-CH2-NR′R″; and o is 1 or 2; or their pharmaceutically suitable acid addition salts, excluding: phenetylamide 4-benzyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid, butylamide 4-benzyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid, phenetylamide 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid, butylamide 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]-oxazepine-5-carboxylic acid. The pharmaceutical on basis of the compounds of formula I aimed at the treatment of Alzheimer's disease is described.

EFFECT: production of the new compounds, benzoxazepinone derivatives having useful biological properties.

26 cl, 196 ex

 

The present invention relates to a derivative of benzoxazepine formula

where R1represents hydrogen, lower alkoxy, halogen or-NR'r R";

n denotes 1 or 2;

R', R" independently of one another represent hydrogen or lower alkyl;

R2represents hydrogen, lower alkyl, -(CH2)m-cycloalkyl, -(CH2)m-phenyl, or-(CH2)m-O-(lower alkyl);

m means 0, 1 or 2;

R3represents a lower alkyl, -(CH2)m-C(O)O-(lower alkyl), cycloalkyl or -(CH2)mis phenyl, which is unsubstituted or substituted by one or two substituents selected from the group consisting of halogen or lower alkyl;

R4represents -(CH2)ois phenyl, which is unsubstituted or substituted by one or two substituents which are selected from the group consisting of halogen, trifloromethyl, -R NR'r", nitro or-SO2NH2or

is cycloalkyl, unsubstituted or substituted phenyl,

or represents - (CR'R")about-heterocyclyl, which are selected from the group consisting of tetrahydropyran-4-yl, pyridine-3-yl, indol-3-yl, optionally substituted with halogen or a group of lower alkoxy, or thiophene-2-yl, furan-2-yl, -NH-pyridin-2-yl, neobyazatelnostyu a nitro group,

or benzoimidazol-2-yl, 2-oxitetraciclina, 1-benzylpiperidine-4-yl, or benzo[1,3]dioxol-5-yl,

or is tetrahydronaphthalen-1-yl,

- CHR'-naphthalene-2-yl,

- fluoren-9-yl,

- (CH2)o-S-lower alkyl,

- (CH2)about-S-benzyl,

- (CH2)o-C(O)NH2,

- (CH2)oNR'r R",

- CH[C(O)NH2]-(CH2)about-phenyl,

- (CH2)o-CF3,

- (CH2)o-CR'R"-CH2-NR'r R"

and o represents 1 or 2,

and their pharmaceutically acceptable acid additive salts (salts and the addition products of acids), except for the following connections:

ventilated 4-benzyl-3-oxo-2,3,4,5-tetrahydrobenzo|f][1,4]oxazepine-5-carboxylic acid,

butylamide 4-benzyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

ventilated 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

These excluded compounds are described, in particular, in J. Org. Chem., 1999, 64, 1074-1076, in connection with the method, according to which the use of bifunctional source compounds containing a functional group aldehyde and carboxylic acid.

When used in the text of this application, the term "lower alkyl" means a feast upon whom NUU alkyl group with a linear or branched chain, containing from 1 to 6 carbon atoms, for example methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl and the like groups. Preferred lower alkyl groups are groups containing 1-4 carbon atoms.

The term "cycloalkyl" means a saturated carbocyclic group containing 3-7 carbon atoms.

The term "halogen" means chlorine, iodine, fluorine and bromine.

The term "lower alkoxy" means a group in which the alkyl residues are as defined above, and which are joined through an oxygen atom.

The term "pharmaceutically acceptable acid additive salts" means salts with inorganic and organic acids, such as chloromethane acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methanesulfonate acid, n-toluensulfonate acid and the like acid.

It was found that compounds of General formula I are inhibitors γ-secretase and related compounds can be used for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in old age. From the point of view of the pathology of Alzheimer's disease is characterized about the situation in the brain amyloid, in the extracellular plaques and intracellular neurofibrillary knots. Amyloid plaques consist mainly of amyloid peptides (Abete-peptides)that arise from β-amyloid protein precursor (APP -)). Amyloid Precursor Protein) as a result of several stages of proteolytic cleavage. Identified several forms of ADR, predominant among them are proteins consisting of 695, 751 and 770 amino acids. They all arise from a single gene by differential splicing. The Abete-peptides originate from the same domain of APP, but differ in their N - and C-ends of the major players have a length of 40 and 42 amino acids.

The Abete-peptides are produced from the RDA through sequential steps 2 proteolytic enzymes called β- and γ-secretase. β-Secretase has a splitting action first in the extracellular domain of APP just outside the TRANS-membrane domain (TM)). trans-membrane) with biogas produced in this C-terminal fragment of APP containing the TM domain and the cytoplasmic domain (CTFβ). CTFβ is a substrate for γ-secretase, which has a splitting action in several neighboring positions within the TM domain produced in this Abete-peptide and cytoplasmic fragment. The majority of Abete-peptides have the t length, the corresponding 40 amino acids (Andβ40), a small number of these peptides contains additional 2 amino acids at the C-end. Last, as expected, are the most pathogenic amyloid peptides.

β-Secretase is a typical aspirinplease. γ-Secretase has proteolytic activity and comprises several proteins, their exact structure is not fully installed. However presenilin are essential components of such activity and may represent a new group of atypical aspartate, which has a splitting action within the TM domains of their substrates and which are themselves polytopic membrane proteins. Other essential components of γ-secretase can be nicastrin (nicastrin) and the products of the genes aph1 and pen-2. Approved substrates for γ-secretase are RDAs and protein family receptor Notch, but γ-secretase has specificity towards the hinge of the substrate, and may additionally be split membrane proteins not belonging to the family of APP and Notch.

Activity γ-secretase absolutely necessary for the production of Abete-peptides. It was shown how genetic methods, i.e. the ablation presenilin genes, and inhibition of low-molecular compounds is I. Because, according to the amyloid hypothesis of Alzheimer's production and deposition of Abete-peptides is the main cause of the disease, suggest that selective and effective inhibitors γ-secretase will be useful for the prevention and treatment of Alzheimer's disease.

Thus, the compounds according to the present invention will be useful for the treatment of Alzheimer's disease by blocking the activity γ-secretase and reducing or preventing the formation of various amyloidogenic of Abete-peptides.

Current state of research in the field of inhibition γ-secretase many publications, for example, the following publications:

Nature Reviews/Neuroscience, Vol.3, April 2002/281,

Biochemical Society Transactions (2002), Vol.30, part 4,

Current Topics in Medicinal Chemistry, 2002, 2, 371-383,

Current Medicinal Chemistry, 2002, Vol.9, No.11, 1087-1106,

Drug Development Research, 56, 211-227, 2002,

Drug Discovery Today, Vol.6, No.9, May 2001, 459-462,

FEBS Letters, 483, (2000), 6-10,

Science, Vol.297, 353-356, July 2002, and

Journ. of Medicinal Chemistry, Vol.44, No.13, 2001, 2039-2060.

The aim of the present invention are the compounds of formula I themselves, the use of compounds of the formula I and their pharmaceutically acceptable salts to obtain drugs intended for treatment of diseases associated with inhibition γ-secretase, obtaining these compounds, medicines on the basis of the e compounds according to the present invention, and receipt of them, and also the use of compounds of formula I for the control or prevention of Alzheimer's disease.

Another objective of the present invention are all kinds of optically pure enantiomers, racemates and diastereomeric mixture of compounds of formula I.

The most preferred compounds are such compounds in which R2represents lower alkyl.

Particularly preferred compounds of this group, in which R3is cycloalkyl and R4represents -(CH2)aboutis phenyl, substituted by a group dihalogen or-NR'r R", or means tetrahydropyran-4-yl, or means of tetrahydronaphthalen-1-yl, or means -(CH2)about-pyridin-3-yl.

This group includes the following specific compounds:

cyclohexylamin 7-bromo-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

cyclohexylamin 7-chloro-4-(4-chloro-2-terbisil)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

cyclohexylamin 7-bromo-4-(4-chloro-2-terbisil)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid and

cyclohexylamin 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid, or

cyclohexylamin 7-chloro-2-ethyl-3-oxo-4-(tetrahydropyran-4-yl)2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid, or

cyclohexylamin 7-chloro-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid and

cyclohexylamin 8 diethylamino-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid, or

cyclohexylamin 7-chloro-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

Other preferred compounds are such compounds in which R2means lower alkyl, where R3represents lower alkyl and R4represents -(CH2)aboutis phenyl, substituted by a group dihalogen or R NR'r", or

- (CR'R")aboutindol-3-yl, substituted lower alkoxy, or

- cycloalkyl, or

- (CH2)about-benzo[1,3]dioxol-5-yl, or

- 1-benzylpiperidine-4-yl.

