(R)-(6-nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (R)-(6-nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol
• 英文别名: [(2R)-6-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methanol
• 化学式: C₉H₉NO₅
• 分子量: 211.174
• InChiKey: QSRIKCXVBZGOJP-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-(6-nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol 在 sodium tetrahydroborate 、 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、2.5 MPa 条件下， 反应 49.5h， 生成 4-[[(2R)-6-amino-2,3-dihydro-1,4-benzodioxin-2-yl]methoxy]benzonitrile
  参考文献：
  名称：

  Towards dual antithrombotic compounds – Balancing thrombin inhibitory and fibrinogen GPIIb/IIIa binding inhibitory activities of 2,3-dihydro-1,4-benzodioxine derivatives through regio- and stereoisomerism

  摘要：

  Enantiomers of 2,3-dihydro-1,4-benzodioxine derivatives possessing both thrombin and fibrinogen GPIIb/IIIa binding inhibitory activities were prepared from (R)- and (S)-glycidol as potential dual antithrombotic compounds. The influence of chirality and substitution pattern on thrombin inhibition and on inhibition of fibrinogen binding to GPIIb/IIIa was analyzed. Docking studies were used in an attempt to rationalize the results. The (S)-isomers of both 2,3-dihydro-1,4-benzodioxine regioisomers at positions 6 and 7 were found to be better thrombin inhibitors than the corresponding (R)-enantiomers, whereas we observed that stereochemistry does not display a consistent influence on fibrinogen GPIIb/IIIa binding inhibitory activity. Compound 11b, the (S)-isomer of the 6-substituted regioisomer, possessed the best balanced dual activity, with K-i(thrombin) = 1.67 +/- 0.27 mu M and IC50(GPIIb/IIIa) = 0.665 +/- 0.26 mu M, raising the hope that merging anticoagulant and platelet antiaggregatory activities in the same molecule could lead to successful multitarget antithrombotic agents. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.002
• 作为产物：
  描述：

  (2S)-2-{[(2-{[(methyloxy)methyl]oxy}-5-nitrophenyl)oxy]methyl}oxirane 在 盐酸 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 (R)-(6-nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methanol
  参考文献：
  名称：

  Potent, Selective, and Orally Efficacious Antagonists of Melanin-Concentrating Hormone Receptor 1

  摘要：

  The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists. In general, a good correlation was observed between pK(a)s and activity in the right-hand side of the template, with Asp123 playing an important role in the enhancement of binding affinity. A representative example when evaluated chronically in diet-induced obese mice resulted in good weight loss effects. These antagonists provide a viable lead series in the discovery of new therapies for the treatment of obesity.

  DOI：

  10.1021/jm060572f

文献信息

• Vanilloid receptor ligands and their use in treatments
  申请人：Doherty M. Elizabeth

  公开号：US20050277646A1

  公开（公告）日：2005-12-15

  Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  含有一般结构和组成的化合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠病、炎症性眼病、炎症性或不稳定的膀胱疾病、牛皮癣、带有炎症成分的皮肤病、慢性炎症状况、炎症性疼痛和相关的过敏性和痛觉过敏、神经痛和相关的过敏性和痛觉过敏、糖尿病神经病疼痛、交感神经维持的疼痛、去感觉综合症、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、胃肠或血管区域的内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒症、白癜风、一般胃肠道疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、头发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。
• AMINO-PYRIDINE, -PYRIDINE AND PYRIDAZINE DERIVATIVES FOR USE AS VANILLOID RECEPTOR LIGANDS FOR THE TREATMENT OF PAIN
  申请人：Amgen Inc.

  公开号：EP1542692A1

  公开（公告）日：2005-06-22
• AMINOPYRIMIDINE DERIVATIVES FOR USE AS VANILLOID RECEPTOR LIGANDS FOR THE TREATMENT OF PAIN
  申请人：AMGEN INC.

  公开号：EP1542692B1

  公开（公告）日：2011-01-05
• US7053088B2
  申请人：——

  公开号：US7053088B2

  公开（公告）日：2006-05-30
• US7396831B2
  申请人：——

  公开号：US7396831B2

  公开（公告）日：2008-07-08