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

Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors

…, D Garrido, W Mills, J Peckham, F Preugschat…

Index: Peat, Andrew J.; Boucheron, Joyce A.; Dickerson, Scott H.; Garrido, Dulce; Mills, Wendy; Peckham, Jennifer; Preugschat, Frank; Smalley, Terrence; Schweiker, Stephanie L.; Wilson, Jayme R.; Wang, Tony Y.; Zhou, Huiqiang Q.; Thomson, Stephen A. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 9 p. 2121 - 2125

Full Text: HTML

Citation Number: 62

Abstract

A series of [1-aryl-1H-pyrazolo [3, 4-d] pyrimidin-4-yl] arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar1) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to ...

p-anisylhydrazine Structure

p-anisylhydrazine

~%

4-CHLORO-1-(4-METHOXYPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE Structure

4-CHLORO-1-(4-M...

5-AMINO-1-(4-METHOXYPHENYL)-1H-PYRAZOLE-4-CARBONITRILE Structure

5-AMINO-1-(4-ME...

~%

4-CHLORO-1-(4-METHOXYPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE Structure

4-CHLORO-1-(4-M...

3-Hydrazinopyridinedihydrochloride Structure

3-Hydrazinopyri...

Ethoxymethylenemalononitrile Structure

Ethoxymethylene...

~%

5-amino-1-pyridin-3-ylpyrazole-4-carbonitrile Structure

5-amino-1-pyrid...

M-TOLYLHYDRAZINE Structure

M-TOLYLHYDRAZINE

~%

4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,5-dihydro-1-(3-methylphenyl)- Structure

4H-Pyrazolo[3,4...

M-TOLYLHYDRAZINE Structure

M-TOLYLHYDRAZINE

~%

4-chloro-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-m...

4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,5-dihydro-1-(3-methylphenyl)- Structure

4H-Pyrazolo[3,4...

~%

4-chloro-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-m...

3-Hydrazinopyridinedihydrochloride Structure

3-Hydrazinopyri...

~%

1-pyridin-3-yl-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-pyridin-3-yl-...

Formic Acid Structure

5-amino-1-pyridin-3-ylpyrazole-4-carbonitrile Structure

5-amino-1-pyrid...

~%

1-pyridin-3-yl-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-pyridin-3-yl-...

3-Hydrazinopyridinedihydrochloride Structure

3-Hydrazinopyri...

~%

4-chloro-1-pyridin-3-ylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-pyri...

1-pyridin-3-yl-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-pyridin-3-yl-...

~%

4-chloro-1-pyridin-3-ylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-pyri...

5-amino-1-pyridin-3-ylpyrazole-4-carbonitrile Structure

5-amino-1-pyrid...

~%

4-chloro-1-pyridin-3-ylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-pyri...

4-Methylphenylhydrazine Structure

4-Methylphenylh...

~%

4-CHLORO-1-(P-TOLYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE Structure

4-CHLORO-1-(P-T...

1-(p-tolyl)-1,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(p-tolyl)-1,5...

~%

4-CHLORO-1-(P-TOLYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE Structure

4-CHLORO-1-(P-T...

5-Amino-1-(4-methylphenyl)-1H-pyrazole-4-carbonitrile Structure

5-Amino-1-(4-me...

~%

4-CHLORO-1-(P-TOLYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE Structure

4-CHLORO-1-(P-T...

3-Bromo-phenylhydrazine Structure

3-Bromo-phenylh...

~%

1-(3-bromophenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-bromopheny...

Formic Acid Structure

5-amino-1-(3-bromophenyl)-1H-Pyrazole-4-carbonitrile Structure

5-amino-1-(3-br...

~%

1-(3-bromophenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-bromopheny...

(3-methoxyphenyl)hydrazine Structure

(3-methoxypheny...

~%

1-(3-methoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-methoxyphe...

Formic Acid Structure

5-amino-1-(3-methoxyphenyl)pyrazole-4-carbonitrile Structure

5-amino-1-(3-me...

~%

1-(3-methoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-methoxyphe...

Ethoxymethylenemalononitrile Structure

Ethoxymethylene...

2-hydrazino-6-methoxypyridine Structure

2-hydrazino-6-m...

~%

5-amino-1-(6-methoxypyridin-2-yl)pyrazole-4-carbonitrile Structure

5-amino-1-(6-me...

3-Bromo-phenylhydrazine Structure

3-Bromo-phenylh...

