Substituted cyclic amine inhibitors metalloprotease

 

The invention relates to substituted cyclic aminoven compounds of formula (I)where Ar represents thienyl, substituted pyridine, phenyl unsubstituted or substituted with halogen, hydroxy, alkoxy, C1-C4the alkyl, phenyloxy, NO2or phenyl; R1is NHOR2where R2is hydrogen; W is one or more hydrogen atoms; Y is independently one or more members of the group consisting of hydroxy, SR3, alkoxy, NR6R7where R6and R7independently selected from hydrogen, alkyl, pyridylethyl, SO2R8, COR9or R6and R7can be combined with the formation of the ring containing the nitrogen to which they relate, formulaswhere Y' is CH2Oh , SO2; R3represents hydrogen, alkyl, aryl, benzothiazolyl, pyrazinyl, N-methylimidazole; R8represents C1-C4alkyl, phenyl; R9represents hydrogen, alkyl, phenyl; Z is hydrogen; n = 1, and its optical isomer, diastereoisomer, or enantiomer, or its pharmaceutically acceptable salt. The compounds I are inhibitors of metalloprotease that allows I. 3 S. and 8 C.p. f-crystals, 15 PL.

Description text in facsimile form (see graphic part)

Claims

1. Substituted cyclic amine compounds having a structure corresponding to formula (I)

where Ar represents thienyl, substituted pyridine, phenyl unsubstituted or substituted with halogen, hydroxy, alkoxy, C1-C4the alkyl, phenyloxy, NO2or phenyl;

R1is NHOR2where R2represents hydrogen;

W represents one or more hydrogen atoms;

Y is independently one or more members of the group consisting of hydroxy, SR3, alkoxy, NR6R7where R6and R7independently selected from hydrogen, alkyl, pyridylethyl, SO2R8, COR9or R6and R7can be combined with the formation of the ring containing the nitrogen to which they relate, formulas

where Y’ is CH2Oh , SO2;

R3represents hydrogen, alkyl, aryl, benzothiazolyl, pyrazinyl, N-methylimidazole;

R8represents C1-C4alkyl, phenyl;

R9is water timer, or its pharmaceutically acceptable salt.

2. Connection on p. 1, which has the structure of a

where Ar represents thienyl, substituted pyridine, phenyl unsubstituted or substituted with halogen, hydroxy, alkoxy, C1-C4the alkyl, phenyloxy, NO2or phenyl;

R1is NHOR2where R2represents hydrogen;

W represents one or more hydrogen atoms;

Y is independently one or more members of the group consisting of hydroxy, SR3, alkoxy, NR6R7where R6and R7independently selected from hydrogen, alkyl, pyridylethyl, SO2R8, COR9or R6and R7can be combined with the formation of the ring containing the nitrogen to which they relate, formulas

where Y’ is CH2Oh , SO2;

R3represents hydrogen, alkyl, aryl, benzothiazolyl, pyrazinyl, N-methylimidazole;

R8represents C1-C4alkyl, phenyl;

R9represents hydrogen, alkyl, phenyl;

Z represents hydrogen;

n is 1,

and its optical isomer, diastereoisomer, or enantiomer, or its pharmaceutically acceptable salt.

3. Alogena, hydroxy, alkoxy, C1-C4the alkyl, phenyloxy, NO2or phenyl.

4. The compound according to any one of the preceding paragraphs, in which Ar is phenyl, substituted hydroxy, alkoxy, NO2or halogen.

5. The compound according to any one of the preceding paragraphs, in which Y is independently one or more members of the group consisting of hydroxy, alkoxy, NR6R7where R6and R7independently selected from hydrogen, alkyl, pyridylethyl, SO2R8, COR9.

6. The compound according to any one of the preceding paragraphs, in which Y is independently one or more members of the group consisting of hydroxy, and NR6R7where R6and R7independently selected from hydrogen, alkyl, pyridylethyl, SO2R8, COR9.

7. The compound according to any one of the preceding paragraphs, which is selected from:

(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(4S)-hydroxypyrrolidine;

(1N)-4-methoxybenzenesulfonyl-(2S)-N-hydroxycarboxylic-(4R)-hydroxypyrrolidine;

(1N)-4-methoxybenzenesulfonyl-(2S)-N-hydroxycarboxylic-(4S)-hydroxypyrrolidine;

(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(4S)-ethoxypyrrolidine;

(1N)-4-methoxybenzylideneamino-(4R)-(2-mercaptobenzothiazole)pyrrolidine;

(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(4S)-[(1N)-methyl-2-mercaptoimidazole]pyrrolidine;

(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(4R)-[(1N)-methyl-2-mercaptoimidazole]pyrrolidine;

