(4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-1,3-oxazolidin-2-one | 153531-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-1,3-oxazolidin-2-one
• 英文别名: (R)-4-(((tert-butyldimethylsilyl)oxy)methyl)oxazolidin-2-one；(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}metyl)-1,3-oxazolidine-2-one；(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1,3-oxazolidine-2-one；(4R)-4-[[tert-butyl(dimethyl)silyl]oxymethyl]-1,3-oxazolidin-2-one
• CAS: 153531-44-3
• 化学式: C₁₀H₂₁NO₃Si
• 分子量: 231.367
• InChiKey: VNLQVVUJHJBYCE-MRVPVSSYSA-N

物化性质

• 沸点：
  322.8±11.0 °C(Predicted)
• 密度：
  0.986±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.12
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-1,3-oxazolidin-2-one 在 sodium tetrahydroborate 、 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.17h， 生成 S-{2-[(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-oxo-1,3-oxazolidin-3-yl]ethyl}ethanethioate
  参考文献：
  名称：

  Synthesis and evaluation of a potent, well-balanced EP 2 /EP 3 dual agonist

  摘要：

  A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (> 2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.11.035
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 4-羟甲基恶唑烷-2-酮 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以58%的产率得到(4R)-4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Diallyl (Lithiodifluoromethyl)phosphonate: A New Reagent for the Introduction of the (Difluoromethylene)phosphonate Functionality

  摘要：

  DOI：

  10.1021/jo00126a073

文献信息

• COMPOUNDS AND METHODS FOR TREATING BACTERIAL INFECTIONS
  申请人：AstraZeneca AB

  公开号：US20140206677A1

  公开（公告）日：2014-07-24

  Compounds of formula (I), pharmaceutically acceptable salts thereof, and uses of the compounds of formula (I) for treating bacterial infections are disclosed.

  化合物的结构式（I），其药学上可接受的盐，以及利用该结构式（I）化合物治疗细菌感染的用途被披露。
• 8-AZAPROSTAGLANDIN DERIVATIVES AND MEDICAL USE THEREOF
  申请人：Kambe Tohru

  公开号：US20080033033A1

  公开（公告）日：2008-02-07

  The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification.) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP 4 agonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.

  本发明的化合物具有8-氮杂前列腺素骨架，其化学式为(I)，其中所有符号的含义与规范相同。该药物组合物包括该化合物、其盐、溶剂化物或环糊精包合物，或其前药，作为活性成分具有EP4激动作用，因此被认为对预防和/或治疗免疫性疾病、哮喘、神经细胞死亡、关节炎、肺功能衰竭、肺纤维化、肺气肿、支气管炎、慢性阻塞性肺疾病、肝损伤、急性肝炎、肾炎、肾功能不全、高血压、心肌缺血、全身炎症反应综合征、败血症、血液嗜酸细胞综合征、巨噬细胞激活综合征、斯蒂尔氏病、川崎病、烧伤、全身性肉芽肿病、溃疡性结肠炎、克隆氏病、透析时的高细胞因子血症、多器官衰竭、休克和青光眼等具有用处。此外，这些化合物还具有加速骨形成的作用，因此有望用于预防和/或治疗与骨量减少有关的疾病，例如原发性骨质疏松症、继发性骨质疏松症、骨转移性癌症、高钙血症、帕吉特病、骨质流失、骨坏死、骨手术后的骨形成、骨移植的替代治疗。
• 8-azaprostaglandin derivatives and medical use thereof
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：US07256211B1

  公开（公告）日：2007-08-14

  The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP4 agonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.

  本发明的化合物组成物包括具有8-氮杂前列腺素骨架的化合物，其由式（I）表示（其中，所有符号与说明书中的符号相同），其盐，溶剂化物或环糊精包合物，或其前药，作为活性成分具有EP4激动作用，因此被认为对预防和/或治疗免疫性疾病、哮喘、神经元细胞死亡、关节炎、肺衰竭、肺纤维化、肺气肿、支气管炎、慢性阻塞性肺疾病、肝损伤、急性肝炎、肾炎、肾功能不全、高血压、心肌缺血、全身性炎症反应综合征、败血症、血吞噬细胞综合征、巨噬细胞活化综合征、斯蒂尔氏病、川崎病、烧伤、全身性肉芽肿病、溃疡性结肠炎、克隆氏病、透析时的高细胞因子血症、多器官衰竭、休克和青光眼等方面有用。此外，这些化合物还具有加速骨形成的作用，因此预计对与骨量丢失相关的疾病的预防和/或治疗有用，例如原发性骨质疏松症、继发性骨质疏松症、癌症骨转移、高钙血症、帕吉特病、骨丢失、骨坏死、骨手术后的骨形成，以及骨移植的替代治疗。
• EP1707208
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of Novel DNA Gyrase Inhibiting Spiropyrimidinetriones: Benzisoxazole Fusion with N-Linked Oxazolidinone Substituents Leading to a Clinical Candidate (ETX0914)
  作者：Gregory S. Basarab、Peter Doig、Vincent Galullo、Gunther Kern、Amy Kimzey、Amy Kutschke、Joseph P. Newman、Marshall Morningstar、John Mueller、Linda Otterson、Karthick Vishwanathan、Fei Zhou、Madhusudhan Gowravaram

  DOI：10.1021/acs.jmedchem.5b00863

  日期：2015.8.13

  A novel class of bacterial type-II topoisomerase inhibitor displaying a spiropyrimidinetrione architecture fused to a benzisoxazole scaffold shows potent activity against Grampositive and fastidious Gram-negative bacteria. Here, we describe a series of N-linked oxazolidinone substituents on the benzisoxazole that improve upon the antibacterial activity of initially described compounds of the class, show favorable PK properties, and demonstrate efficacy in an in vivo Staphylococcus aureus infection model. Inhibition of the topoisomerases DNA gyrase and topoisomerase IV from both Gram-positive and a Gram-negative organisms was demonstrated. Compounds showed a clean in vitro toxicity profile, including no genotoxicity and no bone marrow toxicity at the highest evaluated concentrations or other issues that have been problematic for some fluoroquinolones. Compound lu was identified for advancement into human clinical trials for treatment of uncomplicated gonorrhea based on a variety of beneficial attributes including the potent activity and the favorable safety profile.