~%

1-(3-bromophenyl)-4-chloropyrazolo[3,4-d]pyrimidine Structure

1-(3-bromopheny...

1-(3-bromophenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-bromopheny...

~%

1-(3-bromophenyl)-4-chloropyrazolo[3,4-d]pyrimidine Structure

1-(3-bromopheny...

5-amino-1-(3-bromophenyl)-1H-Pyrazole-4-carbonitrile Structure

5-amino-1-(3-br...

~%

1-(3-bromophenyl)-4-chloropyrazolo[3,4-d]pyrimidine Structure

1-(3-bromopheny...

Ethoxymethylenemalononitrile Structure

Ethoxymethylene...

(2-METHOXY-NAPHTHALEN-1-YLMETHYL)-HYDRAZINE Structure

(2-METHOXY-NAPH...

~%

5-amino-1-(2-methoxyphenyl)pyrazole-4-carbonitrile Structure

5-amino-1-(2-me...

2-hydrazino-6-methoxypyridine Structure

2-hydrazino-6-m...

~%

4-chloro-1-(6-methoxypyridin-2-yl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(6-m...

1-(6-methoxypyridin-2-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(6-methoxypyr...

~%

4-chloro-1-(6-methoxypyridin-2-yl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(6-m...

5-amino-1-(6-methoxypyridin-2-yl)pyrazole-4-carbonitrile Structure

5-amino-1-(6-me...

~%

4-chloro-1-(6-methoxypyridin-2-yl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(6-m...

4-Chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine Structure

4-Chloro-1-phen...

~%

1H-Pyrazolo[3,4-d]pyrimidine,4-hydrazinyl-1-phenyl- Structure

1H-Pyrazolo[3,4...

5-Amino-1-phenyl-1H-pyrazole-4-carbonitrile Structure

5-Amino-1-pheny...

~%

1H-Pyrazolo[3,4-d]pyrimidine,4-hydrazinyl-1-phenyl- Structure

1H-Pyrazolo[3,4...

4H-Pyrazolo[3,4-d]pyrimidin-4-one,1,5-dihydro-1-phenyl- Structure

4H-Pyrazolo[3,4...

~%

1H-Pyrazolo[3,4-d]pyrimidine,4-hydrazinyl-1-phenyl- Structure

1H-Pyrazolo[3,4...

3-ETHOXY-PHENYL-HYDRAZINE Structure

3-ETHOXY-PHENYL...

~%

1-(3-ethoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-ethoxyphen...

Formic Acid Structure

5-amino-1-(3-ethoxyphenyl)pyrazole-4-carbonitrile Structure

5-amino-1-(3-et...

~%

1-(3-ethoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-ethoxyphen...

3-ETHOXY-PHENYL-HYDRAZINE Structure

3-ETHOXY-PHENYL...

~%

4-chloro-1-(3-ethoxyphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-e...

1-(3-ethoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-ethoxyphen...

~%

4-chloro-1-(3-ethoxyphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-e...

5-amino-1-(3-ethoxyphenyl)pyrazole-4-carbonitrile Structure

5-amino-1-(3-et...

~%

4-chloro-1-(3-ethoxyphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-e...

3-nitrophenylhydrazine Structure

3-nitrophenylhy...

~%

4-chloro-1-(3-nitrophenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-n...

5-amino-1-(3-nitrophenyl)pyrazole-4-carbonitrile Structure

5-amino-1-(3-ni...

~%

4-chloro-1-(3-nitrophenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-n...

Phenylhydrazine Structure

Phenylhydrazine

~%

1H-Pyrazolo[3,4-d]pyrimidine,4-hydrazinyl-1-phenyl- Structure

1H-Pyrazolo[3,4...

2-(1-ethoxybutylidene)malononitrile Structure

2-(1-ethoxybuty...

~%

4-chloro-1-(3-methoxyphenyl)-3-propylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-m...

(3-methoxyphenyl)hydrazine Structure

(3-methoxypheny...

~%

4-chloro-1-(3-methoxyphenyl)-3-propylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-m...

1-(3-methoxyphenyl)-3-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-methoxyphe...

~%

4-chloro-1-(3-methoxyphenyl)-3-propylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-m...

5-amino-1-(3-methoxyphenyl)-3-propylpyrazole-4-carbonitrile Structure

5-amino-1-(3-me...

~%

4-chloro-1-(3-methoxyphenyl)-3-propylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-(3-m...

