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US 2011/0003809 A1Published application
Imidazo [4,5-b] pyridine derivatives used as raf inhibitors
AssigneeArray BioPharma Inc.
InventorKateri A. Ahrendt
Life of this patent
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Abstract
Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
Claims52
A compound selected from Formula I:
- and stereoisomers and pharmaceutically acceptable salts thereof, wherein:
- R1 and R2 are independently selected from hydrogen, halogen, CN, C1-C3 alkyl, and C1-C3 alkoxy;
- R3 is hydrogen, halogen or C1-C3 alkyl;
- R4 is C3-C5 cycloalkyl, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl, wherein the cycloalkyl, alkyl, alkenyl and alkynyl are optionally substituted with ORc, halogen or C3-C4 cycloalkyl;
- R5 is hydrogen, phenyl optionally substituted with one to three Ra groups, —N(Rc)— phenyl optionally substituted with Ra, —CH2-phenyl optionally substituted with one to three Rb groups, a 5-6 membered heteroaryl optionally substituted with one to three Re groups, saturated or partially unsaturated C3-C6 cycloalkyl optionally substituted with halogen or C1-C4 alkyl, a 5-6 membered heterocyclyl, or C1-C6 alkyl optionally substituted with one or more Rg groups;
- each Ra is independently selected from halogen, CN, a 5-6 membered heterocyclyl, NRCRd, —S(O)2Rf, —O(C1-C4 alkyl), and C1-C4 alkyl, wherein the alkyl or alkoxy are optionally substituted with halogen;
- each Rb is independently selected from halogen, OH or OCH3;
- each Rc and Rd are independently selected from hydrogen or C1-C4 alkyl;
- Re is selected from a 5-6 membered heterocyclyl or NRcRd;
- Rf is selected from C1-C4 alkyl or NRcRd;
- and
- each Rg is independently selected from halogen, CN, ORc, C3-C6 cycloalkyl or NRCRd.
9 more elements
A compound selected from Formula III:
- wherein R20 is hydrogen, C1-C6 alkyl, benzyl or phenyl;
- R1 and R2 are independently selected from hydrogen, halogen, CN, C1-C3 alkyl and C1-C3 alkoxy;
- R3 is hydrogen, halogen or C1-C3 alkyl;
- R4 is C3-C5 cycloalkyl, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl, wherein the cycloalkyl, alkyl, alkenyl and alkynyl are optionally substituted with ORc, halogen or C3-C4 cycloalkyl;
- and
- Rc is hydrogen or C1-C4 alkyl.
3 more elements
A process for preparing compounds of Formula I, comprising:
- (a) coupling a compound of Formula 5:
- wherein R5 is hydrogen, phenyl optionally substituted with one to three Ra groups, —N(Rc)-phenyl optionally substituted with Ra, —CH2-phenyl optionally substituted with one to three Rb groups, a 5-6 membered heteroaryl optionally substituted with one to three Re groups, saturated or partially unsaturated C3-C6 cycloalkyl optionally substituted with halogen or C1-C4 alkyl, a 5-6 membered heterocyclyl, or C1-C6 alkyl optionally substituted with one or more Rg groups;
- each Ra is independently selected from halogen, CN, a 5-6 membered heterocyclyl, NRCRd, —S(O)2Rf, —O(C1-C4 alkyl), and C1-C4 alkyl, wherein the alkyl or alkoxy are optionally substituted with halogen;
- each Rb is independently selected from halogen, OH or OCH3;
- each Rc and Rd are independently selected from hydrogen or C1-C4 alkyl;
- Re is selected from a 5-6 membered heterocyclyl or NRcRd;
- Rf is selected from C1-C4 alkyl or NRcRd;
- and each Rg is independently selected from halogen, CN, ORc, C3-C6 cycloalkyl or NRcRd;
- with a compound of Formula 6:
- wherein R1 and R2 are independently selected from hydrogen, halogen, CN, C1-C3 alkyl, and C1-C3 alkoxy;
- R3 is hydrogen, halogen or C1-C3 alkyl;
- R4 is C3-C5 cycloalkyl, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, wherein the cycloalkyl, alkyl, alkenyl and alkynyl are optionally substituted with ORc, halogen or C3-C4 cycloalkyl;
- and Rc is hydrogen or C1-C4 alkyl;
- to provide a compound of Formula I:
- (b) coupling a compound of Formula 5:
- wherein R5 is hydrogen, phenyl optionally substituted with one to three Ra groups, —N(Rc)-phenyl optionally substituted with Ra, —CH2-phenyl optionally substituted with one to three Rb groups, a 5-6 membered heteroaryl optionally substituted with one to three Re groups, saturated or partially unsaturated C3-C6 cycloalkyl optionally substituted with halogen or C1-C4 alkyl, a 5-6 membered heterocyclyl, or C1-C6 alkyl optionally substituted with one or more Rg groups;
- each Ra is independently selected from halogen, CN, a 5-6 membered heterocyclyl, NRcRd, —S(O)2Rf, —O(C1-C4 alkyl), and C1-C4 alkyl, wherein the alkyl or alkoxy are optionally substituted with halogen;
- each Rb is independently selected from halogen, OH or OCH3;
- each Rc and Rd are independently selected from hydrogen or C1-C4 alkyl;
- Re is selected from a 5-6 membered heterocyclyl or NRcRd;
- Rf is selected from C1-C4 alkyl or NRcRd;
- and each Rg is independently selected from halogen, CN, ORc, C3-C6 cycloalkyl or NRcRd;
- with a compound of Formula III:
- wherein R1 and R2 are independently selected from hydrogen, halogen, CN, C1-C3 alkyl, and C1-C3 alkoxy;
- R3 is hydrogen, halogen or C1-C3 alkyl;
- R4 is C3-C5 cycloalkyl, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, wherein the cycloalkyl, alkyl, alkenyl and alkynyl are optionally substituted with ORc, halogen or C3-C4 cycloalkyl;
- and Rc is hydrogen or C1-C4 alkyl;
- to provide a compound of Formula I:
25 more elements
Dependencies are inferred from the claim text.