Exploration of a chemical series as a drug discovery strategy.
Thought process common to many medicinal chemists are exposed in this example dealing with the quest for the discovery of new analgesic agents. The unexpected course of a chemical reaction, and subsequent random screening of the product, led to the serendipidous finding of CNS activity in the phenylcyclohexylamine derivative (9). In the development of the lead, synthetic targets were continually adjusted as the result of subsequent biological testing, and finally produced two compounds (34 and 35) with clinical potential as analgetics. Each failed to enter clinical testing due to their toxicity, but the overall results led to new concepts of the nature of the mu opioid receptor.
Lednicer
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Department of Chemistry, University of Missouri, Columbia 65201.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans
D000700:Analgesics; D003514:Cyclohexylamines