(3aS,13aS)-N-[(2,4-difluorophenyl)methyl]-7,9-dioxo-8-[(phenylmethyl)oxy]-1,2,3,3a,4,5,7,9,13,13a-decahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrrolo[1,2-c]pyrimidine-10-carboxamide | 1309563-52-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (3aS,13aS)-N-[(2,4-difluorophenyl)methyl]-7,9-dioxo-8-[(phenylmethyl)oxy]-1,2,3,3a,4,5,7,9,13,13a-decahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrrolo[1,2-c]pyrimidine-10-carboxamide
• 英文别名: (3aS,13aS)-N-[(2,4-difluorophenyl)methyl]-7,9-dioxo-8-[(phenylmethyl)oxy]-1,2,3,3a,4, 5,7,9,13,13a-decahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrrolo[1,2-c]pyrimidine-10-carb oxamide；(10S,15S)-N-[(2,4-difluorophenyl)methyl]-2,5-dioxo-4-phenylmethoxy-1,8,11-triazatetracyclo[8.7.0.03,8.011,15]heptadeca-3,6-diene-6-carboxamide
• CAS: 1309563-52-7
• 化学式: C₂₉H₂₈F₂N₄O₄
• 分子量: 534.563
• InChiKey: ZENLUUMTCZNQIP-URXFXBBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3aS,13aS)-N-[(2,4-difluorophenyl)methyl]-7,9-dioxo-8-[(phenylmethyl)oxy]-1,2,3,3a,4,5,7,9,13,13a-decahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrrolo[1,2-c]pyrimidine-10-carboxamide 在 钯 氢气 、 resultant mixture 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以to give the title compound (14 mg, 67%) as a white solid的产率得到(3aS,13aS)-N-[(2,4-difluorophenyl)methyl]-8-hydroxy-7,9-dioxo-1,2,3,3a,4,5,7,9,13,13a-decahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrrolo[1,2-c]pyrimidine-10-carboxamide
  参考文献：
  名称：

  POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY

  摘要：

  本发明提供了一种新型化合物(I)，如下所示，具有抗病毒活性，特别是HIV整合酶抑制活性，以及包含该化合物的药物，特别是抗HIV药物，以及其制备方法和中间体。(其中Z1为NR4; R1为氢或较低的烷基; X为单键，选自O、S、SO、SO2和NH的杂原子基团，或者其中杂原子基团可以介入的较低的亚烷基或较低的亚烯基; R2为可选取代芳基; R3为氢、卤素、羟基、可选取代的较低烷基等; R4和Z2共同形成环，形成多环化合物，包括三环或四环化合物等。)

  公开号：

  US20160207939A1
• 作为产物：
  描述：

  (S)-2-(甲苯磺酰氧基甲基)吡咯烷-1-甲酸叔丁酯 在 Raney-Ni 盐酸 、 氨 、 水 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 20.0~140.0 ℃ 、344.75 kPa 条件下， 反应 10.17h， 生成 (3aS,13aS)-N-[(2,4-difluorophenyl)methyl]-7,9-dioxo-8-[(phenylmethyl)oxy]-1,2,3,3a,4,5,7,9,13,13a-decahydropyrido[1',2':4,5]pyrazino[1,2-a]pyrrolo[1,2-c]pyrimidine-10-carboxamide
  参考文献：
  名称：

  WO2006/116764

  摘要：

  公开号：

文献信息

• Polycyclic carbamoylpyridone derivative having hiv integrase inhibitory activity
  申请人：Johns Brian Alvin

  公开号：US20090318421A1

  公开（公告）日：2009-12-24

  The present invention is to provide a novel compound (I) shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z 1 is NR 4 ; R 1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO 2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R 2 is optionally substituted aryl; R 3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R 4 and Z 2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.

  本发明提供了一种新型化合物(I)，如下所示，具有抗病毒活性，特别是HIV整合酶抑制活性，以及含有该化合物的药物，特别是抗HIV药物，以及其制备方法和中间体。(其中Z1为NR4;R1为氢或低碳基;X为单键，从O、S、SO、SO2和NH中选择的杂原子基团，或低碳基或低碳烯基，在其中杂原子基团可以介入;R2为可选取代芳基;R3为氢、卤素、羟基、可选取代的低碳基等;R4和Z2共同形成环，形成多环化合物，包括例如三环或四环化合物。
• Substituted 10-hydroxy-9,11-dioxo-2,3,4a,5,9,11,13,13a-octahydro-1h-pyrido[1,2-α]pyrrolo[1′,2′:3,4]imidazo[1,2-d]pyrazine-8-carboxamides
  申请人：Shionogi & Co., Ltd.

