6-hydroxymethyl-benzo[b]thiophene-2-carboxylic acid ethyl ester | 850072-65-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 6-hydroxymethyl-benzo[b]thiophene-2-carboxylic acid ethyl ester
• 英文别名: ethyl 6-(hydroxymethyl)-1-benzothiophene-2-carboxylate
• CAS: 850072-65-0
• 化学式: C₁₂H₁₂O₃S
• 分子量: 236.291
• InChiKey: GSVSVEZAIOMFSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  74.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-hydroxymethyl-benzo[b]thiophene-2-carboxylic acid ethyl ester 在 palladium on activated charcoal 叠氮磷酸二苯酯 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Benzo[b]thiophene-based histone deacetylase inhibitors

  摘要：

  Benzo[b]thienyl hydroxamic acids, a novel class of historic deacetylase (HDAC) inhibitors, were identified via a targeted screen of small molecule hydroxamic acids. Various substitutions were explored in the C5- and C6-positions of the benzo[b]thiophene core to characterize SAR and develop optimal inhibitors. It was determined that substitution at the C6-position of the benzo[b]thiophene core with a three-atom spacer yielded optimal HDAC I inhibition and anti-proliferative activity in murine erythroleukemia (SC-9) cells. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.091
• 作为产物：
  描述：

  (E)-1-(dimethylamino)-2-[4-(methoxycarbonyl)-2-nitrophenyl]ethene 在 吡啶 、 sodium periodate 、 三氟化硼 、 potassium carbonate 、 lithium iodide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 6-hydroxymethyl-benzo[b]thiophene-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  WO2006/117549

  摘要：

  公开号：

文献信息

• ORTHO AMINOAMIDES FOR THE TREATMENT OF CANCER
  申请人：Liang Chungen

  公开号：US20100216806A1

  公开（公告）日：2010-08-26

  Compounds of formula are HDAC inhibitors. These compounds are useful for the treatment of diseases such as cancer in humans or animals.

  这些化合物的化学式是HDAC抑制剂。这些化合物对于治疗人类或动物的癌症等疾病是有用的。
• ENZYME INHIBITORS
  申请人：Davidson Alan Hornsby

  公开号：US20140163042A1

  公开（公告）日：2014-06-12

  Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R 2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(═O), —S(═O) 2 —, —C(═O)O—, —C(O)NR 3 —, —C(═S)—NR 3 , —C(═NH)NR 3 or —S(═O) 2 NR 3 — wherein R 3 is hydrogen or optionally substituted C 1 -C 6 alkyl; L 1 is a divalent radical of formula -(Alk 1 ) m (Q) n (Alk 2 ) p - wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X 2 -Q 1 - or -Q 1 -X 2 — wherein X 2 is —O—, S— or NR A — wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl, and Q 1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, Alk 1 and Alk 2 independently represent optionally substituted divalent C 3 -C 7 cycloalkyl radicals, or optionally substituted straight or branched, C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NR A —) link wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(═O)NR 4 —, —NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R 4 and R 5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R 1 R 2 NH—Y-L 1 -X 1 -[CH 2 ] Z — and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONIIOII, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.

