IP Library Granted Patent US 8,049,016
Granted Patent B2
US 8,049,016 · App. 12/378,997 · Granted Nov 1, 2011

Thiazole derivatives which inhibit stearoyl-CoA desaturase enzymes

Assignees: Novartis AG; Xenon Pharmaceuticals Inc
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Quick Facts
Patent No.
US 8,049,016
App. No.
12/378,997
Granted
Nov 1, 2011
Kind
B2
Abstract

The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

Claims (179)

1. A compound selected from the group consisting of:

4-methyl-2-{2-oxo-3-[4-(trifluoromethyl)benzyl]imidazolidin-1-yl}thiazole-5-carboxamide;

(S)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(3,4-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4-(trifluoromethoxy)benzyl)imidazolidin-1-yl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-((6-(trifluoromethyl)pyridine-3-yl)methyl)imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-(3-fluoro-4-methoxybenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

(S)-2-(3-(4-fluorobenzyl)-5-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(4-chlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

(R)-2-(3-(3,5-difluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

(R)-4-methyl-2-(4-methyl-2-oxo-3-(4-(trifluoromethyl)benzypimidazolidin-1-yl)thiazole-5-carboxamide;

(S)-2-(3-(4-Fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

(S)—N-(3,4-difluorobenzyl)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((3-methyl-1 H-pyrazol-5-yl)methyl)thiazole-5-carboxamide;

2-(3-(but-3-enyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

(R)—N-(3,4-difluorobenzyl)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

(R)-2-(3-(4-Fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(thiazol-5-ylmethyl)thiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((3-methyl-1 H-pyrazol-5-yl)methyl)thiazole-5-carboxamide;

(R)—N-(3,5-difluorobenzyl)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

(R)-2-(3-(3,5-difluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

(R)-2-(3-(3,5-difluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

(R)-2-(3-(3,5-difluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

(S)-2-(3-(4-fluorobenzyl)-5-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

(S)-2-(3-(4-fluorobenzyl)-5-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

(S)-2-(3-(4-fluorobenzyl)-5-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-5-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-5-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(thiazol-5-yl)methyl)thiazole-5-carboxamide;

(R)-4-methyl-2-(4-methyl-2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(2-(4-fluorobenzylamino)-2-oxoethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

4-methyl-2-(3-(2-(methylamino)-2-oxoethyl)-2-oxoimidazolidin-1-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(2-oxo-2-(pyrrolidin-1-yl)ethyl)imidazolidin-1-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-N-((5-fluoropyridin-3-yl)methyl)-4-methylthiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-N-((3-fluoropyridin-2-yl)methyl)-4-methylthiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolid i n-1-yl)-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

4-methyl-N-(oxazol-4-ylmethyl)-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)thiazole-5-carboxamide;

4-methyl-N-(oxazol-2-ylmethyl)-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)thiazole-5-carboxamide;

4-methyl-N-((6-methylpyrazin-2-yl)methyl)-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)-N-(pyridin-4-ylmethyl)thiazole-5-carboxamide;

N-((1H-pyrazol-4-yl)methyl)-4-methyl-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)thiazole-5-carboxamide;

4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)-2-(2-oxo-3-(4,4,4-trifluorobutyl)imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyrimidin-4-ylmethyl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyrimidin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridazin-3-ylmethyl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-4-ylmethyl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((2-methylthiazol-5-yl)methyl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(oxazol-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(oxazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-4-ylmethyl)thiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((6-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(oxazol-4-ylmethyl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(oxazol-2-ylmethyl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(thiazol-5-yl)methyl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((4-methylthiazol-2-yl)methyl)thiazole-5-carboxamide;

4-methyl-N-((6-methylpyrazin-2-yl)methyl)-2-(2-oxo-3-(4,4,4-trifluorobutyl)-imidazolidin-1-yl)-thiazole-5-carboxamide;

N-((1H-pyrazol-4-yl)-methyl)-4-methyl-2-(2-oxo-3-(4,4,4-trifluorobutyl)-imidazolidin-1-yl)-thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4,4,4-trifluorobutyl)-imidazolidin-1-yl)-N-(pyridin-3-ylmethyl)-thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-N-(3,5-difluorobenzyl)-4-methylthiazole-5-carboxamide;