(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(4S)-phenoxypyridine;

(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(4S)-mercaptopyrimidine;

(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(4S)-(n-hexylamino)pyrrolidine;

(1N)-4-methoxybenzenesulfonyl-(2R)-hydroxycarboxylic-(4S)-tierralinda;

(±)-(1N)-4-methoxybenzenesulfonyl-(2R)-N-hydroxycarboxylic-(3S)-phenylpyrrolidine;

(1N)-4-methylphenylsulfonyl-(2R)-N-hydroxycarboxylic-(4S)-hydroxypyrrolidine;

(1N)-3,4-dimethoxyphenylacetone-(2R)-N-hydroxycarboxylic-(4R)-hydroxypyrrolidine;

(1N)-(2-nitro-4-methoxybenzenesulfonyl)-(2R)-N-hydroxycarboxylic-(4R)-hydroxypyrrolidine;

(1N)-4-n-butoxyaniline-(2R)-N-hydroxycarboxylic-(4R)-hydroxypyrrolidine;

(1N)-4-n-butoxyaniline-(2R)-N-hydroxycarboxylic-(4S)-hydroxypyrrolidine;

(1N)-4-n-butoxyaniline-(2R)-N-hydroxycarboxylic-(4S)-(2-mercaptobenzothiazole)pyrrolidine;

(1N)-(2-nitro-4-methoxybenzenesulfonyl)-(2R)-N-hydroxycarbonyl-phenoxyphenylacetic-(2R)-N-hydroxycarboxylic-(4R)-hydroxypyrrolidine:

(1N)-4-n-butoxyaniline-(2R)-N-hydroxycarboxylic-(4R)-hydroxypyrrolidine:

(1N)-4-n-butoxyaniline-(2R)-N-hydroxycarboxylic-(4S)-hydroxypyrrolidine:

(1N)-4-n-butoxyaniline-(2R)-N-hydroxycarboxylic-(4S)-morpholinopropan:

9. The compound according to any one of the preceding paragraphs for the manufacture of a pharmaceutical composition inhibiting metalloprotease.

10. The method of prevention or treatment of diseases associated with increased activity of metalloprotease in a mammal by introducing an effective amount of a compound according to any one of paragraphs.1-9.

11. Method of inhibiting metalloprotease in the treatment of musculoskeletal disorders or cachexia by introducing to a mammal in need of such treatment, an effective amount of an inhibitor of metalloprotease according to any one of paragraphs.1-9.

 

Same patents:

The invention relates to compounds of formula (I)

< / BR>
in which Ar1denotes a heterocyclic group, which represents a pyrazole which may be substituted by one or more radicals R1, R2or R3; Ar2denotes phenyl, naphthyl or tetrahydronaphthyl, each of which optionally is substituted by one to three groups R2; L denotes a saturated or unsaturated, branched or unbranched carbon C1-C10chain; in which one or more methylene groups are optionally independently replaced by O, NH or S, and in which the linking group is optionally substituted by 0-2 of doxography; Q has a value selected from a range of: a) phenyl, naphthyl, pyridine, imidazole, Piran, etc. b) tetrahydropyran, morpholine, thiomorpholine, thiomorpholine and t

The invention relates to new derivatives of benzothiadiazole, benzoxazoles and benzodiazines formula I in free base form or in the form of a pharmaceutically acceptable acid salt additive that can be used as an anxiolytic drug in the treatment of any condition, which is associated with increased endogenous levels of CRF or in which violated the regulation of the hPa system (hypothalamic - pituitary), or various diseases that are caused by CRF1or the manifestation of which contributes CRF1such as arthritis, asthma, allergies, anxiety, depression, etc

The invention relates to amide derivative of the formula I

< / BR>
where R3represents (1-6C)alkyl or halogen; m is 0, 1, 2 or 3; R1represents hydroxy, halogen, trifluoromethyl, nitro, amino, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino, di-[(1-6C)alkyl] amino, amino-(2-6C)alkylamino, (1-6C)alkylamino-(2-6C)alkylamino etc

The invention relates to new derivatives of phenyl - and aminobenzenesulfonamide formula

< / BR>
where a denotes (R1SO2NR2-), (R3R60NSO2NR2-); X represents-NH-, -CH2- or-OCH2-; Y represents 2-imidazoline, 2-oxazoline or 4-imidazole; R1means (NISS

