Cyclopropylamino acid amide as a pharmacophoric replacement for 2,3-diaminopyridine. Application to the design of novel bradykinin B1 receptor antagonists.
Antagonism of the bradykinin B1 receptor represents a potential treatment for chronic pain and inflammation. Novel antagonists were designed that display low-nanomolar affinity for the human bradykinin B1 receptor and good bioavailability in the rat.
Michael R
MR
Wood
Kathy M
KM
Schirripa
June J
JJ
Kim
Bang-Lin
BL
Wan
Kathy L
KL
Murphy
Richard W
RW
Ransom
Raymond S L
RS
Chang
Cuyue
C
Tang
Thomayant
T
Prueksaritanont
Theodore J
TJ
Detwiler
Lisa A
LA
Hettrick
Elizabeth R
ER
Landis
Yvonne M
YM
Leonard
Julie A
JA
Krueger
Sidney D
SD
Lewis
Douglas J
DJ
Pettibone
Roger M
RM
Freidinger
Mark G
MG
Bock
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D065169:Bradykinin B1 Receptor Antagonists; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008968:Molecular Conformation; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D065169:Bradykinin B1 Receptor Antagonists; D003521:Cyclopropanes; D011725:Pyridines