Derivatives of 1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione as anxiolytic agents

A study of the pharmacological properties of pyrrolo[2,1-c][1,4]benzodiazepine derivatives led to the choice of (+)-1,2,3,11a-tetrahydro-10-methyl-5H-pyrrolol[2,1-c][1,4]benzodiazepine-5,11)10H)-dione as a candidate for anxiolytic evaluation in a limited clinical trial in man. Metabolism studies in...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1978-10, Vol.21 (10), p.1087-1089
Main Authors: Wright, William B, Brabander, Herbert J, Greenblatt, Eugene N, Day, Ivana P, Hardy, Robert A
Format: Article
Language:English
Subjects:
Animals
Anti-Anxiety Agents - chemical synthesis
Anticonvulsants - chemical synthesis
Benzodiazepinones - chemical synthesis
Benzodiazepinones - pharmacology
Conflict (Psychology)
Dogs
Dose-Response Relationship, Drug
Haplorhini
Humans
Mice
Pentylenetetrazole - antagonists & inhibitors
Rats
Saimiri
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Summary:A study of the pharmacological properties of pyrrolo[2,1-c][1,4]benzodiazepine derivatives led to the choice of (+)-1,2,3,11a-tetrahydro-10-methyl-5H-pyrrolol[2,1-c][1,4]benzodiazepine-5,11)10H)-dione as a candidate for anxiolytic evaluation in a limited clinical trial in man. Metabolism studies in laboratory animals have pointed to rapid hydroxylation, possibly in the 3 and 11a positions. A series of compouds containing methyl groups in one or more of these positions has been prepared in an effort to block metabolism and thereby obtain more active or longer acting compounds. All of these derivatives were less active than the parent compound.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00208a017