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热门化合物HOT

喹啉
水杨醛
二溴甲烷
谷胱甘肽
L-乳酸
苯巴比妥
辣椒碱
非那明
百草枯
联苯烯

2'-C-甲基-6-O-甲基鸟苷 | 714249-80-6

分子结构分类

有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷

中文名称

2'-C-甲基-6-O-甲基鸟苷

中文别名

——

英文名称

(2R,3R,4R,5R)-2-(2-amino-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol

英文别名

2-(2-amino-6-methoxypurin-9-yl)-5-hydroxymethyl-3-methyltetrahydrofuran-3,4-diol；(2R,3R,4R,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol

CAS

714249-80-6

化学式

C₁₂H₁₇N₅O₅

mdl

——

分子量

311.297

InChiKey

OAIGYKVLSKBAJZ-GSWPYSDESA-N

BEILSTEIN

——

EINECS

——

物化性质

沸点：

690.2±65.0 °C(Predicted)
密度：

1.82

计算性质

辛醇/水分配系数(LogP)：

-0.7
重原子数：

22
可旋转键数：

3
环数：

3.0
sp3杂化的碳原子比例：

0.58
拓扑面积：

149
氢给体数：

4
氢受体数：

9

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
6-氯-9-(2,3,5-三-O-苯甲酰基-2-C-甲基-BETA-D-呋喃核糖基)-9H-嘌呤-2-胺	(2R,3R,4R,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-5-((benzoyloxy)methyl)-3-methyltetrahydrofuran-3,4-diyl dibenzoate	641571-44-0	C₃₂H₂₆ClN₅O₇	628.041

