Bradykinin B1 antagonists: biphenyl SAR studies in the cyclopropanecarboxamide series.
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.
Kuduk
Scott D
SD
Department of Medicinal Chemistry, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA. scott_d_kuduk@merck.com <scott_d_kuduk@merck.com>
DiPardo
Robert M
RM
Chang
Ronald K
RK
Di Marco
Christina N
CN
Murphy
Kathy L
KL
Ransom
Richard W
RW
Reiss
Duane R
DR
Tang
Cuyue
C
Prueksaritanont
Thomayant
T
Pettibone
Douglas J
DJ
Bock
Mark G
MG
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
D000577:Amides; D065169:Bradykinin B1 Receptor Antagonists; D003521:Cyclopropanes; D011725:Pyridines; D019800:Phenol; D002713:Chlorine; C030797:cyclopropane; C023666:pyridine