Discovery of a potent, peripherally selective trans-3, 4-dimethyl-4-(3-hydroxyphenyl) piperidine opioid antagonist for the treatment of gastrointestinal motility disorders

…, DD Schoepp, BG Johnson, JD Leander

Index: Zimmerman, Dennis M.; Gidda, Jaswant S.; Cantrell, Buddy E.; Schoepp, Darryle D.; Johnson, Bryan G.; Leander, J. David Journal of Medicinal Chemistry, 1994 , vol. 37, # 15 p. 2262 - 2265

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Citation Number: 127

Abstract

Structure-activity relationship studies were pursued within N-substituted-truns-3, 4-dimethyl- 4-(3-hydroxyphenyl) piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (Ki= 0.77, 40, and 4.4 nM for p, K, and 6 receptors, respectively ...