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

Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia

…, J Pandit, TA Chappie, JM Humphrey…

Index: Helal, Christopher J.; Kang, Zhijun; Hou, Xinjun; Pandit, Jayvardhan; Chappie, Thomas A.; Humphrey, John M.; Marr, Eric S.; Fennell, Kimberly F.; Chenard, Lois K.; Fox, Carol; Schmidt, Christopher J.; Williams, Robert D.; Chapin, Douglas S.; Siuciak, Judith; Lebel, Lorraine; Menniti, Frank; Cianfrogna, Julia; Fonseca, Kari R.; Nelson, Frederick R.; O Connor, Rebecca; MacDougall, Mary; McDowell, Laura; Liras, Spiros Journal of Medicinal Chemistry, 2011 , vol. 54, # 13 p. 4536 - 4547

Full Text: HTML

Citation Number: 33

Abstract

Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and ...

4,5-Dimethoxy-2-nitrobenzoic acid Structure

4,5-Dimethoxy-2...

~10%

5-Hydroxy-4-methoxy-2-nitrobenzoic acid Structure

5-Hydroxy-4-met...

2-Quinolineacetic acid methyl ester Structure

2-Quinolineacet...

~54%

2-(2-Quinolinyl)ethanol Structure

2-(2-Quinolinyl...

Methyl 5-(benzyloxy)-4-methoxy-2-nitrobenzoate Structure

Methyl 5-(benzy...

~%

7-methoxy-6-phenylmethoxy-1H-quinazolin-4-one Structure

7-methoxy-6-phe...

Methyl 5-hydroxy-4-methoxy-2-nitrobenzoate Structure

Methyl 5-hydrox...

~%

7-methoxy-6-phenylmethoxy-1H-quinazolin-4-one Structure

7-methoxy-6-phe...

Methyl 2-amino-4-methoxy-5-(phenylmethoxy)benzoate Structure

Methyl 2-amino-...

~%

7-methoxy-6-phenylmethoxy-1H-quinazolin-4-one Structure

7-methoxy-6-phe...

5-Hydroxy-4-methoxy-2-nitrobenzoic acid Structure

5-Hydroxy-4-met...

~%

7-methoxy-6-phenylmethoxy-1H-quinazolin-4-one Structure

7-methoxy-6-phe...

4,5-Dimethoxy-2-nitrobenzoic acid Structure

4,5-Dimethoxy-2...

~%

7-methoxy-6-phenylmethoxy-1H-quinazolin-4-one Structure

7-methoxy-6-phe...

Methanol Structure

5-Hydroxy-4-methoxy-2-nitrobenzoic acid Structure

5-Hydroxy-4-met...

~95%

Methyl 5-hydroxy-4-methoxy-2-nitrobenzoate Structure

Methyl 5-hydrox...

2,4-Dichloro-6,7-dimethoxyquinazoline Structure

2,4-Dichloro-6,...

~66%

6,7-dimethoxyquinazoline Structure

6,7-dimethoxyqu...

7-methoxy-6-phenylmethoxy-1H-quinazolin-4-one Structure

7-methoxy-6-phe...

~99%

6-(Benzyloxy)-4-chloro-7-methoxyquinazoline Structure

6-(Benzyloxy)-4...

2-amino-4-methoxy-5-phenylmethoxybenzoic acid Structure

2-amino-4-metho...

~%

6-(Benzyloxy)-4-chloro-7-methoxyquinazoline Structure

6-(Benzyloxy)-4...

5-Hydroxy-4-methoxy-2-nitrobenzoic acid Structure

5-Hydroxy-4-met...

~%

6-(Benzyloxy)-4-chloro-7-methoxyquinazoline Structure

6-(Benzyloxy)-4...

4,5-Dimethoxy-2-nitrobenzoic acid Structure

4,5-Dimethoxy-2...

~%

6-(Benzyloxy)-4-chloro-7-methoxyquinazoline Structure

6-(Benzyloxy)-4...

Methyl 2-amino-4-methoxy-5-(phenylmethoxy)benzoate Structure

Methyl 2-amino-...

~95%

2-amino-4-methoxy-5-phenylmethoxybenzoic acid Structure

2-amino-4-metho...

Methyl 5-(benzyloxy)-4-methoxy-2-nitrobenzoate Structure

Methyl 5-(benzy...

~%

2-amino-4-methoxy-5-phenylmethoxybenzoic acid Structure

2-amino-4-metho...

Methyl 5-hydroxy-4-methoxy-2-nitrobenzoate Structure

Methyl 5-hydrox...

~%

2-amino-4-methoxy-5-phenylmethoxybenzoic acid Structure

2-amino-4-metho...

5-Hydroxy-4-methoxy-2-nitrobenzoic acid Structure

5-Hydroxy-4-met...

~%

2-amino-4-methoxy-5-phenylmethoxybenzoic acid Structure

2-amino-4-metho...

4,5-Dimethoxy-2-nitrobenzoic acid Structure

4,5-Dimethoxy-2...

~%

2-amino-4-methoxy-5-phenylmethoxybenzoic acid Structure

2-amino-4-metho...

Methyl 5-hydroxy-4-methoxy-2-nitrobenzoate Structure

Methyl 5-hydrox...

Benzyl bromide Structure

~91%

Methyl 5-(benzyloxy)-4-methoxy-2-nitrobenzoate Structure

Methyl 5-(benzy...