KRas G12C inhibitors

Patent metadata

Field	Value
Publication number	US-10125134-B2
Application number	US-201715814279-A
Country	US
Kind code	B2
Filing date	Nov 15, 2017
Priority date	May 18, 2016
Publication date	Nov 13, 2018
Grant date	Nov 13, 2018

Abstract

The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

First claim

What is claimed is:

1. A compound, wherein the compound is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

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

3. A method for inhibiting KRas G12C activity in a cell, comprising contacting the cell in which inhibition of KRas G12C activity is desired with an effective amount of a compound of claim 1 , a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof.

4. A method for treating a cancer associated with a KRas G12C mutation comprising administering to a patient having a cancer associated with a KRas G12C mutation a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt of a compound claim 1 , alone or combined with a pharmaceutically acceptable carrier, excipient or diluents.

5. The method of claim 4 , wherein the therapeutically effective amount of the compound is between about 0.01 to 100 mg/kg per day.

6. The method of claim 5 , wherein the therapeutically effective amount of the compound is between about 0.1 to 50 mg/kg per day.

7. The method of claim 6 , wherein the 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 sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumors; Nervous system: skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform, oligodendroglioma, schwannoma, retino

Assignees

• Mirati Therapeutics Inc
• Array Biopharma Inc

Inventors

• Blake James F
• Burgess Laurence E
• Chicarelli Mark Joseph
• Christensen James Gail
• Fell Jay Bradford
• Fischer John P
• Gaudino John J
• Hicken Erik James
• Hinklin Ronald Jay
• Lee Matthew Randolf
• Marx Matthew Arnold
• Mejia Macedonio J
• Rodriguez Martha E
• Savechenkov Pavel
• Tang Tony P
• Vigers Guy P A
• Zecca Henry J

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/519

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