The invention relates to new imidazole derivative of formula I and II

< / BR>
or

< / BR>
where 1, m, r, s, and t = 0 or 1; n = 1 or 2; provided that when 1 and m = 0, n = 2 Y - SO2or CH2; Z - CR12, NR32SO; NR13, NR36CO., OCONR15, SO2NR14; R1selected from the group consisting of hydrogen, alkyl, or aralkyl, the symbola single or double bond, R7, R8selected from the group consisting of hydrogen, aryl, - CN, halogen, and U-R44group, where U = O and R44and R11selected from the group consisting of hydrogen, alkyl, aralkyl, aryl; R32selected from the group consisting of hydrogen, lower alkyl, unsubstituted or substituted phenyl, and tanila; R9, R10, R12, R13, R14, R15, R36, R57and R58represent hydrogen or lower alkyl; one of R, S and T is CH2or CH(CH2)pQ, where Q denotes NR57R58; where p = 0,1 or 2; provided that when Y is - SO2, R11cannot be hydrogen; its enantiomers, diastereoisomers, pharmaceutically priemel the

The invention relates to new indole derivative of the formula I

< / BR>
where R1- H, halogen, CN; R2and R3the same or different is H, C1-C4alkyl, halogen; R4- H, C1-C4alkyl; And means cyanoaniline, aminosulphonylphenyl, aminopyridine, aminopyrimidine, halogenopyrimidines or cianciarulo group, provided that if all R1, R2and R3- N, when both R2and R3- N or when ring A - aminosulphonylphenyl group and both R1and R2the halogen atoms is excluded; and, in addition, when the ring a represents cyanophenyl group, 2-amino-5-pyridyloxy group or 2-halogen-5-pyridyloxy group, and R1represents a cyano or halogen group, at least one of R2and R3must not be a hydrogen atom

The invention relates to new derivatives of arylpiperazines General formula I, where X Is O or S1- C1-C4alkoxy, CF3, R2- C1-C6alkyl, saturated WITH3-C6cycloalkyl; heteroseksualci of 3-6 ring atoms, heteroatom of which is O, S or N, optionally N-substituted WITH1-C6by alkyl; phenyl, optionally substituted by F, Cl, Br, NH2CH3CF3or OCH3; 5-6-membered heteroaryl, the heteroatom of which is O, S or N, possibly substituted, or condensed heteroaromatic system containing 9 atoms

Arylalkylamine // 2201923
The invention relates to arylalkylamines formula I, where B - A, OA, NH2, CF3, aromatic heterocycle selected from pyridine, pyrazine and pyrimidine; Q is absent or denotes alkylene with 1-6 carbon atoms; R1and R2independently from each other represent OR5where R5- Or cycloalkyl with 3-7 carbon atoms; And the alkyl with 1-10 carbon atoms, and their physiologically acceptable salts

The invention relates to 2-substituted 4,5-dailyedition General formula (I), where R1- 4-pyridyl; R2- phenyl, naphthas-1-yl or naphthas-2-yl, which optionally can contain up to 5 substituents selected from halogen; R3is hydrogen; R4- pyridyl, optionally substituted with halogen or amino group

The invention relates to 1-methyl-5-alkylsulfonyl-, 1-methyl-5-alkylsulfonyl - 1-methyl-5-alkylthiomethyl pyrazolylborate and herbicide tool based on them

The invention relates to a derivative of 1,2,4-thiadiazole, substituted in the 5-position of General formula I, in which X Is N; R1- C1-6alkyl; R2is hydrogen, R3, R4and R5each independently selected from hydrogen; trifloromethyl;is Ar2, Ar2CH2or Het2; AG2is phenyl; Het2is a monocyclic heterocycle selected from thiadiazolyl, pyridinyl, pyrimidinyl or pyrazinyl, their N-oxide forms, the pharmaceutically acceptable acid additive salts and stereochemical isomeric forms

The invention relates to derivatives of 1-(N-phenyliminomethyl)piperazine of the formula I, where R is H, alkyl -, cycloalkyl-substituted cycloalkyl-WITH or monocyclic heteroaryl-CO; R1Is h or lower alkyl; R2- halogen, alkoxy, phenoxy, NO2, CN, acyl, NH2, NH(acyl), alkyl-SO2NH, alkoxycarbonyl, NH2WITH, (alkyl)NHCO (alkyl)2NCO, (acyl)NHCO, CF3or polyporaceae; benzyl or mono - or bicyclic aryl, or heteroaryl, all of which are optionally substituted

The invention relates to new substituted pyrazolylborate General formula (I) in which R1-R6have the meanings given in the description of the invention

The invention relates to a method for producing derivatives of imidazole of formula A, where R1represents a substituted heterocycle, R4is phenyl, optionally substituted, R2represents the алкилN3, -(CR10R20)nOR9further as stated in the description

The invention relates to 4-hydroxy-3-chinainternational and hydrazides of General formula (I), where a represents a-CH2- or-NH-, a R1, R2, R3and R4such as defined in the claims
Up!