2-Hydrazinylpyridine Structure

2-Hydrazinylpyridine

~%

1-pyridin-2-yl-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-pyridin-2-yl-...

Formic Acid Structure

5-AMINO-1-(PYRIDIN-2-YL)-1H-PYRAZOLE-4-CARBONITRILE Structure

5-AMINO-1-(PYRI...

~%

1-pyridin-2-yl-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-pyridin-2-yl-...

5-Amino-1-phenyl-1H-pyrazole-4-carbonitrile Structure

5-Amino-1-pheny...

~%

4-Chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine Structure

4-Chloro-1-phen...

Phenylhydrazine Structure

Phenylhydrazine

~%

4-Chloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine Structure

4-Chloro-1-phen...

2-(1-Ethoxypropylidene)malononitrile Structure

2-(1-Ethoxyprop...

(3-methoxyphenyl)hydrazine Structure

(3-methoxypheny...

~%

5-amino-3-ethyl-1-(3-methoxyphenyl)pyrazole-4-carbonitrile Structure

5-amino-3-ethyl...

2-(1-Ethoxypropylidene)malononitrile Structure

2-(1-Ethoxyprop...

~%

4-chloro-3-ethyl-1-(3-methoxyphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-3-ethy...

3-ethyl-1-(3-methoxyphenyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Structure

3-ethyl-1-(3-me...

~%

4-chloro-3-ethyl-1-(3-methoxyphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-3-ethy...

5-amino-3-ethyl-1-(3-methoxyphenyl)pyrazole-4-carbonitrile Structure

5-amino-3-ethyl...

~%

4-chloro-3-ethyl-1-(3-methoxyphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-3-ethy...

Formic Acid Structure

5-amino-1-(1,3-thiazol-2-yl)pyrazole-4-carbonitrile Structure

5-amino-1-(1,3-...

~%

1-(1,3-thiazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(1,3-thiazol-...

1-(1,3-thiazol-2-yl)-2H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(1,3-thiazol-...

~%

2-(4-chloropyrazolo[3,4-d]pyrimidin-1-yl)-1,3-thiazole Structure

2-(4-chloropyra...

5-amino-1-(1,3-thiazol-2-yl)pyrazole-4-carbonitrile Structure

5-amino-1-(1,3-...

~%

2-(4-chloropyrazolo[3,4-d]pyrimidin-1-yl)-1,3-thiazole Structure

2-(4-chloropyra...

1-(3-(trifluoromethoxy)phenyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Structure

1-(3-(trifluoro...

~%

4-chloro-1-[3-(trifluoromethoxy)phenyl]pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-[3-(...

5-amino-1-[3-(trifluoromethoxy)phenyl]pyrazole-4-carbonitrile Structure

5-amino-1-[3-(t...

~%

4-chloro-1-[3-(trifluoromethoxy)phenyl]pyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-[3-(...

(3-methoxyphenyl)hydrazine Structure

(3-methoxypheny...

~%

4-chloro-3-ethyl-1-(3-methoxyphenyl)pyrazolo[3,4-d]pyrimidine Structure

4-chloro-3-ethy...

4-Hydrazinopyridine Structure

4-Hydrazinopyridine

~%

4-chloro-1-pyridin-4-ylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-pyri...

5-AMINO-1-(PYRIDIN-4-YL)-1H-PYRAZOLE-4-CARBONITRILE Structure

5-AMINO-1-(PYRI...

~%

4-chloro-1-pyridin-4-ylpyrazolo[3,4-d]pyrimidine Structure

4-chloro-1-pyri...

A one step synthesis of 1-alkylpyrazolo [5, 4-d] pyrimidines

[Boyd, Scott; Campbell, Leonie; Liao, Wensheng; Meng, Qinghong; Peng, Zuozhong; Wang, Xiaoping; Waring, Michael J. Tetrahedron Letters, 2008 , vol. 49, # 52 p. 7395 - 7397]

N–N Bond-Forming Cyclization for the One-Pot Synthesis of N-...

[Evans, Lindsay E.; Cheeseman, Matthew D.; Jones, Keith Organic Letters, 2012 , vol. 14, # 13 p. 3546 - 3549]

N–N Bond-Forming Cyclization for the One-Pot Synthesis of N-...

[Evans, Lindsay E.; Cheeseman, Matthew D.; Jones, Keith Organic Letters, 2012 , vol. 14, # 13 p. 3546 - 3549]