Neuroleptics from the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole series. 3. Carboxamidoalkyl derivatives

Substitution of position 2 of the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole nucleus with omega-carboxamidoalkyl substituents leads to compounds with exceedingly potent neuroleptic activity in in vitro and in vivo models. Although duration of activity is not as long as that of the an...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1986-10, Vol.29 (10), p.2108-2111
Main Authors: Welch, Willard M, Harbert, Charles A, Sarges, Reinhard, Weissman, Albert, Koe, B. Kenneth
Format: Article
Language:English
Subjects:
Animals
Antipsychotic Agents - chemical synthesis
Antipsychotic Agents - pharmacology
Carbolines - chemical synthesis
Carbolines - pharmacology
Hydrogen Bonding
Rats
Receptors, Dopamine - drug effects
Structure-Activity Relationship
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Summary:Substitution of position 2 of the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole nucleus with omega-carboxamidoalkyl substituents leads to compounds with exceedingly potent neuroleptic activity in in vitro and in vivo models. Although duration of activity is not as long as that of the analogous 4-hydroxy-4-(4-fluorophenyl)butyl derivatives reported previously, the absolute potency in vivo is greater. The ability of these compounds to bind with great affinity to dopamine (DA) receptors further defines the nature of the DA receptor auxiliary binding site as a hydrogen-bond donating site in addition to or instead of a lipophilic site as has been previously proposed.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00160a053