Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 4. Central nervous system depressants

Journal of Medicinal Chemistry
1978.0

Abstract

The synthesis of 1'-[3-(4-fluorobenzyoyl)propyl]-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (2a) and eight halo and methoxy analogues is described. The compounds were generally more potent per os than chlorpromazine in the Sidman avoidance paradigm in rats and less potent than haloperido. 1'-[3-(4-Fluorobenzoyl)propyl]-3-(4-fluorophenyl)spiro[isobenzofuran-1(3H),4'-piperidine] (2e) approached the per os potency of haloperidol in this test and was shown to be active in inhibiting monkey avoidance also. Compound 2e was much less active than haloperidol in antagonizing apomorphine-induced emesis in dogs, apomorphine-induced stereotypy in rats, and amphetamine-induced circling in lesioned rats. This lack of nonselective, dopamine-receptor blocking effects makes 2e attrative as a potential neuroleptic.

Knowledge Graph

Similar Paper

Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 4. Central nervous system depressants
Journal of Medicinal Chemistry 1978.0
Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 6. Synthesis, carbon-13 NMR, and biological evaluation of cis- and trans-4-amino-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives
Journal of Medicinal Chemistry 1981.0
Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines as potential central nervous system agents. 2. Compounds containing a heteroatom attached to nitrogen
Journal of Medicinal Chemistry 1977.0
A novel class of potential central nervous system agents. 3-Phenyl-2-(1-piperazinyl)-5H-1-benzazepines
Journal of Medicinal Chemistry 1988.0
Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 5. Conformationally mobile analogs derived by furan ring opening
Journal of Medicinal Chemistry 1979.0
Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles
Journal of Medicinal Chemistry 1985.0
Novel tetracyclic spiropiperidines. 1. 3-Aryl-1,3-dihydrospiro[benzo[c]thiophene-1,4'-piperidines] as potential antidepressants
Journal of Medicinal Chemistry 1981.0
Potential neuroleptic agents. 4. Chemistry, behavioral pharmacology, and inhibition of [3H]spiperone binding of 3,5-disubstituted N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides
Journal of Medicinal Chemistry 1986.0
Derivatives of 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine as central nervous system agents
Journal of Medicinal Chemistry 1980.0
5-Piperazinylalkyl-2(3H)-oxazolones with neuroleptic activity
Journal of Medicinal Chemistry 1989.0