title: Synthesis and pharmacological evaluation of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives as new analgesic agents.
abstract: A series of carbamic acid 1-phenyl-3-(4-phenyl-piperazine-1-yl)-propyl ester derivatives were synthesized through discovery strategies for balancing target-based in vitro screening and phenotypic in vivo screening. All the newly synthesized compounds were screened for their analgesic activities and compared with standard drug morphine. Among them, compound 44r, a potent analgesic agent that has favorable pharmacokinetic properties in rats and most importantly, has a wide safety margin. We demonstrated with in vitro and in vivo functional assays that its analgesic activity might be through 5-HT(2A) antagonism to some extent. Hence, it is concluded that there is ample scope for further study in developing compound 44r as a good lead candidate for an analgesic agent.
authors.affiliation: Life Science Division, SK Biopharmaceuticals, Daejeon 305-712, Republic of Korea. Eunhee.chae@sk.com
authors.forename: Eunhee
authors.initials: E
authors.lastname: Chae
authors.forename: Hanju
authors.initials: H
authors.lastname: Yi
authors.forename: Yeonjung
authors.initials: Y
authors.lastname: Choi
authors.forename: Hyeon
authors.initials: H
authors.lastname: Cho
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Hongsik
authors.initials: H
authors.lastname: Moon
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology; D004952:Esters; D051379:Mice; D015394:Molecular Structure; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D002219:Carbamates; D004952:Esters; D010879:Piperazines; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D009020:Morphine