(2R,3R,4R,5R)-2-((苯甲酰氧基)甲基)-5-(4-氯-5-碘-7H-吡咯并[2 | 480439-89-2

分子结构分类

有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸

中文名称

(2R,3R,4R,5R)-2-((苯甲酰氧基)甲基)-5-(4-氯-5-碘-7H-吡咯并[2

中文别名

——

英文名称

(2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diyl dibenzoate

英文别名

4-chloro-5-iodo-N7-(2’,3’,5’-tri-O-benzoyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine；[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methyl benzoate

(2R,3R,4R,5R)-2-((苯甲酰氧基)甲基)-5-(4-氯-5-碘-7H-吡咯并[2化学式

CAS

480439-89-2

化学式

C₃₂H₂₃ClIN₃O₇

mdl

——

分子量

723.908

InChiKey

WHVWNDLPQYBIGY-CTDWIVFPSA-N

BEILSTEIN

——

EINECS

——

物化性质

沸点：

796.0±60.0 °C(Predicted)
密度：

1?+-.0.1 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

6.8
重原子数：

44
可旋转键数：

11
环数：

6.0
sp3杂化的碳原子比例：

0.16
拓扑面积：

119
氢给体数：

0
氢受体数：

9

上下游信息

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	4-chloro-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	29914-75-8	C₃₂H₂₄ClN₃O₇	598.011
——	4-chloro-5-cyano-7-[(2,3,5-tri-O-benzoyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine	——	C₃₃H₂₃ClN₄O₇	623.021
——	4-methyl-7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-54-9	C₃₃H₂₇N₃O₇	577.593
——	4-(1-methylhydrazino)-5-cyano-7-[(2,3,5-tri-O-benzoyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine	699011-59-1	C₃₄H₂₈N₆O₇	632.632
5-碘代杀结核菌素	5-iodotubercidin	24386-93-4	C₁₁H₁₃IN₄O₄	392.153
——	3,7-dihydro-5-iodo-7-(β-D-ribofuranosyl)-4H-pyrrolo[2,3-d]pyrimidin-4-one	952429-18-4	C₁₁H₁₂IN₃O₅	393.138
——	4-methoxy-5-iodo-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	426823-20-3	C₁₂H₁₄IN₃O₅	407.165
——	4-dimethylamino-5-iodo-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536109-63-3	C₁₃H₁₇IN₄O₄	420.207
——	5-iodo-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	144928-11-0	C₁₂H₁₄IN₃O₄S	423.231
——	4-methoxy-5-phenyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-68-5	C₁₈H₁₉N₃O₅	357.366
——	5-phenyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-one	1536111-73-5	C₁₇H₁₇N₃O₅	343.339
——	6-(4-methoxylphenyl)-9β-D-ribofuranosyl-7-desazapurine	1172127-49-9	C₁₈H₁₉N₃O₅	357.366
——	4-methoxy-7-(β-D-ribofuranosyl)pyrrolo<2,3-d>pyrimidine	16754-81-7	C₁₂H₁₅N₃O₅	281.268
——	4-dimethylamino-5-phenyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-17-7	C₁₉H₂₂N₄O₄	370.408
——	5-(furan-3-yl)-4-methoxy-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-59-4	C₁₆H₁₇N₃O₆	347.327
——	4-methylamino-5-phenyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-02-0	C₁₈H₂₀N₄O₄	356.381
——	4-dimethylamino-7-(β-D-ribofuranosyl)-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-13-3	C₁₇H₂₀N₄O₄S	376.436
——	6-phenyl-9β-D-ribofuranosyl-7-deazapurine	144928-12-1	C₁₇H₁₇N₃O₄	327.34
——	4-methylamino-7-(β-D-ribofuranosyl)-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-00-8	C₁₆H₁₈N₄O₄S	362.409
——	4-dimethylamino-5-(furan-3-yl)-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-07-5	C₁₇H₂₀N₄O₅	360.37
