IP Library › Granted Patent US 8,802,688
Granted Patent B2
US 8,802,688 · App. 13/452,839 · Granted Aug 12, 2014

Substituted acetyl-coa carboxylase inhibitors

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Quick Facts
Patent No.
US 8,802,688
App. No.
13/452,839
Granted
Aug 12, 2014
Kind
B2
Abstract

The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R 1 , R 2 and R 3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.

Claims (86)

1. A compound selected from the group consisting of

6-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-3-carboxamide;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indazole-3-carboxamide;

6-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-pyrrolo[3,2-b]pyridine-3-carboxamide;

6-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indazole-3-carboxamide;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-2-carboxamide;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-3-carboxamide;

1′-[(2-amino-1H-benzimidazol-5-yl)carbonyl]-1-isopropyl-1,4-dihydrospiro[indazole-5,4′-piperidin]-7(6H)-one;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-methyl-1H-indazole-3-carboxamide;

N-ethyl-5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indazole-3-carboxamide;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-(2,2,2-trifluoroethyl)-1H-indazole-3-carboxamide;

6-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-2-carboxamide;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-pyrazolo[3,4-b]pyridine-3-carboxamide;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide;

1-isopropyl-1′-{[2-(methylamino)-1H-benzimidazol-5-yl]carbonyl}-1,4-dihydrospiro[indazole-5,4′-piperidin]-7(6H)-one;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-benzimidazole-2-carboxamide;

5-[(1-tert-butyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indazole-3-carboxamide;

5-[(1-tert-butyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-2-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-indole-2-carboxamide;

1′-[(2-amino-1H-benzimidazol-5-yl)carbonyl]-2-tert-butyl-2,4-dihydrospiro[indazole-5,4′-piperidin]-7(6H)-one;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-ethyl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-methyl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-(2,2,2-trifluoroethyl)-1H-indazole-3-carboxamide;

2-tert-butyl-1′-{[2-(methylamino)-1H-benzimidazol-5-yl]carbonyl}-2,4-dihydrospiro[indazole-5,4′-piperidin]-7(6H)-one;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-1H-pyrrolo[3,2-b]pyridine-3-carboxamide;

6-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-indazole-3-carboxamide;

6-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-indole-2-carboxamide;

6-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-indole-3-carboxamide;

5-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-indazole-3-carboxamide;

5-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-indole-2-carboxamide;

5-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-indole-3-carboxamide;

5-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide;

1-[(2-amino-1H-benzimidazol-5-yl)carbonyl]-2′-tert-butyl-2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one;

2′-tea-butyl-1-{[2-(methylamino)-1H-benzimidazol-5-yl]carbonyl}-2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one;

6-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-pyrrolo[3,2-b]pyridine-3-carboxamide; and

5-[(2′-tert-butyl-7′-oxo-6′,7′-dihydro-1H,2′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-1-yl)carbonyl]-1H-benzimidazole-2-carboxamide;

or a pharmaceutically acceptable salt thereof.

2. A compound selected from the group consisting of

1′-[(2-aminoquinolin-6-yl)carbonyl]-2-tert-butyl-2,4-dihydrospiro[indazole-5,4′-piperidin]-7(6H)-one;

5-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-methyl-1H-indole-3-carboxamide;

6-[(1-isopropyl-7-oxo-1,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-methyl-1H-indole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-cyclopropyl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-isopropyl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-propyl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-(2-methoxyethyl)-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-cyclobutyl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-oxetan-3-yl-1H-indazole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-Ncyclopropyl-1H-indazole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-methyl-1H-indazole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-ethyl-1H-indazole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-(2-methoxyethyl)-1H-indazole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-isopropyl-1H-indazole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-propyl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-cyclopropyl-1H-indole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-cyclobutyl-1H-indazole-3-carboxamide;

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-oxetan-3-yl-1H-indazole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-(2-methoxyethyl)-1H-indole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-methyl-1H-indole-3-carboxamide;

5-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-ethyl-1H-indole-3-carboxamide; and

6-[(2-tert-butyl-7-oxo-2,4,6,7-tetrahydro-1′H-spiro[indazole-5,4′-piperidin]-1′-yl)carbonyl]-N-cyclopropyl-1H-indole-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

3. 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, diluent, or carrier.

4. A method for treating Type 2 diabetes, diabetes or hepatic insulin resistance in a human comprising the step of administering to the human in need of such treatment a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

5. A method for treating Type 2 diabetes or hepatic insulin resistance in a human comprising the step of administering to the human in need of such treatment the pharmaceutical composition of claim 3 .

6. A compound of structure

or a pharmaceutically acceptable salt thereof.

7. A compound of structure

8. A compound of structure

or a pharmaceutically acceptable salt thereof.

9. A compound of structure

10. A compound of structure

or a pharmaceutically acceptable salt thereof.

11. A compound of structure

12. A compound structure

or a pharmaceutically acceptable salt thereof.

13. A compound of structure

14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, diluent, or carrier.

15. A method for treating Type 2 diabetes or hepatic insulin resistance in a human comprising the step of administering to the human in need of such treatment a therapeutically effective amount of the compound of claim 6 or a pharmaceutically acceptable salt thereof.

16. A method for treating Type 2 diabetes or hepatic insulin resistance in a human comprising the step of administering to the human in need of such treatment the pharmaceutical composition of claim 14 .

Assignments (1)
ASSIGNEE ADDRESS CORRECTION Recorded Mar 20, 2023
From: PFIZER INC.
To: PFIZER INC.
Reel/Frame 063119/0087 →