2,3-dihydro-1H-indole compounds

Patent metadata

Field	Value
Publication number	US-9872853-B2
Application number	US-201715609115-A
Country	US
Kind code	B2
Filing date	May 31, 2017
Priority date	Jun 10, 2016
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

Abstract

The present invention relates to certain novel 2,3-dihydro-1H-indole compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds to treat cancer, more particularly for the treatment of cancer selected from the group consisting of melanoma, acute myeloid leukemia, chronic lymphocytic leukemia, colorectal cancer, breast cancer, lung cancer, ovarian cancer, fallopian tube carcinoma, primary peritoneal carcinoma, cervical cancer, gastric cancer, liver cancer, pancreatic cancer, thyroid cancer, glioma, non-Hodgkin's lymphoma, and Hodgkin's lymphoma.

First claim

We claim:

1. A compound of the formula:

wherein:
R1a is hydrogen, methyl, ethenyl, cyano, fluoro, chloro, fluoromethyl, or difluoromethyl;
R1b is hydrogen, fluoro, or chloro;
R1c is hydrogen, hydroxy, fluoro, benzyloxy, or hydroxyethylamino;
R2 is hydrogen or methyl;
R2a is hydrogen or methyl; and
R3a is tetrahydropyranyl.

2. The compound according to claim 1 which is:

3. The compound according to claim 2 which is:

4. The compound according to claim 2 which is:

5. The compound according to claim 3 which is crystalline 4-fluoro-N-{(1R)-1-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-2,3-dihydro-1H-indol-5-yl]ethyl}benzamide.

6. The compound according to claim 5 which is crystalline 4-fluoro-N-{(1R)-1-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)-2,3-dihydro-1H-indol-5-yl]ethyl}benzamide characterized by an X-ray powder diffraction pattern (Cu radiation, λ-1.54060 Å) comprising at least one peak at 17.38° in combination with one or more peaks selected from the group consisting of 12.51°, 15.65°, 16.37°, 17.56°, 21.48° and 25.23° (2θ±0.2°).

7. A pharmaceutical composition comprising a compound of the formula:

wherein:
R1a is hydrogen, methyl, ethenyl, cyano, fluoro, chloro, fluoromethyl, or difluoromethyl;
R1b is hydrogen, fluoro, or chloro;
R1c is hydrogen, hydroxy, fluoro, benzyloxy, or hydroxyethylamino;
R2 is hydrogen or methyl;
R2a is hydrogen or methyl; and
R3a is tetrahydropyranyl; with one or more pharmaceutically acceptable excipients, carriers or diluents.

8. A method of treating a patient with a cancer selected from the group consisting of melanoma, acute myeloid leukemia, chronic lymphocytic leukemia, colorectal cancer, renal cell carcinoma, breast cancer, lung cancer, ovarian cancer, fallopian tube carcinoma, primary peritoneal carcinoma, cervical cancer, gastric cancer, liver cancer, pancreatic cancer, thyroid cancer, glioma, non-Hodgkin's lymphoma, and Hodgkin's lymphoma comprising administering to the patient an effective amount of a compound of the formula:

wherein:
R1a is hydrogen, methyl, ethenyl, cyano, fluoro, chloro, fluoromethyl, or difluoromethyl;
R1b is hydrogen, fluoro, or chloro;
R1c is hydrogen, hydroxy, fluoro, benzyloxy, or hydroxyethylamino;
R2 is hydrogen or methyl;
R2a is hydrogen or methyl; and
R3a is tetrahydropyranyl.

Assignees

• Lilly Co Eli

Inventors

• Bastian Jolie Anne
• Chen Jiehao
• Cohen Jeffrey Daniel
• Henry James Robert
• Mcmillen William Thomas
• Reaman Bradley Earl
• Rubio Almudena
• Sall Daniel Jon
• Zhao Gaiying

Classifications

• C07D209/02

  condensed with one carbocyclic ring · CPC title

• C07D405/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C233/01

  having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• A61K31/4045

  Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin · CPC title