——	TH1008	——	C₁₆H₁₇N₅O₄	343.342
——	4-methylsulfanyl-5-phenyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-83-4	C₁₈H₁₉N₃O₄S	373.433
——	5-(furan-3-yl)-4-methylamino-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-91-4	C₁₆H₁₈N₄O₅	346.343
——	5-(benzofuran-2-yl)-4-dimethylamino-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-19-9	C₂₁H₂₂N₄O₅	410.429
——	5-(benzofuran-2-yl)-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-87-8	C₂₀H₁₉N₃O₅S	413.454
——	4-dimethylamino-5-ethynyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-44-0	C₁₅H₁₈N₄O₄	318.332
——	3,7-dihydro-5-(prop-1-ynyl)-7-(β-D-ribofuranosyl)-4H-pyrrolo[2,3-d]pyrimidin-4-one	——	C₁₄H₁₅N₃O₅	305.29
——	5-(benzofuran-2-yl)-4-methylamino-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-05-3	C₂₀H₂₀N₄O₅	396.403
——	4-dimethylamino-7-(β-D-ribofuranosyl)-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-10-0	C₁₇H₂₀N₄O₄S	376.436
——	5-ethynyl-4-methylamino-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-40-6	C₁₄H₁₆N₄O₄	304.305
——	4-dimethylamino-5-(furan-2-yl)-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536109-98-4	C₁₇H₂₀N₄O₅	360.37
——	5-(furan-2-yl)-4-methylamino-7-(β-D-ribofuranosyl)-7H-pyrrolo-[2,3-d]pyrimidine	1536109-92-8	C₁₆H₁₈N₄O₅	346.343
——	4-methylamino-7-(β-D-ribofuranosyl)-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-98-1	C₁₆H₁₈N₄O₄S	362.409
——	4-methylsulfanyl-7-(β-D-ribofuranosyl)-5-(thiophen-3-yl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-80-1	C₁₆H₁₇N₃O₄S₂	379.461
——	jaspamycin	22242-96-2	C₁₂H₁₂N₄O₅	292.251
——	5-(furan-2-yl)-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536109-87-1	C₁₆H₁₇N₃O₅S	363.394
——	5-(furan-3-yl)-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-74-3	C₁₆H₁₇N₃O₅S	363.394
——	5-ethynyl-4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-47-3	C₁₄H₁₅N₃O₄	289.291
——	(2R,3R,4S,5R)-2-(4-(dimethylamino)-5-((trimethylsilyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol	1536112-59-0	C₁₈H₂₆N₄O₄Si	390.514
——	4-methylsulfanyl-7-(β-D-ribofuranosyl)-5-(thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidine	1536110-77-6	C₁₆H₁₇N₃O₄S₂	379.461
——	(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(4-(methylamino)-5-((trimethylsilyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol	1536112-56-7	C₁₇H₂₄N₄O₄Si	376.487
——	4-dimethylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine	20371-00-0	C₁₃H₁₈N₄O₄	294.31
——	4-methylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine	13241-46-8	C₁₂H₁₆N₄O₄	280.283
——	5-ethynyl-4-methylsulfanyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine	1536111-37-1	C₁₄H₁₅N₃O₄S	321.357
——	4-(methylthio)-7-(β-D-ribofuranosyl)-7H-pyrrolo<2,3-d>pyrimidine	16754-86-2	C₁₂H₁₅N₃O₄S	297.335

反应信息

作为反应物：

描述：

(2R,3R,4R,5R)-2-((苯甲酰氧基)甲基)-5-(4-氯-5-碘-7H-吡咯并[2 在 lithium chloro-isopropyl-magnesium chloride 、氨作用下，以四氢呋喃为溶剂，以88 %的产率得到杀结核菌素