This group includes the following specific compounds:

tert-butylamide 7-chloro-4-(2,6-diferensial)-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 7-chloro-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 4-(4-dimethylaminobenzoyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f]1,4]oxazepine-5-carboxylic acid,

tert-butylamine 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

tert-butylamide 9 ethoxy-2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

tert-butylamide 7-chloro-4-cyclopentyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

tert-butylamide 4-benzo[1,3]dioxol-5-ylmethyl-8 diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

tert-butylamide 4-(1-benzylpiperidine-4-yl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

Also preferred are such compounds in which R2represents lower alkyl, R3means -(CH2)m-funel and R4means cycloalkyl.

This group includes the following specific connection:

benzylated 7-chloro-4-cyclohexyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

Also preferred are such compounds in which R2represents lower alkyl, R3means -(CH2)m-C(O)O-lower alkyl, and R4means -(CH2)aboutis phenyl, substituted by a group of CF3or halogen.

This group includes the following specific compounds:

tre the-butyl ester {[7-chloro-2-isopropyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid and

tert-butyl ester {[7-bromo-4-(2-Chlorobenzyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid.

The compounds of formula I according to the present invention and their pharmaceutically acceptable salts may be obtained using methods known from the prior art, for example in accordance with the methods described below, such methods include:

a) interaction of the compounds of formula

with the compound of the formula

and with the compound of the formula

obtaining thus the compounds of formula

and if necessary, the conversion of the compounds obtained into pharmaceutically acceptable salts with acids (salt - addition products of acids).

The compounds of formula I can be obtained in accordance with the following scheme 1.

Scheme 1

In this scheme, R1-R4are as described above.

Total synthesis of the skeleton benzoxazepine described in Zhang et al.: J. Org. Chem. 1999, 64, 1074 ff. The corresponding o-hydroxybenzaldehyde (V) is subjected to interaction with alkilany complex ester of alpha-bromocarbons acid (VI) with getting this Olkiluoto of ester 2-formylphenoxy the acetic acid (VII), then amyraut, thus obtaining 2-formylphenoxy acid (II). This acid is subjected to interaction with the amine (III) and isonitrile (IV) according to reaction type IGO (Ugi) obtaining thus derived benzoxazepine formula I.

The parent compound (hydroxybenzaldehyde V α-poslednie esters (VI) are commercially available or can be obtained in accordance with known methods.

A detailed description can be found below and in the examples 1-196.

Some compounds of formula I can be converted into the corresponding acid salt additive, for example compounds containing the amino group.

The transformation is implemented by processing at least a stoichiometric amount of a suitable acid, such as chloromethane acid, Hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like acids, or stoichiometric amounts of an organic acid such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic (β-phenylacrylate) acid, mandelic acid, methansulfonate to the slot, econsultancy acid, n-toluensulfonate acid, salicylic acid and similar acids. Usually the free base is dissolved in an inert organic solvent such as diethyl simple ether, ethyl acetate, chloroform, ethanol or methanol and the like solvents, and add the acid in this solvent. The temperature maintained within the range from 0 to 50°C. the Obtained salt precipitates spontaneously or may be precipitated less polar solvent.

Acid additive salts of compounds of formula I can be converted into the corresponding free base by processing at least a stoichiometric equivalent of a suitable base, such as sodium hydroxide or potassium hydroxide, potassium carbonate, sodium bicarbonate, ammonia and similar reasons.

The compounds of formula I and their pharmaceutically acceptable additive salts have valuable pharmacological properties. In particular, it was found that the compounds according to the present invention can inhibit γ-secretase.

Compounds were investigated in accordance with the methods below.

Description of the research γ-secretase

The activity of test compounds can be evaluated in the study, according to which quantify proteomic the economic breakdown of the respective substrates under the action γ -secretase. It can be the study of cells, where, for example, substrate γ-secretase are merging in its cytoplasmic domain transcription factor. Cells transfection with the merged gene and gene-reporter, for example, luciferase beetles, fireflies, as a reinforcing agent such expression using a transcription factor. Splitting merged substrate under the influence of γ-secretase will lead to gene expression of the reporter, which may be subject to monitoring by using appropriate techniques. Activity γ-secretase can also be established by analysis of in vitro without the use of cells, according to which, for example, cell lysate containing complex γ-secretase, incubated with the appropriate RDA-derived substrate, which is cleaved with the formation of Abete-peptides. The number of produced peptides may be established by a special analysis by the method of ELISA (ELISA analysis). Cell line of neuronal nature secrete of Abete-peptides, which can be quantitatively analyzed using a special analysis using ELISA method. Treatment with compounds that inhibit γ-secretase, leads to a reduction in the amount of secreted Abete-pcidev that allows quantitative assessment of inhibi the Finance.

In vitro activity γ-secretase carried out using the membrane fraction of NC source γ-secretase and using recombinant substrate ARR. The latter consists of the C-terminal 100 amino acids of APP man, flushed with 6 x his-tag "tail" for cleaning, and is expressed in E. coli in the regulated expression vector, for example, such as pEt15. This recombinant protein corresponds to a truncated ARR-piece, which is formed after cleavage γ-secretaty extracellular domain and which is γ-Secretary substrate. The principles on which the study disclosed in Y.M. Li et al PNAS 97(11), 6138-6143 (2000). Cells NEC mechanically destroy and produce microsomal fraction by differential centrifugation. Membrane solubilizing in detergent (of 0.25% CHAPSO) and incubated with the substrate ARR. The Abete-peptides, which are produced by the cleavage of a substrate under the influence of γ-secretase register using specific research ELISA, as described in M. Brockhaus et al., Neuroreport 9(7), 1481-1486 (1998).

Preferred compounds are characterized by the value of the IC50˜and 1.0. The following table lists some of the characteristics of inhibition γ-secretase

Example No. IC50in vitroExample No.IC50in vitro
10,281150,97
100,971170,89
121,051220,96
160,891330,31
301,101340,18
360,771500,67
761,161600,46
860,831650,88
891,041780,81
960,621860,52

The compounds of formula I and pharmaceutical salts of the compounds of formula I can be used as medicines, for example in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, for example in the form of tablets, coated tablets, dragées, hard and soft gelatine capsules, solutions, emulsions or suspensions. In addition, the introduction can be effectively carried out rectally, for example in the form of suppositories, parenterally, e.g. in the form of solutions for injection.

Connection fo the formula I can be used together with pharmaceutically inert, inorganic or organic carriers for pharmaceutical compositions. As carriers for tablets, coated tablets, dragées and hard gelatin capsules can be used, for example, lactose, corn starch or its derivatives, talc, stearic acid or their salts and similar compounds. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like compounds. However, depending on the nature of the active compounds in the case of soft gelatin capsules the media may not be used. Suitable carrier materials for obtaining of solutions and syrups are, for example, water, polyols, glycerine, vegetable oil, and the like compounds. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like compounds.

Pharmaceutical compositions can also contain preservatives, soljubilizatory, stabilizers, agents for improving wettability, emulsifiers, sweeteners, tinted agents, agents for improving taste and smell, salts for regulating the osmotic pressure, buffers, masking agents or antioxidants. They can also contain the other therapeutically important compounds.

Drugs, containing a compound of formula I or its pharmaceutically acceptable salt and a therapeutically inert carrier are also an object of the present invention, as well as the way they are received, which includes the introduction of one or more compounds of formula I and/or pharmaceutically acceptable additive salts with an acid and, if necessary, one or more therapeutic substances in the composition of a medicinal product, together with one or more therapeutically inert carrier.

In accordance with the present invention the compounds of formula I and their pharmaceutically acceptable salts can be used for control or prevention of illnesses based on the inhibition activity γ-secretase, for example, for the control or prevention of such diseases as Alzheimer's disease.

The dosage may vary within wide limits and will, of course, be adjusted depending on the individual requirements in each particular case. In the case of oral administration the dosage for adults can vary from about 0.01 mg to about 1000 mg per day of the compounds of General formula I or the corresponding number of its pharmaceutically acceptable salts. The daily dosage may be entered as a single dose or divided into several d is C and in addition to this, you may be exceeded, if it is found that it is necessary according to the testimony.

Manufacturing of tablets (wet granulation)

PositionIngredientsmg tablet
5 mg25 mg100 mg500 mg
1.The compound of the formula I525100500
2.Anhydrous lactose DTG12510530150
3.Sta-Rx 150066630
4.Microcrystalline cellulose303030150
5.Magnesium stearate1111
The total number of167167167831

Method get

1. Mixed connection positions 1, 2, 3 and 4 and carry out granulation, using purified water.

2. Dry the granules at 50°C.

3. Pass the granules through a suitable device for grinding.

4. Add Aut substance according to the position 5 and stirred for three minutes, then pressed, using a suitable press.

Getting capsules

PositionIngredientsmg/capsule
5 mg25 mg100 mg500 mg
1. The compound of formula IA or IB525100500
2. Water lactose159123148-
3. Corn starch25354070
4. Talc10151025
5. Magnesium stearate1225
The total number of200200300600

The method of cooking

1. Mixed connection positions 1, 2 and 3 in a suitable mixer for 30 minutes.

2. Add connection according to the positions 4 and 5 and mix for 3 minutes.

3. Placed in suitable capsules

The following examples illustrate the present invention without limiting it. Examples are connected to the I, which may exist in the form of diastereoisomeric mixtures, racemates or in the form of optically pure compounds.

