tert-butyl (9aR)-4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylate | 1147422-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl (9aR)-4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylate
• 英文别名: (R)-4-oxohexahydropyrazino[2,1-c][1,4]oxazine-8-carboxylic acid tert-butyl ester；(R)-4-Oxo-hexahydro-pyrazino[2,1-c][1,4]oxazine-8-carboxylic acid tert-butyl ester；tert-butyl (9aR)-4-oxo-6,7,9,9a-tetrahydro-1H-pyrazino[2,1-c][1,4]oxazine-8-carboxylate
• CAS: 1147422-40-9
• 化学式: C₁₂H₂₀N₂O₄
• 分子量: 256.302
• InChiKey: GUKNFXRSSGYLPU-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (9aR)-4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylate 在 盐酸 、 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 19.5h， 生成 (9aR)-八氢吡嗪并[2,1-c][1,4]恶嗪
  参考文献：
  名称：

  [EN] BICYCLIC RING SYSTEM SUBSTITUTED AMIDE FUNCTIONALISED PHENOLS AS MEDICAMENTS
  [FR] PHÉNOLS À FONCTIONNALITÉ AMIDE SUBSTITUÉS PAR UN SYSTÈME CYCLIQUE BICYCLIQUE EN TANT QUE MÉDICAMENTS

  摘要：

  这项发明涉及通式1的双环环系统取代酰胺功能化酚，其用作CXCR2活性抑制剂，含有这些化合物的药物组合物，以及将其用作治疗和/或预防呼吸系统或消化系统疾病、关节、皮肤或眼睛的炎症性疾病、外周或中枢神经系统疾病或癌症的药剂的方法，以及含有这些化合物的药物组合物。

  公开号：

  WO2012080456A1
• 作为产物：
  描述：

  (R)-1-BOC-3-羟甲基哌嗪 在 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 tert-butyl (9aR)-4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylate
  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] 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。
• PYRROLE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：LES LABORATOIRES SERVIER

  公开号：US20150031673A1

  公开（公告）日：2015-01-29

  Compounds of formula (I): wherein A 1 , A 2 , R a , R b , R c , R d , R 3 , R 4 , R 5 and T are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.

  式(I)的化合物： 其中A 1 ，A 2 ，R a ，R b ，R c ，R d ，R 3 ，R 4 ，R 5 和T的定义如描述中所述。 含有这些化合物的药物产品对于治疗涉及凋亡缺陷的病理，如癌症、自身免疫疾病和免疫系统疾病，具有益处。
• [EN] BICYCLIC RING SYSTEM SUBSTITUTED AMIDE FUNCTIONALISED PHENOLS AS MEDICAMENTS<br/>[FR] PHÉNOLS À FONCTIONNALITÉ AMIDE SUBSTITUÉS PAR UN SYSTÈME CYCLIQUE BICYCLIQUE EN TANT QUE MÉDICAMENTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012080456A1

  公开（公告）日：2012-06-21

  This invention relates to bicyclic ring system substituted amide functionalized phenols of general formula 1, their use as inhibitors of CXCR2 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system or cancers, as well as pharmaceutical compositions which contain these compounds.

  这项发明涉及通式1的双环环系统取代酰胺功能化酚，其用作CXCR2活性抑制剂，含有这些化合物的药物组合物，以及将其用作治疗和/或预防呼吸系统或消化系统疾病、关节、皮肤或眼睛的炎症性疾病、外周或中枢神经系统疾病或癌症的药剂的方法，以及含有这些化合物的药物组合物。
• BICYCLIC RING SYSTEM SUBSTITUTED AMIDE FUNCTIONALISED PHENOLS AS MEDICAMENTS
  申请人：GIOVANNINI Riccardo

  公开号：US20120329773A1

  公开（公告）日：2012-12-27

  This invention relates to bicyclic ring system substituted amide functionalized phenols of general formula 1, their use as inhibitors of CXCR2 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system or cancers, as well as pharmaceutical compositions which contain these compounds.

  这项发明涉及通式1的双环环系统取代酰胺功能化酚，其用作CXCR2活性抑制剂，含有相同化合物的药物组合物，以及将其用作治疗和/或预防呼吸道或胃肠道疾病、关节、皮肤或眼睛的炎症性疾病、外周或中枢神经系统疾病或癌症的药剂的方法，以及含有这些化合物的药物组合物。
• [EN] BICYCLIC RING SYSTEM SUBSTITUTED SULFONAMIDE FUNCTIONALISED PHENOLS AS MEDICAMENTS<br/>[FR] PHÉNOLS À FONCTIONNALITÉ SULFONAMIDE SUBSTITUÉE PAR UN SYSTÈME DE CYCLES BICYCLIQUE EN TANT QUE MÉDICAMENTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012080457A1

  公开（公告）日：2012-06-21

  This invention relates to bicyclic ring system substituted sulfonamide functionalized phenols of general formula (1), their use as inhibitors of CXCR2 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system or cancers, as well as pharmaceutical compositions which contain these compounds.

  这项发明涉及通式（1）的双环环系统取代磺酰胺官能化酚，其作为CXCR2活性抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗和/或预防呼吸道或消化道疾病、关节、皮肤或眼睛的炎症性疾病、外周或中枢神经系统疾病或癌症的药剂的方法，以及含有这些化合物的药物组合物。