2-(3-(2,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(2,4-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)thiazole-5-carboxamide;

N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-methyl-2-(2-oxo-3-(4-(trifluoromethyl)-benzyl)imidazolidin-1-yl)-thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4-(trifluoromethyl)-benzyl)imidazolidin-1-yl)-N-((2-(trifluoromethyl)-thiazol-4-yl)-methyl)thiazole-5-carboxamide;

2-(3-(3-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(1-phenylethyl)-imidazolidin-1-yl)-N-(pyridin-3-yl-methyl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(1-phenylethyl)-imidazolidin-1-yl)-N-(thiazol-5-yl-methyl)thiazole-5-carboxamide;

2-(3-(2-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(1-phenylethyl)-imidazolidin-1-yl)-thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4-(trifluoromethyl)-benzypimidazolidin-1-yl)-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(2,6-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(2,3-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4-(trifluoromethyl)-benzypimidazolidin-1-yl)-N-(thiazol-2-ylmethyl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)-methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,4-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((6-methylpyrazin-2-yl)-methyl)thiazole-5-carboxamide;

2-(3-(3,4-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,4-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(oxazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,4-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(4-(trifluoromethoxy)-benzyl)imidazolidin-1-yl)-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

4-methyl-N-((5-methylisoxazol-3-yl)methyl)-2-(2-oxo-3-(4-(trifluoromethoxy)-benzyl)imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)-methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(thiazol-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((2-methylthiazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(4-methoxybenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(3-fluoro-4-methoxybenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-((6-(trifluoromethyl)-pyridin-3-yl)methyl)-imidazolidin-1-yl)-N-(pyridin-2-ylmethyl)-thiazole-5-carboxamide;

4-methyl-N-((5-methylisoxazol-3-yl)methyl)-2-(2-oxo-3-((6-(trifluoromethyl)-pyridin-3-yl)methyl)-imidazolidin-1-yl)-thiazole-5-carboxamide;

4-methyl-N-((5-methylisoxazol-3-yl)methyl)-2-(2-oxo-3-(4-(trifluoromethyl)-benzyl)imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-(3-fluoro-4-methoxybenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-(1-phenylethyl)-imidazolidin-1-yl)-N-(pyridin-2-ylmethyl)-thiazole-5-carboxamide;

N-(isoxazol-3-ylmethyl)-4-methyl-2-(2-oxo-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)-imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)-2-(2-oxo-3-(4-(trifluoromethyl)-benzyl)imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-(3-fluoro-4-(trifluoromethoxy)-benzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)-methyl)thiazole-5-carboxamide;

2-(3-(3-fluoro-4-(trifluoromethoxy)-benzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

2-(3-(3-fluoro-4-(trifluoromethoxy)-benzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(3-fluoro-4-(trifluoromethoxy)-benzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(4-methoxybenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(4-chlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)-thiazole-5-carboxamide;

2-(3-(3,5-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(4-chlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-((6-(4-fluorophenyl)pyridin-3-yl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(thiazol-2-yl)methyl)thiazole-5-carboxamide;

2-(3-((6-(4-fluorophenyl)pyridin-3-yl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-((6-(4-fluorophenyl)pyridin-3-yl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-(4-chlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(thiazol-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,5-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,5-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(2-cyclopropylethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

4-methyl-N-((5-methylpyrazin-2-yl)methyl)-2-(2-oxo-3-(4-(trifluoromethoxy)-benzyl)imidazolidin-1-yl)thiazole-5-carboxamide;

2-(3-(3-fluoro-4-methoxybenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,4-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3,4-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridine-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3-fluoro-4-(trifluoromethoxy)-benzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-((2,2-difluorocyclopropyl)-methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(2-cyclopropylethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(2-cyclopropylethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

4-methyl-N-((5-methylpyrazin-2-yl)methyl)-2-(2-oxo-3-((6-(trifluoromethyl)-pyridin-3-yl)methyl)-imidazolidin-1-yl)-thiazole-5-carboxamide;

2-(3-(3,4-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-a1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(2-cyclopropylethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide;

2-(3-(2-cyclopropylethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-(3-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

2-(3-((6-chloropyridin-3-yl)methyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

2-(3-(3-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)-thiazole-5-carboxamide;