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	(2R,3R,4R,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(dichlorophosphoryloxymethyl)-3-methyloxolane-3,4-diol	——	C₁₂H₁₆Cl₂N₅O₆P	428.169
——	(2R,3R,4R,5R)-2-(2-(4-fluorobenzylamino)-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol	1234491-54-3	C₁₉H₂₂FN₅O₅	419.413
——	((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methyl di-N-butylphosphinate	1350765-77-3	C₂₀H₃₆N₇O₆P	501.523
——	6-methoxy-N-[(4-methoxyphenyl)(diphenyl)-methyl]-9-(2-C-methyl-b-d-ribofuranosyl)-9H-purin-2-amine	1401699-50-0	C₃₂H₃₃N₅O₆	583.644
——	2-amino-6-methoxy-9-(2'-C-methyl-β-D-ribofuranosyl)purine-5'-O-bis(methoxy-L-alaninyl)phosphate	1350765-03-5	C₂₀H₃₂N₇O₁₀P	561.489
——	(2S,2'S)-diethyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1336974-22-1	C₂₂H₃₆N₇O₁₀P	589.542
——	((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methyl dimorpholinophosphinate	1350765-78-4	C₂₀H₃₂N₇O₈P	529.49
——	(2S,2'S)-dipropyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-06-8	C₂₄H₄₀N₇O₁₀P	617.596
——	(2S,2'S)-diisobutyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-27-3	C₂₆H₄₄N₇O₁₀P	645.65
——	(2S,2'S)-diisopropyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-12-6	C₂₄H₄₀N₇O₁₀P	617.596
——	(2S,2'S)-dibutyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-08-0	C₂₆H₄₄N₇O₁₀P	645.65
——	(2S,2'S)-dipentyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-10-4	C₂₈H₄₈N₇O₁₀P	673.704
——	propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-chlorophosphoryl]amino]propanoate	——	C₁₈H₂₈ClN₆O₈P	522.882
——	(2S,2'S)-dineopentyl-((((2R,3S,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)(2,2')-bisamino-dipropanoate	1350765-26-2	C₂₈H₄₈N₇O₁₀P	673.704
——	(2S,2'S)-di-sec-butyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-14-8	C₂₆H₄₄N₇O₁₀P	645.65
——	(2S,2'S)-bis(3,3-dimethylbutyl) 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-16-0	C₃₀H₅₂N₇O₁₀P	701.758
——	(2S,2'S)-bis(tetrahydro-2H-pyran-4-yl) 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-24-0	C₂₈H₄₄N₇O₁₂P	701.671
——	(25,2'5)-dicyclohexyl-((((2R,35,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy) phosphoryl)-(2,2')-bis-amino-dipropanoate	1350765-20-6	C₃₀H₄₈N₇O₁₀P	697.726
——	(2S,2'S)-dicyclopentyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-19-3	C₂₈H₄₄N₇O₁₀P	669.672
——	(2R,3R,4R,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-[[[2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]ethylamino]-phenoxyphosphoryl]oxymethyl]-3-methyloxolane-3,4-diol	1604813-52-6	C₃₈H₄₈N₁₂O₁₄P₂	958.819
——	propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(2-oxo-2-propan-2-yloxyethoxy)phosphoryl]amino]propanoate	1427287-26-0	C₂₃H₃₇N₆O₁₁P	604.554
——	2-amino-6-methoxy-9-(2'-C-methyl-β-D-ribofuranosyl)purine-5'-O-bis(benzoxy-L-alaninyl)phosphate	1350765-21-7	C₃₂H₄₀N₇O₁₀P	713.684
——	(2S)-benzyl 2-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(butylamino)phosphorylamino)propanoate	1350765-85-3	C₂₆H₃₈N₇O₈P	607.604
——	2,2-dimethylpropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S)-1-(2,2-dimethylpropoxy)-4-methylsulfanyl-1-oxobutan-2-yl]amino]phosphoryl]amino]-4-methylsulfanylbutanoate	1350765-59-1	C₃₂H₅₆N₇O₁₀PS₂	793.943
——	propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(2-ethoxy-2-oxoethoxy)phosphoryl]amino]-4-methylpentanoate	1427287-58-8	C₂₅H₄₁N₆O₁₁P	632.608
——	(2S)-neopentyl 2-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(benzylamino)phosphorylamino)propanoate	1350765-89-7	C₂₇H₄₀N₇O₈P	621.63
——	[(1S)-1-phenylethyl] (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S)-1-oxo-1-[(1S)-1-phenylethoxy]propan-2-yl]amino]phosphoryl]amino]propanoate	1350765-22-8	C₃₄H₄₄N₇O₁₀P	741.738