Example 1

Cyclohexylamin 7-bromo-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

a) 2-(4-Bromo-2-formylphenoxy)-3-matlakala acid

To a solution of 0.67 g (3.3 mmol) of 5-bromosalicylaldehyde in dimethylformamide (6 ml) is added in small portions 0.2 g of sodium hydride (60%suspension in mineral oil, 5 mmol) at 0°C. After stirring for about half an hour added slowly at room temperature of 1.05 g of ethyl ester of 2-bromo-3-methylmalonic acid (5 mmol) and the resulting mixture was stirred at 90°With during the night. After cooling, add ice water (25 ml) and 1N. the sodium hydroxide solution to an alkaline pH value of the solution. The resulting mixture was extracted three times with ethyl acetate, the combined organic layers dried (MgSO4) and evaporated. After filtration on a short column, the obtained residue receive ester, which is used in the next stage without additional purification.

The obtained ester is dissolved in 2 ml of methanol and add 2n. an aqueous solution of sodium hydroxide (2 ml). After stirring for 1 hour at room temperature the solvent is removed on a rotary evaporator. We use the t water (3 ml) and 4n. the solution chloroethanol acid to achieve rn. The resulting mixture was extracted three times with ethyl acetate, the combined organic layers dried (MgSO4) and evaporated, thus obtaining 0.125 g specified in the title compounds as a colorless oily substance. Mass spectrum, m/e (%): 299,0 (M-N+, 93); 301,0 (M-N+, 100).

b) Cyclohexylamin 7-bromo-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

To a solution of 0.12 g of 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid (0.4 mmol) in dimethyl sulfoxide (0.8 ml) is added 0,057 g 2,6-differentiatin (0.4 mmol) and 0.044 g of cyclohexyldiamine (0.4 mmol) and stirred the mixture overnight. Then add a 10%aqueous solution of sodium chloride (5 ml), after which the resulting mixture was extracted three times with ethyl acetate. The combined organic layers dried (MgSO4) and evaporated in vacuo. The resulting residue is purified using column chromatography with a mixture of ethyl acetate/hexane (1:4 ratio) as eluent, thus obtaining 0.03 g specified in the title compound as a pale yellow foam substance.

Mass spectrum, m/e (%): 535,3 (M+N+, 100); 537,3 (M+H+, 95).

Example 2

3,4-Dichloraniline 7-bromo-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound are obtained from comparable yield according to the procedure described in example 1 using, for example, 1,2-dichloro-4-socialemotional instead of cyclohexyldiamine at the stage b).

Mass spectrum, m/e (%): 629 (M+H2O+N+, 58); 630 (M+H2O+N+, 100).

Example 3

Cyclohexylamin 7-bromo-4-(2,6-diferensial)-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

2,6-Differentiatin (51 mg, 0.35 mmol) and cyclohexylethane (39 mg, 0.36 mmol) are added to a solution of 2-(4-bromo-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-3-methylmalonic acid (100 mg, 0.35 mmol) in methanol (0.5 ml). After stirring for 2 h at room temperature specified in the title compound (diastereoisomer 1 [has inhibitory activity], retention time of 2.09 min, 17.9 mg; diastereoisomer 2 [has inhibitory activity], retention time of 2.28 min, 7,3 mg, total yield 14%, mass spectrum: m/e=521,1 [M+H+]) was isolated from the reaction mixture by reversed-phase, preparative GHUR (liquid chromatography high resolution) (column YMC CombiPrep C18, 50×20 mm, solvent gradient 5-95% CH2CN in 0.1% TFU (aq.) during 6,0 min, λ=230 nm, flow rate 40 ml/is in.).

Example 4

Cyclohexylamin 7-bromo-2-cyclohexylmethyl-4-(2,6-diferensial)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=589,4 [M+H+]receive according to the method similar to that described in example 3 from 2-(4-bromo-2-formylphenoxy)-3-cyclohexylpropionic acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-3-cyclohexylpropionic acid) as a mixture of diastereoisomers.

Example 5

Cyclohexylamin 7-bromo-2-butyl-4-(2,6-diferensial)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=549,4 [M+H+]receive according to the method similar to that described in example 3 from 2-(4-bromo-2-formylphenoxy)hexanoic acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], from methyl (2-bromopropane) as a mixture of diastereoisomers.

Example 6

Cyclohexylamin 7-chloro-4-cyclohexyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=433,5 (M+N+)get the method similar to that described in example 3 from cyclohexylamine and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained is about technique, similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], ethyl 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 7

Cyclohexylamin 7-chloro-4-(2-Chlorobenzyl)-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=475,3 (M+N+)get the method similar to that described in example 3 from 2-chlorobenzylamino and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], from ethyl-2-bromo-n-butyrate and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 8

Cyclohexylamin 7-chloro-4-cyclobutyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=405,4 (M+N+)get the method similar to that described in example 3 from cyclobutylamine and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) as a mixture of diastereoisomers.

Example 9

Cyclohexylamin 7-chloro-4-cyclopentyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=419,4 (M+N+)get the method similar to that described in example 3 from cyclopentylamine and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 10

Cyclohexylamin 7-chloro-2-ethyl-3-oxo-4-(tetrahydropyran-4-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=435,4 (M+N+)get the method similar to that described in example 3 from 4-aminotetrahydrofuran and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 11

Cyclohexylamin 7-chloro-2-ethyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the header soy is inania, mass spectrum: m/e=509,3 (M+N+)get the method similar to that described in example 3 from 3-triptorelin and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 12

tert-Butylamide 7-chloro-4-(2,6-diferensial)-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=451,3 (M+N+)get the method similar to that described in example 3, from 2,6-differentiatin, tert-utilizationa and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 13

tert-Butylamide 7-chloro-4-cyclohexyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=407,4 (M+N+)get the method similar to that described in example 3 from cyclohexylamine, tert-utilizationa -(4-chloro-2-formylphenoxy)butyric acid (obtained according to the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 14

tert-Butylamide 7-chloro-4-(2-Chlorobenzyl)-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=449,3 (M+N+)get the method similar to that described in example 3 from 2-chlorobenzylamino, tert-utilizationa and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 15

tert-Butylamide 7-chloro-4-cyclobutyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=379,3 (M+N+)get the method similar to that described in example 3 from cyclobutylamine, tert-utilizationa and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-oil is Noah acid and 5-chlorosalicylaldehyde).

Example 16

tert-Butylamide 7-chloro-4-cyclopentyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=to 393.3 (M+N+)get the method similar to that described in example 3 from cyclopentylamine, tert-utilizationa and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1], of the ethyl ester of 2-bromo-n-butyrate and 5-chlorosalicylaldehyde) in the form of two partial diastereomers (both have inhibitory activity).

Example 17

tert-Butylamide 7-chloro-2-ethyl-3-oxo-4-(tetrahydropyran-4-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=409,3 (M+N+)get the method similar to that described in example 3 from 4-aminotetrahydrofuran, tert-utilizationa and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1] of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde).

Example 18

tert-Butylamide 7-chloro-2-ethyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e=483,5 (M+N+ )get the method similar to that described in example 3 from 3-triphtalocyaninine, tert-utilizationa and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1] of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) as a mixture of diastereoisomers.

Example 19

tert-Butyl ester {[7-chloro-4-(2,6-diferensial)-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum: m/e=509,3 (M+N+)get the method similar to that described in example 3, from 2,6-differentiatin, tert-butyl methyl ether isocyanurate acid and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1] of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde).

Example 20

tert-Butyl ether [(7-chloro-4-cyclohexyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl)amino]acetic acid

Specified in the title compound, mass spectrum: m/e=465,3 (M+N+)get the method similar to that described in example 3 from cyclohexylamine, tert-butyl methyl ether isocyanurate acid and 2-(4-chloro-2-formylphenoxy)butyric acid (p is obtained according to the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1] of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) as a mixture of diastereoisomers.

Example 21

tert-Butyl ether [(7-chloro-4-cyclobutyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl)amino]acetic acid

Specified in the title compound, mass spectrum: m/e=437,3 (M+N+)get the method similar to that described in example 3 from cyclobutylamine, tert-butyl methyl ether isocyanurate acid and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1] of the ethyl ester of 2-bromo-n-butyric acid and 5-chlorosalicylaldehyde) as a mixture of diastereoisomers.

