title: Bradykinin B1 antagonists: biphenyl SAR studies in the cyclopropanecarboxamide series.
abstract: SAR study of the biphenyl region of cyclopropanecarboxamide derived bradykinin B(1) antagonists was examined. Incorporation of a pyridine in place of the proximal phenyl ring and chlorination of the distal phenyl ring proved to be well tolerated and provided compounds with improved pharmacokinetic profiles, CNS penetration, and enhanced receptor occupancy.
authors.affiliation: Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. scott_d_kuduk@merck.com <scott_d_kuduk@merck.com>
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kuduk
authors.forename: Robert M
authors.initials: RM
authors.lastname: DiPardo
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Chang
authors.forename: Christina N
authors.initials: CN
authors.lastname: Di Marco
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Murphy
authors.forename: Richard W
authors.initials: RW
authors.lastname: Ransom
authors.forename: Duane R
authors.initials: DR
authors.lastname: Reiss
authors.forename: Cuyue
authors.initials: C
authors.lastname: Tang
authors.forename: Thomayant
authors.initials: T
authors.lastname: Prueksaritanont
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Pettibone
authors.forename: Mark G
authors.initials: MG
authors.lastname: Bock
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists; D002490:Central Nervous System / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002713:Chlorine / Q000737:chemistry; D003521:Cyclopropanes / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D019800:Phenol / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D065169:Bradykinin B1 Receptor Antagonists; D003521:Cyclopropanes; D011725:Pyridines; D019800:Phenol; D002713:Chlorine; C030797:cyclopropane; C023666:pyridine