e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Conformationally Constrained ortho-Anilino Diaryl Ureas: Discovery of 1-(2-(1′-Neopentylspiro [indoline-3, 4′-piperidine]-1-yl) phenyl)-3-(4-(trifluoromethoxy) …

…, R Ruel, C Thibeault, A L'Heureux…

Index: Qiao, Jennifer X.; Wang, Tammy C.; Ruel, Rejean; Thibeault, Carl; L'Heureux, Alexandre; Schumacher, William A.; Spronk, Steven A.; Hiebert, Sheldon; Bouthillier, Gilles; Lloyd, John; Pi, Zulan; Schnur, Dora M.; Abell, Lynn M.; Hua, Ji; Price, Laura A.; Liu, Eddie; Wu, Qimin; Steinbacher, Thomas E.; Bostwick, Jeffrey S.; Chang, Ming; Zheng, Joanna; Gao, Qi; Ma, Baoqing; McDonnell, Patricia A.; Huang, Christine S.; Rehfuss, Robert; Wexler, Ruth R.; Lam, Patrick Y. S. Journal of Medicinal Chemistry, 2013 , vol. 56, # 22 p. 9275 - 9295

Full Text: HTML

Citation Number: 16

Abstract

Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y1 antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y12 antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino ...

Ethyl Isonipecotate Structure

Ethyl Isonipecotate

~%

[1-(2,2-dimethylpropyl)piperidin-4-yl]methanol Structure

[1-(2,2-dimethy...

Pivaloyl chloride Structure

Pivaloyl chloride

~%

[1-(2,2-dimethylpropyl)piperidin-4-yl]methanol Structure

[1-(2,2-dimethy...

spiro[cyclobutane-1,3'-[3H]indol]-2'(1'H)-one Structure

spiro[cyclobuta...

~%

1',2'-dihydro-Spiro[cyclobutane-1,3'-[3H]indole] Structure

1',2'-dihydro-S...

cyclobutancarbonylchlorid Structure

cyclobutancarbo...

~%

1',2'-dihydro-Spiro[cyclobutane-1,3'-[3H]indole] Structure

1',2'-dihydro-S...

Oxindole Structure

1,5-Dibromopentane Structure

1,5-Dibromopentane

~83%

Spiro[cyclohexane-1,3'-indolin]-2'-one Structure

Spiro[cyclohexa...

Spiro[cyclohexane-1,3'-indolin]-2'-one Structure

Spiro[cyclohexa...

~89%

spiro[1,2-dihydroindole-3,1'-cyclohexane] Structure

spiro[1,2-dihyd...

Oxindole Structure

~%

spiro[1,2-dihydroindole-3,1'-cyclohexane] Structure

spiro[1,2-dihyd...

1,5-Dibromopentane Structure

1,5-Dibromopentane

~%

spiro[1,2-dihydroindole-3,1'-cyclohexane] Structure

spiro[1,2-dihyd...

Ethyl Isonipecotate Structure

Ethyl Isonipecotate

~%

1-Neopentylpiperidine-4-carbaldehyde Structure

1-Neopentylpipe...

Pivaloyl chloride Structure

Pivaloyl chloride

~%

1-Neopentylpiperidine-4-carbaldehyde Structure

1-Neopentylpipe...

1-Acetyloxindole Structure

1-Acetyloxindole

~%

3,3-Dimethylindoline Structure

3,3-Dimethylindoline

3,3-DIBROMO-1-((2-(TRIMETHYLSILYL)ETHOXY)METHYL)-1H-PYRROLO[2,3-B]PYRIDIN-2(3H)-ONE Structure

3,3-DIBROMO-1-(...

~77%

1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one Structure

1-((2-(Trimethy...

7-Azaindole Structure

~%

SPIRO[PIPERIDINE-4,3'-PYRROLO[2,3-B]PYRIDIN]-2'(1'H)-ONE Structure

SPIRO[PIPERIDIN...

3,3-DIBROMO-1-((2-(TRIMETHYLSILYL)ETHOXY)METHYL)-1H-PYRROLO[2,3-B]PYRIDIN-2(3H)-ONE Structure

3,3-DIBROMO-1-(...

~%

SPIRO[PIPERIDINE-4,3'-PYRROLO[2,3-B]PYRIDIN]-2'(1'H)-ONE Structure

SPIRO[PIPERIDIN...

1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one Structure

1-((2-(Trimethy...

~%

SPIRO[PIPERIDINE-4,3'-PYRROLO[2,3-B]PYRIDIN]-2'(1'H)-ONE Structure

SPIRO[PIPERIDIN...

4,4-Dimethyl-1,2,3,4-tetrahydroquinoline Structure

4,4-Dimethyl-1,...

