(S)-2-amino-N-(cyclopropylsulfonyl)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanamide | 1434125-73-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-amino-N-(cyclopropylsulfonyl)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanamide
• 英文别名: (S)-2-Amino-N-(cyclopropylsulfonyl)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanamide；(2S)-2-amino-N-cyclopropylsulfonyl-3-(4-prop-2-ynoxyphenyl)propanamide
• CAS: 1434125-73-1
• 化学式: C₁₅H₁₈N₂O₄S
• 分子量: 322.385
• InChiKey: RAKYHLOVLBMDQN-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-N-(cyclopropylsulfonyl)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanamide 、 (S)-2-((2S,4S)-4-Allyl-1-((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino) propanamido)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamido)-3-(naphthalen-2-yl)propanoic acid 在 N-甲基吗啉 、 盐酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以76%的产率得到tert-butyl ((2S)-1-(((2S)-1-((2S,4S)-4-allyl-2-(((2S)-1-(((2S)-1-(cyclopropanesulfonamido)-1-oxo-3-(4-(prop-2-yn-1-yloxy)phenyl)propan-2-yl)amino)-3-(naphthalen-2-yl)-1-oxopropan-2-yl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate
  参考文献：
  名称：

  Dimeric Macrocyclic Antagonists of Inhibitor of Apoptosis Proteins for the Treatment of Cancer

  摘要：

  A series of dimeric macrocyclic compounds were prepared and evaluated as antagonists for inhibitor of apoptosis proteins. The most potent analogue 11, which binds to XLAP and c-IAP proteins with high affinity and induces caspase-3 activation and ultimately cell apoptosis, inhibits growth of human melanoma and colorectal cell lines at low nanomolar concentrations. Furthermore, compound 11 demonstrated significant antitumor activity in the A875 human melanoma xenograft model at doses as low as 2 mg/kg on a q3d schedule.

  DOI：

  10.1021/acsmedchemlett.5b00091
• 作为产物：
  描述：

  (S)-tert-butyl (1-(cyclopropanesulfonamido)-1-oxo-3-(4-(prop-2-yn-1-yloxy)phenyl)propan-2-yl)carbamate 、 盐酸 在 盐酸 作用下， 以 乙酸乙酯 、 1,4-二氧六环 为溶剂， 反应 4.0h， 以to give the title compound (720 mg, 99%) as a HCl salt的产率得到(S)-2-amino-N-(cyclopropylsulfonyl)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanamide
  参考文献：
  名称：

  MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS

  摘要：

  本发明揭示了一种调节凋亡抑制因子（IAPs）活性的化合物，以及含有该化合物的药物组合物和利用本发明化合物治疗增殖性疾病和失调凋亡疾病（如癌症）的方法。

  公开号：

  US20140135270A1

文献信息

• [EN] MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR L'INHIBITION D'INHIBITEURS DE L'APOPTOSE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014074658A1

  公开（公告）日：2014-05-15

  There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  这里公开了调节凋亡抑制剂（IAPs）活性的化合物，包含所述化合物的药物组合物以及使用本发明的化合物治疗增殖性疾病和凋亡失调疾病的方法，例如癌症。
• THIADIAZOLE MODULATORS OF BETA ADRENERGIC RECEPTOR
  申请人：Rao Tadimeti

  公开号：US20110086847A1

  公开（公告）日：2011-04-14

  The present invention relates to new thiadiazole modulators of beta adrenergic receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
• MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS
  申请人：Ensemble Therapeutics Corp.

  公开号：US20140135270A1

  公开（公告）日：2014-05-15

  There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  这里公开了调节凋亡抑制剂（IAPs）活性的化合物，包含所述化合物的药物组合物以及使用本发明的化合物治疗增殖性疾病和凋亡失调疾病的方法，例如癌症。
• Dimeric Macrocyclic Antagonists of Inhibitor of Apoptosis Proteins for the Treatment of Cancer
  作者：Yong Zhang、Benjamin A. Seigal、Nicholas K. Terrett、Randy L. Talbott、Joseph Fargnoli、Joseph G. Naglich、Charu Chaudhry、Shana L. Posy、Ragini Vuppugalla、Georgia Cornelius、Ming Lei、Chunlei Wang、Yingru Zhang、Robert J. Schmidt、Donna D. Wei、Michael M. Miller、Martin P. Allen、Ling Li、Percy H. Carter、Gregory D. Vite、Robert M. Borzilleri

  DOI：10.1021/acsmedchemlett.5b00091

  日期：2015.7.9

  A series of dimeric macrocyclic compounds were prepared and evaluated as antagonists for inhibitor of apoptosis proteins. The most potent analogue 11, which binds to XLAP and c-IAP proteins with high affinity and induces caspase-3 activation and ultimately cell apoptosis, inhibits growth of human melanoma and colorectal cell lines at low nanomolar concentrations. Furthermore, compound 11 demonstrated significant antitumor activity in the A875 human melanoma xenograft model at doses as low as 2 mg/kg on a q3d schedule.