3(S)-(2,3-dihydrobenzofuran-6-yl)-β-alanine ethyl ester | 204452-97-1

• 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: 3(S)-(2,3-dihydrobenzofuran-6-yl)-β-alanine ethyl ester
• 英文别名: ethyl 3(S)-amino-3-(2,3-dihydro-1-benzofuran-6-yl)propionate；(S)-ethyl 3-amino-3-(2,3-dihydrobenzofuran-6-yl)propanoate；3(S)-Amino-3-(2,3-dihydro-benzofuran-6-yl)-propionic acid ethyl ester；ethyl (3S)-3-amino-3-(2,3-dihydro-1-benzofuran-6-yl)propanoate
• CAS: 204452-97-1
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: JZGAAVIDIKQUFE-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3(S)-(2,3-dihydrobenzofuran-6-yl)-β-alanine ethyl ester 在 sodium acetate 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 异丙醇 为溶剂， 生成 3(S)-(2-{Tert-butoxycarbonyl-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propyl]-amino}-ethylamino)-3-(2,3-dihydro-benzofuran-6-yl)-propionic acid ethyl ester
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. 8. In Vitro and in Vivo Evaluation of a Potent α_vβ₃ Antagonist for the Prevention and Treatment of Osteoporosis

  摘要：

  3(S)-(6-Methoxypyridin-3-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]-imidazolidin-1-yl}propionic acid 6 was identified as a potent and selective antagonist of the alpha(v)beta(3) receptor. This compound has an excellent in vitro profile (IC50 = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.

  DOI：

  10.1021/jm030306r
• 作为产物：
  描述：

  2,3-二氢苯并呋喃 在 palladium dihydroxide 氢氧化钾 、 正丁基锂 、 氢气 、 溴 、 palladium diacetate 、 溶剂黄146 、 三乙胺 、 三(邻甲基苯基)磷 、 potassium bromide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 乙腈 为溶剂， 生成 3(S)-(2,3-dihydrobenzofuran-6-yl)-β-alanine ethyl ester
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. 8. In Vitro and in Vivo Evaluation of a Potent α_vβ₃ Antagonist for the Prevention and Treatment of Osteoporosis

  摘要：

  3(S)-(6-Methoxypyridin-3-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]-imidazolidin-1-yl}propionic acid 6 was identified as a potent and selective antagonist of the alpha(v)beta(3) receptor. This compound has an excellent in vitro profile (IC50 = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.

  DOI：

  10.1021/jm030306r

文献信息

• [EN] CYCLOBUTANE- AND AZETIDINE-CONTAINING MONO AND SPIROCYCLIC COMPOUNDS AS ALPHA V INTEGRIN INHIBITORS<br/>[FR] COMPOSÉS MONO ET SPIROCYCLIQUES CONTENANT DU CYCLOBUTANE ET DE L'AZÉTIDINE EN TANT QU'INHIBITEURS DE L'INTÉGRINE ALPHA V
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018089355A1

  公开（公告）日：2018-05-17

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αv- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of av-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式(I)的化合物：或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量如本文所定义。这些化合物是αv-含有整合素的拮抗剂。本发明还涉及包括这些化合物的药物组合物以及利用这些化合物和药物组合物治疗与αv-含有整合素失调相关的疾病、紊乱或病况的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• [EN] PYRROLE AMIDES AS ALPHA V INTEGRIN INHIBITORS<br/>[FR] AMIDES DE PYRROLE EN TANT QU'INHIBITEURS D'INTÉGRINE ALPHA V
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018089360A1

  公开（公告）日：2018-05-17

  The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了具有式（I）的化合物或其立体异构体、互变异构体、或其药用可接受的盐或溶剂，其中所有变量均如本文所定义。这些化合物是αv-含有整合素的抑制剂。本发明还涉及包含这些化合物的药物组合物以及利用这些化合物和药物组合物治疗与αv-含有整合素失调相关的疾病、紊乱或病况的方法，例如病理纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• [EN] INTEGRIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR DE L'INTEGRINE
  申请人：MERCK & CO., INC.

  公开号：WO1999030709A1

  公开（公告）日：1999-06-24

  (EN) The present invention relates to compounds and derivatives thereof, their synthesis, and their use as vitronectin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the vitronectin receptors $g(a)v$g(b)3 and/or $g(a)v$g(b)5 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, viral disease, and tumor growth.(FR) L'invention concerne des composés et des dérivés desdits composés, leurs synthèses et leur utilisation comme antagonistes du récepteur de vitronectine. Plus particulièrement, les composés de l'invention sont des antagonistes des récepteurs $g(a)$g(n)$g(b)3 et/ou $g(a)$g(n)$g(b)5 de vitronectine, et conviennent comme inhibiteurs de la résorption osseuse, produits de traitement ou de prévention de l'ostéoporose, ou inhibiteurs de la resténose vasculaire, de la rétinopathie diabétique, de la dégénérescence maculaire, de l'angiogenèse, de l'athérosclérose, de l'inflammation, de maladies virales et de la croissance tumorale.

  本发明涉及化合物及其衍生物、它们的合成以及它们作为vitronectin受体拮抗剂的用途。更具体地说，本发明的化合物是vitronectin受体$g(a)v$g(b)3和/或$g(a)v$g(b)5的拮抗剂，适用于抑制骨吸收、治疗和预防骨质疏松症、抑制血管再狭窄、糖尿病视网膜病变、黄斑变性、血管新生、动脉硬化、炎症、病毒性疾病和肿瘤生长。 本发明涉及化合物及其衍生物、其合成以及其作为vitronectin受体拮抗剂的用途。更具体地说，本发明的化合物是vitronectin受体$g(a)$g(n)$g(b)3和/或$g(a)$g(n)$g(b)5的拮抗剂，适用于抑制骨吸收、治疗和预防骨质疏松症、抑制血管再狭窄、糖尿病视网膜病变、黄斑变性、血管新生、动脉硬化、炎症、病毒性疾病和肿瘤生长。
• Integrin receptor antagonists
  申请人：——

  公开号：US20020010176A1

  公开（公告）日：2002-01-24

  The present invention relates to compounds and derivatives thereof, their synthesis, and their use as integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors &agr;v&bgr;3, &agr;v&bgr;5, and/or &agr;v&bgr;6 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, wound healing, viral disease, tumor growth, and metastasis.

  本发明涉及化合物及其衍生物，其合成以及它们作为整合素受体拮抗剂的用途。更具体地说，本发明的化合物是整合素受体αvβ3、αvβ5和/或αvβ6的拮抗剂，可用于抑制骨吸收，治疗和预防骨质疏松症，抑制血管再狭窄，糖尿病视网膜病变，黄斑变性，血管生成，动脉粥样硬化，炎症，伤口愈合，病毒性疾病，肿瘤生长和转移。
• Pyrrole amides as alpha V integrin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10717736B2

  公开（公告）日：2020-07-21

  The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式(I)化合物或其立体异构体、同系物或药学上可接受的盐或溶液，其中所有变量如本文所定义。这些化合物是含αv整合素的抑制剂。本发明还涉及包含这些化合物的药物组合物，以及通过使用这些化合物和药物组合物治疗与含αv整合素失调相关的疾病、紊乱或病症的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。