4-[2-(4-bromomethyl-phenoxy)-ethyl]-5-methyl-2-phenyl-oxazole | 201660-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[2-(4-bromomethyl-phenoxy)-ethyl]-5-methyl-2-phenyl-oxazole
• 英文别名: 4-[2-[4-(bromomethyl)phenoxy]ethyl]-5-methyl-2-phenyl-1,3-oxazole
• CAS: 201660-20-0
• 化学式: C₁₉H₁₈BrNO₂
• 分子量: 372.261
• InChiKey: WIRXGODKBIKKNG-UHFFFAOYSA-N

物化性质

• 沸点：
  513.7±60.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[2-(4-bromomethyl-phenoxy)-ethyl]-5-methyl-2-phenyl-oxazole 在 potassium tert-butylate 、 乙酸酐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.58h， 生成 ethyl 2-cyano-2-[2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,1-dioxo-1,2-benzothiazol-3-ylidene]acetate
  参考文献：
  名称：

  Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents

  摘要：

  Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.

  DOI：

  10.1021/jm00102a016
• 作为产物：
  描述：

  4-<2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy>benzyl alcohol 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 4-[2-(4-bromomethyl-phenoxy)-ethyl]-5-methyl-2-phenyl-oxazole
  参考文献：
  名称：

  [EN] ORGANIC COMPOUNDS
  [FR] COMPOSES ORGANIQUES

  摘要：

  (I)式化合物提供与过氧化物酶体增殖物激活受体（PPARs）结合的药理剂。因此，本发明的化合物对于治疗哺乳动物中由PPAR受体活性介导的疾病是有用的。这些疾病包括脂质代谢异常、高脂血症、高胆固醇血症、动脉粥样硬化、高甘油三酯血症、心力衰竭、心肌梗死、血管疾病、心血管疾病、高血压、肥胖、炎症、关节炎、癌症、阿尔茨海默病、皮肤疾病、呼吸系统疾病、眼科疾病、炎症性肠病（IBDs）、溃疡性结肠炎和克罗恩病。本发明的化合物在哺乳动物中作为降糖剂特别有用，用于治疗和预防与糖耐量受损、高血糖和胰岛素抵抗有关的疾病，如1型和2型糖尿病以及X综合征。

  公开号：

  WO2005026134A1

文献信息

• Organic compounds
  申请人：Damon Edson Robert

  公开号：US20070004704A1

  公开（公告）日：2007-01-04

  Compounds of the formula provide pharmacological agents which bind to Peroxisome Proliferator-Activated Receptors (PPARs). Accordingly, the compounds of the present invention are useful for the treatment of conditions mediated by the PPAR receptor activity in mammals. Such conditions include dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, hypertriglyceridemia, heart failure, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, inflammation, arthritis, cancer, Alzheimer's disease, skin disorders, respiratory diseases, ophthalmic disorders, inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease. The compounds of the present invention are particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which impaired glucose tolerance, hyperglycemia and insulin resistance are implicated, such as type-1 and type-2 diabetes, and Syndrome X.

  本发明的化合物具有以下公式，可提供与过氧化物酶体增殖物激活受体（PPARs）结合的药理剂。因此，本发明的化合物对于治疗哺乳动物中由PPAR受体活性介导的疾病是有用的。这些疾病包括失调脂质代谢、高脂血症、高胆固醇血症、动脉粥样硬化、高甘油三酯血症、心力衰竭、心肌梗死、血管疾病、心血管疾病、高血压、肥胖症、炎症、关节炎、癌症、阿尔茨海默病、皮肤疾病、呼吸系统疾病、眼部疾病、炎症性肠病（IBD）、溃疡性结肠炎和克罗恩病。本发明的化合物在哺乳动物中作为降糖药物特别有用，用于治疗和预防因受损葡萄糖耐受性、高血糖和胰岛素抵抗而引起的疾病，例如1型和2型糖尿病以及X综合症。
• Organic Compounds
  申请人：Damon Robert Edson

  公开号：US20100152255A1

  公开（公告）日：2010-06-17

  Compounds of the formula provide pharmacological agents which bind to Peroxisome Proliferator-Activated Receptors (PPARs). Accordingly, the compounds of the present invention are useful for the treatment of conditions mediated by the PPAR receptor activity in mammals. Such conditions include dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, hypertriglyceridemia, heart failure, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, inflammation, arthritis, cancer, Alzheimer's disease, skin disorders, respiratory diseases, ophthalmic disorders, inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease. The compounds of the present invention are particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which impaired glucose tolerance, hyperglycemia and insulin resistance are implicated, such as type-1 and type-2 diabetes, and Syndrome X.

  公式化合物提供了与过氧化物酶体增殖物激活受体（PPARs）结合的药理剂。因此，本发明的化合物对于治疗哺乳动物中PPAR受体活性介导的疾病是有用的。这些疾病包括失调脂质代谢症、高脂血症、高胆固醇血症、动脉硬化、高三酰甘油血症、心力衰竭、心肌梗死、血管疾病、心血管疾病、高血压、肥胖症、炎症、关节炎、癌症、阿尔茨海默病、皮肤疾病、呼吸系统疾病、眼科疾病、炎症性肠病（IBDs）、溃疡性结肠炎和克罗恩病。本发明的化合物在哺乳动物中作为降糖剂特别有用，用于治疗和预防因糖耐量受损、高血糖和胰岛素抵抗而引起的疾病，例如1型和2型糖尿病和X综合症。
• ORGANIC COMPOUNDS
  申请人：Novartis AG

  公开号：EP1664002A1

  公开（公告）日：2006-06-07
• US7700637B2
  申请人：——

  公开号：US7700637B2

  公开（公告）日：2010-04-20
• Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents
  作者：Jay Wrobel、Arlene Dietrich、Shiela A. Woolson、Jane Millen、Michael McCaleb、Maria C. Harrison、Thomas C. Hohman、Janet Sredy、Donald Sullivan

  DOI：10.1021/jm00102a016

  日期：1992.11

  Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.