1-(3-azido-2,3-dideoxy-5-O-trityl-β-D-erythro-pentofuranosyl)uracil | 84472-84-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-(3-azido-2,3-dideoxy-5-O-trityl-β-D-erythro-pentofuranosyl)uracil
• 英文别名: 3'-azido-5'-O-trityl-2',3'-dideoxyuridine；5'-O-trityl-3'-azido-2',3'-dideoxyuridine；3'-Azido-5'-trityl-2',3'-dideoxyuridine；1-[(2R,4S,5S)-4-azido-5-(trityloxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 84472-84-4
• 化学式: C₂₈H₂₅N₅O₄
• 分子量: 495.538
• InChiKey: UXZVJXHFRPKVBE-BFLUCZKCSA-N

物化性质

• 熔点：
  67-70 °C

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3-azido-2,3-dideoxy-5-O-trityl-β-D-erythro-pentofuranosyl)uracil 在 ice 、 chloroform methanol 、 silica gel 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 以yielding 23 g (70%) of 3'-azido-2',3'-dideoxyuridine的产率得到Navuridine
  参考文献：
  名称：

  5'-diphosphohexose nucleoside pharmaceutical compositions

  摘要：

  本发明提供了一种化合物和制药组合物，其中包括式子的化合物：##STR1## 其中A、B和C是氢、卤素或叠氮基；D是氢、卤素、叠氮基或OH；A和B或C和D可以被双键替换；R是醛基己糖、醛基己糖胺或N-乙酰基醛基己糖胺，W是O或S；X是O、S或CH.sub.2；Y是嘌呤或嘧啶碱基，Z是C、S或O，其中当Z是S或O时，A和C不存在。这些化合物具有增强的制药或生物活性或与相应的母核苷酸相比具有增加的细胞内吸收能力，这是由于5'-二磷酸己糖基团的功能。这些化合物中的许多具有抗病毒，包括抗HIV活性。其他具有抗菌活性。在一种实施方式中，本发明是一种同时治疗HIV感染和机会性感染的方法。

  公开号：

  US05118672A1
• 作为产物：
  描述：

  3'-O-(methylsulfonyl)-5'-O-trityl-2'-deoxyuridine 在 四甲基乙二胺 、 叠氮基三甲基硅烷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium fluoride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 1-(3-azido-2,3-dideoxy-5-O-trityl-β-D-erythro-pentofuranosyl)uracil
  参考文献：
  名称：

  修饰的5'-Trityl核苷作为恶性疟原虫dUTPase的抑制剂

  摘要：

  2'-脱氧尿苷三磷酸核苷酸水解酶（dUTPase）是治疗疟疾的潜在药物靶标。我们之前曾报道过发现脱氧尿苷的5'-三苯甲基化类似物可作为恶性疟原虫的选择性抑制剂酶。在这里，我们报告了进一步的结构活动研究；特别是5'-三苯甲基的变体，在脱氧尿苷的3'-位置引入了各种取代基以及修饰了碱基。测试了针对酶和寄生虫的化合物。5'-三苯甲基和3'-取代基的变异具有良好的耐受性，并产生了活性化合物。然而，由于尿嘧啶环的修饰导致酶抑制作用的丧失和抗血浆作用的显着降低，因此对尿嘧啶碱基的活性有明确的要求。

  DOI：

  10.1002/cmdc.201000445

文献信息

• Synthesis and anti-HIV evaluation of 2',3'-dideoxyribo-5-chloropyrimidine analogs: reduced toxicity of 5-chlorinated 2',3'-dideoxynucleosides
  作者：Arthur Van Aerschot、Dirk Everaert、Jan Balzarini、Koen Augustyns、Liu Jie、Gerard Janssen、Oswald Peeters、Norbert Blaton、Camiel De Ranter

