# US 2026/0062425 A1 · Aza-tetracyclic oxazepine compounds and uses thereof

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- Number: US 2026/0062425 A1
- Document ID: US20260062425A1
- Status: Published application
- Kind: A1
- Application number: 19/190,368
- Filed: 2025-04-25
- Published: 2026-03-05
- Earliest claimed: 2022-05-19
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Matthew Leo Landry; Christian Nilewski; Michael Siu; Elisia Villemure; Yong Wang; BinQing Wei; Melissa Ann Ashley; Steven Do; Lewis John Gazzard; Samantha Alyson Green
- Web page: https://patentgrep.com/patent/US20260062425A1

## CPC

- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07D 498/22: in which the condensed system contains four or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided herein are aza-tetracyclic oxazepinyl compounds useful in the treatment of cancers.

## Claims

### Claim at position 1

1-81. (canceled)

### Claim 82

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.

### Claim 83 (depends on 82)

The method of claim 82, wherein L1 is methylene.

### Claim 84 (depends on 82)

The method of claim 82, wherein R2 is:
or a stereoisomer thereof,
wherein:
R9 is independently halogen or R10-substituted or unsubstituted C1-3 alkylidene;
each R10 is independently hydrogen or halogen; and
r is 1 or 2.

### Claim 85 (depends on 82)

The method of claim 82, wherein R2 is:

### Claim 86 (depends on 82)

The method of claim 82, wherein R1 is:

### Claim 87 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is selected from the group consisting of:
or an atropisomer, or pharmaceutically acceptable salt thereof.

### Claim 88 (depends on 8)

The method of claim 8, wherein the compound of formula (I) is:
or a pharmaceutically acceptable salt thereof.

### Claim 89 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:
or a pharmaceutically acceptable salt thereof.

### Claim 90 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:
or a pharmaceutically acceptable salt thereof.

### Claim 91 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:
or a pharmaceutically acceptable salt thereof.

### Claim 92 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:
or a pharmaceutically acceptable salt thereof.

### Claim 93 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:

### Claim 94 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:

### Claim 95 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:

### Claim 96 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:

### Claim 97 (depends on 82)

The method of claim 82, wherein the compound of formula (I) is:

### Claim 98

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.

### Claim 99

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.