  式(I)的化合物是组蛋白去乙酰化酶活性抑制剂，可用于治疗癌症等疾病，其中R1是羧酸基（-COOH）或可由一个或多个细胞内羧酸酯酶水解为羧酸基的酯基；R2是天然或非天然α氨基酸的侧链；Y是键，-C（=O），-S（=O）2-，-C（=O）O-，-C（=O）NR3-，-C（=S）-NR3，-C（=NH）NR3或-S（=O）2NR3-，其中R3是氢或可选取代的C1-C6烷基；L1是式-(Alk1)m(Q)n(Alk2)p-的二价基团，其中m、n和p独立地为0或1，Q是（i）一个可选取代的二价单环或双环碳环或杂环基团，具有5-13个环成员，或（ii）在m和p均为0的情况下，是式-Q1-X2-或-X2-Q1-的二价基团，其中X2是-O-，-S-或-NRA-，其中RA是氢或可选取代的C1-C3烷基，Q1是可选取代的二价单环或双环碳环或杂环基团，具有5-13个环成员，Alk1和Alk2独立地表示可选取代的二价C3-C7环烷基基团，或可选取代的直链或支链，C1-C6烷基，C2-C6烯基或C2-C6炔基基团，其可以可选地含有或终止于醚（-O-），硫醚（-S-）或氨基（-NRA-）链，其中RA是氢或可选取代的C1-C3烷基；X1表示键，-C（=O）或-S（=O）2-；-NR4C（=O）-，-C（=O）NR4-，-NR4C（=O）NR5-，-NR4S（=O）2-或-S（=O）2NR4-，其中R4和R5独立地为氢或可选取代的C1-C6烷基；z为0或1；A表示可选取代的单环、双环或三环碳环或杂环系统，其中基团R1R2NH-Y-L1-X1-[CH2]Z-和HONHCO-[LINKER]-附着在不同的环原子上；-[Linker]-表示将A中的一个环原子与羟酰胺酸基团CONIIOII连接的二价连接基团，连接基团的长度，从连接到A环原子的末端原子到连接到羟酸胺基团的末端原子，相当于从3-10个碳原子的直链饱和碳氢链的长度。
• Thiophene and Benzothiophene Hydroxamic Acid Derivatives
  申请人：Miller A. Thomas

  公开号：US20070213392A1

  公开（公告）日：2007-09-13

  The present invention relates to a novel class of hydroxamic acid derivatives having a benzothiophene or thiophene backbone. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit historic 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 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胺酸衍生物，其具有苯并噻吩或噻吩骨架。这些羟胺酸化合物可用于治疗癌症。这些羟胺酸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，阻止肿瘤细胞的生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物对于治疗具有肿瘤细胞增殖特征的患者是有用的。本发明的化合物还适用于预防和治疗TRX介导的疾病，例如自身免疫性、过敏性和炎症性疾病，以及预防和/或治疗中枢神经系统（CNS）疾病，例如神经退行性疾病。本发明还提供了包含羟胺酸衍生物的药物组合物和这些药物组合物的安全剂量方案，其易于遵循，并且在体内产生治疗有效量的羟胺酸衍生物。
• Fluorinated Arylamide Derivatives
  申请人：Miller Thomas A.

  公开号：US20090012075A1

  公开（公告）日：2009-01-08

  The present invention relates to a novel class of fluorinated arylamide derivatives. The instant compounds can be used to treat cancer. The fluorinated arylamide derivatives 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 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氟化芳基酰胺衍生物。这些化合物可用于治疗癌症。氟化芳基酰胺衍生物还可以抑制组蛋白去乙酰化酶，并适用于选择性诱导终末分化、阻止肿瘤细胞的生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的这些化合物在治疗具有肿瘤细胞增殖特征的患者中是有用的。本发明的这些化合物也可能在预防和治疗TRX介导的疾病中有用，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，如神经退行性疾病。本发明还提供了包含羟酰胺衍生物的药物组合物和这些药物组合物的安全用量方案，这些方案易于遵循，并在体内产生治疗有效量的羟酰胺衍生物。
• Benzothiophene hydroxamic acid derivatives
  申请人：Hubbs Jed Lee

  公开号：US20090069391A1

  公开（公告）日：2009-03-12

  The present invention relates to a novel class of hydroxamic acid derivatives. 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 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 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基酰胺衍生物。这些羟基酰胺化合物可用于治疗癌症。这些羟基酰胺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，本发明的化合物可用于治疗具有肿瘤细胞增殖特征的患者。本发明的化合物还可用于预防和治疗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。本发明还提供包含羟基酰胺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，这些方案易于遵循，并在体内产生治疗有效量的羟基酰胺衍生物。