(4R,6R,7S)-(4-(2,4-dioxopyrimidin-1(2H)-yl)-6-[(4-methoxyphenyldiphenyl)methoxymethyl]-5-oxaspiro[2.4]-hept-7-yl) isobutyrate | 1202488-01-4

• 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: (4R,6R,7S)-(4-(2,4-dioxopyrimidin-1(2H)-yl)-6-[(4-methoxyphenyldiphenyl)methoxymethyl]-5-oxaspiro[2.4]-hept-7-yl) isobutyrate
• 英文别名: [(4R,6R,7S)-4-(2,4-dioxopyrimidin-1-yl)-6-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]-5-oxaspiro[2.4]heptan-7-yl] 2-methylpropanoate
• CAS: 1202488-01-4
• 化学式: C₃₅H₃₆N₂O₇
• 分子量: 596.68
• InChiKey: CXSJAGAYRKNPJC-BHYWQNONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4R,6R,7S)-(4-(2,4-dioxopyrimidin-1(2H)-yl)-6-[(4-methoxyphenyldiphenyl)methoxymethyl]-5-oxaspiro[2.4]-hept-7-yl) isobutyrate 在 ammonium hydroxide 、 水 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 ((4R,6R,7S)-4-(4-amino-2-oxopyrimidin-1(2H)-yl)-6-hydroxymethyl-5-oxaspiro[2.4]hept-7-yl) isobutyrate
  参考文献：
  名称：

  Cyclopropyl polymerase inhibitors

  摘要：

  公开号：

  EP2141172B1
• 作为产物：
  描述：

  3-benzoyl-1-((6aR,8R,9aS)-2,2,4,4-tetraisopropyl-4',5',6,6a,8,9a-hexahydrospiro[furo[3,2-f][1,3,5,2,4]-trioxadisilocine-9,3'-pyrazole]-8-yl)pyrimidine-2,4(1H,3H)-dione 在 吡啶 、 二苯甲酮 、 四丁基氟化铵 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 反应 2.75h， 生成 (4R,6R,7S)-(4-(2,4-dioxopyrimidin-1(2H)-yl)-6-[(4-methoxyphenyldiphenyl)methoxymethyl]-5-oxaspiro[2.4]-hept-7-yl) isobutyrate
  参考文献：
  名称：

  Cyclopropyl polymerase inhibitors

  摘要：

  公开号：

  EP2141172B1

文献信息

• CYCLOPROPYL POLYMERASE INHIBITORS
  申请人：Jonckers Tim Hugo Maria

  公开号：US20110092460A1

  公开（公告）日：2011-04-21

  Compounds of formula I: wherein: R 2 is hydrogen or C 1 -C 4 alkyl; R 3 and R 4 are hydrogen, —C(═O)R 5 , or —C(═O)CHR 6 —NH 2 ; or R 3 is hydrogen and R 4 is a monophosphate-, diphosphate-, or triphosphate ester; or R 3 is hydrogen, —C(═O)CHR 5 , or —C(═O)CHR 6 —NH 2 and R 4 is each R 5 is hydrogen, C 1 -C 6 alkyl, or C 3 -C 7 cycloalkyl; R 6 is hydrogen or C 1 -C 6 alkyl; R 7 is optionally substituted phenyl; naphthyl; or indolyl; R 8 and R 8′ are hydrogen, C 1 -C 6 alkyl, benzyl; or R 8 and R 8′ combined form C 3 -C 7 cycloalkyl; R 9 is C 1 -C 6 alkyl, benzyl, or optionally substituted phenyl; provided that R 2 , R 3 and R 4 are not all hydrogen; or a pharmaceutically acceptable salt or solvate thereof; pharmaceutical formulations with the compounds I; the use of compounds I, including the compounds of formula I wherein R 2 , R 3 and R 4 are all hydrogen, as HCV inhibitors.

