Journal of Medicinal Chemistry p. 642 - 646 (1991)
Update date:2022-08-05
Topics:
Flouret
Brieher
Mahan
We prepared nine analogues (1-9) of MCPA-D-Phe-Phe-Ile-Asn-Cys-Pro-Arg-Gly-NH2, [MCPA1,D-Phe2,Phe3, Ile4, Arg8]oxytocin (MCPA = β-mercapto-β,β-pentamethylenepropionic acid), a potent antagonist of the rat uterotonic action of oxytocin (OT). We replaced D-Phe with D-Trp and made [MCPA1,D-Trp2,Phe3,Ile4,Arg8]OT (1), which had OT pA2 of 7.51, somewhat higher than that of the D-Phe2 antagonist which has OT pA2 = 7.35 in our rat uterotonic assay. Both compounds are equipotent as antagonists of [Arg8]vasopressin in the rat antidiuretic assay, with pA2 = 8.1. Other substitutions gave [MCPA1,D-Trp2,4-Cl-Phe3,Ile4,Arg8]OT (2), OT pA2 7.44; [MCPA1,D-Trp2,Phe3,Ile4,3,4-dehydro-Pro7,Arg8]OT (3), OT pA2 = 7.42; [MCPA1,D-Trp2,Phe3,Arg8]OT (4), OT pA2 = 7.58; [MCPA1,D-Trp2,Phe3,Arg8,Gly9-NHEt]OT (5), OT pA2 = 7.49; [MCPA1,D-Trp2,Ile4,Arg8]OT (6), OT pA2 = 7.46; [MCPA1,D-Trp2,Val4,Arg8]OT (7), OT pA2 = 7.58; [MCPA1,D-Trp2,Thr4,Arg8]OT (8), pA2 = 7.48; and finally, [MCPA1,D-Trp2,Arg8]OT (9), which was a more potent and more selective OT antagonist, with OT pA2 = 7.77 in the uterotonic assay and ADH pA2 < 5.9 in the antidiuretic assay and hence is an important lead for the design of OT antagonists.
View MoreWuhan Soleado Technology Co.,Ltd.
Contact:86-2783341481 18971291927
Address:RM2405 Unit 1 Builing 1, Taiyin Tower, Changqing Road,Wuhan China
Anhui Qingyun Pharmaceutical and Chemical Co.,Ltd
Contact:+86-551-63633067
Address:Shuangfeng Road Hefei Anhui
Contact:86 311 85902108 / 85902109
Address:room 1001-1005 ,huanghe Road ,shijiazhuang ,China
Heliosense Biotechnologies, Inc.
Contact:+86-592-5667290
Address:Xiamen Torch Hi-tech Zone Venture Weiye Building S506
Contact:0572-2722882
Address:1201,F3,xinghuibandao,
Doi:10.1021/ja110405q
(2011)Doi:10.1021/ja203660r
(2011)Doi:10.1007/s10593-011-0696-1
(2011)Doi:10.1016/S0040-4039(99)00360-3
(1999)Doi:10.1002/adfm.201002502
(2011)Doi:10.1039/c1cc11176k
(2011)