ethyl amino[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetate | 947753-95-9

• 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: ethyl amino[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetate
• 英文别名: Ethyl 2-amino-2-[4-[(2-amino-5-thiophen-2-ylphenyl)carbamoyl]phenyl]acetate
• CAS: 947753-95-9
• 化学式: C₂₁H₂₁N₃O₃S
• 分子量: 395.482
• InChiKey: APJKLGVYOURSOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Ethyl [(tert-butoxycarbonyl)amino][4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 ethyl amino[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetate
  参考文献：
  名称：

  Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1)

  摘要：

  An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (> 100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and improved physical properties. Dose-dependent efficacy in a mouse HCT116 xenograft model was demonstrated with a phenylglycine SHI-1 analog. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.012

文献信息

• Inhibitors of Histone Deacetylase
  申请人：Grimm Jonathan B.

  公开号：US20090069250A1

  公开（公告）日：2009-03-12

  The present invention relates to a novel class of compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and sale dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

  本发明涉及一类新型化合物。这些化合物可以抑制组蛋白去乙酰化酶，并适用于在选择性诱导终末分化、阻止肿瘤细胞生长和/或凋亡的过程中使用，从而抑制这些细胞的增殖。因此，本发明的化合物在治疗具有肿瘤特征的患者方面是有用的，这些肿瘤由肿瘤细胞增殖引起。本发明的化合物还可能在预防和治疗TRX介导的疾病方面有用，如自身免疫、过敏和炎症性疾病，以及预防和/或治疗中枢神经系统（CNS）疾病，如神经退行性疾病。本发明还提供包含本发明化合物的药物组合物，以及这些药物组合物的销售用剂量方案，易于遵循，并在体内产生这些化合物的治疗有效量。
• INHIBITORS OF HISTONE DEACETYLASE
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1991226B1

  公开（公告）日：2013-03-20
• US8168658B2
  申请人：——

  公开号：US8168658B2

  公开（公告）日：2012-05-01
• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：MERCK & CO INC

  公开号：WO2007100657A2

  公开（公告）日：2007-09-07

  [EN] The present invention relates to a novel class of compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.
  [FR] La présente invention concerne une nouvelle classe de composés. Ces composés sont capables d'inhiber l'histone désacétylase et ils peuvent être utilisés pour induire sélectivement la différenciation terminale et pour stopper la croissance cellulaire et/ou l'apoptose de cellules néoplasiques, inhibant ainsi la prolifération de ces cellules. Les composés de la présente invention sont donc utiles pour traiter un patient présentant une tumeur caractérisée par la prolifération de cellules néoplasiques. Les composés de l'invention peuvent aussi avoir une utilité dans la prévention et le traitement de maladies médiées par la TRX, par exemple des maladies auto-immunes, allergiques et inflammatoires, et dans la prévention et/ou le traitement de maladies du système nerveux central (SNC), par exemple des maladies neurodégénératives. L'invention concerne en outre des compositions pharmaceutiques comprenant les composés de l'invention, ainsi que des schémas posologiques sûrs de ces compositions pharmaceutiques, qui sont faciles à respecter et qui donnent une quantité thérapeutiquement efficace de ces composés in vivo.
• Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1)
  作者：Kevin J. Wilson、David J. Witter、Jonathan B. Grimm、Phieng Siliphaivanh、Karin M. Otte、Astrid M. Kral、Judith C. Fleming、Andreas Harsch、Julie E. Hamill、Jonathan C. Cruz、Melissa Chenard、Alexander A. Szewczak、Richard E. Middleton、Bethany L. Hughes、William K. Dahlberg、J. Paul Secrist、Thomas A. Miller

  DOI：10.1016/j.bmcl.2008.02.012

  日期：2008.3

  An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (> 100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and improved physical properties. Dose-dependent efficacy in a mouse HCT116 xenograft model was demonstrated with a phenylglycine SHI-1 analog. (C) 2008 Elsevier Ltd. All rights reserved.