7-(tert-butyloxycarbonylamino)-5,7,8,9-tetrahydro-benzocyclohepten-6-one | 1023620-26-9

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 7-(tert-butyloxycarbonylamino)-5,7,8,9-tetrahydro-benzocyclohepten-6-one
• 英文别名: 7-(tert-butoxycarbonyl-amino)-5,7,8,9-tetrahydro-benzocyclohepten-6-one；tert-butyl N-(6-oxo-5,7,8,9-tetrahydrobenzo[7]annulen-7-yl)carbamate
• CAS: 1023620-26-9
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: NWEUEAHSGYCXLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-(tert-butyloxycarbonylamino)-5,7,8,9-tetrahydro-benzocyclohepten-6-one 在 盐酸 、 5%-palladium/activated carbon 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 六甲基磷酰三胺 、 水 为溶剂， 反应 27.83h， 生成 7-amino 5-benzylidene-5,7,8,9-tetrahydrobenzocyclohepten-6-one
  参考文献：
  名称：

  Rapid and efficient synthesis of a novel series of substituted aminobenzosuberone derivatives as potent, selective, non-peptidic neutral aminopeptidase inhibitors

  摘要：

  Racemic 5-substituted 7-aminobenzocyclohepten-6-one were synthesized and evaluated for their ability to inhibit metalloaminopeptidase activities. Unexpectedly, 5-thio substituted compounds showed enhanced inhibition potency with K-i values in the nanomolar range against the 'one zinc' aminopeptidases from the M1 family, while most of them were rather poor inhibitors of the 'two zincs' enzymes from the M17 family. This interesting selectivity profile may guide the design of new, specific inhibitors of target mammalian aminopeptidases with one active site zinc. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.041
• 作为产物：
  描述：

  在 sodium tetrahydroborate 、 cobalt(II) chloride hexahydrate 、 盐酸羟胺 、 sodium carbonate 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 11.0h， 生成 7-(tert-butyloxycarbonylamino)-5,7,8,9-tetrahydro-benzocyclohepten-6-one
  参考文献：
  名称：

  Aminobenzosuberone Scaffold as a Modular Chemical Tool for the Inhibition of Therapeutically Relevant M1 Aminopeptidases

  摘要：

  对于甲基取代的7-氨基-5,7,8,9-四氢苯并环庚烯-6-酮盐酸盐的合成进行了优化，以增强可重复性并提高总产量。为了研究它们的特异性，进行了一系列酶抑制实验，针对多种蛋白酶，包括天冬氨酸蛋白酶、半胱氨酸蛋白酶、金属蛋白酶和丝氨酸内切肽酶的代表性成员，以及单金属M1家族氨基肽酶的八个成员，以及双金属M17和M28氨基肽酶家族的两个成员。这种氨基苯并苏二酮骨架确实表现出对M1氨基肽酶的选择性抑制，而不影响其他测试的蛋白酶家族；它对哺乳动物APN以及其细菌/寄生物同源物EcPepN和PfAM1表现出特别强效。

  DOI：

  10.3390/molecules23102607

文献信息

• AMINOBENZOCYCLOHEPTENE DERIVATIVES, METHODS FOR PREPARING THE SAME AND USES THEREOF IN THERAPY
  申请人：Tarnus-Rondeau Céline

  公开号：US20100069504A1

  公开（公告）日：2010-03-18

  A compound of the general formula (I) as an active principle for treating cancer, specifically tumors, in particular diseases involving inhibition of metalloproteases, such as Aminopeptidase-N. Pharmaceutical compositions comprising the compound of general formula (I). Methods of treatment using the compound of general formula (I).

  一种具有一般化学式（I）的化合物作为治疗癌症的活性成分，特别是肿瘤，特别是涉及金属蛋白酶抑制的疾病，如氨基肽酶-N。包括具有一般化学式（I）的化合物的药物组合物。使用一般化学式（I）的化合物进行治疗的方法。
• Amino-benzosuberone: A novel warhead for selective inhibition of human aminopeptidase-N/CD13
  作者：Sébastien Albrecht、Mira Al-Lakkis-Wehbe、Alban Orsini、Albert Defoin、Patrick Pale、Emmanuel Salomon、Céline Tarnus、Jean-Marc Weibel

  DOI：10.1016/j.bmc.2011.01.008

  日期：2011.2

  This paper describes the design and synthesis of compounds belonging to a novel class of highly selective mammalian CD13 inhibitors. Racemic homologues of 3-amino-2-tetralone 1 were synthesised and evaluated for their ability to selectively inhibit the membrane-bound, zinc-dependent aminopeptidase-N/CD13 (EC 3.4.11.2). Some of these novel non-peptidic compounds are potent, competitive inhibitors of

