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US 2026/0062425 A1Published application
Aza-tetracyclic oxazepine compounds and uses thereof
AssigneeGenentech, Inc.
InventorsMatthew Leo Landry, Christian Nilewski, Michael Siu, Elisia Villemure, Yong Wang, BinQing Wei, Melissa Ann Ashley, Steven Do, Lewis John Gazzard, Samantha Alyson Green
Life of this patent
Estimating the term…
Abstract
Provided herein are aza-tetracyclic oxazepinyl compounds useful in the treatment of cancers.
Claims19
1-81. (canceled)
A method of treating lung cancer comprising a KRasG12D mutation in a patient having such lung cancer, the method comprising administering to the patient an effective amount of a compound of formula (I)
- or an atropisomer, or pharmaceutically acceptable salt thereof,
- wherein:
- R1 is (E2) or (E3)
- each R7A is independently hydrogen, halogen, unsubstituted C1-3 alkyl or unsubstituted C1-3 haloalkyl;
- wherein at least one R7A is unsubstituted C1-3 haloalkyl;
- L1 is RL1-substituted or unsubstituted C1-4 alkylene;
- RL1 is halogen or unsubstituted C1-3 alkyl, or two RL1 together form an unsubstituted C3-4 cycloalkyl;
- R2 is R9-substituted or unsubstituted 4-10 membered heterocycle comprising one or more heteroatoms selected from N, S, and O;
- each R9 is independently halogen, CN, OH, OCF3, OCHF2, OCH2F, R10-substituted or unsubstituted C1-3 alkyl, R10-substituted or unsubstituted C1-3 haloalkyl, unsubstituted C1-3 alkoxy, R10-substituted or unsubstituted C1-3 alkylidene, R10-substituted or unsubstituted C3-4 cycloalkyl, or R10-substituted or unsubstituted 3 or 4-membered heterocycle;
- or two R9 together form an R10-substituted or unsubstituted C3-5 cycloalkyl or an R10-substituted or unsubstituted C3-5 heterocycle comprising one or more oxygen atoms;
- or two R9 together form a bridge between two carbon atoms of the heterocycle, wherein the bridge comprises 1-3 carbons;
- each R10 is independently hydrogen, oxo, CN, halogen, or C1-3 unsubstituted alkyl;
- R3 is hydrogen, —CN, halogen, unsubstituted C1-3 alkyl, or unsubstituted cyclopropyl;
- and
- one R4 is hydrogen and one R4 is methyl.
12 more elements
The method of claim 8, wherein the compound of formula (I) is:
- or a pharmaceutically acceptable salt thereof.
A method of treating pancreatic cancer comprising a KRasG12D mutation in a patient having such lung cancer, the method comprising administering to the patient an effective amount of a compound of formula (I)
- or an atropisomer, or pharmaceutically acceptable salt thereof,
- wherein:
- R1 is (E2) or (E3)
- each R7A is independently hydrogen, halogen, unsubstituted C1-3 alkyl or unsubstituted C1-3 haloalkyl;
- wherein at least one R7A is unsubstituted C1-3 haloalkyl;
- L1 is RLi-substituted or unsubstituted C1-4 alkylene;
- RLi is halogen or unsubstituted C1-3 alkyl, or two RL1 together form an unsubstituted C3-4 cycloalkyl;
- R2 is R9-substituted or unsubstituted 4-10 membered heterocycle comprising one or more heteroatoms selected from N, S, and O;
- each R9 is independently halogen, CN, OH, OCF3, OCHF2, OCH2F, R10-substituted or unsubstituted C1-3 alkyl, R10-substituted or unsubstituted C1-3 haloalkyl, unsubstituted C1-3 alkoxy, R10-substituted or unsubstituted C1-3 alkylidene, R10-substituted or unsubstituted C3-4 cycloalkyl, or R10-substituted or unsubstituted 3 or 4-membered heterocycle;
- or two R9 together form an R10-substituted or unsubstituted C3-5 cycloalkyl or an R10-substituted or unsubstituted C3-5 heterocycle comprising one or more oxygen atoms;
- or two R9 together form a bridge between two carbon atoms of the heterocycle, wherein the bridge comprises 1-3 carbons;
- each R10 is independently hydrogen, oxo, CN, halogen, or C1-3 unsubstituted alkyl;
- R3 is hydrogen, —CN, halogen, unsubstituted C1-3 alkyl, or unsubstituted cyclopropyl;
- and
- one R4 is hydrogen and one R4 is methyl.
12 more elements
A method of treating colorectal cancer comprising a KRasG12D mutation in a patient having such lung cancer, the method comprising administering to the patient an effective amount of a compound of formula (I)
- or an atropisomer, or pharmaceutically acceptable salt thereof,
- wherein:
- R1 is (E2) or (E3)
- each R7A is independently hydrogen, halogen, unsubstituted C1-3 alkyl or unsubstituted C1-3 haloalkyl;
- wherein at least one R7A is unsubstituted C1-3 haloalkyl;
- L1 is RLi-substituted or unsubstituted C1-4 alkylene;
- RLi is halogen or unsubstituted C1-3 alkyl, or two RL1 together form an unsubstituted C3-4 cycloalkyl;
- R2 is R9-substituted or unsubstituted 4-10 membered heterocycle comprising one or more heteroatoms selected from N, S, and O;
- each R9 is independently halogen, CN, OH, OCF3, OCHF2, OCH2F, R10-substituted or unsubstituted C1-3 alkyl, R10-substituted or unsubstituted C1-3 haloalkyl, unsubstituted C1-3 alkoxy, R10-substituted or unsubstituted C1-3 alkylidene, R10-substituted or unsubstituted C3-4 cycloalkyl, or R10-substituted or unsubstituted 3 or 4-membered heterocycle;
- or two R9 together form an R10-substituted or unsubstituted C3-5 cycloalkyl or an R10-substituted or unsubstituted C3-5 heterocycle comprising one or more oxygen atoms;
- or two R9 together form a bridge between two carbon atoms of the heterocycle, wherein the bridge comprises 1-3 carbons;
- each R10 is independently hydrogen, oxo, CN, halogen, or C1-3 unsubstituted alkyl;
- R3 is hydrogen, —CN, halogen, unsubstituted C1-3 alkyl, or unsubstituted cyclopropyl;
- and
- one R4 is hydrogen and one R4 is methyl.
12 more elements
Dependencies are inferred from the claim text.