N-[[4-[[[4-[[叔丁氧羰基]氨基][1,1'-联苯]-3-基]氨基]羰基]苯基]甲基]氨基甲酸甲酯 | 1013330-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[[4-[[[4-[[叔丁氧羰基]氨基][1,1'-联苯]-3-基]氨基]羰基]苯基]甲基]氨基甲酸甲酯
• 英文名称: 1,1-dimethylethyl [3-({[4-({[(methyloxy)carbonyl]amino}methyl)phenyl]carbonyl}amino)biphenyl-4-yl]carbamate
• 英文别名: N-[[4-[[[4-[[tert-Butyloxycarbonyl]amino][1,1'-biphenyl]-3-yl]amino]carbonyl]phenyl]methyl]carbamic acid methyl ester；tert-butyl N-[2-[[4-[(methoxycarbonylamino)methyl]benzoyl]amino]-4-phenylphenyl]carbamate
• CAS: 1013330-69-2
• 化学式: C₂₇H₂₉N₃O₅
• 分子量: 475.544
• InChiKey: OXWCHHJNJHVURH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[[4-[[[4-[[叔丁氧羰基]氨基][1,1'-联苯]-3-基]氨基]羰基]苯基]甲基]氨基甲酸甲酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-[[4-[[(4-氨基[1,1'-联苯]-3-基)氨基]羰基]苯基]甲基]氨基甲酸甲酯
  参考文献：
  名称：

  Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2)

  摘要：

  A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC isoforms most closely associated with cancer. The hypothesis for the increased selectivity is the binding of a pendant aromatic group in the internal cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a series of potent and selective inhibitors with reduced off-target activity and tumor growth inhibition activity in a HCT-116 xenograft model. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.047
• 作为产物：
  描述：

  N-[3-[[4-[(1,3-二氢-1,3-二氧代-2H-异吲哚-2-基)甲基]苯甲酰基]氨基][1,1'-联苯]-4-基]氨基甲酸叔丁酯 在 一水合肼 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 N-[[4-[[[4-[[叔丁氧羰基]氨基][1,1'-联苯]-3-基]氨基]羰基]苯基]甲基]氨基甲酸甲酯
  参考文献：
  名称：

  WO2009/2495

  摘要：

  公开号：

文献信息

• 4-CARBOXYBENZYLAMINO DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
  申请人：Harrington Paul

  公开号：US20130137690A1

  公开（公告）日：2013-05-30

  The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also 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 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

  本发明涉及一种新型的4-羧基苯甲基氨基衍生物。这些4-羧基苯甲基氨基化合物可用于治疗癌症。这些4-羧基苯甲基氨基化合物还可以抑制组蛋白去乙酰化酶，并适用于选择性诱导末端分化，阻止肿瘤细胞生长和/或凋亡，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细胞增殖特征的患者中非常有用。本发明的化合物也可用于预防和治疗TRX介导的疾病，如自身免疫、过敏和炎症性疾病，以及中枢神经系统（CNS）疾病的预防和/或治疗，如神经退行性疾病。本发明还提供了包含4-羧基苯甲基氨基衍生物的药物组合物和这些药物组合物的安全剂量方案，这些方案易于遵循，并且在体内产生治疗有效量的4-羧基苯甲基氨基衍生物。
• US8389553B2
  申请人：——

  公开号：US8389553B2

  公开（公告）日：2013-03-05
• US9096559B2
  申请人：——

  公开号：US9096559B2

  公开（公告）日：2015-08-04
• [EN] 4-CARBOXYBENZYLAMINO DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS<br/>[FR] DÉRIVÉS DE 4-CARBOXYBENZYLAMINO UTILISÉS EN TANT QU'INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：MERCK & CO INC

  公开号：WO2009002495A1

  公开（公告）日：2008-12-31

  [EN] The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also 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 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.
  [FR] La présente invention concerne une classe inédite de dérivés de 4-carboxybenzylamino. Ces composés de 4-carboxybenzylamino peuvent être utilisés pour le traitement du cancer. Ces composés de 4-carboxybenzylamino peuvent également inhiber l'histone désacétylase et peuvent tout à fait être utilisés en vue de l'induction sélective de la différenciation terminale, de l'arrêt de la croissance cellulaire et/ou de l'apoptose des cellules néoplasiques, ce qui a pour résultat une inhibition de la prolifération desdites cellules. Ainsi, les composés de la présente invention se révèlent utiles en vue du traitement d'un patient souffrant d'une tumeur caractérisée par la prolifération de cellules néoplasiques. Les composés de l'invention peuvent également se révéler utiles dans le cadre de la prévention et du traitement des maladies à médiation par TRX, comme les maladies auto-immunes, allergiques et inflammatoires, ainsi que dans le cadre de la prévention et/ou du traitement de maladies du système nerveux central (SNC), comme les maladies neurodégénératives. La présente invention concerne, en outre, des compositions pharmaceutiques contenant lesdits dérivés de 4-carboxybenzylamino, ainsi que des régimes posologiques sûrs, applicables à ces compositions pharmaceutiques, faciles à respecter et ayant pour résultat l'administration d'une dose efficace d'un point de vue thérapeutique de dérivés de 4-carboxybenzylamino in vivo.
• Optimization of biaryl Selective HDAC1&amp;2 Inhibitors (SHI-1:2)
  作者：David J. Witter、Paul Harrington、Kevin J. Wilson、Melissa Chenard、Judith C. Fleming、Brian Haines、Astrid M. Kral、J. Paul Secrist、Thomas A. Miller

  DOI：10.1016/j.bmcl.2007.11.047

  日期：2008.1

  A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC isoforms most closely associated with cancer. The hypothesis for the increased selectivity is the binding of a pendant aromatic group in the internal cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a series of potent and selective inhibitors with reduced off-target activity and tumor growth inhibition activity in a HCT-116 xenograft model. (c) 2007 Elsevier Ltd. All rights reserved.