KRas G12D inhibitors

Patent metadata

Field	Value
Publication number	US-11964989-B2
Application number	US-202217869575-A
Country	US
Kind code	B2
Filing date	Jul 20, 2022
Priority date	Aug 29, 2019
Publication date	Apr 23, 2024
Grant date	Apr 23, 2024

Abstract

Compounds that inhibit KRas G12D. In particular, compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor, and in particular, methods of treating cancer. The compounds have a general structure represented by Formula (I):

or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1. A compound selected from:

and pharmaceutically acceptable salts thereof.

2. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

3. A method for inhibiting KRas G12D activity in a cell, comprising contacting the cell in which inhibition of KRas G12D activity is desired with an effective amount of a compound of according to claim 1 or a pharmaceutically acceptable salt thereof.

4. A method for inhibiting KRas G12D activity in a cell, comprising contacting the cell in which inhibition of KRas G12D activity is desired with the pharmaceutical composition of claim 2 .

5. A method for treating a KRas G12D-associated cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

6. A method for treating a KRas G12D-associated cancer comprising administering to a patient in need thereof the pharmaceutical composition of claim 2 .

7. The method of claim 5 , wherein the therapeutically effective amount of the compound is between about 0.01 to 100 mg/kg per day.

8. The method of claim 5 , wherein the KRas G12D-associated cancer is selected from the group consisting of Cardiac: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma; Gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (adenocarcinoma, lymphoma, carcinoid tumors, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); Genitourinary tract: kidney (adenocarcinoma, Wilm's tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma); Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Biliary tract: gall bladder carcinoma, ampullary carcinoma, cholangiocarcinoma; Bone: osteogenic

Assignees

• Mirati Therapeutics Inc
• Array Biopharma Inc

Inventors

• Wang Xiaolun
• Burns Aaron Craig
• Christensen James Gail
• Ketcham John Michael
• Lawson John David
• Marx Matthew Arnold
• Smith Christopher Ronald
• Allen Shelley
• Blake James F
• Chicarelli Mark Joseph
• Dahlke Joshua Ryan
• Dai Donghua
• Fell Jay Bradford
• Fischer John Peter
• Mejia Macedonio J
• Newhouse Brad
• Nguyen Phong
• O'Leary Jacob Matthew
• Pajk Spencer
• Rodriguez Martha E
• Savechenkov Pavel
• Tang Tony P
• Vigers Guy P A
• Zhao Qian
• Kahn Dean Russell
• Gaudino John
• Hilton Michael Christopher

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D498/08

  Bridged systems · CPC title

• A61K31/5386

  spiro-condensed or forming part of bridged ring systems · CPC title

• C07D487/08 Primary

  Bridged systems · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title