Journal of Medicinal Chemistry p. 1729 - 1738 (1988)
Update date:2022-07-30
Topics:
Borcherding
Narayanan
Hasobe
McKee
Keller
Borchardt
A series of 9-(hydroxyalkenyl)purines (adenines and 3-deazaadenines), which are analogues of neplanocin A, were synthesized. The analogues were tested as inhibitors of bovine liver and murine L929 cell S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus replication in murine L929 cells. Compounds 1b, 2a, 2b, 4a, 4b, 7, 9a, and 9b showed the best inhibitory effects toward bovine liver AdoHcy hydrolase, with compound 4b being the most potent. The compounds that were shown to be the most potent inhibitors of the bovine liver AdoHcy hydrolase all contained an allylic hydroxyl group in the cis position to the adenine or the 3-deazaadenine rings. It was concluded that the cis arrangement of the allylic hydroxyl groups in these acyclic compounds represented the minimum structural requirement of the trihydroxycyclopentenyl ring of neplanocin A to show inhibitory effects against AdoHcy hydrolase. The antiviral effects of these acyclic analogues were significantly less than neplanocin A; however, there appears to be a correlation between the antiviral activity and the inhibition of AdoHcy hydrolase for compounds 2a, 2b, 4a, 4b, and 7. Analogue 4b, which exhibited the best antiviral activity (IC50=70 μM) in this acyclic series, is substantially less potent than neplanocin A (IC50=0.08 μM) as an antiviral agent.
View MoreHangzhou Deli Chemical Co.,Ltd.
website:http://www.dlchemical.com
Contact:86 571 28006267
Address:Tangxi Industrial Area, Yuhang District, Hangzhou
Jiangxi Hito Chemical Co., Ltd.
Contact:+86-792-3170318
Address:No. 6, Tianhong Ave., Xinghuo Industry Park, Yongxiu, Jiujiang, Jiangxi, China
Xi'an North Information Industry Co., Ltd. Weilv Chemical Department
Contact:+86-29-88156413
Address:Jixiang Road 99 Xi'an Shaanxi Province
Contact:+86-20-32051076
Address:1105,Building A, International Business Incubator,Science City
Weihao Chemtech (ChangZhou) Co., Ltd.(expird)
Contact:051989185693
Address:NO 217 huangshan Rd ,Changzhou
Doi:10.1021/jm060325b
(2006)Doi:10.1016/S0040-4039(00)96384-6
(1987)Doi:10.1055/s-0028-1087545
(2009)Doi:10.1016/j.tetasy.2009.02.023
(2009)Doi:10.1021/om900114m
(2009)Doi:10.1039/b817433d
(2009)