ABSTRACT
The pharmacokinetic based optimisation of a novel series of indole-2-carboxamide antagonists of the cannabinoid CB(1) receptor is disclosed. Compound 24 was found to be a highly potent and selective cannabinoid CB(1) antagonist with high predicted human oral bioavailability.
Subject(s)
Indoles/pharmacokinetics , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Administration, Oral , Biological Availability , Humans , Indoles/administration & dosage , Indoles/chemistry , Structure-Activity RelationshipABSTRACT
The discovery and structure-activity relationship of a novel series of indole-2-carboxamide antagonists of the cannabinoid CB(1) receptor is disclosed. Compound 26i was found to be a high potency, selective cannabinoid CB(1) antagonist.
Subject(s)
Amides/chemistry , Indoles/chemistry , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Amides/chemical synthesis , Amides/pharmacokinetics , Animals , Dogs , Drug Evaluation, Preclinical , Indoles/chemical synthesis , Indoles/pharmacokinetics , Male , Mice , Models, Molecular , Rats , Rats, Wistar , Receptor, Cannabinoid, CB1/metabolism , Structure-Activity RelationshipSubject(s)
Cannabinoids/chemistry , Cannabinoids/pharmacology , Research , Animals , Cannabinoid Receptor Agonists , Humans , Imidazoles/chemistry , Imidazoles/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Receptors, Cannabinoid/metabolism , Structure-Activity RelationshipABSTRACT
On December 2, 2004, the Society for Medicines Research held the seventh Trends in Medicinal Chemistry one-day meeting. The meeting brought together speakers from Europe representing both academia and industry and provided an overview of some of the latest approaches being taken in a range of therapeutic areas such as oncology, antiinfectives, CNS disease and reproductive medicine.
Subject(s)
Biomedical Research/trends , Chemistry, Pharmaceutical/trends , Drug Therapy/trends , Societies, Scientific , Animals , Congresses as Topic , Humans , United KingdomABSTRACT
A series of 3-phenoxypropyl piperidine analogues have been discovered as novel ORL1 receptor agonists. Structure-activity relationships have been explored around the 3-phenoxypropyl region with several potent and selective analogues identified.
