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学科主题: 药学
题名:
The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase
作者: Wang, Xiaowei1; Lou, Qinghua1; Guo, Ying1; Xu, Yang1; Zhang, Zhili1; Liu, Junyi1
刊名: ORGANIC & BIOMOLECULAR CHEMISTRY
发表日期: 2006
DOI: 10.1039/b607972p
卷: 4, 期:17, 页:3252-3258
收录类别: SCI ; IC ; CCR
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Organic
研究领域[WOS]: Chemistry
关键词[WOS]: HUMAN-IMMUNODEFICIENCY-VIRUS ; ANNELATED ANALOGS ; ANTI-HIV-1 AGENTS ; INVITRO ; MKC-442 ; TYPE-1 ; 3&prime ; -AZIDO-3&prime ; -DEOXYTHYMIDINE ; REPLICATION ; RESISTANCE ; COMPLEX
英文摘要:

Novel compounds, which can be considered as conformationally restricted analogues of MKC-442, have been synthesized and tested as inhibitors of the reverse transcriptase of human immunodeficiency virus type-1 (HIV-1). Reaction of urea with a beta-ketoester furnished 6,7,8,9-tetrahydro-9-phenyl- 1H-cyclohepta[d] pyrimidine-2,4-(3H,5H)-dione (6a) and 6,7,8,9-tetrahydro-9-p-tolyl-1H-cyclohepta[ d] pyrimidine-2,4-( 3H, 5H)-dione (6b) which were then alkylated at the N-1 position with chloromethyl ether, allyl bromide and benzyl bromide to afford the target compounds 7a - b, 8a - b, 9 and 10, respectively. The seven-membered, annelated compounds have a relatively rigid structures and can lock the orientation of the aromatic ring. Chemical modi. cation at N-1 of the pyrinidine ring and the 9-phenyl ring was attempted, with the aim of improving the antiretroviral activity. In particular, replacement of the aliphatic group with the phenyl moiety at the terminus of N-1 side chain can enhance the activity. The most active compounds showed activity in the low micromolar range with IC50 values comparable to that of nevirapine. The biological activity results are in accordance with the docking results.

语种: 英语
WOS记录号: WOS:000239915500014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50437
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, Beijing 100083, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China

Recommended Citation:
Wang, Xiaowei,Lou, Qinghua,Guo, Ying,et al. The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2006,4(17):3252-3258.
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