ABSTRACT
High throughput screening of our compound library revealed a series of N-pyridyl-3-benzamides as low micromolar agonists of the human TRPV1 receptor. Synthesis of analogs in this series led to the discovery of a series of N-quinolin-3-yl-benzamides as low nanomolar antagonists of human TRPV1.
Subject(s)
Benzamides/chemical synthesis , Benzamides/pharmacology , Isoquinolines/chemistry , Pyridines/chemistry , TRPV Cation Channels/antagonists & inhibitors , TRPV Cation Channels/metabolism , Animals , Benzamides/chemistry , Benzamides/therapeutic use , Cross-Linking Reagents/chemistry , Humans , Hyperalgesia/drug therapy , Molecular Structure , Rats , Structure-Activity RelationshipABSTRACT
Two parallel synthetic methods were developed to explore the structure-activity relationships (SAR) of a series of potent opioid agonists. This series of tropanylidene benzamides proved extremely tolerant of structural variation while maintaining excellent opioid activity. Evaluation of several representative compounds from this series in the mouse hot plate test revealed potent antinociceptive effects upon oral administration.
Subject(s)
Analgesics , Benzamides , Receptors, Opioid, delta/agonists , Receptors, Opioid, mu/agonists , Analgesics/chemical synthesis , Analgesics/chemistry , Animals , Benzamides/chemical synthesis , Benzamides/chemistry , Mice , Molecular Structure , Pain Measurement/drug effects , Structure-Activity RelationshipABSTRACT
The synthesis and structure-activity relationships of a novel series of aroylpyrrole alkylamides as potent selective bradykinin B(2) receptor antagonists are described. Several members of this series display nanomolar affinity at the B(2) receptor and show activity in an animal model of antinociception.
