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US 2003/0207900 A1Published application
Bicyclic pyridine and pyrimidine p38 kinase inhibitors
AssigneeRoche Palo Alto LLC
InventorsJian Jeffrey Chen, Nolan James Dewdney, Christoph Martin Stahl
Life of this patent
Estimating the term…
Abstract
The present invention discloses compounds corresponding to formula 1 wherein A, R, X, Y, R, R1 and R2 are as defined above, pharmaceutical formulations, methods of making and uses thereof.
Claims44
A compound represented by formula I:
- 58
- wherein:
- A is N or CH;
- R1 is hydrogen, alkyl or arylalkyl;
- R2 is alkyl, heteroalkyl, (R″)2NCO-alkylene- (where each R″ is independently hydrogen or alkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- X is O, NR3 or S, wherein R3 is hydrogen, alkyl or aryl;
- and
- Y is a bond, O, NR′, C(═O), CH(OR′), CH(R′), or S(O)n, wherein n is 0, 1, or 2;
- and R′ is hydrogen or alkyl;
- and
- R is aryl or heteroaryl;
- or an isomer, a pharmaceutically acceptable salt, an ester or a prodrug thereof.
9 more elements
A process for producing a compound of the formula:
- 59
- wherein
- A is N or CH;
- R is aryl or heteroaryl;
- R1 is hydrogen, alkyl or arylalkyl;
- R2 is alkyl, heteroalkyl, (R″)2NCO-alkylene- (where each R″ is independently hydrogen or alkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- X is O, NR3 or S, wherein R3 is hydrogen, alkyl or aryl;
- and
- Y1 is C(═O), CH(OR′), or CH(R′), wherein R′ is hydrogen or alkyl,
- said process comprising:
- a) contacting a thioether of the formula:
- 60
- wherein
- A, R, X and Y1 are as defined above;
- and
- Ra is alkyl or aryl,
- with an oxidizing agent to produce an alkylsulfone compound of the formula:
- 61
- and
- b) contacting the alkylsulfone compound with an amine compound of the formula NHR1R2 to produce the compound of Formula IA.
17 more elements
A process of producing a compound of Formula IB:
- 62
- wherein
- A is N or CH;
- R is aryl or heteroaryl;
- R1 is hydrogen, alkyl or arylalkyl;
- R2 is alkyl, heteroalkyl, (R″)2NCO-alkylene- (where each R″ is independently hydrogen or alkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- X is O, NR3 or S, wherein R3 is hydrogen, alkyl or aryl;
- and
- Y1 is O, NR′, or S(O)n, wherein n is 0, 1, or 2;
- and R′ is hydrogen or alkyl;
- said process comprising contacting a compound of the formula:
- 63
- wherein
- A, X, R1 and R2 are as defined above;
- and
- Z is halide,
- with an aromatic or heteroaromatic compound of the formula HY1—R, optionally in the presence of a base, to produce the compound of Formula IB, where Y1 is O, NR′, or S, and when Y1 is S, said process further comprising:
- contacting the compound of Formula IB, where Y1 is S with an oxidizing agent to produce the compound of Formula IB, where Y1 is S(O)n, where n is 1 or 2.
15 more elements
A process of producing a compound of Formula IC:
- 64
- wherein
- n is 0, 1 or 2;
- A is N or CH;
- R is aryl or heteroaryl;
- R1 is hydrogen, alkyl or arylalkyl;
- R2 is alkyl, heteroalkyl, (R″)2NCO-alkylene- (where each R″ is independently hydrogen or alkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- and
- X is O, NR3 or S, wherein R3 is hydrogen, alkyl or aryl;
- said process comprising:
- (a) contacting a compound of the formula:
- 65
- wherein
- R1, R2, A and X are as defined above;
- and
- Z is halide,
- with an organometallic reagent;
- and
- (b) adding an aryl or heteroaryl disulfide of the formula:
- R—S—S—R
- to produce a thioether compound of the formula:
- 66
- and when n is 1 or 2, said process further comprising:
- (c) contacting the thioether compound with an oxidizing agent to produce the compound of Formula IC where n is 1 or 2.
21 more elements
A compound represented by Formula V:
- 67
- wherein:
- A is N or CH;
- X is O, NR3 or S, wherein R3 is hydrogen, alkyl or aryl;
- and
- Y is a bond, O, NR′, C(═O), CH(OR′), CH(R′), or S(O)n, wherein n is 0, 1, or 2;
- and R′ is hydrogen or alkyl;
- R is aryl or heteroaryl;
- and
- L is Ra—S(O)n1, where Ra is alkyl or aryl and n1 is 0, 1 or 2.
7 more elements
A compound of Formula VI
- 68
- wherein:
- A is N or CH;
- R1 is hydrogen, alkyl or arylalkyl;
- R2 is alkyl, heteroalkyl, (R″)2NCO-alkylene- (where each R″ is independently hydrogen or alkyl), cycloalkyl, heterocyclyl, aryl, or heteroaryl;
- X is O, NR3 or S, wherein R3 is hydrogen, alkyl or aryl;
- and
- Z is hydrogen or halo.
5 more elements
Dependencies are inferred from the claim text.