(2S)-N-[[4-[(4,10-二氢-1-甲基吡唑并[3,4-b][1,5]苯并二氮杂-5(1H)-基)羰基]-2-甲基苯基]甲基]-2-[(六氢-4-甲基-1H-1,4-二氮杂-1-基)硫代甲基]-1-吡咯烷甲酰胺 | 479232-57-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: (2S)-N-[[4-[(4,10-二氢-1-甲基吡唑并[3,4-b][1,5]苯并二氮杂-5(1H)-基)羰基]-2-甲基苯基]甲基]-2-[(六氢-4-甲基-1H-1,4-二氮杂-1-基)硫代甲基]-1-吡咯烷甲酰胺
• 英文名称: (2S)-N-[[4-[(4,10-dihydro-1-methylpyrazolo[3,4-b][1,5]benzodiazepin-5(1H)-yl)carbonyl]-2-methylphenyl]methyl]-2-[(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)thioxomethyl]-1-pyrrolidinecarboxamide
• 英文别名: TC-OT-39；(2S)-N-[[4-[(4,10-Dihydro-1-methylpyrazolo[3,4-b][1,5]benzodiazepin-5(1H)-yl)carbonyl]-2-methylphenyl]methyl]-2-[(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)thioxomethyl]-1-pyrrolidinecarboxamide；(2S)-2-(4-methyl-1,4-diazepane-1-carbothioyl)-N-[[2-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]pyrrolidine-1-carboxamide
• CAS: 479232-57-0
• 化学式: C₃₂H₄₀N₈O₂S
• 分子量: 600.788
• InChiKey: KSNHHKZYKYNBEI-NDEPHWFRSA-N

物化性质

• 溶解度：
  溶于 DMSO > 10 mM

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  43
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴-2-甲基苯腈 在 sodium tetrahydroborate 、 正丁基锂 、 氯化亚砜 、 二乙基异丙基胺 、 三乙胺 、 cobalt(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 (2S)-N-[[4-[(4,10-二氢-1-甲基吡唑并[3,4-b][1,5]苯并二氮杂-5(1H)-基)羰基]-2-甲基苯基]甲基]-2-[(六氢-4-甲基-1H-1,4-二氮杂-1-基)硫代甲基]-1-吡咯烷甲酰胺
  参考文献：
  名称：

  Non-peptide oxytocin agonists

  摘要：

  A library of compounds targeted to the vasopressin/oxytocin family of receptors was screened for activity at a cloned human oxytocin receptor using a reporter gene assay. Potency and selectivity were optimised to afford compound 39, EC50 = 33 nM. This series of compounds represents the first disclosed, non-peptide, low molecular weight agonists of the hormone oxytocin (OT). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.107

文献信息

• Molecular composition for enhancing and rejuvenating maintenance and repair of mammalian tissues
  申请人：The Regents of the University of California

  公开号：US10265372B2

  公开（公告）日：2019-04-23

  Methods, pharmaceutical compositions, and kits are provided for treating a subject with an effective amount of an oxytocin receptor (OXTR) agonist and an effective amount of an ALK5 antagonist. In certain aspects, the OXTR agonist may be oxytocin or an oxytocin analog (e.g., a small molecule). The ALK 5 antagonist may be a small molecule, such as 2-(3-(6-Methyl-pyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine, LY2157299, A 83-01, D 4476, GW 788388, LY 364947, Rep Sox, SB 431542, SB 505124, SB 525334, or SD 208. In certain aspects, the amounts of the OXTR agonist and ALK5 antagonist may be sufficient to induce muscle regeneration and/or neural cell regeneration in the subject.

  提供了用有效量的催产素受体（OXTR）激动剂和有效量的ALK5拮抗剂治疗受试者的方法、药物组合物和试剂盒。在某些方面，OXTR 激动剂可以是催产素或催产素类似物（如小分子）。ALK 5 拮抗剂可以是小分子，如 2-(3-(6-甲基吡啶-2-基)-1H-吡唑-4-基)-1,5-萘啶、LY2157299、A 83-01、D 4476、GW 788388、LY 364947、Rep Sox、SB 431542、SB 505124、SB 525334 或 SD 208。在某些方面，OXTR 激动剂和 ALK5 拮抗剂的用量可能足以诱导受试者的肌肉再生和/或神经细胞再生。
• Subtlety of the Structure−Affinity and Structure−Efficacy Relationships around a Nonpeptide Oxytocin Receptor Agonist
  作者：Marie-Céline Frantz、Jordi Rodrigo、Laure Boudier、Thierry Durroux、Bernard Mouillac、Marcel Hibert

  DOI：10.1021/jm901084f

  日期：2010.2.25

  Very Few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In all attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of representative ligands of the V-1a, V-2, and OT receptor subtypes. Despite apparently obvious similarity between the ligand structures on one hand, and between the receptor subtypes on the other hand, the binding affinity and the functional activity profiles of truncated and hybrid ligands highlight the subtlety of ligand-receptor interactions for obtaining nonpeptide OT receptor agonists.
• Molecular Composition for Enhancing and Rejuvenating Maintenance and Repair of Mammalian Tissues
  申请人：The Regents of the University of California

  公开号：US20170239320A1

  公开（公告）日：2017-08-24

  Methods, pharmaceutical compositions, and kits are provided for treating a subject with an effective amount of an oxytocin receptor (OXTR) agonist and an effective amount of an ALK5 antagonist. In certain aspects, the OXTR agonist may be oxytocin or an oxytocin analog (e.g., a small molecule). The ALK 5 antagonist may be a small molecule, such as 2-(3-(6-Methyl-pyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine, LY2157299, A 83-01, D 4476, GW 788388, LY 364947, Rep Sox, SB 431542, SB 505124, SB 525334, or SD 208. In certain aspects, the amounts of the OXTR agonist and ALK5 antagonist may be sufficient to induce muscle regeneration and/or neural cell regeneration in the subject.
• Enhancing Oxytocin Receptor Expression Using an Oxytocin Receptor Agonist and an Alk5 Antagonist
  申请人：The Regents of the University of California

  公开号：US20200155638A1

  公开（公告）日：2020-05-21

  Methods are provided for treating a subject with an effective amount of an oxytocin receptor (OXTR) agonist and an effective amount of an ALK5 antagonist (ALK5i) to enhance OXTR expression in the subject. Methods are also provided for treating a subject with an effective amount of an OXTR agonist and an effective amount of an ALK5i to enhance hippocampal neurogenesis, enhance functional learning and reduce senescence in a tissue of the subject. In certain aspects, the amounts of the OXTR agonist and ALK5i may be sufficient to protect tissue maintenance and repair during acute and chronic viral infections. In certain aspects, the amount of the OXTR agonist and ALK5 antagonist may be sufficient to provide the subject with a sense of psychological well-being.
• Non-peptide oxytocin agonists
  作者：Gary Pitt、Andrzej Batt、Robert Haigh、Andrew Penson、Peter Robson、David Rooker、André Tartar、Julie Trim、Christopher Yea、Michael Roe

  DOI：10.1016/j.bmcl.2004.04.107

  日期：2004.9

  A library of compounds targeted to the vasopressin/oxytocin family of receptors was screened for activity at a cloned human oxytocin receptor using a reporter gene assay. Potency and selectivity were optimised to afford compound 39, EC50 = 33 nM. This series of compounds represents the first disclosed, non-peptide, low molecular weight agonists of the hormone oxytocin (OT). (C) 2004 Elsevier Ltd. All rights reserved.