title: Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity.
abstract: CB1 receptor antagonists that are peripherally restricted were targeted. Compounds with permanent charge as well as compounds that have increased polar surface area were made and tested against CB1 for binding and activity. Sulfonamide and sulfamide with high polar surface area and good activity at CB1 were rationally designed and pharmacologically tested. Further optimization of these compounds and testing could lead to the development of a new class of therapeutics to treat disorders where the CB1 receptor system has been implicated.
authors.affiliation: Pharmacology and Toxicology, RTI International, 3040 Cornwallis Rd., Research Triangle Park, NC 27709-2194, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Fulp
authors.forename: Katherine
authors.initials: K
authors.lastname: Bortoff
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Herbert
authors.initials: H
authors.lastname: Seltzman
authors.forename: Rodney
authors.initials: R
authors.lastname: Snyder
authors.forename: Rangan
authors.initials: R
authors.lastname: Maitra
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D063385:Cannabinoid Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004285:Dogs; D015195:Drug Design; D055808:Drug Discovery; D008024:Ligands; D015394:Molecular Structure; D010880:Piperidines / Q000378:metabolism; D011485:Protein Binding; D011720:Pyrazoles / Q000378:metabolism; D011869:Radioligand Assay; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000077285:Rimonabant; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D063385:Cannabinoid Receptor Modulators; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides; D000077285:Rimonabant