methyl 3-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)propanoate | 865450-59-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: methyl 3-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)propanoate
• 英文别名: 3-(2-oxo-2,3-dihydro-benzooxazol-6-yl)-propionic acid methyl ester；methyl 3-(2-oxo-3H-1,3-benzoxazol-6-yl)propanoate
• CAS: 865450-59-5
• 化学式: C₁₁H₁₁NO₄
• 分子量: 221.213
• InChiKey: CBUBDYCUWZJUKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)propanoate 在 lithium hydroxide 、 三氯化铝 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 6,7-dihydro-3H-indeno[5,6-d]oxazole-2,5-dione
  参考文献：
  名称：

  Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating hormone receptor 1 antagonists: The effects of chirality on substituted indan-1-ylamines

  摘要：

  The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHrl antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.061
• 作为产物：
  描述：

  3-羟基-4-硝基苯甲醛 在 palladium on activated charcoal 氢气 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 3-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)propanoate
  参考文献：
  名称：

  Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating hormone receptor 1 antagonists: The effects of chirality on substituted indan-1-ylamines

  摘要：

  The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHrl antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.061

文献信息

• Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor
  申请人：Lynch K. John

  公开号：US20050209274A1

  公开（公告）日：2005-09-22

  The present invention is directed to compounds of formula (I), which antagonize of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.

  本发明涉及式(I)的化合物，通过对抗黑素浓集激素（MCH）的作用，通过对抗黑素浓集激素受体，有助于预防或治疗进食障碍、体重增加、肥胖、生殖和性行为异常、甲状腺激素分泌、利尿和水/电解质稳态、感觉处理、记忆、睡眠、觉醒、焦虑、抑郁、癫痫、神经退行性疾病和精神障碍。
• Novel Autotaxin Inhibitors for the Treatment of Osteoarthritis Pain: Lead Optimization via Structure-Based Drug Design
  作者：Spencer B. Jones、Lance A. Pfeifer、Thomas J. Bleisch、Thomas J. Beauchamp、Jim D. Durbin、V. Joseph Klimkowski、Norman E. Hughes、Christopher J. Rito、Yen Dao、Joseph M. Gruber、Hai Bui、Mark G. Chambers、Srinivasan Chandrasekhar、Chaohua Lin、Denis J. McCann、Daniel R. Mudra、Jennifer L. Oskins、Craig A. Swearingen、Kannan Thirunavukkarasu、Bryan H. Norman

  DOI：10.1021/acsmedchemlett.6b00207

  日期：2016.9.8

  In an effort to develop a novel therapeutic agent aimed at addressing the unmet need of patients with osteoarthritis pain, we set out to develop an inhibitor for autotaxin with excellent potency and physical properties to allow for the clinical investigation of autotaxin-induced nociceptive and neuropathic pain. An initial hit identification campaign led to an aminopyrimidine series with an autotaxin IC50 of 500 nM. X-ray crystallography enabled the optimization to a lead compound that demonstrated favorable potency (IC50 = 2 nM), PK properties, and a robust PK/PD relationship.
• Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating hormone receptor 1 antagonists: The effects of chirality on substituted indan-1-ylamines
  作者：Andrew J. Souers、Rajesh R. Iyengar、Andrew S. Judd、David W.A. Beno、Ju Gao、Gang Zhao、Michael E. Brune、James J. Napier、Mathew M. Mulhern、John K. Lynch、Jennifer C. Freeman、Dariusz Wodka、Chong J. Chen、H. Doug Falls、Sevan Brodjian、Brian D. Dayton、Gilbert J. Diaz、Eugene N. Bush、Robin Shapiro、Brian A. Droz、Victoria Knourek-Segel、Lisa E. Hernandez、Kennan C. Marsh、Regina M. Reilly、Hing L. Sham、Christine A. Collins、Philip R. Kym

  DOI：10.1016/j.bmcl.2006.11.061

  日期：2007.2

  The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHrl antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss. (c) 2006 Elsevier Ltd. All rights reserved.