(S)-3-(phenyl)-2-(7-hydroxyaminoformyl-heptanoylamino)-propanoic acid methyl ester

• 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)-3-(phenyl)-2-(7-hydroxyaminoformyl-heptanoylamino)-propanoic acid methyl ester
• 英文别名: (S)-3-(phenyl)-2-(7-hydroxycarbamoyl-heptanoylamino)-propionic acid methyl ester；2-(7-Hydroxycarbamoyl-heptanoylamino)-3-phenyl-propionic acid methyl ester；methyl (2S)-2-[[8-(hydroxyamino)-8-oxooctanoyl]amino]-3-phenylpropanoate
• 化学式: C₁₈H₂₆N₂O₅
• 分子量: 350.415
• InChiKey: AXUYKQYDXYCOFL-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  辛二酸单甲酯 在 palladium on activated charcoal 盐酸 、 N-乙基马来酰亚胺 、 lithium hydroxide 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 生成 (S)-3-(phenyl)-2-(7-hydroxyaminoformyl-heptanoylamino)-propanoic acid methyl ester
  参考文献：
  名称：

  Analogues of trichosтatin a and trapoxin B as histone deacetylase inhibitors

  摘要：

  Inhibitors of histone deacetylase are potent inducers of differentiation and bear considerable potential as drugs for chemoprevention and treatment of cancer. So far only complex natural products and a few synthetic congeners have been identified as specific inhibitors. We have prepared a set of simple analogues in as little as four synthetic steps that have inhibitory potencies in the range of known cyclotetrapeptide inhibitors. These compounds are interesting leads for the design of potent inhibitors of histone deacetylase. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00284-9

文献信息

• Carbamic acid compounds comprising a sulfonamide linkage as HDAC inhibitors
  申请人：Kalvinsh Ivars

  公开号：US20070004806A1

  公开（公告）日：2007-01-04

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q 1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O) 2 NR 1 — and —NR 1 S(═O) 2 —; R 1 is a sulfonamido substituent; and, Q 2 is an acid leader group; with the proviso that if J is —S(═O) 2 NR 1 —, then Q 1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

  本发明涉及抑制HDAC活性的某些活性碳酸酰化合物，其具有以下式子：（I）其中A是芳基；Q1是共价键或芳基引导基团；J是选自磺酰胺连接的以下链：—S（═O）2NR1—和—NR1S（═O）2—；R1是磺酰胺取代基；Q2是酸引导基团；但是，如果J是—S（═O）2NR1—，则Q1是芳基引导基团；以及其药学上可接受的盐，溶剂化物，酰胺，酯，醚，化学保护形式和前药。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物抑制HDAC，例如抑制增殖性疾病，如癌症和银屑病。
• CARBAMIC ACID COMPOUNDS COMPRISING A SULFONAMIDE LINKAGE AS HDAC INHIBITORS
  申请人：Watkins Clare J.

  公开号：US20080161401A1

  公开（公告）日：2008-07-03

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q 1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O) 2 NR 1 — and —NR 1 S(═O) 2 —; R 1 is a sulfonamido substituent; and, Q 2 is an acid leader group; with the proviso that if J is —S(═O) 2 NR 1 —, then Q 1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

  本发明涉及某些活性碳酰胺酸化合物，其抑制HDAC活性，具有以下公式：（I）其中，A是芳基基团；Q1是共价键或芳基引导基团；J是从以下选择的磺酰胺键连接：—S（═O）2NR1—和—NR1S（═O）2—；R1是磺酰胺取代基；Q2是酸引导基团；但是，如果J是—S（═O）2NR1—，则Q1是芳基引导基团；以及其药学上可接受的盐，溶剂化合物，酰胺，酯，醚，化学保护形式和前药。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物来抑制HDAC，例如，抑制增殖性疾病，如癌症和牛皮癣。
• CARBAMIC ACID COMPOUNDS COMPRISING AN AMIDE LINKAGE AS HDAC INHIBITORS
  申请人：Watkins Clare J.

  公开号：US20110105572A1

  公开（公告）日：2011-05-05

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: wherein: A is a C 5-20 heteroaryl or C 5-20 carboaryl group and is optionally substituted; Q 1 is a C 2-7 alkylene group having a backbone of at least 2 carbon atoms, and is optionally substituted; J is —N(R 1 )C(═O)— or —C(═O)N(R 1 )—; R 1 is hydrogen, C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl; and, Q 2 is C 1-7 alkylene, C 5-20 arylene, C 5-20 arylene-C 1-7 alkylene, or C 1-7 alkylene-C 5-20 arylene having a backbone of at least 3 carbon atoms, and is optionally substituted; and pharmaceutically acceptable salts thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to treat proliferative conditions, such as cancer and psoriasis.

  本发明涉及某些活性碳酰胺酸化合物，其抑制HDAC活性，并具有以下公式：其中：A是C5-20杂环芳基或C5-20羰基芳基基团，并可选择性地取代；Q1是具有至少2个碳原子的C2-7烷基链，可选择性地取代；J是-N（R1）C（═O）-或-C（═O）N（R1）-；R1是氢，C1-7烷基，C3-20杂环芳基或C5-20芳基；Q2是具有至少3个碳原子的C1-7烷基链，C5-20芳基链，C5-20芳基链-C1-7烷基链，或C1-7烷基链-C5-20芳基链，并可选择性地取代；以及其药学上可接受的盐。本发明还涉及包含这种化合物的制药组合物，以及使用这种化合物和组合物在体内外抑制HDAC，例如治疗增殖性疾病，如癌症和牛皮癣。
• Analogues of trichosтatin a and trapoxin B as histone deacetylase inhibitors
  作者：Manfred Jung、Katharina Hoffmann、Gerald Brosch、Peter Loidl

  DOI：10.1016/s0960-894x(97)00284-9

  日期：1997.7

  Inhibitors of histone deacetylase are potent inducers of differentiation and bear considerable potential as drugs for chemoprevention and treatment of cancer. So far only complex natural products and a few synthetic congeners have been identified as specific inhibitors. We have prepared a set of simple analogues in as little as four synthetic steps that have inhibitory potencies in the range of known cyclotetrapeptide inhibitors. These compounds are interesting leads for the design of potent inhibitors of histone deacetylase. (C) 1997 Elsevier Science Ltd.
• Carbamic acid compounds comprising an amide linkage for the treatment of malaria
  申请人：TopoTarget UK Limited

  公开号：EP1598067B1

  公开（公告）日：2009-05-06