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

Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1, 2-benzisoxazoles

JT Strupczewski, RC Allen, BA Gardner…

Index: Strupczewski, Joseph T.; Allen, Richard C.; Gardner, Beth Ann; Schmid, Blaine L.; Stache, Ulrich; et al. Journal of Medicinal Chemistry, 1985 , vol. 28, # 6 p. 761 - 769

Full Text: HTML

Citation Number: 87

Abstract

The synthesis of a series of 34 l-substituted-4-piperidinyl)-1, 2-benzisoxazoles is described. The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of [3H] spiroperidol binding. Structureactivity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents. Maximum neuroleptic activity was realized when there ...

(E)-1-Acetyl-N-(acetyloxy)-α-(5-fluoro-2-hydroxyphenyl)-4-piperidinemethanimine Structure

(E)-1-Acetyl-N-...

~%

3-(1-Acetyl-4-piperidinyl)-5-fluoro-1,2-benzisoxazole Structure

3-(1-Acetyl-4-p...

(E)-1-Acetyl-α-(5-fluoro-2-hydroxyphenyl)-N-hydroxy-4-piperidinemethanimine Structure

(E)-1-Acetyl-α-...

~%

3-(1-Acetyl-4-piperidinyl)-5-fluoro-1,2-benzisoxazole Structure

3-(1-Acetyl-4-p...

Isonipecotic acid Structure

Isonipecotic acid

Formyl acetate Structure

~74%

1-Formyl-4-piperidinecarboxylic Acid Structure

1-Formyl-4-pipe...

Ethanoic anhydride Structure

Ethanoic anhydride

(E)-1-Acetyl-α-(5-fluoro-2-hydroxyphenyl)-N-hydroxy-4-piperidinemethanimine Structure

(E)-1-Acetyl-α-...

~%

(E)-1-Acetyl-N-(acetyloxy)-α-(5-fluoro-2-hydroxyphenyl)-4-piperidinemethanimine Structure

(E)-1-Acetyl-N-...

Benzyl chloroformate Structure

Benzyl chloroformate

2-(5-Methoxy)phenol 4-Piperidinyl Ketone Hydrochloride Structure

2-(5-Methoxy)ph...

~73%

2-(5-Methoxy)phenol 4-(N-Benzyloxycarbonyl)piperidinyl Ketone Structure

2-(5-Methoxy)ph...

4-(N-Acetyl)piperidinyl 2-(5-Methoxy)phenol Ketone Structure

4-(N-Acetyl)pip...

~%

2-(5-Methoxy)phenol 4-(N-Benzyloxycarbonyl)piperidinyl Ketone Structure

2-(5-Methoxy)ph...

1-Acetylisonipecotoyl Chloride Structure

1-Acetylisonipe...

~%

2-(5-Methoxy)phenol 4-(N-Benzyloxycarbonyl)piperidinyl Ketone Structure

2-(5-Methoxy)ph...

1-Acetyl-4-piperidinecarboxylic acid Structure

1-Acetyl-4-pipe...

~%

2-(5-Methoxy)phenol 4-(N-Benzyloxycarbonyl)piperidinyl Ketone Structure

2-(5-Methoxy)ph...

1,3-Dimethoxybenzene Structure

1,3-Dimethoxybenzene

~%

2-(5-Methoxy)phenol 4-(N-Benzyloxycarbonyl)piperidinyl Ketone Structure

2-(5-Methoxy)ph...

1-Formyl-4-piperidinecarboxylic Acid Structure

1-Formyl-4-pipe...

~%

1-FORMYL-PIPERIDINE-4-CARBONYL CHLORIDE Structure

1-FORMYL-PIPERI...

1-Acetyl-4-piperidinecarboxylic acid Structure

1-Acetyl-4-pipe...

~%

1-[4-(5-Fluoro-2-hydroxybenzoyl)-1-piperidinyl]-ethanone Structure

1-[4-(5-Fluoro-...

4-Fluorobenzyl alcohol Structure

4-Fluorobenzyl ...

1-Acetylisonipecotoyl Chloride Structure

1-Acetylisonipe...

~%

1-[4-(5-Fluoro-2-hydroxybenzoyl)-1-piperidinyl]-ethanone Structure

1-[4-(5-Fluoro-...

