IP Library › Granted Patent US 8,269,014
Granted Patent B2
US 8,269,014 · App. 13/172,477 · Granted Sep 18, 2012

Thiophene analogues for the treatment or prevention of flavivirus infections

Assignee: Vertex Pharmaceuticals (Canada) Incorporated
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Quick Facts
Patent No.
US 8,269,014
App. No.
13/172,477
Granted
Sep 18, 2012
Kind
B2
Abstract

Compounds represented by formula I: or pharmaceutically acceptable salts and solvates thereof, wherein R 1 , X, Y, and Z are as defined herein, are useful for treating flaviviridae viral infections.

Claims (35)

1. A compound selected from:

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHOXY-CYCLOHEXYL)-(TRANS-4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(CIS-4-[1,2,4]TRIAZOL-1-YL-CYCLOHEXYL) -AMINO]-THIOPHENE-2-CARBOXYLIC ACID;

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(TRANS-4-[1,2,4]TRIAZOL-1-YL-CYCLOHEXYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(CIS-4-HYDROXY-CYCLOHEXYL)-(TRANS-4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(1-METHYL-PIPERIDIN-4-YL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID; HYDROCHLORIDE;

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-](TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(4-CIS-[1,2,3]TRIAZOL-1-YL-CYCLOHEXYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID;

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(TRANS-4-[1,2,3]TRIAZOL-1-YL-CYCLOHEXYL) -AMINO]-THIOPHENE-2-CARBOXYLIC ACID;

5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-FLUORO-CYCLOHEXYL)-(TRANS-4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID; and pharmaceutically acceptable salts thereof.

2. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHOXY-CYCLOHEXYL)-(TRANS-4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID.

3. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-](TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(CIS-4-[1,2,4]TRIAZOL-1-YL-CYCLOHEXYL) -AMINO]-THIOPHENE-2-CARBOXYLIC ACID.

4. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(TRANS-4-[1,2,4]TRIAZOL-1-YL-CYCLOHEXYL) -AMINO]-THIOPHENE-2-CARBOXYLIC ACID.

5. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-](CIS-4-HYDROXY-CYCLOHEXYL)-(TRANS-4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID.

6. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(1-METHYL-PIPERIDIN-4-YL)-AMIN]-THIOPHENE-2-CARBOXYLIC ACID; HYDROCHLORIDE.

7. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(4-CIS-[1,2,3]TRIAZOL-1-YL-CYCLOHEXYL) -AMINO]-THIOPHENE-2-CARBOXYLIC ACID.

8. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-METHYL -CYCLOHEXANECARBONYL)-(TRANS-4-[1,2,3]TRIAZOL-1-YL-CYCLOHEXYL) -AMINO]-THIOPHENE-2-CARBOXYLIC ACID.

9. A compound of claim 1 , wherein the compound is 5-(3,3-DIMETHYL-BUT-1-YNYL)-3-[(TRANS-4-FLUORO-CYCLOHEXYL)-(TRANS-4-METHYL-CYCLOHEXANECARBONYL)-AMINO]-THIOPHENE-2-CARBOXYLIC ACID.

10. A compound selected from:

3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclo-hexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3-(4-[1,2,3]triazol-1-yl-cyclohexylamino) -thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3-(4-[1,2,4]triazol-1-yl-cyclohexylamino) -thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3-(tert-butoxycarbonyl)amino-thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3-amino-thiophene-2-carboxylic acid methyl ester;

3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl) -amino]-5-iodo-thiophene-2-carboxylic acid methyl ester; or

3-[(trans-4-Hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl) -amino]-5-trimethyl-silanylethynyl-thiophene-2-carboxylic acid methyl ester.

11. A compound selected from:

5-bromo-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester;

5-bromo-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl -cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester;

3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester;

3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl) -amino]-thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3 -[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(4-oxo -cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester;

5-(3,3-dimethyl-but-1-ynyl)-3-[(4-hydroxy-cyclohexyl)-(trans-4-methyl -cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester; and

5 -(3,3-Dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexane-carbonyl)-amino]-thiophene-2-carboxylic acid methyl ester.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 12, 2011
From: CHAN CHUN KONG, LAVAL; DAS, SANJOY KUMAR; POISSON, CARL; YANNOPOULOS, CONSTANTIN G.; FALARDEAU, GUY; VAILLANCOURT, LOUIS; DENIS, REAL
To: VIROCHEM PHARMA INC.
Reel/Frame 026885/0031 →
MERGER Recorded Sep 12, 2011
From: VIROCHEM PHARMA INC.
To: VERTEX PHARMACEUTICALS (CANADA) INCORPORATED
Reel/Frame 026885/0133 →
Continuity (3)
Continuation 11984330 · Nov 15, 2007
Provisional Application 60858939 · Nov 15, 2006
Related Publication 20120059170A1 · Mar 8, 2012