Synthesis and bradykinin inhibitory activity of novel non-peptide compounds, and evaluation of in vivo analgesic activity.
A series of novel non-peptide diamide compounds was synthesized and evaluated as antibradykinin agents by utilizing guinea-pig ileum smooth muscle. Among the final compounds, (Z)-4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-4-oxo-N-(4-phenylbutan-2-yl)but-2-enamide showed most favorable bradykinin inhibitory activity and demonstrated analgesic efficacies in the rat models of inflammatory and neuropathic pain.
Kam
Yoo Lim
YL
School of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
Rhee
Hee-Kyung
HK
Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Kim
Hwa-Jung
HJ
School of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
Back
Seung Keun
SK
Department of Physiology, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
Na
Heung Sik
HS
Department of Physiology, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
Choo
Hea-Young Park
HP
School of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003958:Diamide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D003958:Diamide; D001920:Bradykinin