((2S)-1-[(3',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indol]-8'-yl)sulfonyl]pyrrolidin-2-yl)methyl 4-methylbenzenesulfonate | 869223-82-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ((2S)-1-[(3',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indol]-8'-yl)sulfonyl]pyrrolidin-2-yl)methyl 4-methylbenzenesulfonate
• 英文别名: {(2S)-1-[(3',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indol]-8'-yl)sulfonyl]pyrrolidin-2-yl}methyl 4-methylbenzenesulfonate；[(2S)-1-(3',3'-dimethylspiro[1,3-dioxane-2,10'-2,4-dihydropyrimido[1,2-a]indole]-8'-yl)sulfonylpyrrolidin-2-yl]methyl 4-methylbenzenesulfonate
• CAS: 869223-82-5
• 化学式: C₂₈H₃₅N₃O₇S₂
• 分子量: 589.734
• InChiKey: BMHATPSZNJCBFT-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ((2S)-1-[(3',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indol]-8'-yl)sulfonyl]pyrrolidin-2-yl)methyl 4-methylbenzenesulfonate 、 2-氯-4-甲氧基苯酚 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3

  摘要：

  Cysteine-dependant aspartyl protease (caspase) activation has been implicated as a part of the signal transduction pathway leading to apoptosis. It has been postulated that caspase-3 inhibition could attenuate cell damage after an ischemic event and thereby providing for a novel neuroprotective treatment for stroke. As part of a program to develop a small molecule inhibitor of caspase-3, a novel series of 3,4-dihydropyrimido(1,2-a)indol-10(2H)-ones (pyrimidoindolones) was identified. The synthesis, biological evaluation and structure-activity relationships of the pyrimidoindolones are described. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.036
• 作为产物：
  描述：

  ((2S)-1-[(3',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indol]-8'-yl)sulfonyl]pyrrolidin-2-yl)methanol 、 对甲苯磺酰氯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以97%的产率得到((2S)-1-[(3',3'-dimethyl-3',4'-dihydro-2'H-spiro[1,3-dioxane-2,10'-pyrimido[1,2-a]indol]-8'-yl)sulfonyl]pyrrolidin-2-yl)methyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Pyrimidoindolones and methods for using same

  摘要：

  揭示了一种新型的嘧啶吲哚酮化合物。还揭示了使用这些嘧啶吲哚酮化合物的方法，以及包含这些化合物的组合物在治疗和/或预防与炎症、神经退行性疾病、骨关节炎和细胞凋亡相关的疾病和其他情况中的应用。

  公开号：

  US20050250798A1

文献信息

• Pyrimidoindolones and methods for using same
  申请人：Dollings Jeffrey Paul

  公开号：US20050250798A1

  公开（公告）日：2005-11-10

  Novel pyrimidoindolone compounds are disclosed. Methods of using the pyrimidoindolone compounds and compositions containing the compounds in the treatment and/or prevention of disease and other conditions related to inflammation, neurodegeneration, osteoarthritis and apoptosis are also disclosed.

  揭示了一种新型的嘧啶吲哚酮化合物。还揭示了使用这些嘧啶吲哚酮化合物的方法，以及包含这些化合物的组合物在治疗和/或预防与炎症、神经退行性疾病、骨关节炎和细胞凋亡相关的疾病和其他情况中的应用。
• PYRIMIDOINDOLONES AND METHODS FOR USING SAME
  申请人：Dollings Jeffrey Paul

  公开号：US20070270587A1

  公开（公告）日：2007-11-22

  Novel pyrimidoindolone compounds are disclosed. Methods of using the pyrimidoindolone compounds and compositions containing the compounds in the treatment and/or prevention of disease and other conditions related to inflammation, neurodegeneration, osteoarthritis and apoptosis are also disclosed.

  本发明揭示了新型嘧啶并吲哚酮类化合物。还揭示了使用这些嘧啶并吲哚酮类化合物和含有这些化合物的组合物在治疗和/或预防与炎症、神经退行性、骨关节炎和细胞凋亡等疾病和其他相关病症方面的方法。
• US7256198B2
  申请人：——

  公开号：US7256198B2

  公开（公告）日：2007-08-14
• [EN] NEW PLEUROMUTILIN DERIVATIVE AND ITS USE<br/>[FR] NOUVEAU DERIVE DE LA PLEUROMUTILINE ET SON UTILISATION
  申请人：GLAXO GROUP LTD

  公开号：WO2007062335A2

  公开（公告）日：2007-05-31

  (EN) The invention is directed to the succinate salt of trans-4-aminocyclohexyl (1S,2R,3S,4S,6R,7R,8R,14R)-4-ethenyl-3-hydroxy-2,4,7,14-tetramenthyl-9-oxotricyclo[5.4.3.01,8]tetradec-6-yl imidodicarbonate (Compound IA). Compound IA is useful for the treatment of a variety of diseases and conditions, such as respiratory tract and skin and skin structure infections. Accordingly, the invention is still further directed to methods of treating respiratory tract and skin and skin structure infections using Compound IA or a pharmaceutical composition comprising Compound IA.(FR) La présente invention concerne le sel succinate du trans-4-aminocyclohexyl (1S,2R,3S,4S,6R,7R,8R,14R)-4-éthényl-3-hydroxy-2,4,7,14-tétraméthyl-9-oxotricyclo [5.4.3.01,8]tétradec-6-yl imido dicarbonate (composé IA). Le composé IA est utilisable pour le traitement de maladies et d'états variés tels que des infections des voies respiratoires et de la peau et des structures cutanées. L'invention concerne en outre le traitement d'infections des voies respiratoires et de la peau et des structures cutanées à l'aide du composé IA ou d'une composition pharmaceutique comprenant le composé IA.
• 3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3
  作者：Lisa M. Havran、Dan C. Chong、Wayne E. Childers、Paul J. Dollings、Arlene Dietrich、Boyd L. Harrison、Vasilios Marathias、Gregory Tawa、Ann Aulabaugh、Rebecca Cowling、Bhupesh Kapoor、Weixin Xu、Lidia Mosyak、Franklin Moy、Wah-Tung Hum、Andrew Wood、Albert J. Robichaud

  DOI：10.1016/j.bmc.2009.09.036

  日期：2009.11

  Cysteine-dependant aspartyl protease (caspase) activation has been implicated as a part of the signal transduction pathway leading to apoptosis. It has been postulated that caspase-3 inhibition could attenuate cell damage after an ischemic event and thereby providing for a novel neuroprotective treatment for stroke. As part of a program to develop a small molecule inhibitor of caspase-3, a novel series of 3,4-dihydropyrimido(1,2-a)indol-10(2H)-ones (pyrimidoindolones) was identified. The synthesis, biological evaluation and structure-activity relationships of the pyrimidoindolones are described. (C) 2009 Elsevier Ltd. All rights reserved.