——	ethyl 1-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(propan-2-ylamino)phosphoryl]amino]cyclopentane-1-carboxylate	1336974-54-9	C₂₃H₃₈N₇O₈P	571.571
——	(2S,2'S)-bis(2,3-dihydro-1H-inden-2-yl) 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate	1350765-25-1	C₃₆H₄₄N₇O₁₀P	765.76
——	(2S)-propyl 2-((((2R,3R,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalene-1-yloxy)phosphorylamino)propanoate	1234490-79-9	C₂₈H₃₅N₆O₉P	630.594
——	(2S)-isopropyl 2-((((2R,3R,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalene-1-yloxy)phosphorylamino)propanoate	1234490-86-8	C₂₈H₃₅N₆O₉P	630.594
——	ethyl 2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(2-ethoxy-2-oxoethoxy)phosphoryl]amino]-2-phenylacetate	1427287-73-7	C₂₆H₃₅N₆O₁₁P	638.571
N-(2'-C-甲基-6-O-甲基-P-1-萘基-5'-鸟苷酰基)-L-丙氨酸 2,2-二甲基丙酯	(2S)-neopentyl 2-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propanoate	1234490-83-5	C₃₀H₃₉N₆O₉P	658.648
——	(S)-neopentyl 2-(((R)-(((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphoryl)amino)propanoate	1234490-85-7	C₃₀H₃₉N₆O₉P	658.648
——	(S)-P-neopentyl 2-((S)-(((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propanoate	1234490-84-6	C₃₀H₃₉N₆O₉P	658.648
——	(2S)-3,3-dimethylbutyl 2-((((2R,3R,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalene-1-yloxy)phosphorylamino)propanoate	1234490-80-2	C₃₁H₄₁N₆O₉P	672.675
——	propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[2-[(4-fluorophenyl)methylamino]-2-oxoethoxy]phosphoryl]amino]-4-methylpentanoate	1427287-70-4	C₃₀H₄₃FN₇O₁₀P	711.684
——	(2R,3R,4R,5R)-5-[[[2-[[[(2R,3R,4R,5R)-5-(2-amino-6-ethoxypurin-9-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]ethylamino]-phenoxyphosphoryl]oxymethyl]-2-(2-amino-6-methoxypurin-9-yl)-3-methyloxolane-3,4-diol	1604813-50-4	C₃₉H₄₉FN₁₂O₁₃P₂	974.837
——	(2S)-cyclopentyl 2-((((2R,3R,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalene-1-yloxy)phosphorylamino)propanoate	1234490-88-0	C₃₀H₃₇N₆O₉P	656.632
——	(2S)-cyclohexyl 2-((((2R,3R,4R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalene-1-yloxy)phosphorylamino)propanoate	1234490-89-1	C₃₁H₃₉N₆O₉P	670.659
——	(2S)-neopentyl 2-(((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorothioyl)amino)propanoate	1365634-88-3	C₃₀H₃₉N₆O₈PS	674.715
——	benzyl (2S)-(((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy(naphthalene-1-yloxy)phosphorylamino)propanoate	1234490-75-5	C₃₂H₃₅N₆O₉P	678.638
——	propan-2-yl (2R)-3-[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S)-1-oxo-1-propan-2-yloxypropan-2-yl]amino]phosphoryl]sulfanyl-2-(methoxycarbonylamino)propanoate	——	C₂₆H₄₂N₇O₁₂PS	707.699
——	(2S,2'S)-dicyclohexyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)bis(2-phenylacetate)	1350765-73-9	C₄₀H₅₂N₇O₁₀P	821.868
——	2(R)-(2-amino-6-methoxy-9(H)-purinyl)-4(R)-(4(S)-(3-chlorophenyl)-2-oxo-1,3,2-dioxaphosphorinan-2(R)-yloxymethyl)-1(R)-methyl-7-oxo-3,6,8-trioxa-cis-bicyclo[3.3.0]octane	1447584-15-7	C₂₂H₂₃ClN₅O₉P	567.879
——	(2R,3R,4R,5R)-5-[[[4-[[(2R,3R,4R,5R)-5-(2-amino-6-ethoxypurin-9-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]piperazin-1-yl]-phenoxyphosphoryl]oxymethyl]-2-(2-amino-6-methoxypurin-9-yl)-3-methyloxolane-3,4-diol	1604813-47-9	C₄₁H₅₁FN₁₂O₁₃P₂	1000.87
——	methyl (2S,3S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S,3S)-1-methoxy-3-methyl-1-oxopentan-2-yl]amino]phosphoryl]amino]-3-methylpentanoate	1336974-06-1	C₂₅H₄₂N₇O₁₀P	631.623
——	cyclopentyl (2S,4S)-2-[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy]-2-oxo-4,5-dihydro-3H-1,3,2lambda5-benzothiazaphosphepine-4-carboxylate	——	C₂₆H₃₃N₆O₈PS	620.623
——	cyclopentyl (2R,4S)-2-[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy]-2-oxo-4,5-dihydro-3H-1,3,2lambda5-benzothiazaphosphepine-4-carboxylate	——	C₂₆H₃₃N₆O₈PS	620.623