  DOI：10.1021/jm00168a046

  日期：1990.6

  While chlorination of 2',3'-dideoxycytidine removed the anti-HIV activity, introduction of a chlorine at the C-5 position of 3'-fluoro-, 3'-azido- or 2',3'-didehydro-2',3'-dideoxycytidine led to reduced cytotoxicity with only slightly reduced anti-HIV activity. X-ray analysis showed compound 11 to have two molecules in the asymmetric unit with chi = -168.8 (3) degrees and -131.3 (3) degrees and P = 179

  鉴于2'，3'-dideoxy-3'-fluoro-5-chlorouridine（11）的选择性抗HIV活性，合成了8个2'，3'-dideoxy-5-chloropyrimidines并评估了它们对MT-4细胞中1型人类免疫缺陷病毒（HIV-1）复制的抑制活性。注意到2，3-二脱氧核糖呋喃糖，3-叠氮基-2，3-二脱氧核糖呋喃糖和3-氟-2，3-二脱氧核糖呋喃糖的5-氯尿嘧啶衍生物的选择性显着改善，这主要是由于该化合物对宿主细胞。虽然氯化2'，3'-二脱氧胞苷可消除抗HIV活性，但在3'-氟-，3'-叠氮基或2'，3'-二氢-2'的C-5位置引入了氯，3'-二脱氧胞苷导致细胞毒性降低，而抗HIV活性仅略微降低。X射线分析表明化合物11在不对称单元中具有两个分子，分别为chi = -168.8（3）度和-131.3（3）度，P = 179（1）度和163（1）度。因此显示与3'-叠氮基-3'-脱氧胸苷（AZT）没有相似之处。
• 5'-Diphosphohexose nucleoside pharmaceutical compositions
  申请人：University of Georgia Research Foundation Inc.

  公开号：US05159067A1

  公开（公告）日：1992-10-27

  Compounds of the general formula: ##STR1## wherein A, B, and C are hydrogen, halogen, or azido; D is hydrogen, halogen, azido, or OH; A and B or C and D can be replaced with a double bond; R is an aldohexose, aldohexosamine, or N-acetyl aldohexosamine, R.sub.1 and R.sub.2 are hydrogen or alkyl groups of from C.sub.1 to C.sub.10 ; W is oxygen or sulfur; X is oxygen, sulfur, or CH.sub.2 ; Y is a purine or pyrimidine base, and Z is carbon, sulfur, or oxygen. Y can be any purine or pyrimidine base, natural or synthetic, which combines with a sugar to form a biologically active nucleoside. In combination with an appropriate pharmaceutical carrier, the compositions have enhanced activity or increased intracellular absorbment over the parent nucleoside as a function of the 5'-O-diphosphosugar. Another embodiment of the present invention is the enhancement of biologically active nucleosides into cells by preparing and administering the 5'-O-diphosphohexose, 5'-diphospho-N-acetylhexosamine or 5'-diphosphohexosamine derivative of the nucleoside. In the preferred embodiment for therapeutic use, the compounds are provided in a pharmaceutical carrier in an amount sufficient to exhibit as known in vitro or in vivo biological activity.

  一般式为：##STR1## 的化合物，其中A、B和C为氢、卤素或叠氮基；D为氢、卤素、叠氮基或羟基；A和B或C和D可以被双键替换；R为醛基己糖、醛基己糖胺或N-乙酰醛基己糖胺，R.sub.1和R.sub.2为C.sub.1到C.sub.10的氢或烷基；W为氧或硫；X为氧、硫或CH.sub.2；Y为嘌呤或嘧啶碱基，Z为碳、硫或氧。Y可以是任何嘌呤或嘧啶碱基，天然或合成的，与糖结合形成生物活性核苷的。与适当的药物载体结合后，这些组合物具有比母核苷更强的活性或增加细胞内吸收的功能，这是由于5'-O-二磷酸糖的作用。本发明的另一实施例是通过制备和给予核苷的5'-O-二磷酸己糖、5'-二磷酰N-乙酰己糖胺或5'-二磷酸己糖胺衍生物，增强生物活性核苷进入细胞。在治疗用的优选实施例中，这些化合物以足够量提供在体外或体内已知的生物活性，以药物载体的形式提供。
• Dutpase Inhibitors
  申请人：Gilbert Ian

