[2-(2,6-Dichloro-phenyl)-benzooxazol-5-yl]-methanol | 327618-18-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [2-(2,6-Dichloro-phenyl)-benzooxazol-5-yl]-methanol
• 英文别名: [2-(2,6-Dichlorophenyl)-1,3-benzoxazol-5-yl]methanol
• CAS: 327618-18-8
• 化学式: C₁₄H₉Cl₂NO₂
• 分子量: 294.137
• InChiKey: PYDQQMAEMCBGNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [2-(2,6-Dichloro-phenyl)-benzooxazol-5-yl]-methanol 在 cesium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 二甲基硫 、 cinchona alkaloid 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-3-[2-(2,6-Dichloro-phenyl)-benzooxazol-5-yl]-2-[(3,5-dichloro-pyridine-4-carbonyl)-amino]-propionic acid tert-butyl ester
  参考文献：
  名称：

  Bioisosteric replacement of anilide with benzoxazole: potent and orally bioavailable antagonists of VLA-4

  摘要：

  We have designed and synthesized a series of heterocyclic bioisosteres for an anilide based on molecular modeling. Excellent potency was retained in the benzoxazole and the benzimidazole derivatives, where a hydrogen bond acceptor is appropriately positioned to mimic the amide bond oxygen. The deletion of the hydrogen bond donor (N-H) led to improved lipophilicity and bioavailability. In the process, 9a was identified as a potent, specific, and bioavailable VLA-4 antagonist, while 9c was found to be a potent and bioavailable dual antagonist of VLA-4 and alpha(4)beta(7). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.098
• 作为产物：
  描述：

  3-氨基-4-羟基苯甲酸甲酯 在 lead(IV) acetate 、 lithium aluminium tetrahydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成 [2-(2,6-Dichloro-phenyl)-benzooxazol-5-yl]-methanol
  参考文献：
  名称：

  Bioisosteric replacement of anilide with benzoxazole: potent and orally bioavailable antagonists of VLA-4

  摘要：

  We have designed and synthesized a series of heterocyclic bioisosteres for an anilide based on molecular modeling. Excellent potency was retained in the benzoxazole and the benzimidazole derivatives, where a hydrogen bond acceptor is appropriately positioned to mimic the amide bond oxygen. The deletion of the hydrogen bond donor (N-H) led to improved lipophilicity and bioavailability. In the process, 9a was identified as a potent, specific, and bioavailable VLA-4 antagonist, while 9c was found to be a potent and bioavailable dual antagonist of VLA-4 and alpha(4)beta(7). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.098

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。
• US6420418B1
  申请人：——

  公开号：US6420418B1

  公开（公告）日：2002-07-16
• Bioisosteric replacement of anilide with benzoxazole: potent and orally bioavailable antagonists of VLA-4
  作者：Linus S Lin、Thomas J Lanza、Laurie A Castonguay、Theodore Kamenecka、Ermenegilda McCauley、Gail Van Riper、Linda A Egger、Richard A Mumford、Xinchun Tong、Malcolm MacCoss、John A Schmidt、William K Hagmann

  DOI：10.1016/j.bmcl.2004.01.098

  日期：2004.5

  We have designed and synthesized a series of heterocyclic bioisosteres for an anilide based on molecular modeling. Excellent potency was retained in the benzoxazole and the benzimidazole derivatives, where a hydrogen bond acceptor is appropriately positioned to mimic the amide bond oxygen. The deletion of the hydrogen bond donor (N-H) led to improved lipophilicity and bioavailability. In the process, 9a was identified as a potent, specific, and bioavailable VLA-4 antagonist, while 9c was found to be a potent and bioavailable dual antagonist of VLA-4 and alpha(4)beta(7). (C) 2004 Elsevier Ltd. All rights reserved.