反应信息

作为反应物：

描述：

2'-C-甲基-6-O-甲基鸟苷在三乙胺作用下，以四氢呋喃、二氯甲烷为溶剂，反应 21.0h，生成 (2S,2'S)-diethyl 2,2'-((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosphoryl)bis(azanediyl)dipropanoate

参考文献：

名称：

Phosphorodiamidates as a Promising New Phosphate Prodrug Motif for Antiviral Drug Discovery: Application to Anti-HCV Agents

摘要：

We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterified amino acids, both D and L., and also from various simple amines. All of the compounds were evaluated versus hepatitis C virus in replicon assay, and nanomolar activity levels were observed. Many compounds were noncytotoxic at 100 mu M, leading to high antiviral selectivities. The agents are stable in acidic, neutral, and moderately basic media and in selected biological media but show efficient processing by carboxypeptidases and efficiently yield the free nucleoside monophosphate in cells. On the basis of in vitro data, eight leads were selected for additional in vivo evaluation, with the intent of selecting one candidate for progression toward clinical studies. This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases.

DOI：

10.1021/jm2011673
作为产物：

描述：

2-氨基-6-氯嘌呤在三氟甲磺酸三甲基硅酯、 1,8-二氮杂双环[5.4.0]十一碳-7-烯作用下，以甲醇、乙腈为溶剂，反应 24.0h，生成 2'-C-甲基-6-O-甲基鸟苷

参考文献：

名称：

[EN] CRYSTALLINE SOLVATES OF NUCLEOSIDE PHOSPHOROAMIDATES, THEIR STEREOSELECTIVE PREPARATION, NOVEL INTERMEDIATES THEREOF, AND THEIR USE IN THE TREATMENT OF VIRAL DISEASE
[FR] SOLVATES CRISTALLINS DE NUCLÉOSIDE PHOSPHOROAMIDATES, LEUR PRÉPARATION STÉRÉOSÉLECTIVE, NOUVEAUX INTERMÉDIAIRES DE CEUX-CI ET LEUR UTILISATION DANS LE TRAITEMENT D'UNE MALADIE VIRALE

摘要：

该发明涉及抗HCV核苷磷酸酰胺的(S)-P对映体的新型晶体溶剂化合物，(2S)-新戊基2-((((2R,3R,4R,5R)-5-(2-氨基-6-甲氧基-9H-嘌呤-9-基)-3,4-二羟基-4-甲基四氢呋喃-2-基)甲氧基)(萘基氧基)磷酰胺)丙酸酯（也称为INX-08189或INX-189），以及用于分离INX-08189两个对映体的重结晶方法。此外，该申请涉及一种新颖的立体选择性制备两个对映体的方法，以及用于这种立体选择性合成的新型合成中间体。该发明还涉及利用晶体溶剂化合物提高2'-C-甲基鸟苷三磷酸酯从口服剂量中的肝脏暴露。

公开号：

WO2013066991A1

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文献信息

Macroheterocyclic nucleoside derivatives and their analogues, production and use thereof

申请人：Ivachtchenko Alexandre Vasilievich

公开号：US20180099989A1

公开（公告）日：2018-04-12

Nucleosides and nucleotides (nucleos(t)ides) have been in clinical use for almost 50 years and have become cornerstones of treatment for patients with viral infections or cancer. The approval of several additional drugs over the past decade demonstrates that this family still possesses strong potential. Therefore nucleos(t)ide are of great interest as promising chemotherapeutic agents, including: 2′-deoxy-L-uridine (CAS No 31501-19-6), 2′-deoxy-D-uridine (CAS No 951-78-0), telbivudine (CAS No 3424-98-4), zidovudine (AZT, CAS No 30516-87-1), trifluridine (CAS No 70-00-8), clevudine (CAS No 163252-36-6), PSI-6206 (CAS No 863329-66-2), 2′-(5)-2′-chloro-2′-deoxy-2′-fluorouridine (CAS No 1673560-41-2), ND06954 (CAS No 114248-23-6), stavudine (CAS No 3056-17-5), 5-ethynyltavudine (Festinavir, CAS No 634907-30-5), torcitabine (CAS No 40093-94-5), (−)-beta-D-(2R,4R)-dioxolane-thymine (DOT, 1-((2R,4R)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)-5-methyl-2,4 (1H,3H)-pyrimidinedione, CAS No. 127658-07-5), 2-(6-amino-purin-9-yl)-ethanol (CAS No 707-99-3), 2′-C-methylcytidine (CAS No 20724-73-6), PSI-6130 (CAS No 817204-33-4), gemcitabine (CAS No 95058-81-4), 2′-chloro-2′-deoxy-2′-fluorocytidine (CAS No 1786426-19-4), 2′,2′-dichloro-2′-deoxycytidine (CAS No 1703785-65-2), 2′-C-methylcytidine (CAS No 20724-73-6), PSI-6130 (CAS No 817204-33-4), lamivudine (3TC, CAS No 134678-17-4), emtricitabine (CAS No 143491-57-0), 2′-deoxyadenosine (CAS No 958-09-8), 2′-deoxy-β-L-adenosine (CAS No 14365-45-8), 2′-deoxy-4′-C-ethynyl-2-fluoroadenosine (CAS No 865363-93-5), didanosine (CAS No 69655-05-6), entecavir (CAS No 209216-23-9), FMCA (CAS No 1307273-70-6), dioxolane-G (DOG, CAS No 145514-01-8), β-D-2′-deoxy-2′-(R)-fluoro-2′-β-C-methylguanosine (CAS No 817204-45-8), abacavir (ABC, CAS No 136470-78-5), dioxolane-A (DOA, CAS #145514-02-9), [(2R,4R)-4-(6-cyclopropylamino-purin-9-yl)-[1,3]dioxolan-2-yl]-methanol (CAS No 1446751-04-7), amdoxovir (AMDX, CAS No 145514-04-1), (R)-1-(6-amino-purin-9-yl)-propan-2-ol (CAS No 14047-28-0), and [(2S,5R)-5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yl]-methanol. Macroheterocyclic nucleoside derivative and its analogue of the general formula 1 or general formula 2, a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, wherein: Ar is aryl or hetaryl; R 1 and R 2 are not necessarily the same substituents selected from H, F, Cl, CH 3 , OH; R 3 is H or CH 3 ; X is oxygen or ethanediyl-1,1 (C═CH 2 ); Y is CH(R 4 )(CH 2 ) k , CH(R 4 )(CH 2 ) m C(O)O(CH 2 ) n ; R 4 is H or CH 3 ; k has a value from zero to six; m has a value from zero to two; n has a value of one to four; Q is a radical selected from Q1-Q4; wherein: R 5 is the substituent selected from H, F, Cl, CH 3 , OH; the arrow (→) indicates the location, joined by Q1-Q4.

