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

Tetrahedron

Strategies for the synthesis of N-(azacycloalkyl) bisindolylmaleimides: selective inhibitors of PKCβ

…, JL Grutsch, ME Kobierski, ME Kopach, CA Krumrich…

Index: Faul, Margaret M.; Grutsch, John L.; Kobierski, Michael E.; Kopach, Michael E.; Krumrich, Christine A.; Staszak, Michael A.; Udodong, Uko; Vicenzi, Jeffrey T.; Sullivan, Kevin A. Tetrahedron, 2003 , vol. 59, # 36 p. 7215 - 7229

Full Text: HTML

Citation Number: 24

Abstract

N-(Azacycloalkyl) bisindolylmaleimides 1 have been identified to be selective inhibitors of PKCβ. This manuscript will describe the synthetic approaches employed to prepare this class of compounds that resulted in development of efficient methods for preparation of N- (azacycloalkyl) indole 5, indole-3-acetamide 8 and indole-3-glyoxylate ester 4 derivatives.

N,N-bis(2-ethoxycarbonylethyl)-N-(2-pyridilmethyl)amine Structure

N,N-bis(2-ethox...

~%

1-(pyridin-2-ylmethyl)piperidin-4-one Structure

1-(pyridin-2-yl...

tert-butyl 4-(indolin-1-yl)piperidine-1-carboxylate Structure

tert-butyl 4-(i...

~89%

4-(1H-Indol-1-yl)-1-Piperidinecarboxylic Acid Tert-Butyl Ester Structure

4-(1H-Indol-1-y...

N-(tert-Butoxycarbonyl)-4-piperidone Structure

N-(tert-Butoxyc...

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

~92%

4-(1H-Indol-1-yl)-1-Piperidinecarboxylic Acid Tert-Butyl Ester Structure

4-(1H-Indol-1-y...

2-(1-METHYL-1H-INDOL-3-YL)-2-OXOACETIC ACID METHYL ESTER Structure

2-(1-METHYL-1H-...

2-(1-(1-(pyridin-2-ylmethyl)piperidin-4-yl)-1H-indol-3-yl)acetamide Structure

2-(1-(1-(pyridi...

~51%

Enzastaurin (LY317615) Structure

Enzastaurin (LY...

2-(1-Methyl-1H-indol-3-yl)acetamide Structure

2-(1-Methyl-1H-...

Methyl 2-oxo-2-(1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indol-3-yl)acetate Structure

Methyl 2-oxo-2-...

~77%

Enzastaurin (LY317615) Structure

Enzastaurin (LY...

1-Benzyl-4-(1-indolyl)-piperidine Structure

1-Benzyl-4-(1-i...

~97%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

4-(1H-Indol-1-yl)-1-Piperidinecarboxylic Acid Tert-Butyl Ester Structure

4-(1H-Indol-1-y...

~71%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

~%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

1-[2-(2-nitrophenyl)ethenyl]pyrrolidine Structure

1-[2-(2-nitroph...

~%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

1-(2,2-Dimethoxyethyl)-2-nitrobenzene Structure

1-(2,2-Dimethox...

~%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

N-(tert-Butoxycarbonyl)-4-piperidone Structure

N-(tert-Butoxyc...

~%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

Indoline Structure

~%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

tert-butyl 4-(indolin-1-yl)piperidine-1-carboxylate Structure

tert-butyl 4-(i...

~%

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

N-Methyl-4-piperidone Structure

N-Methyl-4-pipe...

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

~89%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

1-(1-methylpiperidin-4-yl)indoline Structure

1-(1-methylpipe...

~80%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

Dimethyl sulfate Structure

Dimethyl sulfate

~49%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

1-[2-(2-nitrophenyl)ethenyl]pyrrolidine Structure

1-[2-(2-nitroph...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

1-(2,2-Dimethoxyethyl)-2-nitrobenzene Structure

1-(2,2-Dimethox...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

1-Benzyl-4-(1-indolyl)-piperidine Structure

1-Benzyl-4-(1-i...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

N-Methyl-4-piperidone Structure

N-Methyl-4-pipe...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

Indoline Structure

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

N-(tert-Butoxycarbonyl)-4-piperidone Structure

N-(tert-Butoxyc...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

4-(1H-Indol-1-yl)-1-Piperidinecarboxylic Acid Tert-Butyl Ester Structure

4-(1H-Indol-1-y...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

tert-butyl 4-(indolin-1-yl)piperidine-1-carboxylate Structure

tert-butyl 4-(i...

