title: Bradykinin B1 receptor antagonists: an alpha-hydroxy amide with an improved metabolism profile.
abstract: A series of carbo- and heterocyclic alpha-hydroxy amide-derived bradykinin B1 antagonists was prepared and evaluated. A 4,4-difluorocyclohexyl alpha-hydroxy amide was incorporated along with a 2-methyl tetrazole in lieu of an oxadiazole to afford a suitable compound with good pharmacokinetic properties, CNS penetration, and clearance by multiple metabolic pathways.
authors: Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. scott_d_kuduk@merck.com
authors: Scott D
authors: SD
authors: Kuduk
authors: Ronald K
authors: RK
authors: Chang
authors: Robert M
authors: RM
authors: Dipardo
authors: Christina N
authors: CN
authors: Di Marco
authors: Kathy L
authors: KL
authors: Murphy
authors: Richard W
authors: RW
authors: Ransom
authors: Duane R
authors: DR
authors: Reiss
authors: Cuyue
authors: C
authors: Tang
authors: Thomayant
authors: T
authors: Prueksaritanont
authors: Douglas J
authors: DJ
authors: Pettibone
authors: Mark G
authors: MG
authors: Bock
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists; D002490:Central Nervous System / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000577:Amides; D065169:Bradykinin B1 Receptor Antagonists; D013777:Tetrazoles