2-(3-(3-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3-chlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)-thiazole-5-carboxamide;

2-(3-(3-chlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylpyrazin-2-yl)methyl)thiazole-5-carboxamide;

2-(3-(3-chlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((1-methyl-1 H-pyrazol-4-yl)methyl)thiazole-5-carboxamide;

N-((1H-pyrazol-4-yl)methyl)-2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide;

4-methyl-2-(2-oxo-3-((6-(trifluoromethyl)-pyridin-3-yl)methyl)-imidazolidin-1-yl)-N-(thiazol-2-ylmethyl)-thiazole-5-carboxamide;

4-methyl-N-(oxazol-2-ylmethyl)-2-(2-oxo-3-((6-(trifluoromethyl)-pyridin-3-yl)methyl)-imidazolidin-1-yl)thiazole-5-carboxamide;

4-methyl-2-(3-(4-(methylsulfonyl)benzyl)-2-oxoimidazolidin-1-yl)-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide;

4-methyl-2-(3-(4-(methylsulfonyl)benzyl)-2-oxoimidazolidin-1-yl)thiazole-5-carboxamide;

(R)-2-(3-(4-fluorobenzyl)-5-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide; and

(S)-2-(2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamido)-2-phenylacetic acid; or

a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is 2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is (R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide.

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is 4-methyl-2-(2-oxo-3-(1-phenylethyl)-imidazolidin-1-yl)-N-(thiazol-5-yl-methyl)thiazole-5-carboxamide.

5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide.

6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is 2-(3-(3,5-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide.

7. A pharmaceutical composition, comprising:

a compound of Formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof; and

a pharmaceutically acceptable excipient or carrier.

8. A method of treating a disease or condition mediated by stearoyl-CoA desaturase (SCD) in a mammal in need thereof, comprising:

identifying the mammal in need thereof; and

administering to the mammal in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the disease or condition is insulin resistance, decreased glucose tolerance, non-insulin-dependent diabetes mellitus, Type II diabetes, or obesity.

9. A method of treating a disease or condition mediated by stearoyl-CoA desaturase (SCD) in a mammal in need thereof, comprising:

identifying the mammal in need thereof; and

administering to the mammal in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the disease or disorder is eczema, acne, psoriasis, or keloid scar formation or prevention.

10. A pharmaceutical composition according to claim 7 , wherein the compound is 2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition according to claim 7 , wherein the compound is (R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition according to claim 7 , wherein the compound is 4-methyl-2-(2-oxo-3-(1-phenylethyl)-imidazolidin-1-yl)-N-(thiazol-5-yl-methyl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition according to claim 7 , wherein the compound is 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methylisoxazol-3-yl)methyl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition according to claim 7 , wherein the compound is 2-(3-(3,5-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

15. The method of claim 8 , wherein the compound is 2-(3-(3,5-difluorobenzyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

16. The method of claim 8 , wherein the compound is (R)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

17. The method of claim 8 , wherein the compound is 4-methyl-2-(2-oxo-3-(1-phenyl ethyl)-imidazolidin-1-yl)-N-(thiazol-5-yl-methyl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

18. The method of claim 8 , wherein the compound is 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-((5-methyl isoxazol-3-yl)methyl)thiazol a-5-carboxamide, or a pharmaceutically acceptable salt thereof.

19. The method of claim 8 , wherein the compound is 2-(3-(3,5-dichlorobenzyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-2-ylmethyl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 28, 2016
From: NOVARTIS AG
To: XENON PHARMACEUTICALS INC.
Reel/Frame 039876/0645 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 9, 2011
From: CHOWDHURY, SULTAN; FONAREV, JULIA; FU, JIANMIN; HOU, DUANJIE; JIA, QI; KODUMURU, VISHNUMURTHY; POKROVSKAIA, NATALIA; ZHANG, ZAIHUI; SUN, SHAOYI
To: XENON PHARMACEUTICALS INC.
Reel/Frame 026414/0200 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 9, 2011
From: DALES, NATALIE
To: NOVARTIS AG
Reel/Frame 026414/0357 →
Continuity (2)
Provisional Application 61030137 · Feb 20, 2008
Related Publication 20090264444A1 · Oct 22, 2009