核苷和核苷酸（核苷（t）酸）已经在临床上使用了近50年，已成为治疗病毒感染或癌症患者的治疗基石。过去十年批准了几种额外的药物，表明这个家族仍然具有强大的潜力。因此，核苷（t）酸作为有前途的化疗药物具有很大的吸引力，包括：2'-脱氧-L-尿苷（CAS号31501-19-6）、2'-脱氧-D-尿苷（CAS号951-78-0）、替比夫定（CAS号3424-98-4）、阿司匹林（AZT，CAS号30516-87-1）、三氟胸苷（CAS号70-00-8）、克雷胸苷（CAS号163252-36-6）、PSI-6206（CAS号863329-66-2）、2'-(5)-2'-氯-2'-脱氧-2'-氟尿苷（CAS号1673560-41-2）、ND06954（CAS号114248-23-6）、司他夫定（CAS号3056-17-5）、5-乙炔基司他夫定（费司那韦，CAS号634907-30-5）、托西他滨（CAS号40093-94-5）、（-）-β-D-(2R,4R)-二氧杂环己嘧啶（DOT，1-((2R,4R)-2-(羟甲基)-1,3-二氧杂环己-4-基)-5-甲基-2,4(1H,3H)-嘧啶二酮，CAS号127658-07-5）、2-(6-氨基嘌呤-9-基)-乙醇（CAS号707-99-3）、2'-C-甲基胞苷（CAS号20724-73-6）、PSI-6130（CAS号817204-33-4）、吉西他滨（CAS号95058-81-4）、2'-氯-2'-脱氧-2'-氟胞苷（CAS号1786426-19-4）、2',2'-二氯-2'-脱氧胞苷（CAS号1703785-65-2）、2'-C-甲基胞苷（CAS号20724-73-6）、PSI-6130（CAS号817204-33-4）、拉米夫定（3TC，CAS号134678-17-4）、恩替卡韦（CAS号143491-57-0）、2'-脱氧腺苷（CAS号958-09-8）、2'-脱氧-β-L-腺苷（CAS号14365-45-8）、2'-脱氧-4'-C-乙炔基-2-氟腺苷（CAS号865363-93-5）、地达诺辛（CAS号69655-05-6）、恩替卡韦（CAS号209216-23-9）、FMCA（CAS号1307273-70-6）、二氧杂环己胞苷（DOG，CAS号145514-01-8）、β-D-2'-脱氧-2'-(R)-氟-2'-β-C-甲基鸟苷（CAS号817204-45-8）、阿巴卡韦（ABC，CAS号136470-78-5）、二氧杂环己-A（DOA，CAS号145514-02-9）、[(2R,4R)-4-(6-环丙基氨基嘌呤-9-基)-[1,3]二氧杂环己-2-基]-甲醇（CAS号1446751-04-7）、阿姆多氧韦（AMDX，CAS号145514-04-1）、(R)-1-(6-氨基嘌呤-9-基)-丙醇（CAS号14047-28-0）、和[(2S,5R)-5-(6-氨基嘌呤-9-基)-4-氟-2,5-二氢呋喃-2-基]-甲醇。宏环核苷衍生物及其一般式1或一般式2的类似物，立体异构体，同位素富集类似物，药学上可接受的盐，水合物，溶剂合物，或其结晶或多形式，其中： Ar是芳基或杂芳基； R 1 和R 2 不一定相同，选自H，F，Cl，CH 3 ，OH的取代基； R 3 是H或CH 3 ； X是氧或乙烯二基-1,1（C═CH 2 ）； Y是CH(R 4 )(CH 2 ) k ，CH(R 4 )(CH 2 ) m C(O)O(CH 2 ) n ； R 4 是H或CH 3 ； k的值从零到六； m的值从零到二； n的值从一到四； Q是从Q1-Q4中选择的基团；其中：R 5 是选自H，F，Cl，CH 3 ，OH的取代基；箭头（→）表示位置，由Q1-Q4连接。
NUCLEOTIDES CONTAINING AN N-[(S)-1-CYCLOBUTOXYCARBONYL]PHOSPHORAMIDATE FRAGMENT, ANALOGS THEREOF, AND USE THEREOF

