DERIVATIVES OF INDOLE ORDER AS p38 KINASE INHIBITORS Russian patent published in 2006 - IPC C07D401/06 C07D403/06 A61K31/437 A61P19/02 A61P29/00 

Abstract RU 2278115 C2

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of indole of the formula (1): and their pharmaceutically acceptable salts wherein represents a double bond; Z1 represents nitrogen atom (N), -CR5 wherein R5 represents hydrogen atom (H), (C1-C6)-alkyl, hydroxy-group (OH),(C1-C6)-alkoxy-group or halogen atom; Z2 at position 2 represents CR1 and at position it represents CA wherein each R1 means independently (C1-C6)-alkyl; A represents -Wi-COXjY wherein Y means -COR2 wherein R2 means -OR, -NR2, -NRNR2 or -NROR wherein each R represents independently hydrogen atom (H), (C1-C6)-alkyl, or (C5-C6)-heteroaryl comprising one or two heteroatoms in ring chosen from atoms N, O and S wherein each of them is substituted with one or some groups chosen from -NR'2, -OR', -COOR', (C1-C6)-alkyl, -CN, =O, and -SR' wherein each R' represents hydrogen atom (H) or (C1-C6)-alkyl and wherein two R or R' jointed to the same nitrogen atom (N) can form 3-8-membered ring chosen from the group comprising piperazine ring, morpholine ring, thiazolidine ring, oxazolidine ring, pyrrolidine ring, piperidine ring, azacyclopropane ring, azacyclobutane ring and azacyclooctane ring and wherein indicated ring can be substituted additionally with (C1-C6)-alkyl or -COO-(C1-C6)-alkyl; X represents unsubstituted (C1-C6)-alkylene, or Y means imidazole substituted with methyl group; i = 0; j = 0 or 1; R7 means hydrogen atom (H) or (C1-C6)-alkyl, -SOR, -SO2R, -RCO, -COOR, (C1-C6)-alkyl-COR, -CONR2, -SO2NR2,-CN, -OR, (C1-C6)-alkyl-SR, (C1-C6)-alkyl-OCOR, (C1-C6)-alkyl-COOR, (C1-C6)-alkyl-CN, or (C1-C6)-alkyl-CONR2 wherein each R represent independently hydrogen atom (H), (C1-C6)-alkyl or aryl that is substituted optionally with halogen atom, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; or R7 represents methoxymethyl, methoxyethyl, ethoxymethyl, benzyloxymethyl or 2-methoxyethyloxymethyl; each R3 represent independently halogen atom, (C1-C6)-alkyl, -OR, -SR or -NR2 wherein R represents hydrogen atom (H) or (C1-C6)-alkyl; n = 0-3; L1 means -CO; L2 means (C1-C4)-alkylene optionally substituted with one or two groups of (C1-C4)-alkyl; each R4 is chosen independently from the group comprising (C1-C6)-alkyl, halogen atom, -OR, -NR2, -SR, -SOR, -SO2R, -RCO, -COOR, -CONR2, -SO2NR2 wherein each R represents independently hydrogen atom (H) or (C1-C6)-alkyl; or R4 represents =O; m = 0-4; Ar means aryl group substituted with from 0 to 5 substitutes chosen from the group comprising (C1-C6)-alkyl, halogen atom, -OR, -NR2, -SR, -SOR, -SO2R, -RCO, -COOR, -CONR2 and -SO2NR2 wherein each R represents independently hydrogen atom (H) or (C1-C6)-alkyl. Compounds of the formula (I) possess the inhibitory activity with respect to p38-α kinase that allows their using as components of the pharmaceutical composition.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

63 cl, 3 tbl, 9 sch, 16 ex

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RU 2 278 115 C2

Authors

Mavunkel Babu Dzh.

Chakravarti Sarvadzhit

Perumattam Dzhon Dzh.

Dugar Sandip

Lu Kving

Liang Ksi

Dates

2006-06-20Published

2000-05-19Filed