1-Bromo-2-nitrobenzene Structure

1-Bromo-2-nitro...

~%

4,4-dimethyl-1-(2-nitrophenyl)-2,3-dihydroquinoline Structure

4,4-dimethyl-1-...

Structure

~%

4,4-dimethyl-1-(2-nitrophenyl)-2,3-dihydroquinoline Structure

4,4-dimethyl-1-...

3-methylcrotonoyl chloride Structure

3-methylcrotono...

~%

4,4-dimethyl-1-(2-nitrophenyl)-2,3-dihydroquinoline Structure

4,4-dimethyl-1-...

3-methyl-N-phenylbut-2-enamide Structure

3-methyl-N-phen...

~%

4,4-dimethyl-1-(2-nitrophenyl)-2,3-dihydroquinoline Structure

4,4-dimethyl-1-...

4,4-Dimethyl-3,4-dihydroquinolin-2(1H)-one Structure

4,4-Dimethyl-3,...

~%

4,4-dimethyl-1-(2-nitrophenyl)-2,3-dihydroquinoline Structure

4,4-dimethyl-1-...

Structure

~%

2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)aniline Structure

2-(4,4-dimethyl...

3-methylcrotonoyl chloride Structure

3-methylcrotono...

~%

2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)aniline Structure

2-(4,4-dimethyl...

3-methyl-N-phenylbut-2-enamide Structure

3-methyl-N-phen...

~%

2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)aniline Structure

2-(4,4-dimethyl...

4,4-Dimethyl-3,4-dihydroquinolin-2(1H)-one Structure

4,4-Dimethyl-3,...

~%

2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)aniline Structure

2-(4,4-dimethyl...

4,4-Dimethyl-1,2,3,4-tetrahydroquinoline Structure

4,4-Dimethyl-1,...

~%

2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)aniline Structure

2-(4,4-dimethyl...

ethyl 2-bromoacetate Structure

ethyl 2-bromoacetate

o-Phenylenediamine Structure

o-Phenylenediamine

~80%

3,4-dihydroquinoxalin-2-ol Structure

3,4-dihydroquin...

1-Acetyloxindole Structure

1-Acetyloxindole

~%

3,3-dimethyl-1-(3-nitropyridin-2-yl)-2H-indole Structure

3,3-dimethyl-1-...

3,3-Dimethylindolin-2-one Structure

3,3-Dimethylind...

~%

3,3-dimethyl-1-(3-nitropyridin-2-yl)-2H-indole Structure

3,3-dimethyl-1-...

1-Acetyloxindole Structure

1-Acetyloxindole

~%

2-(3,3-dimethyl-2H-indol-1-yl)pyridin-3-amine Structure

2-(3,3-dimethyl...

3,3-Dimethylindolin-2-one Structure

3,3-Dimethylind...

~%

2-(3,3-dimethyl-2H-indol-1-yl)pyridin-3-amine Structure

2-(3,3-dimethyl...

3,3-Dimethylindoline Structure

3,3-Dimethylindoline

~%

2-(3,3-dimethyl-2H-indol-1-yl)pyridin-3-amine Structure

2-(3,3-dimethyl...

[1-(2,2-dimethylpropyl)piperidin-4-yl]methanol Structure

[1-(2,2-dimethy...

~%

1'-(2,2-dimethylpropyl)spiro[1,2-dihydroindole-3,4'-piperidine] Structure

1'-(2,2-dimethy...

Ethyl Isonipecotate Structure

Ethyl Isonipecotate

~%

1'-(2,2-dimethylpropyl)spiro[1,2-dihydroindole-3,4'-piperidine] Structure

1'-(2,2-dimethy...

Pivaloyl chloride Structure

Pivaloyl chloride

~%

1'-(2,2-dimethylpropyl)spiro[1,2-dihydroindole-3,4'-piperidine] Structure

1'-(2,2-dimethy...

1-Neopentylpiperidine-4-carbaldehyde Structure

1-Neopentylpipe...

~%

1'-(2,2-dimethylpropyl)spiro[1,2-dihydroindole-3,4'-piperidine] Structure

1'-(2,2-dimethy...

1-Acetyloxindole Structure

1-Acetyloxindole

1,2-Dibromoethane Structure

1,2-Dibromoethane

~%

Spiro[cyclopropane-1,3'-indolin]-2'-one Structure

Spiro[cycloprop...

1-Acetyloxindole Structure

1-Acetyloxindole

~%

3,3-dimethyl-1-(2-nitrophenyl)-2H-indole Structure

3,3-dimethyl-1-...

3,3-Dimethylindolin-2-one Structure

3,3-Dimethylind...

~%

3,3-dimethyl-1-(2-nitrophenyl)-2H-indole Structure

3,3-dimethyl-1-...