  化合物I的式子如下： 其中： R2是氢或C1-C4烷基； R3和R4是氢，-C(═O)R5，或-C(═O)CHR6-NH2；或者R3是氢，而R4是单磷酸酯、二磷酸酯或三磷酸酯；或者R3是氢，-C(═O)CHR5，或-C(═O)CHR6-NH2，而R4是每个R5，其中R5是氢、C1-C6烷基或C3-C7环烷基； R6是氢或C1-C6烷基； R7是可选取代的苯基、萘基或吲哚基； R8和R8'是氢、C1-C6烷基、苄基；或者R8和R8'组成C3-C7环烷基； R9是C1-C6烷基、苄基或可选取代的苯基； 但要求R2、R3和R4不全为氢；或其药学上可接受的盐或溶剂；化合物I的药物配方；化合物I的用途，包括其中R2、R3和R4均为氢的化合物作为HCV抑制剂。
• 2′-Deoxy-2′-spirocyclopropylcytidine Revisited: A New and Selective Inhibitor of the Hepatitis C Virus NS5B Polymerase
  作者：Tim H. M. Jonckers、Tse-I Lin、Christophe Buyck、Sophie Lachau-Durand、Koen Vandyck、Steven Van Hoof、Leen A. M. Vandekerckhove、Lili Hu、Jan Martin Berke、Leen Vijgen、Lieve L. A. Dillen、Maxwell D. Cummings、Herman de Kock、Magnus Nilsson、Christian Sund、Christina Rydegård、Bertil Samuelsson、Åsa Rosenquist、Gregory Fanning、Kristof Van Emelen、Kenneth Simmen、Pierre Raboisson

  DOI：10.1021/jm101050a

  日期：2010.11.25

  The current therapy for hepatitis C virus (HCV) infection has limited efficacy, in particular against the genotype 1 virus, and a range of side effects. In this context of high unmet medical need, more efficacious drugs targeting HCV nonstructural proteins are of interest. Here we describe 2'-deoxy-2'-spirocyclo-propylcytidine (5) as a new inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC50 of 7.3 mu M measured in the Huh7-Rep cell line and no associated cytotoxicity (CC50 > 98.4 mu M). Computational results indicated high similarity between 5 and related HCV inhibiting nucleosides. A convenient synthesis was devised, facilitating synthesis of multigram quantities of 5. As the exposure measured after oral administration of 5 was found to be limited, the 3'-mono- and 3',5'-diisobutyryl ester prodrugs 20 and 23, respectively, were evaluated, The oral dosing of 23 led to substantially increased exposure to 5 in both rats and dogs.
• US8431588B2
  申请人：——

  公开号：US8431588B2

  公开（公告）日：2013-04-30
• [EN] CYCLOPROPYL POLYMERASE INHIBITORS<br/>[FR] INHIBITEURS DE CYCLOPROPYLE POLYMÉRASE
  申请人：CENTOCOR ORTHO BIOTECH PRODUCT

  公开号：WO2010000459A1

  公开（公告）日：2010-01-07

  Compounds of formula I: wherein: R2 is hydrogen or C1-C4alkyl; R3 and R4 are hydrogen, -C(=O)R5, or -C(=O)CHR6-NH2; or R3 is hydrogen and R4 is a monophosphate-, diphosphate-, or triphosphate ester; or R3 is hydrogen, -C(=O)CHR5, or -C(=O)CHR6-NH2 and R4 is (formula 2) each R5 is hydrogen, C1-C6alkyl, or C3-C7cycloalkyl; R6 is hydrogen or C1-C6alkyl; R7 is optionally substituted phenyl; naphthyl; or indolyl; R8 and R8 are hydrogen, C3-C7alkyl, benzyl; or R8 and R8 combined form C3-C7cycloalkyl; R9 is C1-C6alkyl, benzyl, or optionally substituted phenyl; provided that R2, R3 and R4 are not all hydrogen; or a pharmaceutically acceptable salt or solvate thereof; pharmaceutical formulations with the compounds I; the use of compounds I, including the compounds of formula I wherein R2, R3 and R4 are all hydrogen, as HCV inhibitors.