  本文介绍了属于新型一类高选择性哺乳动物CD13抑制剂的化合物的设计和合成。合成了3-氨基-2-四氢萘酮1的外消旋同源物，并评估了其选择性抑制膜结合的锌依赖性氨基肽酶-N / CD13的能力（EC 3.4.11.2）。这些新颖的非肽类化合物中的某些是哺乳动物酶的有效竞争性抑制剂，尽管其最小尺寸（MW <200 Da），但K i值仍在低微摩尔范围内。而且，它们对氨肽酶家族的代表性成员，即亮氨酸氨肽酶（EC 3.4.11.1），解毒气单胞菌显示出有趣的选择性。氨基肽酶（EC 3.4.11.10）和白三烯A4水解酶的氨基肽酶活性（EC 3.3.2.6）。就效力，稳定性和选择性而言，氨基-苯并亚砜酮衍生物4是最有前途的化合物。根据观察到的结构-活性关系，从已知三维结构的氨基肽酶-N同源物的结构见解，提出了一种假设的4与催化锌和几个保守的活性位点残基的结合模式。
• DERIVES D'AMINOBENZOCYCLOHEPTENE, LEURS PROCEDES DE PREPARATION ET LEUR UTILISATION EN THERAPEUTIQUE
  申请人：Universite De Haute Alsace

  公开号：EP2084125A1

  公开（公告）日：2009-08-05
• [EN] AMINOBENZOCYCLOHEPTENE DERIVATIVES, METHODS FOR PREPARING THE SAME AND USES THEREOF IN THERAPY<br/>[FR] DERIVES D' AMINOBENZOCYCLOHEPTENE, LEURS PROCEDES DE PREPARATION ET LEUR UTILISATION EN THERAPEUTIQUE
  申请人：UNIV HAUTE ALSACE

  公开号：WO2008059141A1

  公开（公告）日：2008-05-22

  [EN] The invention relates to a compound of the general formula (I) : F(I) in which: R₁, R₂, R₃, R₄, R₅, R₆, R₉, R₁₀, R₁₁ further represent a (C₁-C₆) alkoxy, (C₁-C₆) aralkyloxy, (C₁-C₆) alkylthio, (Q₁- C₆) aralkylthio radical; R₉ et R₁₁ can also form together a carbonated cycle or heterocycle or can form a double bond with the two carbon atoms adjacent to the heptene cycle; R₁ et R₂ can form together a carbonated cycle or heterocycle; or R₁ can be bonded to the heptene cycle by a double bond while R₂ is absent; R₃, R₄, R₅ and R₆ further represent a polyfluoro (C₁-C₆) alkyl, (C₁-C₆) alkoxy radical, an aryl or heteroaryl group; R₃ and R₄, R₄ and R₅, R₅ and R₆ can further form together a methylenedioxy radical joining the adjacent carbon atoms or an aromatic carbonated cycle or an aromatic heterocycle; R₇ is a hydrogen atom, a (C₁-C₆) alkyl radical; X is an oxygen or sulphur atom, N-R₁₂, N-O-R₁₃, in which R₁₂ and R₁₃ represent a hydrogen atom, a (C₁-C₆) alkyl, (C₁- C₆) (cycloalkyl) alkyl, (C₁-C₆) (heterocycloalkyl) alkyl, (C₁-C₆) aralkyl, (Ci-C6) heteroaralkyl radical; Y is a carbon atom; a nitrogen atom R₈ or R₉ being then absent; the invention also relates to addition salts with acids except the compound for which R₄, R₅, R₆ represent a methoxy radical, R₁, R₂, R₃, R₇ to R₁₁ represent a hydrogen atom, X represents an oxygen atom and Y represents a carbon atom.
  [FR] Composé répondant à la formule générale (I): F(I) dans laquelle R₁, R₂, R₃, R₄, R₅, R₆, R₉, R₁₀, R₁₁ représentent en outre un radical (C₁-C₆) alcoxy, (C₁-C₆) aralkyloxy, (C₁-C₆) al kylthio, (Q₁- C₆) aralkylthio; R₉ et R₁₁
• Rapid and efficient synthesis of a novel series of substituted aminobenzosuberone derivatives as potent, selective, non-peptidic neutral aminopeptidase inhibitors
  作者：Sébastien Albrecht、Emmanuel Salomon、Albert Defoin、Céline Tarnus

  DOI：10.1016/j.bmc.2012.06.041

  日期：2012.8

  Racemic 5-substituted 7-aminobenzocyclohepten-6-one were synthesized and evaluated for their ability to inhibit metalloaminopeptidase activities. Unexpectedly, 5-thio substituted compounds showed enhanced inhibition potency with K-i values in the nanomolar range against the 'one zinc' aminopeptidases from the M1 family, while most of them were rather poor inhibitors of the 'two zincs' enzymes from the M17 family. This interesting selectivity profile may guide the design of new, specific inhibitors of target mammalian aminopeptidases with one active site zinc. (C) 2012 Elsevier Ltd. All rights reserved.