2-(2-tert-butyl-dimethylsilyloxyethyl)-2-tetrahydrofuroic acid | 327618-59-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 英文名称: 2-(2-tert-butyl-dimethylsilyloxyethyl)-2-tetrahydrofuroic acid
• 英文别名: 2-[2-[Tert-butyl(dimethyl)silyl]oxyethyl]oxolane-2-carboxylic acid
• CAS: 327618-59-7
• 化学式: C₁₃H₂₆O₄Si
• 分子量: 274.433
• InChiKey: AAZACLCMOJMGAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.03
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-tert-butyl-dimethylsilyloxyethyl)-2-tetrahydrofuroic acid 在 四丁基氟化铵 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (S)-3-(2',6'-Dimethoxy-biphenyl-4-yl)-2-{[2-(2-methoxy-ethyl)-tetrahydro-furan-2-carbonyl]-amino}-propionic acid tert-butyl ester
  参考文献：
  名称：

  Substituted tetrahydrofuroyl-1-phenylalanine derivatives as potent and specific VLA-4 antagonists

  摘要：

  A series of substituted tetra hydrofuroyl-1-phenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. Substitution of the a carbon of the tetrahydrofuran with aryl groups increased the specificity for VLA-4 versus alpha(4)beta(7) while amide substitution increased the potency of the series without increasing the specificity. Substitution of the P carbon of the tetrahydrofuran with keto or amino groups slightly improved the specificity for VLA-4 versus alpha(4)beta(7) but with a significant loss in binding affinity for VLA-4. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00211-1
• 作为产物：
  描述：

  benzyl (+/-)-tetrahydrofuran-2-carboxylate 在 palladium on activated charcoal 氢气 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 甲醇 、 六甲基磷酰三胺 为溶剂， 生成 2-(2-tert-butyl-dimethylsilyloxyethyl)-2-tetrahydrofuroic acid
  参考文献：
  名称：

  Substituted tetrahydrofuroyl-1-phenylalanine derivatives as potent and specific VLA-4 antagonists

  摘要：

  A series of substituted tetra hydrofuroyl-1-phenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. Substitution of the a carbon of the tetrahydrofuran with aryl groups increased the specificity for VLA-4 versus alpha(4)beta(7) while amide substitution increased the potency of the series without increasing the specificity. Substitution of the P carbon of the tetrahydrofuran with keto or amino groups slightly improved the specificity for VLA-4 versus alpha(4)beta(7) but with a significant loss in binding affinity for VLA-4. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00211-1
• 作为试剂：
  描述：

  (L)-4-(2',6'-dimethoxyphenyl)phenylalanine, tert-butyl ester hydrochloride 以 2-(2-tert-butyl-dimethylsilyloxyethyl)-2-tetrahydrofuroic acid 为溶剂， 生成 N-(2-(2-tert-Butyldimethylsiloxyethyl)-2-tetrahydrofuroyl)-(L)-4-(2',6'-dimethoxyphenyl)phenylalanine
  参考文献：
  名称：

  Heterocycle amides as cell adhesion inhibitors

  摘要：

  公式I的化合物是VLA-4和/或α4β7的拮抗剂，因此可用于抑制或预防细胞粘附和细胞粘附介导的病理。这些化合物可配制成药物组合物，适用于治疗与艾滋病相关的痴呆、过敏性结膜炎、过敏性鼻炎、阿尔茨海默病、哮喘、动脉粥样硬化、自体骨髓移植、某些类型的中毒和免疫性肾炎、接触性皮肤超敏反应、炎症性肠病包括溃疡性结肠炎和克罗恩病、炎症性肺病、病毒感染的炎症后遗症、脑膜炎、多发性硬化、多发性骨髓瘤、心肌炎、器官移植、银屑病、肺纤维化、再狭窄、视网膜炎、类风湿性关节炎、化脓性关节炎、中风、肿瘤转移、葡萄膜炎和I型糖尿病。

  公开号：

  US06420418B1

文献信息

• Heterocycle amides as cell adhesion inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06420418B1

  公开（公告）日：2002-07-16

  Compounds of Formula I are antagonists of VLA-4 and/or &agr;4&bgr;7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of AIDS-related dementia, allergic conjunctivitis, allergic rhinitis, Alzheimer's disease, asthma, atherosclerosis, autologous bone marrow transplantation, certain types of toxic and immune-based nephritis, contact dermal hypersensitivity, inflammatory bowel disease including ulcerative colitis and Crohn's disease, inflammatory lung diseases, inflammatory sequelae of viral infections, meningitis, multiple sclerosis, multiple myeloma, myocarditis, organ transplantation, psoriasis, pulmonary fibrosis, restenosis, retinitis, rheumatoid arthritis, septic arthritis, stroke, tumor metastasis, uveititis, and type I diabetes.

  公式I的化合物是VLA-4和/或α4β7的拮抗剂，因此可用于抑制或预防细胞粘附和细胞粘附介导的病理。这些化合物可配制成药物组合物，适用于治疗与艾滋病相关的痴呆、过敏性结膜炎、过敏性鼻炎、阿尔茨海默病、哮喘、动脉粥样硬化、自体骨髓移植、某些类型的中毒和免疫性肾炎、接触性皮肤超敏反应、炎症性肠病包括溃疡性结肠炎和克罗恩病、炎症性肺病、病毒感染的炎症后遗症、脑膜炎、多发性硬化、多发性骨髓瘤、心肌炎、器官移植、银屑病、肺纤维化、再狭窄、视网膜炎、类风湿性关节炎、化脓性关节炎、中风、肿瘤转移、葡萄膜炎和I型糖尿病。
• Substituted tetrahydrofuroyl-1-phenylalanine derivatives as potent and specific VLA-4 antagonists
  作者：George A. Doherty、Ginger X. Yang、Edite Borges、Linda L. Chang、Malcolm MacCoss、Sharon Tong、Usha Kidambi、Linda A. Egger、Ermenegilda McCauley、Gail Van Riper、Richard A. Mumford、John A. Schmidt、William K. Hagmann

  DOI：10.1016/s0960-894x(02)00211-1

  日期：2002.6

  A series of substituted tetra hydrofuroyl-1-phenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. Substitution of the a carbon of the tetrahydrofuran with aryl groups increased the specificity for VLA-4 versus alpha(4)beta(7) while amide substitution increased the potency of the series without increasing the specificity. Substitution of the P carbon of the tetrahydrofuran with keto or amino groups slightly improved the specificity for VLA-4 versus alpha(4)beta(7) but with a significant loss in binding affinity for VLA-4. (C) 2002 Elsevier Science Ltd. All rights reserved.