Example 22

tert-Butyl ether [(7-chloro-4-cyclopentyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl)amino]acetic acid

Specified in the title compound, mass spectrum: m/e=451,4 (M+N+)get the method similar to that described in example 3 from cyclopentylamine, tert-butyl methyl ether isocyanurate acid and 2-(4-chloro-2-formylphenoxy)butyric acid (obtained by the method similar to the method of obtaining 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid [example 1] of the ethyl ester of 2-bromo-n-butyric acid and chlorosalicylaldehyde).

Example 23

Cyclohexylamin 7-chloro-4-(2,6-diferensial)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 449,14 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, (4-chloro-2-formylphenoxy)acetic acid and socialecological.

Example 24

tert-Butylamide 4-(2,6-diferensial)-6,8-dimethoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 449,18 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, (2-formyl-3,5-dimethoxyphenoxy)acetic acid and 2-isocyano-2-methylpropane.

Example 25

Cyclohexylamin 6,8-dimethoxy-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 479,25 (M+1), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, (2-formyl-3,5-dimethoxyphenoxy)acetic acid and socialecological.

Example 26

Cyclohexylamin 7-chloro-4-(4-chloro-2-terbisil)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 465,1 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, (4-chloro-formylphenoxy)acetic acid and socialecological.

Example 27

tert-Butylamide 4-(2,6-diferensial)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 461,2 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 28

tert-Butylamide 2-isopropyl-8-methoxy-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 493,2 (M+1), receive according to the method similar to that described in example 3 from 3-triphtalocyaninine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 29

tert-Butylamide 4-[2-(5-fluoro-1H-indol-3-yl)-1-methylethyl]-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 510,3 (M+1), receive according to the method similar to that described in example 3 from 2-(5-fluoro-1H-indol-3-yl)-1-methylethylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 30

Butylamide 4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 438,3 (M+1), get method is ke, similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 31

Cyclohexylamin 2-isopropyl-4-[2-(5-nitropyridine-2-ylamino)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 496,2 (M+1), receive according to the method similar to that described in example 3 from 2-(5-nitropyridine-2-ylamino)ethylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 32

tert-Butylamide 7-bromo-4-(N-fluoren-9-yl)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 505,1 (M+1), receive according to the method similar to that described in example 3 from N-fluoren-9-ylamine, (4-bromo-2-formylphenoxy)acetic acid and 2-isocyano-2-methylpropane.

Example 33

tert-Butylamide 8 diethylamino-4-(N-fluoren-9-yl)-2-methyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 512,3 (M+1), receive according to the method similar to that described in example 3 from N-fluoren-9-ylamine, 2-(5-diethylamino-2-formylphenoxy)propionic acid and 2-isocyano-2-methylpropane.

Example 34

tert-Butylamide 7-chloro-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Pointed to by the e in the title compound, mass spectrum, m/e: 465,2 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 35

Cyclohexylamin 7-chloro-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 491,2 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 36

7-Chloro-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid butylamide

Specified in the title compound, mass spectrum, m/e: 472,2 (M+1), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 37

Cyclohexylamin 7-chloro-2-isopropyl-4-(2-methylsulfonylamino)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 439,2 (M+1), receive according to the method similar to that described in example 3 from 2-methylsulfonylamino, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 38

tert-Butylamide 7-chloro-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,45-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: RUB 482.2 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 39

Cyclohexylamin 7,9-dichloro-4-(2,6-diferensial)-2-methyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 497,11 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(2,4-dichloro-6-formylphenoxy)propionic acid and socialecological.

Example 40

tert-Butylamide, 7-bromo-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 509,12 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 41

Cyclohexylamin 7-bromo-4-(2-Chlorobenzyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 533,2 (M+1), receive according to the method similar to that described in example 3 from 2-chlorobenzylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 42

Benzylamine 4-(4-chloro-2-terbisil)-8-diet the laminitis-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 552,4 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 43

7-Bromo-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid butylamide

Specified in the title compound, mass spectrum, m/e: 509,1 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 44

tert-Butylamide 7-bromo-4-cyclohexyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 487,2 (M+23), receive according to the method similar to that described in example 3 from cyclohexylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 45

Cyclohexylamin 7-bromo-2-isopropyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 567,2 (M+1), receive according to the method similar to that described in example 3 from 3-triphtalocyaninine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 46

4-(1-Benzylpiperidine-4-yl)-7-bromo-2-from ropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid butylamide

Specified in the title compound, mass spectrum, m/e: 556,21 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 47

tert-Butylamide 7,9-dichloro-2-methyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 497,15 (M+23), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(2,4-dichloro-6-formylphenoxy)propionic acid and 2-isocyano-2-methylpropane.

Example 48

tert-Butylamide 7-bromo-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 535,17 (M+23), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 49

Cyclohexylamin 7-bromo-4-(1-carbarnoyl-2-phenylethyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 556,17 (M+1), receive according to the method similar to that described in example 3 from 2-amino-3-phenylpropionamide, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and isocyanic is clohexane.

Example 50

Butylamide 7-bromo-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 535,17 (M+23), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 51

tert-Butylamide 7-bromo-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 474,13 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 52

Cyclohexylamin 7-bromo-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 500,15 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 53

Butylamide 7-bromo-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 474,13 (M+1), receive according to the method similar to that described in example 3 of the PI is one-3-ylmethylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 54

tert-Butylamide 7-bromo-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 526,16 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 55

Cyclohexylamin 7-bromo-2-isopropyl-3-oxo-4-(2,2,2-triptorelin)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 491,11 (M+1), receive according to the method similar to that described in example 3, from 2,2,2-triptorelin, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 56

Butylamide 7-bromo-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 526,16 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 57

tert-Butylamide 7-bromo-4-[2-(5-fluoro-1H-indol-3-yl)-1-methylethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e:580,2 (M+23), get the method similar to that described in example 3 from 2-(5-fluoro-1H-indol-3-yl)-1-methylethylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 58

tert-Butylamide 4-cyclohexyl-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 417,27 (M+1), receive according to the method similar to that described in example 3 from cyclohexylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 59

Cyclohexylamin 4-(3,5-dichlorobenzyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 541,17 (M+23), receive according to the method similar to that described in example 3 of the 3.5-dichloroaniline, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 60

Cyclohexylamin 4-(2-Chlorobenzyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 485,22 (M+1), receive according to the method similar to that described in example 3 from 2-chlorobenzylamino, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 61

Cyclohexylamin 4-(2,6-diferensial)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetr is hydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 487,23 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 62

Butylamide 2-isopropyl-8-methoxy-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 493,22 (M+1), receive according to the method similar to that described in example 3 from 3-triphtalocyaninine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 63

tert-Butylamide 4-(1-benzylpiperidine-4-yl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 508,31 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 64

Cyclohexylamin 4-(1-benzylpiperidine-4-yl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 534,33 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

P the emer 65

Butylamide 4-(1-benzylpiperidine-4-yl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 508,31 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 66

tert-Butylamide 2-isopropyl-8-methoxy-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 487,27 (M+23), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 67

Cyclohexylamin 2-isopropyl-8-methoxy-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 513,28 (M+23), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 68

Butylamide 2-isopropyl-8-methoxy-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 465,27 (M+1), we shall have the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 69

tert-Butylamide 2-isopropyl-8-methoxy-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 426,23 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 70

tert-Butylamide 4-benzo[1,3]dioxol-5-ylmethyl-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 469,23 (M+1), receive according to the method similar to that described in example 3 from benzo[1,3]dioxol-5-ylmethylamino, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 71

Cyclohexylamin 2-isopropyl-8-methoxy-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 452,25 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 72

Cyclohexylamin 4-benzo[1,3]dioxol-5-ylmethyl-2-isopropyl-8-methox the-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 495,24 (M+1), receive according to the method similar to that described in example 3 from benzo[1,3]dioxol-5-ylmethylamino, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 73

tert-Butylamide 4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 478,26 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 74

4-Cyclohexylamin [2-(1H-indol-3-yl)ethyl]-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 504,28 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 75

Cyclohexylamin 4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 457,22 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 76

tert-Buti is amide 4-(1-benzylpiperidine-4-yl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 478,3 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 77

Cyclohexylamin 4-(1-benzylpiperidine-4-yl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 504,32 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 78

tert-Butylamide 2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 396,22 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 79

Cyclohexylamin 2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 422,24 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 80

Cyclohexylamin 4-(3-dimethylamino-2,2-dimethylpropyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 444,32 (M+1), receive according to the method similar to that described in example 3, 2,2,N',N'-tetramethylchroman-1,3-diamine, 2-(2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 81

tert-Butylamide 4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 448,25 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 82