~%

1-(1-methylpiperidin-4-yl)indole Structure

1-(1-methylpipe...

Methanol Structure

1-[2-(2-nitrophenyl)ethenyl]pyrrolidine Structure

1-[2-(2-nitroph...

~83%

1-(2,2-Dimethoxyethyl)-2-nitrobenzene Structure

1-(2,2-Dimethox...

Pyrrolidine Structure

2-Nitrotoluene Structure

N,N-Dimethylformamide dimethyl acetal Structure

N,N-Dimethylfor...

~94%

1-[2-(2-nitrophenyl)ethenyl]pyrrolidine Structure

1-[2-(2-nitroph...

1-(2,2-Dimethoxyethyl)-2-nitrobenzene Structure

1-(2,2-Dimethox...

~98%

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

1-[2-(2-nitrophenyl)ethenyl]pyrrolidine Structure

1-[2-(2-nitroph...

~%

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

4,4-Piperidinediol hydrochloride Structure

4,4-Piperidined...

(Bromomethyl)cyclopropane Structure

(Bromomethyl)cy...

~64%

1-(Cyclopropylmethyl)piperidin-4-one Structure

1-(Cyclopropylm...

1-(1-(pyridin-2-ylmethyl)piperidin-4-yl)indoline Structure

1-(1-(pyridin-2...

~89%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

2-(Chloromethyl)pyridine HCl Structure

2-(Chloromethyl...

1-(Piperidin-4-yl)-1H-indole Structure

1-(Piperidin-4-...

~98%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

1-(pyridin-2-ylmethyl)piperidin-4-one Structure

1-(pyridin-2-yl...

~77%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

1-(2,2-Dimethoxyethyl)-2-nitrobenzene Structure

1-(2,2-Dimethox...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

1-[2-(2-nitrophenyl)ethenyl]pyrrolidine Structure

1-[2-(2-nitroph...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

2-(2,2-dimethoxyethyl)aniline Structure

2-(2,2-dimethox...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

1-Benzyl-4-(1-indolyl)-piperidine Structure

1-Benzyl-4-(1-i...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

1-(pyridin-2-ylmethyl)piperidin-4-one Structure

1-(pyridin-2-yl...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

Indoline Structure

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

N,N-bis(2-ethoxycarbonylethyl)-N-(2-pyridilmethyl)amine Structure

N,N-bis(2-ethox...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

2-Picolylamine Structure

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

N-(tert-Butoxycarbonyl)-4-piperidone Structure

N-(tert-Butoxyc...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

4-(1H-Indol-1-yl)-1-Piperidinecarboxylic Acid Tert-Butyl Ester Structure

4-(1H-Indol-1-y...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

tert-butyl 4-(indolin-1-yl)piperidine-1-carboxylate Structure

tert-butyl 4-(i...

~%

1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indole Structure

1-{1-[(pyridin-...

Green chemistry approach to the synthesis of N-substituted p...

[Faul, Margaret M.; Kobierski, Michael E.; Kopach, Michael E. Journal of Organic Chemistry, 2003 , vol. 68, # 14 p. 5739 - 5741]

Green chemistry approach to the synthesis of N-substituted p...

[Faul, Margaret M.; Kobierski, Michael E.; Kopach, Michael E. Journal of Organic Chemistry, 2003 , vol. 68, # 14 p. 5739 - 5741]

Green chemistry approach to the synthesis of N-substituted p...

[Faul, Margaret M.; Kobierski, Michael E.; Kopach, Michael E. Journal of Organic Chemistry, 2003 , vol. 68, # 14 p. 5739 - 5741]

Green chemistry approach to the synthesis of N-substituted p...

[Faul, Margaret M.; Kobierski, Michael E.; Kopach, Michael E. Journal of Organic Chemistry, 2003 , vol. 68, # 14 p. 5739 - 5741]

Development of a Manufacturing Process for 1-(1-Pyridin-2-yl...

[Boini, Sathish; Moder, Kenneth P.; Vaid, Radhe K.; Kopach, Micheal; Kobierski Organic Process Research and Development, 2006 , vol. 10, # 6 p. 1205 - 1211]