title: Synthesis and structure-activity relationship of naphtho[1,2-b]furan-2-carboxamide derivatives as melanin concentrating hormone receptor 1 antagonists.
abstract: The discovery that novel naphtho[1,2-b]furan-2-carboxamides containing linked piperidinylphenylacetamide groups serve as melanin concentrating hormone receptor 1 (MCH-R1) antagonists is described. An extensive structure-activity relationship (SAR) study, probing members of this family that contain a variety of aryl and heteroaryl groups at C-5 of the naphtho[1,2-b]furan-2-carboxamide skeleton and having different chain linker lengths, led to the identification of the 5-(4-pyridinyl) substituted analog 10b as a highly potent MCH-R1 antagonist with an IC50 value of 3 nM. This substance also displays good metabolic stability and it does not significantly inhibit cytochrome P450 (CYP450) enzymes. However, 10b has unacceptable oral bioavailability.
authors.affiliation: Division of Drug Discovery Research, Korea Research Institute of Chemical Technology.
authors.forename: Chae Jo
authors.initials: CJ
authors.lastname: Lim
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Lee
authors.forename: Kwang-Seok
authors.initials: KS
authors.lastname: Oh
authors.forename: Kyu Yang
authors.initials: KY
authors.lastname: Yi
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007028:Hypothalamic Hormones / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010907:Pituitary Hormones / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D005663:Furans; D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D011994:Recombinant Proteins; C019463:melanin-concentrating hormone