Butylamide 4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 448,25 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 83

tert-Butylamide 2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 478,26 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 84

Cyclohexylamin 2-isopropyl-4-[2-(5-methox what-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 504,28 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 85

Cyclohexylamin 7-chloro-4-(2-Chlorobenzyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 489,16 (M+1), receive according to the method similar to that described in example 3 from 2-chlorobenzylamino, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 86

Cyclohexylamin 7-chloro-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 517,3943 (M+23), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 87

Cyclohexylamin 4-(2-benzylmalonate)-7-chloro-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 537,2 (M+23), receive according to the method similar to that described in example 3 from 2-benzylmethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 88

tert-Butylamide 7-chloro-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 430,18 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 89

Cyclohexylamin 7-chloro-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 456,2 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 90

Butylamide 7-chloro-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 430,18 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 91

Cyclohexylamin 7-chloro-4-(3-diethylaminopropyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 478,28 (M+1), receive according to the method similar to that described in example 3, N',N'-diethylpropane-1,3-diamine, 2-(-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 93

Cyclohexylamin 7-chloro-2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 538,24 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 93

tert-Butylamide 4-(4-chloro-2-terbisil)-7-methoxy-3-oxo-2-phenyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 511,17 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, (2-formyl-4-methoxyphenoxy)phenylacetic acid and 2-isocyano-2-methylpropane.

Example 94

Butylamide 7-chloro-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 482,21 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 95

tert-Butylamide 7-chloro-2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 512,22 (M+1), get the technique similar to the description of the Noi in example 3, from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 96

Cyclohexylamin 7-chloro-4-(4-chloro-2-terbisil)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 507,15 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 97

Cyclohexylamin 7,9-dichloro-4-(4-chloro-2-terbisil)-2-methyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 513,08 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, 2-(2,4-dichloro-6-formylphenoxy)propionic acid and socialecological.

Example 98

Cyclohexylamin 4-(N-fluoren-9-yl)-7-methoxy-2-methyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 497,24 (M+1), receive according to the method similar to that described in example 3 from N-fluoren-9-ylamine, 2-(2-formyl-4-methoxyphenoxy)propionic acid and socialecological.

Example 99

tert-Butylamide 4-(3,5-dichlorobenzyl)-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Pointed to by the e in the title compound, mass spectrum, m/e: 534,22 (M+1), receive according to the method similar to that described in example 3 of the 3.5-dichloroaniline, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 100

Cyclohexylamin 4-(3,5-dichlorobenzyl)-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 560,24 (M+1), receive according to the method similar to that described in example 3 of the 3.5-dichloroaniline, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 101

Cyclohexylamin 8 diethylamino-2-isopropyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 560,3 (M+1), receive according to the method similar to that described in example 3 from 3-triphtalocyaninine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 102

Cyclohexylamin 8 diethylamino-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 545,34 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 103

<> Cyclohexylamin 4-(4-dimethylaminobenzoyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 494,29 (M+1), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 104

tert-Butylamide 4-(2-Chlorobenzyl)-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 500,3 (M+1), receive according to the method similar to that described in example 3 from 2-chlorobenzylamino, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 105

tert-Butylamide 8 diethylamino-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 502,3 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 106

Cyclohexylamin 4-(2-Chlorobenzyl)-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: to 526.4 (M+1), get the technique similar to opican the th in example 3, 2-chlorobenzylamino, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 107

Cyclohexylamin 8 diethylamino-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 528,4 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 108

Butylamide 4-(2-Chlorobenzyl)-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 500,4 (M+1), receive according to the method similar to that described in example 3 from 2-chlorobenzylamino, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 109

Butylamide 8 diethylamino-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 502,4 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 110

tert-Butylamide 4-cyclohexyl-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the connection, mass spectrum, m/e: 458,4 (M+1), receive according to the method similar to that described in example 3 from cyclohexylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 111

tert-Butylamide 8 diethylamino-2-isopropyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 534,4 (M+1), receive according to the method similar to that described in example 3 from 3-triphtalocyaninine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 112

Butylamide 8 diethylamino-2-isopropyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 534,4 (M+1), receive according to the method similar to that described in example 3 from 3-triphtalocyaninine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 113

tert-Butylamide 4-(1-benzylpiperidine-4-yl)-8-diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo|f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 549,4 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 114

tert-Butylamide 8 diethylamino-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 506,4 (M+1), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 115

Cyclohexylamin 8 diethylamino-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 532,4 (M+1), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 116

Butylamide 8 diethylamino-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 506,4 (M+1), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 117

tert-Butylamide 4-benzo[1,3]dioxol-5-ylmethyl-8 diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the header is the connection, mass spectrum, m/e: 510,4 (M+1), receive according to the method similar to that described in example 3 from benzo[1,3]dioxol-5-ylmethylamino, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 118

Cyclohexylamin 4-benzo[1,3]dioxol-5-ylmethyl-8 diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 536,4 (M+1), receive according to the method similar to that described in example 3 from benzo[1,3]dioxol-5-ylmethylamino, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 119

Butylamide 4-benzo[1,3]dioxol-5-ylmethyl-8 diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 510,4 (M+1), receive according to the method similar to that described in example 3 from benzo[1,3]dioxol-5-ylmethylamino, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 120

tert-Butylamide 8 diethylamino-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 519,4 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylp is OPANA.

Example 121

Butylamide 8 diethylamino-2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 549,4 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 122

Butylamide 4-(4-dimethylaminobenzoyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 468,4 (M+1), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 123

tert-Butylamide 4-(4-chloro-2-terbisil)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 477,2 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 124

Cyclohexylamin 4-(4-chloro-2-terbisil)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 503,3 (M+1), get the method, analogichnoi described in example 3, from 4-chloro-2-forbindelsen, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 125

Butylamide 4-(4-chloro-2-terbisil)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 477,3 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 126

Cyclohexylamin 7-bromo-4-(2,6-diferensial)-2-methyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 529,2 (M+23), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(4-bromo-2-formylphenoxy)propionic acid and socialecological.

Example 127

tert-Butyl ester {[4-(1-benzylpiperidine-4-yl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 536,4 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 128

tert-Butyl ether ({7-chloro-2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-carbonyl}amino)acetic acid

Specified in the title compound, mass spectrum, m/e: 592,2 (M+23), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 129

tert-Butyl ether ({7-chloro-2-isopropyl-4-[2-(4-nitrophenyl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl}amino)acetic acid

Specified in the title compound, mass spectrum, m/e: 546,2 (M+1), receive according to the method similar to that described in example 3 from 4-nitrophenylacetylene, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 130

tert-Butylamide 4-(1H-benzoimidazol-2-ylmethyl)-9-ethoxy-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 479,3 (M+1), receive according to the method similar to that described in example 3 of benzoimidazol-2-ylmethylamino, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 131

Cyclohexylamin 4-(1H-benzoimidazol-2-ylmethyl)-9-ethoxy-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 505,3 (M+1), receive according to the method similar to that described in example 3 of benzoimidazol-2-ylmethyl the ina, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 132

Benzylated 7-chloro-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 499,2 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 133

Benzylated 7-chloro-4-cyclohexyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 455,3 (M+1), receive according to the method similar to that described in example 3 from cyclohexylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 134

tert-Butyl ester {[7-chloro-2-isopropyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 577,18 (M+23), receive according to the method similar to that described in example 3 from 3-triphtalocyaninine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 135

Benzylamine 4-(1-benzylpiperidine-4-yl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the header with the unity, mass spectrum, m/e: 512,4 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 136

Benzylamine 4-(1-benzylpiperidine-4-yl)-7-chloro-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 546,3 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 137

tert-Butyl ester {[4-(1-benzylpiperidine-4-yl)-7-chloro-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 570,3 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 138

tert-Butyl ester {[4-(1-carbarnoyl-2-phenylethyl)-7-chloro-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 566,21 (M+23), receive according to the method similar to that described in example 3 from 2-amino-3-phenylpropionamide, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl EPE is and isocyanurates acid.

Example 139

Benzylated 7-chloro-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 516,3 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 140

Benzylated 7-chloro-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: consists 528.3 (M+23), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 141

tert-Butyl ester {[4-(2-benzylmalonate)-7-chloro-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 569,3 (M+23), receive according to the method similar to that described in example 3 from 2-benzylmethylamine, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 142

tert-Butyl ester {[7-chloro-2-isopropyl-4-(2-methylsulfonylamino)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass SPECT is, m/e: 493,3 (M+23), receive according to the method similar to that described in example 3 from 2-methylsulfonylamino, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 143

tert-Butyl ester {[7-chloro-2-isopropyl-3-oxo-4-(4-sulfamoylbenzoyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 588,3 (M+23), receive according to the method similar to that described in example 3 from 4-aminomethylenemalonate, 2-(4-chloro-2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 144

tert-Butyl ether ({2-isopropyl-4-[2-(5-nitropyridine-2-ylamino)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl}amino)acetic acid

Specified in the title compound, mass spectrum, m/e: consists 528.3 (M+1), receive according to the method similar to that described in example 3 from 2-(5-nitropyridine-2-ylamino)ethylamine, 2-(2-formylphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 145

Cyclohexylamin 4-(2,6-diferensial)-9-ethoxy-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 501,3 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(2-ethoxy-6-formylphenol the si)-3-methylmalonic acid and socialecological.