参考文献：

名称：

N6-甲基腺苷的原子突变揭示了人类 m6A 阅读器和擦除器蛋白的独特识别模式

摘要：

N 6 -甲基腺苷 (m 6 A) 是细胞 RNA 中重要的修饰核苷，与多种细胞过程相关，并与疾病有关。与 m 6 A 动态安装和去除相关的酶是药物研究中重点研究的目标，这需要详细了解蛋白质对 m 6 A 的识别模式。在这里，我们利用 m 6 A 的原子诱变系统地研究了两种人类 m 6 A 去甲基化酶 FTO 和 ALKBH5 的机制以及 YTH 阅读器蛋白 YTHDF2/DC1/DC2 的结合模式。原子诱变是指通过化学合成引入的原子特异性变化，例如用碳原子取代氮。通过固相合成制备含有位点特异性掺入的1-脱氮-、3-脱氮-和7-脱氮-m 6 A核苷的合成RNA寡核苷酸，并评估它们的RNA结合和重组蛋白的去甲基化。我们发现底物识别和转化存在明显差异，并揭示了酶活性的结构偏好。这项工作中引入的 deaza m 6 A 类似物将成为 m 6 A 研究中其他蛋白质的有用探针。

DOI：

10.1021/jacs.4c00626
作为产物：

描述：

4-氯-5-碘-7H-吡咯并[2,3-d]嘧啶在三氟甲磺酸三甲基硅酯作用下，以乙腈为溶剂，反应 1.17h，生成 (2R,3R,4R,5R)-2-((苯甲酰氧基)甲基)-5-(4-氯-5-碘-7H-吡咯并[2

参考文献：

名称：

7-Functionalized 7-deazapurine β-d and β-l-ribonucleosides related to tubercidin and 7-deazainosine: glycosylation of pyrrolo[2,3-d]pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d or β-l-ribofuranose

摘要：

Several 7-functionalized 7-deazapurine ribonucleosides were prepared. Glycosylation of 7-halogenated 6-chloro-7-deazapurines with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose or 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-L-ribofuranose gave the protected beta-D-nucleosides 8c-e (53-62%) and the beta-L-nucleosides 9b-e (57-72%), which were transformed to 7-halogenated 7-deazapurine ribonucleosides related to tubercidin and 7-deazainosine. 7-Alkynyl derivatives (1f,g) and (2f,g) were obtained from the 7-iodo nucleosides 1e and 2e employing the palladium-catalyzed Sonogashira cross-coupling reaction. Within the series of 7-deazaadenosine ( tubercidin) analogues and 7-deazainosine derivatives physical data such as pK(a) values, chromatographic mobilities, C-13 NMR chemical shifts were determined and correlated to each other. (C) 2007 Elsevier Ltd. All rights reserved.

DOI：

10.1016/j.tet.2007.06.107

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文献信息

Synthesis and evaluation of analogs of 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (MDL 73811, or AbeAdo) – An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity

作者：Anthony J. Brockway、Oleg A. Volkov、Casey C. Cosner、Karen S. MacMillan、Stephen A. Wring、Thomas E. Richardson、Michael Peel、Margaret A. Phillips、Jef K. De Brabander

DOI：10.1016/j.bmc.2017.07.063

日期：2017.10

describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (1, also known

我们描述了我们为改善基于机制的多胺生物合成酶S-腺苷甲硫氨酸脱羧酶（AdoMetDC）的自杀抑制剂的药代动力学特性而做出的努力，这对于负责人类非洲锥虫病（HAT）的真核寄生虫布鲁氏锥虫的生存至关重要。前导化合物5'-（（（（Z）-4-氨基-2-丁烯基）甲基氨基）-5'-脱氧腺苷（1，也称为MDL 73811或AbeAdo，在HAT的淋巴模型中以低剂量具有疗效，但由于血脑屏障渗透性差，在HAT的CNS期小鼠模型中未显示出明显的作用。因此，我们制备并评估了一系列在氨基丁烯基侧链，5'-胺，核糖和嘌呤片段上有修饰的类似物。尽管我们从这个全面的数据集中获得了有价值的结构活性见解，但我们并没有在保持中枢化合物1的强抗寄生虫活性和代谢稳定性的同时改善中枢神经系统渗透的前景。
[EN] NOVEL 6-SUBSTITUTED 7-DEAZAPURINES AND CORRESPONDING NUCLEOSIDES AS MEDICAMENTS<br/>[FR] NOUVELLES 7-DÉAZAPURINES 6-SUBSTITUÉES ET NUCLÉOSIDES CORRESPONDANTS EN TANT QUE MÉDICAMENTS

申请人：UNIV LEUVEN KATH

公开号：WO2021164848A1

公开（公告）日：2021-08-26

The present invention relates to the synthesis of 6-substituted 7-deazapurines and their corresponding nucleosides by coupling aryl or alkyl Grignard reagents with halogenated purine nucleosides in the presence of iron or an iron/copper mixture such as Fe(acac)3/Cul. The present invention also relates to pharmaceutical compositions comprising said compounds and the use of said pharmaceutical compositions to treat or prevent viral infections.

