8-[4-(3-chloro-phenyl)-piperazin-1-yl]-8-oxo-octanoic acid hydroxyamide | 610801-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 8-[4-(3-chloro-phenyl)-piperazin-1-yl]-8-oxo-octanoic acid hydroxyamide
• 英文别名: 8-[4-(3-chlorophenyl)piperazin-1-yl]-N-hydroxy-8-oxooctanamide
• CAS: 610801-07-5
• 化学式: C₁₈H₂₆ClN₃O₃
• 分子量: 367.876
• InChiKey: RJPROOIZYLSLFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  4

文献信息

• [EN] CARBAMIC ACID COMPOUNDS COMPRISING A PIPERAZINE LINKAGE AS HDAC INHIBITORS<br/>[FR] COMPOSES D'ACIDE CARBAMIQUE COMPRENANT UN CHAINON DE PIPERAZINE TELS QUE LES INHIBITEURS HDAC
  申请人：PROLIFIX LTD

  公开号：WO2003082288A1

  公开（公告）日：2003-10-09

  This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula:[Insert formula]wherein: Cy is independently a cyclyl group; Q1 is independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; J1 is independently a covalent bond or -C(=O)- ; J2 is independently -C(=O)- or -S(=O)2- ; Q2 is independently an acid leader group; wherein: Cy is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is independently: a covalent bond; C1-7alkylene; or C1-7alkylene-X-C1-7alkylene, -X-C1-7alkylene, or C1-7alkylene-X-, wherein X is -O- or -S-; and is optionally substituted; Q2 is independently: C4-8alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Q2 is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or, C1-7alkylene-C5-20arylene-C1-7alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug 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 in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

  本发明涉及一些碳酰胺化合物，其抑制以下式的HDAC（组蛋白去乙酰化酶）活性：[插入式]其中：Cy独立地是环烷基团；Q1独立地是共价键或环烷基团；哌嗪-1,4-二基基团可选地被取代；J1独立地是共价键或-C（=O）-；J2独立地是-C（=O）-或-S（=O）2-；Q2独立地是酸基团；其中：Cy独立地是C3-20碳环烷基、C3-20杂环烷基或C5-20芳基；并可选地被取代；Q1独立地是：共价键；C1-7烷基；或C1-7烷基-X-C1-7烷基、-X-C1-7烷基或C1-7烷基-X-，其中X是-O-或-S-；并可选地被取代；Q2独立地是：C4-8烷基；并可选地被取代；并且具有至少4个原子的骨架长度；或：Q2独立地是：C5-20芳基；C5-20芳基-C1-7烷基；C1-7烷基-C5-20芳基；或C1-7烷基-C5-20芳基-C1-7烷基；并可选地被取代；并且具有至少4个原子的骨架长度；或其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及包含这种化合物的制药组合物，以及这种化合物和组合物的使用，无论是体外还是体内，用于抑制HDAC，并用于治疗由HDAC介导的疾病，如癌症、增殖性疾病、牛皮癣等。
• Carbamic acid compounds comprising a piperazine linkage as hdac inhibitors
  申请人：Watkins J. Clare

  公开号：US20050143385A1

  公开（公告）日：2005-06-30

  This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: wherein: Cy is independently a cyclyl group; Q 1 is independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; J 1 is independently a covalent bond or —C(═;O)—; J 2 is independently —C(═O)— or —S(═O) 2 —; Q 2 is independently an acid leader group; wherein: Cy is independently: C 3-20 carbocyclyl, C 3-20 heterocyclyl, or C 5-20 aryl; and is optionally substituted; Q 1 is independently: a covalent bond; C 1-7 alkylene; or C 1-7 alkylene-X—C 1-7 alkylene, —X—C 1-7 alkylene, or C 1-7 alkylene-X—, wherein X is —O— or —S—; and is optionally substituted; Q 2 is independently: C 4-8 alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Q 2 is independently: C 5-20 arylene; C 5-20 arylene-C 1-7 alkylene; C 1-7 alkylene-C 5-20 arylene; or, C 1-7 alkylene-C 5-20 arylene-C 1-7 alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug 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 in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

  本发明涉及某些卡巴酸类化合物，其抑制以下式中的HDAC（组蛋白去乙酰化酶）活性：其中：Cy独立地是环烷基团；Q1独立地是共价键或环烷基团；哌嗪-1,4-二基基团可选择性取代；J1独立地是共价键或-C（═;O）-；J2独立地是-C（═O）-或-S（═O）2-；Q2独立地是酸性基团；其中：Cy独立地是C3-20碳环烷基、C3-20杂环烷基或C5-20芳基；并且可选择性取代；Q1独立地是：共价键；C1-7烷基；或C1-7烷基-X-C1-7烷基，-X-C1-7烷基或C1-7烷基-X-，其中X为-O-或-S-；并且可选择性取代；Q2独立地是C4-8烷基；并且可选择性取代；并且具有至少4个原子的骨架长度；或：Q2独立地是C5-20芳基、C5-20芳基-C1-7烷基、C1-7烷基-C5-20芳基或C1-7烷基-C5-20芳基-C1-7烷基；并且可选择性取代；并且具有至少4个原子的骨架长度；或其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及包含这样的化合物的制药组合物，以及这样的化合物和组合物的使用，无论是在体外还是体内，以抑制HDAC，并用于治疗由HDAC介导的疾病，如癌症、增殖性疾病、牛皮癣等。
• Diamine and Iminodiacetic Acid Hydroxamic Acid Derivatives
  申请人：Miller Thomas A.

  公开号：US20090023718A1

  公开（公告）日：2009-01-22

  The present invention relates to a novel class of hydroxamic acid derivatives having a diamine or iminodiacetic acid backbone. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit histone deacetylase and are suitable for use in selectively including terminal differentiation, arresting cell growth and/or apoptosis of neo-plastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compound of the invention are also 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 hydroxamic acid derivatives, and safe, dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

  本发明涉及一种新型的羟肟酸衍生物类，其具有二胺或亚胺二乙酸骨架。这些羟肟酸化合物可用于治疗癌症。这些羟肟酸化合物还可以抑制组蛋白去乙酰化酶，并适用于选择性地促进新生物细胞的终端分化，阻止细胞生长和/或细胞凋亡，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新生物细胞增殖特征的肿瘤患者中非常有用。该发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫、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，例如神经退行性疾病。本发明还提供了包含羟肟酸衍生物的药物组合物，以及这些药物组合物的安全、剂量方案，易于遵循，并在体内产生治疗有效量的羟肟酸衍生物。
• CARBAMIC ACID COMPOUNDS COMPRISING A PIPERAZINE LINKAGE AS HDAC INHIBITORS
  申请人：WATKINS Clare J.

  公开号：US20080269237A1

  公开（公告）日：2008-10-30

  This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: 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 in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

  本发明涉及以下化学式中抑制HDAC（组蛋白去乙酰化酶）活性的某些碳酰胺类化合物：同时，本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物的使用，无论是在体内还是体外，以抑制HDAC，并用于治疗由HDAC介导的疾病，如癌症、增殖性疾病、银屑病等。
• DIAMINE AND IMINODIACETIC ACID HYDROXAMIC ACID DERIVATES
  申请人：Aton Pharma, Inc.

  公开号：EP1694329A2

  公开（公告）日：2006-08-30