Example 146

tert-Butylamide 4-(4-dimethylaminobenzoyl)-9-ethoxy-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 482,4 (M+1), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 147

Cyclohexylamin 4-(1-benzylpiperidine-4-yl)-9-ethoxy-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 548,4 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 148

Cyclohexylamin 4-(4-dimethylaminobenzoyl)-9-ethoxy-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 529.4 M. (M+23), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 149

Cyclohexylamin 9 ethoxy-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 518,4 (M+1)are given by the method similar to that described in example 3, 2-(1H-indol-3-yl)ethylamine, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 150

tert-Butylamide 9 ethoxy-2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 522,4 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 151

Cyclohexylamin 9 ethoxy-2-isopropyl-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 548,4 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 152

(2,6-Dimetilfenil)amide 7-bromo-4-(2-Chlorobenzyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 555,2 (M+1), receive according to the method similar to that described in example 3 from 2-chlorobenzylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 153

(2,6-Dimetilfenil)amide 7-bromo-4-cyclohexyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]on azepin-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 513,2 (M+1), receive according to the method similar to that described in example 3 from cyclohexylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 154

(2,6-Dimetilfenil)amide 7-bromo-2-isopropyl-3-oxo-4-(2-thiophene-2-retil)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 541,2 (M+1), receive according to the method similar to that described in example 3 from 2-thiophene-2-ylethylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 155

(2,6-Dimetilfenil)amide 4-(1-benzylpiperidine-4-yl)-7-bromo-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 604,3 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 156

(2,6-Dimetilfenil)amide 7-bromo-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 522,2 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

the example 157

tert-Butylamide 7-bromo-4-carbamoylmethyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 440,2 (M+1), receive according to the method similar to that described in example 3 from 2-aminoacetyl, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 158

tert-Butylamide 7-bromo-4-furan-2-ylmethyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f)[1,4]oxazepan-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 485,1 (M+23), receive according to the method similar to that described in example 3 from n-furan-2-ylmethylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 159

7-Bromo-2-isopropyl-3-oxo-4-(2-vinylcyclopropyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid cyclohexylamine

Specified in the title compound, mass spectrum, m/e: 525,2 (M+1), receive according to the method similar to that described in example 3 from 2-phenylcyclopropane, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 160

tert-Butylamide 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 538,3 (M+23), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzoyl is mine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 161

Butylamide 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 516,3 (M+1), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 162

Cyclohexylamin 4-(2-benzylmalonate)-7-bromo-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 559,2 (M+1), receive according to the method similar to that described in example 3 from 2-benzylmethylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 163

Cyclohexylamin 7-bromo-2-isopropyl-4-(2-methylsulfonylamino)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 483,2 (M+1), receive according to the method similar to that described in example 3 from 2-methylsulfonylamino, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 164

Cyclohexylamin 7-bromo-2-isopropyl-4-[2-(4-nitrophenyl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the header of the group mass spectrum, m/e: 558,3 (M+1), receive according to the method similar to that described in example 3 from 4-nitrophenylacetylene, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 165

Cyclohexylamin 7-bromo-4-(4-chloro-2-terbisil)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 551,2 (M+1), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 166

Cyclohexylamin 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: made 564.3 (M+23), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 167

Cyclohexylamin 7-bromo-2-isopropyl-3-oxo-4-(2-oxitetraciclina-3-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 493,2 (M+1), receive according to the method similar to that described in example 3 from 3-aminopiperidin-2-it, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 168

Cyclohexylamin 7-bromo-2-isopropyl-4-[2-(5-n is terpyridine-2-ylamino)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 574,2 (M+1), receive according to the method similar to that described in example 3 from 2-(5-nitropyridine-2-ylamino)ethylamine, 2-(4-bromo-2-formylphenoxy)-3-methylmalonic acid and socialecological.

Example 169

tert-Butyl ester {[7-bromo-4-(4-chloro-2-terbisil)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 635,1 (M+23), receive according to the method similar to that described in example 3 from 4-chloro-2-forbindelsen, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 170

(2,6-Dimetilfenil)amide 7-bromo-2-isopropyl-9-methoxy-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 634,3 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 171

(2,6-Dimetilfenil)amide 7-bromo-2-isopropyl-9-methoxy-4-[2-(5-nitropyridine-2-ylamino)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 626,3 (M+1), get the technique similar to opican the th in example 3, from 2-(5-nitropyridine-2-ylamino)ethylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 172

Benzylamine 4-(4-dimethylaminobenzoyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 502,4 (M+1), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(2-formyl-4-methoxyphenoxy)-3-methylmalonic acid and socialemotional.

Example 173

(2,6-Dimetilfenil)amide 4-(4-dimethylaminobenzoyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 515,4 (M+1), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(2-formyl-4-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 174

Cyclohexylamin 2-tert-butoxymethyl-7-chloro-4-(2,6-diferensial)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 557,21 (M+23), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 3-tert-butoxy-2-(4-chloro-2-formylphenoxy)propionic acid and socialecological.

Example 175

Cyclohexylamin 2-tert-butoxymethyl-7-chloro-4-furan-2-ylmethyl-3-OK, what about the-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 511,2 (M+23), receive according to the method similar to that described in example 3 from furan-2-ylmethylamino, 3-tert-butoxy-2-(4-chloro-2-formylphenoxy)propionic acid and socialecological.

Example 176

Cyclohexylamin 7-bromo-4-(2,6-diferensial)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 565,2 (M+1), receive according to the method similar to that described in example 3, from 2,6-differentiatin, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 177

tert-Butylamide 4-(1-benzylpiperidine-4-yl)-7-bromo-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 586,3 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 178

Cyclohexylamin 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 594,3 (M+23), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-matilal the Noah acid and socialecological.

Example 179

Butylamide 4-(1-benzylpiperidine-4-yl)-7-bromo-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 586,3 (M+1), receive according to the method similar to that described in example 3 from 1-benzylpiperidine-4-ylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 180

Butylamide 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 568,3 (M+23), receive according to the method similar to that described in example 3 from 4-dimethylaminobenzylidene, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and 1-isocyanurate.

Example 181

Cyclohexylamin 7-bromo-2-isopropyl-9-methoxy-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: us $ 530, 3 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 182

tert-Butylamide 7-bromo-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 556,3 (M+1), produces the t according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 183

tert-Butylamide 7-bromo-2-isopropyl-9-methoxy-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 586,3 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-2-methylpropane.

Example 184

Cyclohexylamin 7-bromo-2-isopropyl-9-methoxy-4-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 612,3 (M+1), receive according to the method similar to that described in example 3 from 2-(5-methoxy-1H-indol-3-yl)ethylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and socialecological.

Example 185

Cyclohexylamin 7-bromo-2-isopropyl-9-methoxy-4-[2-(5-nitropyridine-2-ylamino)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 604,3 (M+1), receive according to the method similar to that described in example 3 from 2-(5-nitropyridine-2-ylamino)ethylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and isocyano is clohexane.

Example 186

tert-Butyl ester {[7-bromo-4-(2-Chlorobenzyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 617,2 (M+23), receive according to the method similar to that described in example 3 from 2-chlorobenzylamino, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 187

tert-Butyl ether [(7-bromo-4-carbamoylmethyl-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl)amino]acetic acid

Specified in the title compound, mass spectrum, m/e: 550,2 (M+23), receive according to the method similar to that described in example 3 from 2-aminoacetyl, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 188

tert-Butyl ester {[7-bromo-4-(3,5-dichlorobenzyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino} acetic acid

Specified in the title compound, mass spectrum, m/e: 651,07 (M+23), receive according to the method similar to that described in example 3 of the 3.5-dichloroaniline, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 189

tert-Butyl ester {[7-bromo-2-isopropyl-9-methoxy-3-oxo-4-(2-vinylcyclopropyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 587,2 (M+1), receive according to the method similar to that described in example 3 from 2-phenylcyclopropane, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 190

tert-Butyl ester {[7-bromo-2-isopropyl-9-methoxy-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid

Specified in the title compound, mass spectrum, m/e: 623,3 (M+23), receive according to the method similar to that described in example 3 of 1,2,3,4-tetrahydronaphthalen-1-ylamine, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 191

tert-Butyl ether [(7-bromo-2-isopropyl-9-methoxy-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl)amino]acetic acid

Specified in the title compound, mass spectrum, m/e: 562,2 (M+1), receive according to the method similar to that described in example 3, from pyridine-3-ylmethylamino, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 192

tert-Butyl ether [(4-benzo[1,3]dioxol-5-ylmethyl-7-bromo-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl)amino]acetic acid

Specified in the title compound, by weight of the spectrum, m/e: 627,3 (M+23), receive according to the method similar to that described in example 3 from benzo[1,3]dioxol-5-ylmethylamino, 2-(4-bromo-2-formyl-6-methoxyphenoxy)-3-methylmalonic acid and tert-butyl methyl ether isocyanurate acid.

