Abstract
The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and beta-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.
MeSH terms
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Acetamides / chemical synthesis*
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Acetamides / chemistry
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Acetamides / pharmacology
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Analgesics / chemical synthesis*
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Analgesics / chemistry
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Analgesics / pharmacology
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Hypnotics and Sedatives / chemical synthesis
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Hypnotics and Sedatives / chemistry
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Hypnotics and Sedatives / pharmacology
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Indans / chemical synthesis*
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Indans / chemistry
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Indans / pharmacology
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Mice
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Monoamine Oxidase / metabolism
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Monoamine Oxidase Inhibitors / chemical synthesis
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Monoamine Oxidase Inhibitors / chemistry
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Monoamine Oxidase Inhibitors / pharmacology
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Muscle Relaxants, Central / chemical synthesis*
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Muscle Relaxants, Central / chemistry
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Muscle Relaxants, Central / pharmacology
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Rats
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Rats, Inbred Lew
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Rats, Wistar
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Stereoisomerism
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Structure-Activity Relationship
Substances
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2-(4,6-difluoro-1-indanylidene)acetamide
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Acetamides
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Analgesics
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Anti-Inflammatory Agents, Non-Steroidal
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Hypnotics and Sedatives
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Indans
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Monoamine Oxidase Inhibitors
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Muscle Relaxants, Central
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Monoamine Oxidase