Antiviral activity of 2',3'-dideoxycytidin-2'-ene (2',3'-dideoxy-2',3'-didehydrocytidine) against human immunodeficiency virus in vitro.
Antiviral activity of 2',3'-dideoxycytidin-2'-ene (2',3'-dideoxy-2',3'-didehydrocytidine) against human immunodeficiency virus in vitro.
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2,3-dideoxycytidin-2-ene (2,3-dideoxy-2,3-didehydrocytidine) 对人类免疫缺陷病毒的体外抗病毒活性。
DOI：
10.1016/0006-2952(87)90287-5
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发表时间：
1987
影响因子：
5.8
通讯作者：
Prusoff,WH
中科院分区：
文献类型：
--
作者：
Lin,TS;Schinazi,RF;Chen,MS;Kinney-Thomas,E;Prusoff,WH
获得性免疫缺陷综合征（AIDS）通常被认为是由人类T淋巴细胞病毒III型（HTLVIII）、人类淋巴结病相关病毒（LAV）、AIDS相关逆转录病毒（ARV）或人类单克隆病毒（HIV）感染的一种继发性疾病。许多化合物对该病毒具有抗病毒活性，其中包括HPA-23 ft，2！f，干扰素（311）利巴韦林（4），膦酰基-O-酸酯（5，6 f）、安索菌素（71）、苏糖醛酸（8-101）、伊莫硫醇（111）、紫杉醇（121）、紫杉醇（13 f）、AL-721（141）、3 ′-叠氮基-3 ′-脱氧胸苷（15-191）以及最近发现的各种21，31-脱氧核苷（20），3~-d~脱氧胞苷（ddCyd）是最有效的。对这些和其他coxpouds抗HIV活性的评价，以及对AIDS问题的一般讨论，已经提出（21）。本文报道了2 ′，3 ′-二脱氧胞苷-α ′-烯（2 ′，3 ′-二脱氧-2c，3 ′-二脱氢胞苷; DIIC）的抗RIV活性，并与2 ′，3 ′-二脱氧胞苷和31-脱氧胸腺嘧啶（AZT，EW A509 U）的抗RIV活性进行了比较。2 '，3 ′-二脱氧胞苷-2'-cue、2 '，3'-d-脱氧胞苷和3 t-脱氧胞苷是Horwitz等首次合成的。(22，二百三十一;然而，采用不同的路线制备两种胞苷获得物，使用2，3 ′-二脱氧尿苷-2 *-ENA作为起始原料（2t，3'-dideo~-21，3t-dide~ drouridine）和2'，3 ′-dideo~~ ddue ~ e，用乙酸酐在吡啶中乙酰化的化合物1（22）在室温下，在吡啶中，将对氯苯基二氯磷酸酯和1，2，4-三唑反应，得到4-三唑基嘧啶二酮衍生物3。随后用氨水/二氧六环（1：3）处理4-三羟甲基吡啶衍生物数小时，然后在室温下用甲醇洗涤过夜
Acquired imunodefiofency syndrome (AIDS) Is generally aooepted to be a oonsequenoe of infection wftb the ratrovirus variously termed human T-lymphotropio virus type III (HTLVIII), l~ phadenopathy-associated virus fLAV), AIDS associated retrovirus (ARV), or human~ unode~~ o~ eney virus (HIV). A number of conpounds have de~ osstrated antiviral activity against this virus which include HPA-23 ft, 2! f, interferona(311 ribavirin(4), phosphono~ o~ ate (5, 6f, ansaawcin (71, suraain (8-101, imuthiol (111, peuioillaxihe(121, rif’abutin f 13 f, AL-721 (141, 3’-azido_3’-deoxythymidine(15-191, and mars recently various 21, 31-d~ deo~ nuoleoaides(20) of whioh 2’, 3~-d~ deo~ oytidine(ddCyd) is the most potent, A review of these and other coxpouods evaluated for their activities against HIV, a § well as a discussion of the AIDS Problem in general, has been presented (21). This report describes the antiviral activity against RIV of 2*, 31-dideoxyoytldin-a’-ene i 2’, 3*-did80xy-2c, 3 (-didehydrooytidine; DIIC), and compares the antiviral activity with that of 2’, 3Q-dideoxyoytidine and 31-azld&-3~-deoxythymldine fAZT, EW A509U). The 2’, 3*-dideoxyoytidin-2’-cue, 2’, 3’-d~ deo~ oytidine, and 3t-~ id~ 3t-deo~ th~ dine were first synthesized by Horwitz at al.(22,231; however, a different route was adopted for the preparation of the two cytidins obtunds using, as starting material, 2,, 3’-dideoxyuridin-2*-ena (2t, 3’-dideo~-21, 3t-dide~ drouridine) and 2’, 3¶-dideo~~~ d~~ e, Compound 1 (22) acetylated with acetic anhydride in pyridine Save the corresponding acetate 2 which was theh’treated with 4-ohlorophenyl phosphorodichloridate and 1, 2, 4-trfasole in pyridine at room temperature to yield the 4-tr~~ olFlpyrim~ dino~ derivative 3. Subsequent treatment OP the 4-tri~ olylpyri~ d~~ ne derivative with aqueous ammonia in dioxane(1: 3) for several hours and then methanolic emaonia overnight at room temperature