Example 193

(2,6-Dimetilfenil)amide 9-ethoxy-4-[2-(1H-indol-3-yl)ethyl]-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 540,4 (M+1), receive according to the method similar to that described in example 3 from 2-(1H-indol-3-yl)ethylamine, 2-(2-ethoxy-6-formylphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

Example 194

Benzylated 8 diethylamino-2-isopropyl-4-(1-naphthalene-1-retil)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 564,4 (M+1), receive according to the method similar to that described in example 3 from 1-naphthalene-1-ylethylamine, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 195

Benzylated 8 diethylamino-4-furan-2-ylmethyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum, m/e: 490,4 (M+1), receive according to the method similar to that described in example 3 from n-furan-2-ylmethylamino, 2-(5-diethylamino-2-formylphenoxy)-3-methylmalonic acid and socialemotional.

Example 19

(2,6-Dimetilfenil)amide 2-isopropyl-8-methoxy-4-(1-naphthalene-1-retil)-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid

Specified in the title compound, mass spectrum: m/e: 559,3 (M+23), receive according to the method similar to that described in example 3 from 1-naphthalene-1-ylethylamine, 2-(2-formyl-5-methoxyphenoxy)-3-methylmalonic acid and 2-isocyano-1,3-xylene.

1. Compounds of General formula

where R1represents hydrogen, C1-C6alkoxy, halogen, or-NR'r R";

n denotes 1 or 2;

R', R" independently of one another represent hydrogen or C1-C6alkyl;

R2represents hydrogen, C1-C6alkyl, -(CH2)m-C3-C7-cycloalkyl, -(CH2)m-phenyl, or -(CH2)m-O-C1-C6alkyl;

m means 0, 1 or 2;

R3represents a C1-C6alkyl, -(CH2)m-C(O)O-C1-C6alkyl, C3-C7cycloalkyl or -(CH2)mis phenyl, which is unsubstituted or substituted by one or two substituents selected from the group consisting of halogen or C1-C6of alkyl;

R4represents -(CH2)ois phenyl, which is unsubstituted or substituted by one or two of the substituents, which is selected from the group consisting of halogen, trifloromethyl, -R NR'r", nitro or-SO2NH2or represents-C3-C7cycloalkyl, unsubstituted or substituted phenyl, or represents -(CR'R")about-heterocyclyl, which are selected from the group consisting of tetrahydropyran-4-yl, pyridine-3-yl, indol-3-yl, optionally substituted with halogen or a group C1-C6alkoxy, or thiophene-2-yl, furan-2-yl, -NH-pyridin-2-yl, optionally substituted by nitro group, or benzoimidazol-2-yl, 2-oxitetraciclina, 1-benzyl-piperidine-4-yl, or benzo[1,3]dioxol-5-yl, or represents tetrahydronaphthalen-1-yl, CHR'-naphthalene-2-yl, fluoren-9-yl, (CH2)about-S-lower alkyl, (CH2)about-S-benzyl, (CH2)o-C(O)NH2, (CH2)oNR'r R", CH[C(O)NH2]-(CH2)about-phenyl, (CH2)about-CF3, (CH2)o-CR'R"-CH2-NR'r R"; o is 1 or 2;

and their pharmaceutically acceptable acid salt additive, except for the following connections:

ventilated 4-benzyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 4-benzyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

ventilated 4-cyclohexyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]-oxazepine-5-carboxylic acid,

butylamide 4-qi is logical-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]-oxazepine-5-carboxylic acid.

2. Compounds according to claim 1, where R2represents a C1-C6alkyl.

3. Compounds according to claim 2, where R3represents a C3-C7cycloalkyl, and R4represents -(CH2)aboutis phenyl, substituted by a group dihalogen or NR'r R".

4. Compounds according to claim 3, which represent the following connections:

cyclohexylamin 7-bromo-4-(2,6-diferensial)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid, cyclohexylamine 7-chloro-4-(4-chloro-2-terbisil)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f|[1,4]oxazepan-5-carboxylic acid, cyclohexylamine 7-bromo-4-(4-chloro-2-terbisil)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid or cyclohexylamin 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

5. Compounds according to claim 2, where R3represents a C3-C7cycloalkyl and R4represents tetrahydropyran-4-yl.

6. The compound according to claim 5, which is cyclohexylamin 7-chloro-2-ethyl-3-oxo-4-(tetrahydropyran-4-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

7. Compounds according to claim 2, where R3is cycloalkyl, and R4represents tetrahydronaphthalen-1-yl.

8. Compounds according to claim 7, which represent sleduyusheye:

cyclohexylamin 7-chloro-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid, or

cyclohexylamin 8 diethylamino-2-isopropyl-3-oxo-4-(1,2,3,4-tetrahydronaphthalen-1-yl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

9. Compounds according to claim 2, where R3represents a C3-C7cycloalkyl and R4represents -(CH2)about-pyridin-3-yl.

10. The connection according to claim 9, which is a

cyclohexylamin 7-chloro-2-isopropyl-3-oxo-4-pyridin-3-ylmethyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

11. Compounds according to claim 2, where R3represents lower alkyl and R4represents -(CH2)aboutis phenyl, substituted by a group dihalogen or NR'r R".

12. Compounds according to claim 11, which represent the following connections:

tert-butylamide 7-chloro-4-(2,6-diferensial)-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 7-chloro-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid,

butylamide 4-(4-dimethylaminobenzoyl)-2-isopropyl-8-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxaze the ine-5-carboxylic acid, or

tert-butylamide 7-bromo-4-(4-dimethylaminobenzoyl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

13. Compounds according to claim 2, where R3represents a C1-C6alkyl, and R4represents -(CR'R")indol-3-yl, substituted C1-C6alkoxy.

14. The connection 13, which represents a tert-butylamide 9 ethoxy-2-isopropyl-4-[2-(5-methoxy-1 H-indol-3-yl)ethyl]-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

15. Compounds according to claim 2, where R3represents a C1-C6alkyl, and R4represents a C3-C7-cycloalkyl.

16. The connection 13, which represents

tert-butylamide 7-chloro-4-cyclopentyl-2-ethyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

17. Compounds according to claim 2, where R3represents a C1-C6alkyl, and R4represents -(CH2)about-benzo[1,3]dioxol-5-yl.

18. The connection 17, which represents

tert-butylamide 4-benzo[1,3]dioxol-5-ylmethyl-8 diethylamino-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

19. Compounds according to claim 2, where R3represents a C1-C6alkyl, and R4is a 1-benzyl-piperidine-4-yl.

20. The connection according to claim 19, which represents

tert-butylamide, 4-(1-benzylpiperidine-4-yl)-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

21. Compounds according to claim 2, where R3represents -(CH2)m-Feyel, and R4represents a C3-C7cycloalkyl.

22. Connection item 21, which represents

benzylated 7-chloro-4-cyclohexyl-2-isopropyl-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carboxylic acid.

23. Compounds according to claim 2, where R3represents a group -(CH2)m-C(O)O-(C1-C6alkyl), and R4represents -(CH2)aboutis phenyl, substituted by a group of CF3or halogen.

24. Compounds according to item 23, which represent the following connections:

tert-butyl ester {[7-chloro-2-isopropyl-3-oxo-4-(3-trifloromethyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino} acetic acid, or

tert-butyl ester {[7-bromo-4-(2-Chlorobenzyl)-2-isopropyl-9-methoxy-3-oxo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-5-carbonyl]amino}acetic acid.

25. Drug containing one or more compounds according to any one of claims 1 to 24 and pharmaceutically acceptable excipients.

26. Drug on A.25 for the treatment of Alzheimer's disease.

Priority items:

19.05.2003 - claims 1 to 26.



 

Same patents:

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I): possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.