N/A Structure

~%

4-fluoro-3-piperidin-4-yl-1,2-benzoxazole Structure

4-fluoro-3-pipe...

4-Chloro-1-methylpiperidine Structure

4-Chloro-1-meth...

~%

4-fluoro-3-piperidin-4-yl-1,2-benzoxazole Structure

4-fluoro-3-pipe...

2,6-Difluorobenzonitrile Structure

2,6-Difluoroben...

~%

4-fluoro-3-piperidin-4-yl-1,2-benzoxazole Structure

4-fluoro-3-pipe...

1-Methyl-4-(2,6-difluorobenzoyl)piperidine Structure

1-Methyl-4-(2,6...

~%

4-fluoro-3-piperidin-4-yl-1,2-benzoxazole Structure

4-fluoro-3-pipe...

4-fluoro-3-(1-methyl-4-piperidinyl)-1,2-benzisoxazole Structure

4-fluoro-3-(1-m...

~%

4-fluoro-3-piperidin-4-yl-1,2-benzoxazole Structure

4-fluoro-3-pipe...

3-(1-methyl-4-piperidinyl)-1,2-benzisoxazole Structure

3-(1-methyl-4-p...

Phenyl chloroformate Structure

Phenyl chloroformate

~77%

3-(4-Piperidinyl)-1,2-benzisoxazole N-Carbamic Acid Phenyl Ester Structure

3-(4-Piperidiny...

4-Chloro-1-methylpiperidine Structure

4-Chloro-1-meth...

~%

3-(4-Piperidinyl)-1,2-benzisoxazole N-Carbamic Acid Phenyl Ester Structure

3-(4-Piperidiny...

(2-fluorophenyl)-(1-methylpiperidin-4-yl)methanone Structure

(2-fluorophenyl...

~%

3-(4-Piperidinyl)-1,2-benzisoxazole N-Carbamic Acid Phenyl Ester Structure

3-(4-Piperidiny...

2-Fluorobenzonitrile Structure

2-Fluorobenzonitrile

~%

3-(4-Piperidinyl)-1,2-benzisoxazole N-Carbamic Acid Phenyl Ester Structure

3-(4-Piperidiny...

Ethanoic anhydride Structure

Ethanoic anhydride

(E)-2-(5-Methoxy)phenol 4-(N-Benzyloxycarbonyl)piperidinyl-methanone Oxime Structure

(E)-2-(5-Methox...

~%

(E)-2-(5-Methoxy)phenol 4-(N-Benzyloxycarbonyl)piperidinyl-methanone O-Acetyl Oxime Structure

(E)-2-(5-Methox...

4-(N-Acetyl)piperidinyl 2-(5-Methoxy)phenol Ketone Structure

4-(N-Acetyl)pip...

~70%

2-(5-Methoxy)phenol 4-Piperidinyl Ketone Hydrochloride Structure

2-(5-Methoxy)ph...

1-Acetyl-4-piperidinecarboxylic acid Structure

1-Acetyl-4-pipe...

~%

2-(5-Methoxy)phenol 4-Piperidinyl Ketone Hydrochloride Structure

2-(5-Methoxy)ph...

1-Acetylisonipecotoyl Chloride Structure

1-Acetylisonipe...

~%

2-(5-Methoxy)phenol 4-Piperidinyl Ketone Hydrochloride Structure

2-(5-Methoxy)ph...

1,3-Dimethoxybenzene Structure

1,3-Dimethoxybenzene

~%

2-(5-Methoxy)phenol 4-Piperidinyl Ketone Hydrochloride Structure

2-(5-Methoxy)ph...

1-Acetyl-4-piperidinecarboxylic acid Structure

1-Acetyl-4-pipe...

~%

4-(N-Acetyl)piperidinyl 2-(5-Methoxy)phenol Ketone Structure

4-(N-Acetyl)pip...

1-Acetylisonipecotoyl Chloride Structure

1-Acetylisonipe...

1,3-Dimethoxybenzene Structure

1,3-Dimethoxybenzene

~%

4-(N-Acetyl)piperidinyl 2-(5-Methoxy)phenol Ketone Structure

4-(N-Acetyl)pip...