申请人：Alla Chem, LLC

公开号：EP3473636A1

公开（公告）日：2019-04-24

The present invention relates to a prodrug and application thereof in the treatment of viral and cancerous diseases. Said prodrug inhibits HCV NS5B of HBV polymerase, DNA polymerase, and HIV-1 of reverse transcriptase (RT) and is used for the treatment of hepatitis B and C infection in mammals. The present invention also relates to the prodrugs of general formula 1 and stereoisomers thereof and their isotopically enriched analogs, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polycrystalline forms of the prodrugs of general formula 1 and stereoisomers thereof, wherein n is 1 or 0; Nuc is R1 is hydrogen or methyl; R2, R3 are optionally identical substituents selected from H, F, CI, CH3, OH provided that a solid line together with a dashed line above thereof (----) denote a carbon-carbon single bond (C-C), or R2 and R3 denote hydrogen provided that a solid line together with a dashed line above thereof (----) denote a carbon-carbon double bond (C=C); X is O, CH2 or C=CH2; Y is O, S, CH2 or a HO-CH group provided that a solid line together with a dashed line above thereof (----) denote a carbon-carbon single bond (C-C), or Y is a CH group provided that a solid line together with a dashed line above thereof (----) denote a carbon-carbon double bond (C=C).

本发明涉及一种前药及其在治疗病毒性和癌症性疾病中的应用。该前药抑制HBV聚合酶的HCV NS5B，DNA聚合酶和HIV-1的逆转录酶（RT），用于治疗哺乳动物中的乙型和丙型肝炎感染。本发明还涉及一般式1及其立体异构体的前药及其同位素富集的类似物，药学上可接受的盐，水合物，溶剂合物，或一般式1及其立体异构体的晶体或多晶形式，其中n为1或0； Nuc为 R1为氢或甲基； R2，R3为可选相同的取代基，选自H，F，CI，CH3，OH，前提是实线与其上方的虚线（----）表示碳-碳单键（C-C），或R2和R3表示氢，前提是实线与其上方的虚线（----）表示碳-碳双键（C=C）；X为O，CH2或C=CH2；Y为O，S，CH2或HO-CH基团，前提是实线与其上方的虚线（----）表示碳-碳单键（C-C），或Y为CH基团，前提是实线与其上方的虚线（----）表示碳-碳双键（C=C）。
THIOPHOSPHATE NUCLEOSIDES FOR THE TREATMENT OF HCV

申请人：IDENIX PHARMACEUTICALS, INC.

公开号：US20140248242A1

公开（公告）日：2014-09-04

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, the compounds are according to Formula 2001: where PD, Base, R A and R B are as provided herein. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

本文提供了用于治疗黄病毒科感染，包括HCV感染的化合物、组合物和方法。在某些实施例中，所述化合物符合以下公式2001：其中PD、Base、R A 和R B 如本文所述。在某些实施例中，披露了核苷类衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。
Substituted Carbonyloxymethylphosphoramidate Compounds and Pharmaceutical Compositions for the Treatment of Viral Infections

申请人：Surleraux Dominique

公开号：US20130064794A1

公开（公告）日：2013-03-14

Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

本文提供了用于治疗肝脏疾病，包括HCV感染的化合物、组合物和方法。在某些实施例中，披露了核苷衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。
3',5'-CYCLIC PHOSPHATE PRODRUGS FOR HCV INFECTION

申请人：Idenix Pharmaceuticals Inc.

公开号：US20130315867A1

公开（公告）日：2013-11-28

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

本文提供了用于治疗黄病毒科感染，包括HCV感染的化合物、组合物和方法。在某些实施例中，披露了核苷类衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。