本发明涉及通过在铁或铁/铜混合物（如Fe(acac)3/Cul）存在下，将芳基或烷基格氏试剂与卤代嘌呤核苷酸偶联来合成6-取代7-脱氮嘌呤及其相应的核苷的方法。本发明还涉及包括所述化合物的药物组合物以及利用所述药物组合物治疗或预防病毒感染的用途。
Iron/Copper Co-Catalyzed Cross-Coupling Reaction for the Synthesis of 6-Substituted 7-Deazapurines and the Corresponding Nucleosides

作者：Qingfeng Li、Leentje Persoons、Dirk Daelemans、Piet Herdewijn

DOI：10.1021/acs.joc.9b02414

日期：2020.1.17

to 6-substituted 7-deazapurine and the corresponding nucleosides by coupling aryl or alkyl Grignard reagents and halogenated purine nucleosides in the presence of Fe(acac)3/CuI is described. A series of 6-substituted 7-deazapurines and the corresponding nucleosides were obtained in medium to good yields. For the synthesis of modified nucleosides that will be the subject of biological testing, we propose

描述了通过在Fe（acac）3 / CuI存在下偶联芳基或烷基格氏试剂和卤代嘌呤核苷来有效获得6-取代的7-脱氮嘌呤和相应的核苷。以中等至良好的产率获得了一系列6-取代的7-脱氮嘌呤和相应的核苷。对于合成修饰的核苷的合成（将成为生物学测试的主题），我们建议使用铁催化而不是钯催化的反应。测试合成的化合物的抗增殖活性。化合物11a-q的细胞毒性研究表明，通过修饰7-脱氮嘌呤核糖核苷的6位，该化合物可能对某些癌细胞系具有选择性。
[EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTION<br/>[FR] COMPOSÉS, COMPOSITIONS, ET PROCÉDÉS POUR LE TRAITEMENT D'UNE INFECTION VIRALE

申请人：CHIMERIX INC

公开号：WO2010135520A1

公开（公告）日：2010-11-25

The present invention describes compounds of formulae I and II and methods for treating viral infection, such as Flaviviridae virus infection, including Hepatitis C infection (HCV).

本发明描述了式I和式II的化合物以及治疗病毒感染的方法，例如黄病毒科病毒感染，包括丙型肝炎病毒感染（HCV）。
Synthesis of 7-trifluoromethyl-7-deazapurine ribonucleoside analogs and their monophosphate prodrugs

作者：Jong Hyun Cho、Leda C. Bassit、Franck Amblard、Raymond F. Schinazi

DOI：10.1080/15257770.2019.1674333

日期：2020.5.3

Abstract Novel 7-trifluoromethyl-7-deazapurine ribonucleoside analogs (13a-c) and their Protides (15a-c) were successfully synthesized from ribolactol or 1-α-bromo-ribose derivatives using Silyl-Hilbert-Johnson or nucleobase-anion substitution reactions followed by key aromatic trifluoromethyl substitution. Newly prepared compounds were evaluated against a panel of RNA viruses, including HCV, Ebola

摘要使用 Silyl-Hilbert-Johnson 或核碱基-阴离子取代反应，从核糖醇或 1-α-溴核糖衍生物成功合成了新型 7-三氟甲基-7-脱氮嘌呤核糖核苷类似物 (13a-c) 及其 Protides (15a-c)其次是关键的芳香族三氟甲基取代。新制备的化合物针对一组 RNA 病毒进行了评估，包括 HCV、埃博拉病毒或寨卡病毒。