Journal of Medicinal Chemistry p. 391 - 396 (1989)
Update date:2022-09-26
Topics:
Callahan
Ashton-Shue
Bryan
Bryan
Heckman
Kinter
McDonald
Moore
Schmidt
Silvestri
Stassen
Sulat
Yim
Huffman
We report the synthesis and biological activity of a series of analogues of the vasopressin antagonists [Pmp1,D-Tyr(Et)2,Val4]arginine-vasopressin (1) and [Pmp1,D-Tyr(Et)2,Val4,desGly9]arginine-vasopressin (2), where part or all of the tripeptide tail has been replaced by a simple alkyldiamine [NH(CH2)(n)NH2] or (aminoalkyl)guanidine [NH(CH2)(n)NHC(=NH)NH2] in order to examine the effects that variation of the length and orientation of the tripeptide tail have on renal vasopressin (V2) receptor antagonist activity. The results show that the entire tripeptide tail (Pro-Arg-Gly-NH2) can be replaced by an alkyldiamine or an (aminoalkyl)guanidine, compounds 15 and 16, respectively, indicating that there is no orientational requirement for the basic functional group coming off the cyclic hexapeptide ring. Also, there seems to be an 'optimal' distance between the basic functional group and the hexapeptide ring since receptor affinity of the antagonists begins to fall off when the basic functional group is too close (compound 13) or extends too far (compounds 8-10) from the hexapeptide ring. These results suggest all that is necessary for retention of antagonist affinity and potency is a basic functional group, amine or guanidine, extended an optimal distance from the hexapeptide ring.
View MoreAirsea(Taizhou) Pharmaceutical Limited(expird)
Contact:+86-576-88057622
Address:Dubei, Duqiao, Linhai, Taizhou, Zhejiang, China Zip: 317016
LIAONING DMSO CHEMICALS CO.,LTD.
website:http://www.chinadmso.com
Contact:+86-427-6503033
Address:FLOOR 16, BLOCK A, FINANCIAL SQUARE, XINGLONGTAI DISTRICT, PANJIN CITY, LIAONING P.R. CHINA
Hangzhou Ledun Technology Co.,Ltd.
Contact:86-571-18767088918
Address:No.6 street,XiaSha,Hangzhou,China.
ZHEJIANG JIANYE CHEMICAL CO.,LTD.
Contact:86-571-64149273,64149234
Address:No. 48, Fuxi Road, Meicheng Town
Angelisun(Chongqing) Pharmaceutical Co., LTD.
Contact:+86-23-68030926-816
Address:D1-7 Tech & Entrepreneurs Park, Kecheng Road, Erlang Hi-Tech Areas, Chongqing, China
Doi:10.1021/jo00366a043
(1986)Doi:10.1016/S0040-4020(01)85435-1
(1990)Doi:10.1021/ja01202a061
(1947)Doi:10.3184/174751914X13888556743823
(2014)Doi:10.1055/s-2008-1032185
(2008)Doi:10.1002/jlac.198619861007
(1986)