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US 2018/0000833 A1Published application
Serine/threonine kinase inhibitors
AssigneeGenentech, Inc.
InventorsAleksandr Kolesnikov, Steven Do
Life of this patent
Estimating the term…
Abstract
Compounds having the formula I wherein R1, X1, X2, X3 and X4 as defined herein are inhibitors of ERK kinase. Also disclosed are compositions and methods for treating hyperproliferative disorders.
Claims29
A compound of formula I:
- a pharmaceutically acceptable salt thereof;
- wherein
- X1 is selected from the group consisting of N and CH;
- X2 is selected from the group consisting of NRa, O and S;
- X3 is selected from the group consisting of C(R4)2, (C(R4)2)2, CH2NRb, C(═O), C(═O)NRb and C(═O)O;
- X4 is selected from the group consisting of CR2R3 and NR3;
- except where X2 is O, then X3 is not (C(R4)2)2;
- R1 is (i) a 4 to 7 membered saturated or partially unsaturated heterocyclyl or, (ii) an optionally substituted 5 to 6 membered heteroaryl;
- R2 is selected from the group consisting of:
- (a) C1-10 alkyl,
- (b) C2-10 alkenyl,
- (c) C1-10 haloalkyl,
- (d) C3-7 cycloalkyl or C3-7 cycloalkyl-C1-6 alkyl,
- (e) C3-7 halocycloalkyl or C3-7 halocycloalkyl-C1-6 alkyl,
- (f) C1-10 hydroxyalkyl or C1-10 dihydroxyalkyl,
- (g) C1-3 alkoxy-C1-6 alkyl,
- (h) C1-3 alkylthio-C1-6 alkyl,
- (i) C1-10 cyanoalkyl,
- (j) phenyl, phenyl-C1-3 alkyl, phenoxy or benzyloxy-C1-3 alkyl,
- (k) heteroaryl, heteroaryl-C1-3 alkyl or heteroaryloxy wherein said heteroaryl moiety is selected from the group consisting of pyrazolyl, imidiazolyl, oxazolyl, isoazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrid-2(1H)-one and 1-alkylpyrid-2(1H)-one and each said heteroaryl is independently optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, oxide, C1-6 alkoxy, C1-6 haloalkoxy, cyano, C3-6 cycloalkyl and C1-6 alkyl wherein said C1-6 alkyl is optionally independently substituted with one or more groups independently selected from halogen, oxo, hydroxyl or C1-6 alkoxy;
- and,
- (l) phenylthio or phenylthio-C1-6 alkyl;
- R3 is hydrogen or C1-3 alkyl;
- R4 is hydrogen or C1-3 alkyl;
- Ra and Rb are independently hydrogen or C1-3 alkyl;
- or,
- wherein any phenyl moiety is optionally substituted with one or more groups independently selected from halogen, cyano, hydroxyl, C1-6 alkoxy, C1-6 haloalkoxy and C1-6 alkyl wherein said C1-6 alkyl is optionally and independently substituted with one or more groups independently selected from halogen, oxo, hydroxyl and C1-6 alkoxy;
- and,
- wherein each cycloalkyl is independently and optionally substituted with one to three groups selected from halogen, C1-6 haloalkyl, C1-6 alkoxy and C1-6 haloalkoxy.
26 more elements
The compound according to claim 21 wherein R2 is selected from (1H-pyrazol-1-yl)methyl, (4-chloro-1H-pyrazol-1-yl)methyl, (4-trifluoromethyl-1H-pyrazol-1-yl)methyl, and (4-cyclopropyl-1H-pyrazol-1-yl)methyl.
Dependencies are inferred from the claim text.