  公开号：US20080300216A1

  公开（公告）日：2008-12-04

  Deoxyuridine derivatives of Formula (I′); where A is O, S or CH 2 ; B is O, S or CHR 3 ; R 1 is H, or various substituents; R 2 is H, F; R 3 is H, F, OH, NH 2 ; or R 2 and R 3 together form a chemical bond; D is —NHCO—, —CONH—, —O—, —C(═O)—, —CH═CH, —C≡C—, —NR 5 —; R 4 is hydrogen or various substituents; R 5 is H, C 1 -C 4 alkyl, C 1 -C 4 alkanoyl; E is Si or C; R 6 , R 7 and R 8 are independently selected from C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, or a stable monocyclic, bicyclic or tricyclic ring system have utility in the prophylaxis of treatment of parasitic diseases such as malaria.

  化合物（I'）的脱氧尿嘧啶衍生物；其中A为O、S或CH2；B为O、S或CHR3；R1为H或各种取代基；R2为H、F；R3为H、F、OH、NH2；或R2和R3共同形成化学键；D为-NHCO-、-CONH-、-O-、-C（═O）-、-CH═CH、-C≡C-、-NR5-；R4为氢或各种取代基；R5为H、C1-C4烷基、C1-C4酰基；E为Si或C；R6、R7和R8分别选择自C1-C8烷基、C2-C8烯基、C2-C8炔基或稳定的单环、双环或三环环系统，在预防或治疗疟疾等寄生虫病方面具有用途。
• Synthesis and antineoplastic activity of 3'-azido and 3'-amino analogs of pyrimidine deoxyribonucleoside
  作者：Tai Shun Lin、William R. Mancini

  DOI：10.1021/jm00358a016

  日期：1983.4

  Several new 3'-azido and 3'-amino nucleosides (8, 9, 12, and 13) have been synthesized and their biological activities evaluated. Among them, 3'-amino-2',3'-dideoxycytidine (13) was found to exhibit potent cytotoxic activity against both L1210 and S-180 cells in vitro with an ID50 of 0.7 and 4.0 microM, respectively. Furthermore, 13 has also shown antitumor activity against L1210 tumor bearing mice with a T/C X 100 value of 283.
• Chemical-Enzymatic Synthesis of 3′-Amino-2′, 3′-dideoxy-β-D-ribofuranosides of Natural Heterocyclic Bases and Their 5′-Monophosphates
  作者：Galina V. Zaitseva、Evgenii I. Kvasyuk、Elena V. Vaaks、Vladimir N. Barai、Sergei B. Bokut、Anatolii I. Zinchenko、Igor A. Mikhailopulo

  DOI：10.1080/15257779408013281

  日期：1994.3

  Treatment of O-2,3'-anhydro-5'-O-trityl derivatives of thymidine (1) and 2'-deoxyuridine (2) with lithium azide in dimethylformamide at 150 degrees C resulted in the formation of the corresponding isomeric 3'-azido-2',3'-dideoxy-5'-O-trityl-beta-D-ribofuranosyl N1- (the major products) and N-3-nucleosides (3/4 and 5/6). 3'-Amino-2',3'-dideoxy-beta-D-ribofuranosides of thymidine [Thd(3'NH2)], uridine [dUrd(3'NH2)], and cytidine [dCyd(3'NH2)] were synthesized from the corresponding 3'-azido derivatives. The Thd(3'NH2) and dUrd(3'NH2) were used as donors of carbohydrate moiety in the reaction of enzymatic transglycosylation of adenine and guanine to afford dAdo(3'NH2) and dGuo(3'NH2). The substrate activity of dN(3'NH2) vs. nucleoside phosphotransferase of the whole cells of Erwinia herbicola was studied.