Salts/cocrystals of (R)-N-(4-chlorophenyl-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide

Patent metadata

Field	Value
Publication number	US-12527783-B2
Application number	US-202017779635-A
Country	US
Kind code	B2
Filing date	Nov 23, 2020
Priority date	Nov 26, 2019
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

The present disclosure relates to amorphous and crystalline forms of (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoro-quinolin-4-yl)cyclohexyl)propanamide and its salts/cocrystals, solvates, and/or hydrates, processes for their production, pharmaceutical compositions comprising them, and methods of treatment using them.

First claim

What is claimed:

1 . Crystalline (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide hydrochloride salt monohydrate Form A, having one or more peaks in its XRPD selected from those at about 14.7, about 16.5, about 17.6, about 23.5 and about 24.3 degrees 2-theta.

2 . The crystalline (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide hydrochloride salt monohydrate Form A according to claim 1 , having two or more peaks in its XRPD selected from those at about 14.7, about 16.5, about 17.6, about 23.5 and about 24.3 degrees 2-theta.

3 . The crystalline (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide hydrochloride salt monohydrate Form A according to claim 1 , having three or more peaks in its XRPD selected from those at about 14.7, about 16.5, about 17.6, about 23.5 and about 24.3 degrees 2-theta.

4 . A method of treating cancer in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of a compound according to claim 1 .

5 . The method of claim 4 , wherein the cancer is a cancer of the prostate, colon, rectum, pancreas, cervix, stomach, endometrium, brain, liver, bladder, ovary, testis, head, neck, skin, mesothelial lining, white blood cell, esophagus, breast, muscle, connective tissue, lung, adrenal gland, thyroid, kidney, or bone; or is glioblastoma, mesothelioma, renal cell carcinoma, gastric carcinoma, sarcoma, choriocarcinoma, cutaneous basocellular carcinoma, or testicular seminoma.

6 . The method of claim 5 , wherein the skin cancer comprises melanoma and basal carcinoma; the white blood cell cancer comprises lymphoma and leukemia; the lung cancer comprises small-cell lung carcinoma and non-small-cell carcinoma; and the sarcoma comprises Kaposi's sarcoma.

7 . The method of claim 4 , further comprising administration of an immune checkpoint inhibitor.

8 . The method of claim 7 , wherein the immune checkpoint inhibitor is ipilimumab, nivolumab, pembroluzimab or a combination thereof.

9 . A method of modulating the activity of indoleamine 2,3-dioxygenase comprising contacting the indoleamine 2,3-dioxygenase with a compound according to claim 1 .

10 . Crystalline (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide anhydrous hydrochloride salt Form B.

11 . The crystalline (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide-anhydrous hydrochloride salt Form B according to claim 10 , having one or more peaks in its XRPD selected from those at about 13.0, about 14.2, about 16.3, about 18.5, about 21.0, about 23.9 and about 24.7 degrees 2-theta.

12 . The crystalline (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide anhydrous hydrochloride salt Form B according to claim 11 , having two or more peaks in its XRPD selected from those at about 13.0, about 14.2, about 16.3, about 18.5, about 21.0, about 23.9 and about 24.7 degrees 2-theta.

13 . The crystalline (R)—N-(4-chlorophenyl)-2-((1S,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide anhydrous hydrochloride salt Form B according to claim 11 , having three or more peaks in its XRPD selected from those at about 13.0, about 14.2, about 16.3, about 18.5, about 21.0, about 23.9 and about 24.7 degrees 2-theta.

14 . A method of treating cancer in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of a compound according to claim 10 .

15 . The method of claim 14 , wherein the cancer is a cancer of the prostate, colon, rectum, pancreas, cervix, stomach, endometrium, brain, liver, bladder, ovary, testis, head, neck, skin, mesothelial lining, white blood cell, esophagus, breast, muscle, connective tissue, lung, adrenal gland, thyroid, kidney, or bone; or is glioblastoma, mesothelioma, renal cell carcinoma, gastric carcinoma, sarcoma, choriocarcinoma, cutaneous basocellular carcinoma, or testicular seminoma.

16 . The method of claim 15 , wherein the skin cancer comprises melanoma and basal carcinoma; the white blood cell cancer comprises lymphoma and leukemia; the lung cancer comprises small-cell lung carcinoma and non-small-cell carcinoma; and the sarcoma comprises Kaposi's sarcoma.

17 . The method of claim 14 , further comprising administration of an immune checkpoint inhibitor.

18 . The method of claim 17 , wherein the immune checkpoint inhibitor is ipilimumab, nivolumab, pembroluzimab or a combination thereof.

19 . A method of modulating the activity of indoleamine 2,3-dioxygenase comprising contacting the indoleamine 2,3-dioxygenase with a compound according to claim 10 .

Assignees

• Bristol Myers Squibb Co

Inventors

• Rosenbaum Tamar I
• Bevill Melanie Janelle

Classifications

• C07D215/14

  Radicals substituted by oxygen atoms · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title