ethyl 3-(6-hydroxybenzo[b]thiophen-3-yl)propanoate | 474658-42-9

• 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: ethyl 3-(6-hydroxybenzo[b]thiophen-3-yl)propanoate
• 英文别名: ethyl 3-(6-hydroxy-1-benzothiophen-3-yl)propanoate
• CAS: 474658-42-9
• 化学式: C₁₃H₁₄O₃S
• 分子量: 250.318
• InChiKey: PCNODKDAKQYVPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 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：

  ethyl 3-(6-hydroxybenzo[b]thiophen-3-yl)propanoate 在 N-甲基吗啉 、 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 3-(6-{2-[6-(Methylamino)-2-pyridyl]ethoxy}benzo[b]thiophen-3-yl)propanoic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Potent and Selective α_vβ₃/α_vβ₅ Integrin Dual Inhibitors with Improved Bioavailability. Selection of the Molecular Core

  摘要：

  A novel series of potent and selective alpha(v)beta(3)/alpha(v)beta(5) dual inhibitors was designed, synthesized, and evaluated against several integrins. These compounds were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhaced rigidity (i.e., (2-pyridylamino)propoxy versus the 2-(6-methylamino-2-pyridyl)ethoxy) led to improved activity toward alpha(v)beta(3). Exemplary oral bioavailability in mice was achieved using the indole central scaffold. Although, oral bioavailability was maintained when the indole molecular core was replace with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity. However, the indole series displayed the best in vivo pharmacokinetic properties. Thus, the indole series was selected for further structure-activity relationships to obtain more potent alpha(v)beta(3)/alpha(v)beta(5) dual antagonist with improved oral bioavailability.

  DOI：

  10.1021/jm049725u
• 作为产物：
  描述：

  ethyl 5-(3-acetyloxyphenylthio)-4-oxopentanoate 在 ice water 、 ice 、 乙酸乙酯 作用下， 以 硫酸 为溶剂， 反应 0.25h， 以to yield 700 mg (82%) of Ethyl 3-(6-hydroxybenzo[b]thiophen-3-yl)propanoate的产率得到ethyl 3-(6-hydroxybenzo[b]thiophen-3-yl)propanoate
  参考文献：
  名称：

  Substituted benzofurans and benzothiophenes, methods of making and methods of use as integrin antagonists

  摘要：

  本发明涉及一种新型的取代苯并呋喃和苯并噻吩化合物，它们是αV(αv)整合素的拮抗剂，例如αvβ3和αvβ5整合素，它们的药学上可接受的盐和制药组合物。这些化合物可用于治疗由αvβ3和αvβ5整合素介导的病理情况，包括肿瘤生长、转移、再狭窄、骨质疏松、炎症、黄斑变性、糖尿病视网膜病变和类风湿性关节炎等病症。这些化合物具有一般式I：其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、m、n、i、j和k在此被定义。

  公开号：

  US06872730B2

文献信息

• Substituted benzofurans and benzothiophenes, methods of making and methods of use as integrin antagonists
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US20030018064A1

  公开（公告）日：2003-01-23

  The present invention relates to novel substituted benzofurans and benzothiophenes compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr; v &bgr; 3 and &agr; v &bgr; 5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by &agr; v &bgr; 3 and &agr; v &bgr; 5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula I: 1 where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , m, n, i, j and k are defined herein.

  本发明涉及一种新的取代苯并呋喃和苯并噻吩化合物，它们是αV（αv）整合素的拮抗剂，例如αvβ3和αvβ5整合素，其药学上可接受的盐以及其药物组合物。这些化合物可用于治疗由αvβ3和αvβ5整合素介导的病理条件，包括肿瘤生长、转移、再狭窄、骨质疏松、炎症、黄斑变性、糖尿病性视网膜病变和类风湿性关节炎等疾病。这些化合物具有通用的化学式I：1，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、m、n、i、j和k在此处被定义。
• SUBSTITUTED BENZOFURANS AND BENZOTHIOPHENES, METHODS OF MAKING AND METHODS OF USE AS INTEGRIN ANTAGONISTS
  申请人：3-DIMENSIONAL PHARMACEUTICALS, INC.

  公开号：EP1390362A1

  公开（公告）日：2004-02-25
• US6872730B2
  申请人：——

  公开号：US6872730B2

  公开（公告）日：2005-03-29
• [EN] SUBSTITUTED BENZOFURANS AND BENZOTHIOPHENES, METHODS OF MAKING AND METHODS OF USE AS INTEGRIN ANTAGONISTS<br/>[FR] BENZOFURANNES ET BENZOTHIOPHENES SUBSTITUES, PROCEDES DE FABRICATION ET PROCEDES D'UTILISATION EN TANT QU'ANTAGONISTES D'INTEGRINES
  申请人：ANACLERIO BETH M

  公开号：WO2002088118A1

  公开（公告）日：2002-11-07

  The present invention relates to novel substituted benzofurans and benzothiophenes compounds that are antagonists of alpha V(αv) integrins, for example agr;vβ3 and αvβ5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by αv6beta;5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneraion, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula (I), where R?1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14¿, m, n, i, j an ka are defined herein.
• Design, Synthesis, and Biological Evaluation of Novel Potent and Selective α_vβ₃/α_vβ₅ Integrin Dual Inhibitors with Improved Bioavailability. Selection of the Molecular Core
  作者：Juan José Marugán、Carl Manthey、Beth Anaclerio、Lou Lafrance、Tianbao Lu、Tom Markotan、Kristi A. Leonard、Carl Crysler、Stephen Eisennagel、Malini Dasgupta、Bruce Tomczuk

  DOI：10.1021/jm049725u

  日期：2005.2.1

  A novel series of potent and selective alpha(v)beta(3)/alpha(v)beta(5) dual inhibitors was designed, synthesized, and evaluated against several integrins. These compounds were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhaced rigidity (i.e., (2-pyridylamino)propoxy versus the 2-(6-methylamino-2-pyridyl)ethoxy) led to improved activity toward alpha(v)beta(3). Exemplary oral bioavailability in mice was achieved using the indole central scaffold. Although, oral bioavailability was maintained when the indole molecular core was replace with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity. However, the indole series displayed the best in vivo pharmacokinetic properties. Thus, the indole series was selected for further structure-activity relationships to obtain more potent alpha(v)beta(3)/alpha(v)beta(5) dual antagonist with improved oral bioavailability.