35 cl, 16 sch, 13 tbl, 43 ex

The invention relates to new derivatives of 4.1-benzoxazepin-2-she is of the formula (I), where R1lower alkyl, substituted by at least one optionally substituted hydroxyl group, R2and R3independently of one another is hydrogen or phenyl, which is substituted by 1-3 substituents selected from the group consisting of lower C1-C4alkoxygroup; X is a bond, methylene group or a linking group with a chain length of 1-7 atoms, selected from the group consisting of -(CH2)m-E-(CHR6)n-, where m and n = 1 or 2 independently from each other: E-bond or an oxygen atom, -NR5-, -CONR7-, where R5-methylsulphonyl, R6and R7independently of one another(i) hydrogen, (ii) lower alkyl, which is not substituted or substituted by substituents selected from the group consisting of piperidine, indolyl, possibly esterified carboxypropyl, (iii) benzyl, Y is optionally substituted carbarnoyl and/or the substituents on the N atom of carbamoyl, taken together, form a ring which may be substituted, or tetrazolyl, or piperidine, and the ring And is substituted by 1-3 substituents selected from the group consisting of atoms of Halogens or their salts

The invention relates to new derivatives of acetic acid, the method of production thereof, pharmaceutical preparations containing such compounds and to the use of these compounds in the manufacture of pharmaceutical preparations

The invention relates to a derivative of 4.1-benzoxazepin-2, or their salts, which are useful for inhibiting stvalentines and fungus growth, and to their use

The invention relates to a condensed heterocyclic compounds or their salts and inhibitors of squalene synthetase containing these compounds as an effective component

The invention relates to new compounds with dual activity, namely the activity of inhibiting angiotensin converting enzyme, and the activity of inhibiting neutral endopeptidase and to methods of producing these compounds

FIELD: chemistry.

SUBSTANCE: invention relates to the compound with formula (I) or to its tartrate salt. The invention also relates to application of the composition as well as the method of inhibiting of monoamine receptor activation to inverse agonist and anti-dyskinesia agent in the combination with inverse agonist.

EFFECT: production of the new biologically active compound having inverse agonist activity of serotonin receptor.

54 cl, 7 ex, 3 tbl

FIELD: medicine; neurology.

SUBSTANCE: invention concerns treatment methods for neurodegenerative brain condition, such as Parkinson' and Alzheimer's disease, and methods of nerve cells death and degeneration. A therapeutically effective quantity of the composition containing brimonidin or its pharmaceutically acceptable salt is administered to a mammal.

EFFECT: treatment or prevention of nerve cells degeneration due to neuroprotective effect of brimonidin in respect of brain neurons.

6 cl, 1 ex, 1 dwg, 2 tbl

FIELD: medicine; neurology.

SUBSTANCE: individuals susceptible to eicosapentaenoic acid (EPA) treatment are identified by defining of CAG repetition number in Huntingtin gene within 36-45. To prevent and heal Huntington's disease (HD) symptom development, the persons with CAG repetition number within 36 to 45 are administered with EPA in any biologically viable form.

EFFECT: reduced brain tissue loss for patients and prevention of symptom development for persons prone to that; improved treatment results for patients with this genetic disease form.

16 cl, 20 ex

FIELD: medicine, pharmacology.

SUBSTANCE: medicine composition, possessing nootropic activity, represents 40% ethanolic extract of herb material, comprising grass of cottonweed, roots of Baikal scutellaria, sprouts of Pentaphylloides fruticosa, rhizome of officinal burnet, roots of deviating peony, fruits of rose, and grass of knotweed, cut to 1-3 mm pieces. The extraction is carried out at raw material to extragent proportion 1:10 and temperature 18-20°C.

EFFECT: medicine develops antiamnesic effect.

6 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, particularly to drug preparation of deanol aceglumate. An injection drug formulation is proposed, containing ingredients as follows: deanol aceglumate, sugars (sorbitol, xylitol, and others), aminoacetic versene, optionally succinic acid, malic acid, and N-dimethylaminoethanol. It was demonstrated, that the injection drug formulation of deanol aceglumate shows neuroprotective action and can be applied to acute cerebral circulation injury, preventing from cerebral ischemia damage.

EFFECT: generation of stable and sterile injection drug formulation of deanol aceglumate, suitable for applying in diabetes cases.

3 cl, 4 ex, 2 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention concerns new enantiomers of (+)-and(-)-trans-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl-1H-pyrido[4,3-b]indol and method of its obtaining. Being optical antipodes for each other, enantiomers exhibit different biological activity and can be applied as an active component in pharmaceutical compositions of nootropic and sedative action for treatment of different individual status of patients.

EFFECT: obtaining of the claimed compound.

1 ex, 5 tbl, 5 cl

FIELD: chemistry.

SUBSTANCE: invention concerns malonamide derivatives of the formulae (IA) or (IB) , and pharmaceutically acceptable acid additive salts of them, where R1, R1',(R2)1,2,3, R3, R4, R14, L, and are such as described in this invention. Also the invention concerns a medicine with inhibition effect on γ-secretase, which can be applied in treatment of Alzheimer's disease.

EFFECT: obtaining new malonamide derivatives with beneficial biological properties.

17 cl, 188 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention concerns application of selective agonist of alpha-2B or alpha-2B/2C adrenoreceptors for manufacture of medical product (MP), applied for treatment of neurodegenerative cerebrum conditions. Applicability of selective agonist of alpha-2B or alpha-2B/2C adrenoreceptors as MP is first shown for diseases causing damaged neurons with endings approaching to black substance or moving away.

EFFECT: products have improved efficiency.

9 cl, 1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention concerns application of polypeptide FGF-9 or its biologically active fragment to produce medical product for multiple sclerosis treatment. Polypeptide can be 94-95% identical to sequence from amino acid 1 to amino acid 208 of human FGF-9, presented on fig. 3 (SEQ ID NO: 5).

EFFECT: invention stimulates myelination, proliferation and persistency of oligodendrocyte neurons, improves nervous regeneration.

6 cl, 9 dwg, 3 tbl, 3 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to application as ligands of 5-NT6 receptor azaheterocyclic compositions of general formula 1 or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and/or hydrates , where R2 and R3 independently represent substitute of amides chosen from hydrogen; substituted carbonyl; substituted aminocarbonyl; substituted aminothiocarbonyl; substituted sulphonyl; C1-C5-alkyl, optionally substituted with C6-C10-aryl, optionally substituted with heterocyclil, C6-C10-arylaminocarbonyl, C6-C10- arylaminothiocarbonyl, C5-C10-azaheteroaryl, optionally substituted with carboxyl, nitrile group; optionally substituted with aryl; R1k are 1 to 3 independent substitutes to cyclic system chosen from hydrogen, optionally substituted C1-C5-alkyl, C1-C5-alkyloxy, C1-C5-alkenyl, C1-C5- alkenyl, halogen, trifluoromathyl, nitrile, carboxyl, optionally substituted heterocyclil, substituted sulphonyl, optionally substituted carboxyl; dashed line with accompanying continuous line () corresponds to single or double bond; n=1.2 or 3. Invention also concerns a pharmaceutical formulation, production method and tabletted, capsulated or injection medical product in pharmaceutically acceptable package.

EFFECT: agent has improved efficiency.

17 cl, 8 tbl, 5 ex, 1 dwg

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I): possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.

35 cl, 16 sch, 13 tbl, 43 ex

FIELD: medicine.

SUBSTANCE: drugs contain H-SGK kinase having lysine substituted by arginine in position 127.

EFFECT: enhanced effectiveness in treating states for which sodium channel and/or Na+, K+, 2Cl- cocarrier activity is to be reduced.

2 cl, 6 dwg

FIELD: organic chemistry.

SUBSTANCE: invention relates to derivatives of general formula I , wherein R1, R2 and R3 are independently H or C1-C4-alkyl; Ar is condensed thiophene or pyridine ring optionally substituted with one or more substituents selected from C1-C4-alkyl, C1-C4-alkyloxy, C1-C4-alkyloxy(C1-C4)-alkyl, CF3, halogen, nitro, cyano, NR4R5 NR4COR6 and CONR4R5 (R4 and R5 are independently H or C1-C4-alkyl; or R4 and R5 together with adjacent nitrogen atom form 5- or 6-membered saturated heterocyclic ring; R6 is C1-C4-alkyl): A is residue of 4-7-membered saturated heterocyclic ring optionally containing nictogen atom and optiomally substituted with 1-3 substituents selected from C1-C4-alkyl, C1-C4-alkyloxy, hydroxyl, halogen, and alkoxy; and pharmaceutical composition based on the same; with the proviso, that compound of formula I wherein A represents condensed [3,2-f]pyridine ring; each R1, R2 and R3 represents H, and A represents (CH2)3. Also described are application of abovementioned derivatives, pharmaceutical composition enhancing of synaptic response mediated with AMPA receptors in CNS based on the same, and method for treatment of neurological diseases or mental disorders.

EFFECT: new compounds with value biological properties.

7 cl, 1 tbl, 12 ex

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