5-Methyl-3-oxo-tetrahydro-furan-2-carboxylic acid tert-butyl ester | 327618-22-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢呋喃
• 英文名称: 5-Methyl-3-oxo-tetrahydro-furan-2-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 5-methyl-3-oxooxolane-2-carboxylate
• CAS: 327618-22-4
• 化学式: C₁₀H₁₆O₄
• 分子量: 200.235
• InChiKey: KNMRBZOXXCOBAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-Methyl-3-oxo-tetrahydro-furan-2-carboxylic acid tert-butyl ester 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (S)-3-(2',6'-Dimethoxy-biphenyl-4-yl)-2-[((R)-2,5-dimethyl-3-oxo-tetrahydro-furan-2-carbonyl)-amino]-propionic 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
• 作为产物：
  描述：

  2-Diazo-5-hydroxy-3-oxo-hexanoic acid tert-butyl ester 在 dirhodium tetraacetate 作用下， 以 1,2-二氯乙烷 、 苯 为溶剂， 生成 5-Methyl-3-oxo-tetrahydro-furan-2-carboxylic 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

文献信息

• [EN] HETEROCYCLE AMIDES AS CELL ADHESION INHIBITORS<br/>[FR] AMIDES HETEROCYCLES COMME INHIBITEURS DE L'ADHESION CELLULAIRE
  申请人：MERCK & CO INC

  公开号：WO2001012183A1

  公开（公告）日：2001-02-22

  Compounds of Formula (I) are antagonists of VLA-4 and/or α4β7, 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.

  化合物I的配合物是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反应。这些化合物可以制成药物组合物，适用于治疗艾滋病相关痴呆症、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、某些类型的毒性和免疫性肾炎、接触性皮肤过敏、炎症性肠病（包括溃疡性结肠炎和克罗恩病）、炎症性肺部疾病、病毒感染后的炎症后遗症、脑膜炎、多发性硬化症、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、脓毒性关节炎、中风、肿瘤转移、葡萄膜炎和1型糖尿病的治疗。
• 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.