  公开号：US08778943B2

  公开（公告）日：2014-07-15

  The present invention is directed to a class of substituted 10-hydroxy-9,11-dioxo-2,3,4a,5,9,11,13,13a-octahydro-1H-pyrido[1,2-a]pyrrolo[1′,2′:3,4]imidazo[1,2-d]pyrazine-8-carboxamides useful as anti-HIV agents. The compounds have the formula (I-1-1): wherein ring A is an optionally substituted hexahydro-1H-pyrrolo[1,2-c]-imidazole; R14 and RX are independently hydrogen or optionally substituted lower alkyl; R3 is selected from various groups; R1 is hydrogen or lower alkyl; R is halogen; m is 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof.

  本发明涉及一类取代的10-羟基-9,11-二氧化-2,3,4a,5,9,11,13,13a-八氢-1H-吡啶[1,2-a]吡咯[1′,2′:3,4]咪唑[1,2-d]吡嗪-8-羧酰胺，用作抗HIV剂。化合物的式子为(I-1-1)：其中环A是可选的取代的六氢-1H-吡咯[1,2-c]-咪唑；R14和RX独立地为氢或可选的取代的低碳基；R3从各种基团中选择；R1为氢或低碳基；R为卤素；m为0、1、2或3；或其药学上可接受的盐。
• SUBSTITUTED CYCLOPENTA[4,5]OXAZOLO[3,2-a]PYRIDO[1,2-d]PYRAZINES AS HIV INTEGRASE INHIBITORS
  申请人：Shionogi & Co., Ltd.

  公开号：US20160137666A1

  公开（公告）日：2016-05-19

  The present invention is to provide a novel compound (I) shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z 1 is NR 4 ; R 1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO 2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R 2 is optionally substituted aryl; R 3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R 4 and Z 2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.

  本发明提供了一种新型化合物(I)，如下所示，具有抗病毒活性，特别是HIV整合酶抑制活性，以及含有该化合物的药物，特别是抗HIV药物，以及其制备方法和中间体。(其中Z1为NR4;R1为氢或低碳基;X为单键，从O、S、SO、SO2和NH中选择的杂原子基团，或杂原子基团可能介入的低碳基或低烯基;R2为可选取代芳基;R3为氢、卤素、羟基、可选取代的低碳基等;R4和Z2共同形成环，形成多环化合物，包括三环或四环化合物等)。
• N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3] oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide having HIV integrase inhibitory activity
  申请人：Shionogi & Co., Ltd.

  公开号：US10927129B2

  公开（公告）日：2021-02-23

  The present invention is directed to N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide of the formula: or a pharmaceutically acceptable salt or stereoisomer thereof, and pharmaceutical compositions comprising the same. The present invention has HIV integrase inhibitory activity.

  本发明涉及式中的 N-[(2,4-二氟苯基)甲基]-6-羟基-3-甲基-5,7-二氧代-2,3,5,7,11,11a-六氢[1,3]恶唑并[3,2-a]吡啶并[1,2-d]吡嗪-8-甲酰胺： 或其药学上可接受的盐或立体异构体，以及由其组成的药物组合物。本发明具有抑制艾滋病毒整合酶的活性。
• N-[(2,4-DIFLUOROPHENYL)METHYL]-6-HYDROXY-3-METHYL-5,7-DIOXO-2,3,5,7,11,11a-HEXAHYDRO[1,3]OXAZOLO[3,2-a]PYRIDO[1,2-d]PYRAZINE-8-CARBOXAMIDE HAVING HIV INTEGRASE INHIBITORY ACTIVITY
  申请人：Shionogi & Co., Ltd.

  公开号：US20190284208A1

  公开（公告）日：2019-09-19

  The present invention is to provide a novol compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. (wherein Z 1 is NR 4 ; R 1 is hydrogen or lower alkyl; X′ is a single bond, a hetoro atom group selected from O, S, SO, SO 2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R 2 is optionally substituted aryl; R 3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R 4 and Z 2 part taken together forms a ring, to form a polycyclic compound; including e.g., a tricyclic or tetracyclic compound.