Aryl sulfones as novel bradykinin B1 receptor antagonists for treatment of chronic pain.
We report the development of aryl sulfones as Bradykinin B1 receptor antagonists. Variation of the linker region identified diol 23 as a potent B1 antagonist, while modifications of the aryl moiety led to compound 26, both of which were efficacious in rabbit biochemical challenge and pain models.
Biswas
Kaustav
K
Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, MS 29-1-B, Thousand Oaks, CA 91320, USA.
Aya
Toshihiro
T
Qian
Wenyuan
W
Peterkin
Tanya A N
TA
Chen
Jian Jeffrey
JJ
Human
Jason
J
Hungate
Randall W
RW
Kumar
Gondi
G
Arik
Leyla
L
Lester-Zeiner
Dianna
D
Biddlecome
Gloria
G
Manning
Barton H
BH
Sun
Hong
H
Dong
Hong
H
Huang
Ming
M
Loeloff
Richard
R
Johnson
Eileen J
EJ
Askew
Benny C
BC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D002908:Chronic Disease; D006801:Humans; D010146:Pain / Q000188:drug therapy*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D013450:Sulfones