Journal of Medicinal Chemistry p. 1457 - 1463 (1989)
Update date:2022-08-04
Topics: -Synthesis -Antiviral activity -Nucleotide analogue -(S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cystosine
Bronson
Ghazzouli
Hitchcock
Webb II
Martin
The acyclic nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (2, HPMPC) was prepared on a multigram scale in 18% overall yield starting from (R)-2,3-O-isopropylideneglycerol. The key step in the nine-step synthetic route is coupling of cytosine with the side-chain derivative 8 which bears a protected phosphonylmethyl ether group. In vitro data showed that HPMPC has good activity against herpes simplex virus types 1 and 2, although it was 10-fold less potent that acyclovir [ACV, 9-[(2-hydroxyethoxy)methyl]guanine]. By comparison, HPMPC exhibited greater activity than ACV against a thymidine kinase deficient strain of HSV 1 and was more potent than ganciclovir [DHPG, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine] against human cytomegalovirus. In vivo, HPMPC showed exceptional potency against HSV 1 systemic infection in mice, having an ED50 of 0.1 mg/kg per day (ip) compared with 50 mg/kg per day for ACV. HPMPc was also more efficacious than ACV in the topical treatment of HSV 1 induced cutaneous lesions in guinea pigs.
View MoreGuangzhou Probig Fine Chemical Co., Ltd.
Contact:020-86297874
Address:No.2, 1/F, No.20, Hetai Road,Hebian Village, Baiyun District,Guangzhou,China
Xinchang Jiu Xin Pharmaceutical Co., Ltd
website:http://www.jiuxinpharm.com
Contact:86 137 5756 8585
Address:Poyang industry Park
Luojiang Chenming Biological Products Co
Contact:+86 15000297032
Address:GROUP NO.4, HE SHENG VILLAGE, PANLONG TOWN,
Nantong LiKai Chemical Co.,Ltd
Contact:+86-513-89068669
Address:Jincheng Science Park
shandong lukang animal & plant drug trading co.,ltd.
Contact:15853765968
Address:floor 9, lukang ,jingying building,#173,taibai building west road,jining city,shandong,china
Doi:10.1002/adsc.201500658
(2016)Doi:10.1039/f19888403347
(1988)Doi:10.1002/hlca.19880710307
(1988)Doi:10.1016/j.jorganchem.2009.09.038
(2010)Doi:10.1021/jacs.6b05738
(2016)Doi:10.1016/S0040-4020(01)00152-1
(2001)