title: Phenylguanidines as selective nonpeptide melanocortin-5 receptor antagonists.
abstract: A series of phenylguanidine analogues represented by 10, 12, and 21 were synthesized and found to have high binding affinities for the human melanocortin-5 receptor. Their binding affinities for three other melanocortin receptor subtypes, MC1, MC3, and MC4, were low. Selected compounds were also tested for their functional activity and exhibited inhibition of alpha-MSH-stimulated cAMP production in cells expressing the human MC5 receptor. Compound 10 had a K(i) value of 2.1 nM in the binding assay and an IC(50) of 72 nM in the functional assay. Some analogues such as 13 from this series possessed weak agonist activity at the human MC4 receptor.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, California 92121, USA. cchen@neurocrine.com
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yu
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Sam R J
authors.initials: SR
authors.lastname: Hoare
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Alan C
authors.initials: AC
authors.lastname: Foster
mesh_terms: D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011869:Radioligand Assay; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors*; D044101:Receptors, Melanocortin; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D006146:Guanidines; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor; D000521:alpha-MSH; D000242:Cyclic AMP