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US 2001/0044538 A1Published application
p38 MAP kinase inhibitors
AssigneeSyntex (U.S.A.) Inc.
InventorsSoan Cheng, David Michael Goldstein, Teresa Alejandra Trejo Martin, Eric Brian Sjogren
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of Formula (I) 1 that are p-38 MAP kinase inhibitors, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
Claims53
A compound selected from the group of compounds represented by Formula (I):
- 66
- wherein:
- R1 is heteroaryl;
- - - - - - - represents a bond between either B and CR1 or Q and CR1 such that:
- (i) when - - - - - - is between Q and —CR1— then:
- B is nitrogen;
- R2 is aryl;
- and
- Q is —CR— wherein:
- R is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, acyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, nitro, cyano, amino, monosubstituted amino, disubstituted amino, acylamino, sulfonylamino, —OR5 (where R5 is hydrogen, alkyl, heteroalkyl or heterocyclylalkyl), —COO7 (where R7 is hydrogen or alkyl) or —CONR′R″ (where R′ and R″ independently represent hydrogen, alkyl or heteroalkyl);
- and
- (ii) when - - - - - - is between B and —CR1— then:
- B is carbon;
- R2 is aryl or heteroaryl;
- and
- Q is —NR4—, —O—, or —S— wherein:
- R4 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, acyl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonyl, —OR5 (where R5 is hydrogen, alkyl, heteroalkyl or heterocyclylalkyl), —SO2R″ (where R″ is alkyl, amino, monosubstituted amino or disubstituted amino), —CONR′R″ (where R′ and R″ independently represent hydrogen, alkyl or heteroalkyl), -(alkylene)-Z or -(alkylene)-CO-(alkylene)-Z wherein:
- Z is cyano;
- —COOR7 where R7 is hydrogen or alkyl;
- —CONR8R9 where R8 is hydrogen or alkyl, R9 is alkoxy or -(alkylene)-COOR7, or R8 and R9 together with the nitrogen atom to which they are attached form a heterocycle;
- —C(═NR10)(NR11R12) where R10, R11 and R12 independently represent hydrogen or alkyl, or R10 and R11 together are —(CH2)n— where n is 2 or 3 and R12 is hydrogen or alkyl;
- or
- —COR13 where R13 is alkyl, heteroalkyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl;
- and
- 67
- where:
- R6 is hydrogen, alkyl, heteroalkyl, heterocyclylalkyl, halo, cyano, nitro, amino, monosubstituted amino, disubstituted amino, —COOR14, -(alkylene)-COOR (where R14 is hydrogen or alkyl), —CONR15R16 (where R15 and R16 independently represent hydrogen or alkyl, or R15 and R16 together with the nitrogen atom to which they are attached form a heterocycle), —S(O)nR17 (where n is an integer from 0 to 2 and R17 is alkyl, amino, monosubstituted amino or disubstituted amino), —OR18 (where R18 is hydrogen, alkyl, heteroalkyl or heterocyclylalkyl), —NRC(O)R′ [where R is hydrogen, alkyl or hydroxyalkyl and R″ is hydrogen, alkyl, cycloalkyl or -(alkylene)-X where X is hydroxy, alkoxy, amino, alkylamino, dialkylamino, heterocyclyl or —S(O)nR′ (where n is 0 to 2 and R′ is alkyl)], —NRSO2R″ [where R is hydrogen or alkyl and R″ is alkyl or -(alkylene)-X where X is hydroxy, alkoxy, amino, alkylamino, dialkylamino or —S(O)nR′ (where n is 0 to 2 and R′ is alkyl)];
- and R3 is hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylthio, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, halo, cyano, nitro, amino, monosubstituted amino, disubstituted amino, acylamino, sulfonylamino, —OR19 (where R19 is hydrogen, alkyl, heteroalkyl or heterocyclylalkyl), —COOR20 (where R20 is hydrogen or alkyl), —CONR21R22 (where R21 and R22 independently represent hydrogen, alkyl or heteroalkyl, or R21 and R22 together with the nitrogen atom to which they are attached form a heterocycle), —S(O)nR23 (where n is an integer from 0 to 2 and R23 is alkyl, heteroalkyl, amino, monosubstituted amino or disubstituted amino), -(alkylene)-Z″ or -(alkylene)-CO-(alkylene)-Z″ wherein:
- Z″ is cyano;
- —COOR24 where R24 is hydrogen or alkyl;
- —CONR25R26 where R25 and R26 independently represent hydrogen or alkyl, or R25 and R26 together with the nitrogen atom to which they are attached form a heterocycle;
- —C(═NR27)(NR28R29) where R27, R28 and R29 independently represent hydrogen or alkyl, or R27 and R28 together are —(CH2)n— where n is 2 or 3 and R29 is hydrogen or alkyl;
- or
- —COR30 where R30 is alkyl, heteroalkyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl;
- and
- their pharmaceutically acceptable salts, prodrugs, individual isomers, and mixtures of isomers, provided that both R3 and R6 are not either amino, monosubstituted amino or disubstituted amino.
33 more elements
A compound of Formula (IIa):
- 74
- wherein:
- One of Z1 and Z2 is nitrogen and the other is —CR6— wherein R6 is hydrogen, alkyl, or alkoxy;
- or both Z1 and Z2 are nitrogen such that:
- (a) when Z1 or Z2 is nitrogen and the other is —CR6— then:
- (i) when Y is halo, then —Q—R is —NH—C(R1)═CH(R2) or —N═C(CH3)(R1);
- (ii) when Y is —C(R2)═C(R1)OX (where X is p-CH3C6H4SO2—, CH3SO2—, or CF3SO2—), then —Q—R is nitro or amino;
- and
- (iii) when Y is —C(O)R2, then —Q—R is —NHC(O)R1, —OCH2CO2R, or —SCH2R1 where:
- R is alkyl;
- R1 is heteroaryl;
- and
- R2 is aryl or heteroaryl;
- and
- (b) when Z1 and Z2 both are nitrogen then:
- Y is halo and —Q—R is —NH—C(R1)═CH(R2) where R1 and R2are as defined above;
- and
- R3 is hydrogen, alkyl, halo, or alkoxy.
15 more elements
A compound of Formula (IIb):
- 75
- wherein:
- Z3 is nitrogen and Z4 is —CR3— wherein R3 is hydrogen, alkyl, or alkoxy;
- or Z4 is nitrogen and Z3 is —CH—;
- such that:
- (a) when Y is hydrogen, then —Q—R is —NH—N═C(R1)CH2(R2);
- and
- (b) when Y is —C(O)R2, then —Q—R is —OCH2CO2R or —SCH2R1 where:
- R is alkyl;
- R1 is heteroaryl;
- and
- R2 is aryl or heteroaryl;
- and
- R is hydrogen, alkyl, halo, or alkoxy.
11 more elements
Dependencies are inferred from the claim text.