(9aR)-八氢吡嗪并[2,1-c][1,4]恶嗪 | 508241-14-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: (9aR)-八氢吡嗪并[2,1-c][1,4]恶嗪
• 中文别名: (9AR)-八氢吡嗪并[2,1-C][1,4]恶嗪
• 英文名称: (R)-octahydropyrazino[2,1-c][1,4]oxazine
• 英文别名: (9aR)-1,3,4,6,7,8,9,9a-octahydropyrazino[2,1-c][1,4]oxazine
• CAS: 508241-14-3
• 化学式: C₇H₁₄N₂O
• 分子量: 142.201
• InChiKey: ZWNWCROZSHWHSF-SSDOTTSWSA-N

物化性质

• 沸点：
  234.4±35.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P210,P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P370+P378,P403+P233,P403+P235,P405,P501
• 危险性描述：
  H315,H319,H335,H227

反应信息

• 作为反应物：
  描述：

  (9aR)-八氢吡嗪并[2,1-c][1,4]恶嗪 在 sodium tetrahydroborate 、 palladium diacetate 、 caesium carbonate 、 溶剂黄146 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 (R)-8-(1,2,3,4-tetrahydroisoquinolin-5-yl)octahydropiperazine[2,1-c][1,4]oxazine
  参考文献：
  名称：

  四氢异喹啉类化合物、其制备方法、药物组合物及其用途

  摘要：

  本发明涉及一种四氢异喹啉类化合物、其制备方法、药物组合物及其用途。前述四氢异喹啉类化合物可由下述通式（1）表示，通式中各符号的定义与说明书中的相同。式（1）。

  公开号：

  CN107540659A
• 作为产物：
  描述：

  (R)-1-BOC-3-羟甲基哌嗪 在 potassium tert-butylate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (9aR)-八氢吡嗪并[2,1-c][1,4]恶嗪
  参考文献：
  名称：

  Novel lead generation of an anti-tuberculosis agent active against non-replicating mycobacteria: exploring hybridization of pyrazinamide with multiple fragments

  摘要：

  The key to shortening tuberculosis (TB) drug regimen lies in eliminating the reservoir of non-replicating persistent (NRP) Mycobacterium tuberculosis (Mtb). Pyrazinamide (PZA) is the only known drug used as part of a combination therapy that is believed to kill NRP Mtb and achieve sterilization. PZA is active only under low pH screening conditions. Screening and identification of NRP-active anti-TB compounds are severely limited because compounds are usually inactive under regular assay conditions. In an effort to design novel NRP-active anti-TB compounds, we used pyrazinamide as a core and hybridized it with the fragments derived from marketed drugs. One of these designs, compound 8, was a hybrid with fluoroquinolone. This compound exhibited > 10 fold improvement in NRP activity under low pH condition as compared to pyrazinamide and a modest activity (0.8 log(10) kill) under nutritionally starved NRP condition. Furthermore, compound 8 was active against fluoroquinolone-resistant strains and did not show any activity in a DNA supercoiling assay (gyrase inhibition), suggesting that its mechanism of action is not that of the parent fluoroquinolone. These results provide a novel avenue in the exploration of new chemotypes that are active against non-replicating Mtb.

  DOI：

  10.1007/s00044-015-1352-6

文献信息

• [EN] THIAZOLE SULFONAMIDE AND OXAZOLE SULFONAMIDE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE THIAZOLE SULFONAMIDE ET OXAZOLE SULFONAMIDE KINASES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010104899A1

  公开（公告）日：2010-09-16

  The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents

  本发明提供了噻唑磺酰胺和恶唑磺酰胺化合物、含有该化合物的组合物，以及它们的制备方法和作为药物的使用方法。
• [EN] PURINE DERIVATIVES USEFUL AS PI3 KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PURINE UTILES COMME INHIBITEURS DE PI3 KINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009053716A1

  公开（公告）日：2009-04-30

  This invention provides a compound which is a purine of formula (Ia) or (Ib): and the pharmaceutically acceptable salts thereof that are inhibitors of PI3K and a selective for the p110δ isoform, which is a class Ia PI3 kinase, over other class Ia PI3 kinases and over class Ib kinases. The compounds may be used to treat diseases and disorders arisi from abnormal cell growth, function or behaviour associated with PI3 kinase such as cance immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

  这项发明提供了一种化合物，其为式(Ia)或(Ib)的嘌呤类化合物：及其药学上可接受的盐，这些化合物是PI3K的抑制剂，并且对p110δ同工型具有选择性，p110δ是Ia类PI3激酶，优于其他Ia类PI3激酶和Ib类激酶。这些化合物可用于治疗由于与PI3激酶相关的异常细胞生长、功能或行为引起的疾病和紊乱，如癌症、免疫紊乱、心血管疾病、病毒感染、炎症、代谢/内分泌功能紊乱和神经系统疾病。
• TANK-BINDING KINASE INHIBITOR COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：US20160096827A1

  公开（公告）日：2016-04-07

  Compounds having the following formula (I) and methods of their use and preparation are disclosed:

  具有以下化学式（I）的化合物以及它们的使用和制备方法已被披露：
• [EN] ATAZANAVIR (ATV) ANALOGUES FOR TREATING HIV INFECTIONS<br/>[FR] ANALOGUES D'ATAZANAVIR (ATV) POUR TRAITER DES INFECTIONS PAR LE VIH
  申请人：GILEAD SCIENCES INC

  公开号：WO2018145021A1

  公开（公告）日：2018-08-09

  The invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, the compound of formula (I) for use in therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I. Preferred compounds are N-[(2S) -1-[2-[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino) -3,3-dimethylbutanoyl]amino]-4-phenylbutyl]-2-[(phenyl) methyl]hydrazinyl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate atazanavir (ATV) analogues substituted by several heterocycles, such as e.g. pyrazole (Rl); e.g. oxetane (substituent of X2); e.g. pyridine or pyrimidine (X1); e.g. piperazine or 3,8-diazabicyclo[3.2.1]octan (X2).

  该发明提供了一种如下式的化合物：或其药学上可接受的盐。该发明还提供了包含如下式化合物的药物组合物，制备如下式化合物的方法，以及利用如下式化合物治疗HIV病毒增殖、治疗艾滋病或延缓哺乳动物艾滋病症状发作的治疗方法中使用的如下式化合物。首选化合物是N-[(2S)-1-[2-[(2S,3S)-2-羟基-3-[[(2S)-2-(甲氧羰基氨基)-3,3-二甲基丁酰]氨基]-4-苯基丁基]-2-[(苯基)甲基]肼基]-3,3-二甲基-1-氧丁酸-2-基]氨基甲酸酯阿扎那韦（ATV）类似物，其被若干杂环取代，例如吡唑（R1）；例如氧杂环（X2的取代基）；例如吡啶或嘧啶（X1）；例如哌嗪或3,8-二氮杂双环[3.2.1]辛烷（X2）。
• [EN] THIAZOLE AND OXAZOLE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE À BASE DE THIAZOLE ET D'OXAZOLE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009032667A1

  公开（公告）日：2009-03-12

  The present invention provides thiazole and oxazole compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.

  本发明提供噻唑和氧唑化合物，含有这些化合物的组合物，以及用作药用剂的制备方法和使用方法。