(R)-methyl 2-(6-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate | 1187197-92-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (R)-methyl 2-(6-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate
• 英文别名: methyl 2-[(1R)-6-hydroxyindan-1-yl]acetate；methyl 2-[(1R)-6-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate
• CAS: 1187197-92-7
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: YIWRHLWWRLWQGG-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-(6-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate 在 水 、 caesium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 31.0h， 生成 (R)-2-(6-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid
  参考文献：
  名称：

  Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles

  摘要：

  GPR40 (FFAR1 or FFA1) is a target of high interest being pursued to treat type II diabetes due to its unique Mechanism leading to :little risk of hypoglycemia. We recently reported the discovery of AM-1638 (2), a potent full agonist. GPR40. In this report, we present the discovery Of GPR40 full agonists containing conformationally constrained tricyclic spirocycles and their structure- activity relationships leading to More potent agonists such as AM-5262 (26) with improved rat PK profile and general selectivity profile. AM-5262 enhanced glucose stimulated insulin secretion (mouse and human islets) and improved glucose homeostasis in vivo (OGTT in HF/STZ mice) when compared to AM-1638.,

  DOI：

  10.1021/ml300427u
• 作为产物：
  描述：

  6-羟基-1-茚酮 在 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 47.37h， 生成 rel-(R)-methyl 2-(6-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate 、 (R)-methyl 2-(6-hydroxy-2,3-dihydro-1H-inden-1-yl)acetate
  参考文献：
  名称：

  Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles

  摘要：

  GPR40 (FFAR1 or FFA1) is a target of high interest being pursued to treat type II diabetes due to its unique Mechanism leading to :little risk of hypoglycemia. We recently reported the discovery of AM-1638 (2), a potent full agonist. GPR40. In this report, we present the discovery Of GPR40 full agonists containing conformationally constrained tricyclic spirocycles and their structure- activity relationships leading to More potent agonists such as AM-5262 (26) with improved rat PK profile and general selectivity profile. AM-5262 enhanced glucose stimulated insulin secretion (mouse and human islets) and improved glucose homeostasis in vivo (OGTT in HF/STZ mice) when compared to AM-1638.,

  DOI：

  10.1021/ml300427u

文献信息

• [EN] CONFORMATIONALLY CONSTRAINED CARBOXYLIC ACID DERIVATIVES USEFUL FOR TREATING METABOLIC DISORDERS<br/>[FR] DÉRIVÉS D'ACIDE CARBOXYLIQUE CONFORMATIONNELLEMENT DÉPENDANTS, UTILES DANS LE TRAITEMENT DE TROUBLES DU MÉTABOLISME
  申请人：AMGEN INC

  公开号：WO2009111056A1

  公开（公告）日：2009-09-11

  The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I or the general formula III: where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.

  本发明提供了用于治疗主体内的代谢紊乱的化合物，例如，II型糖尿病。这些化合物具有通用公式I或通用公式III：其中变量的定义如下。本发明还提供了包括这些化合物的组合物，以及用于制备药物和治疗代谢紊乱如II型糖尿病的方法。
• Conformationally Constrained Carboxylic Acid Derivatives Useful for Treating Metabolic Disorders
  申请人：Brown Sean P.

  公开号：US20100298367A1

  公开（公告）日：2010-11-25

  The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I or the general formula III: where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.

  本发明提供了一些化合物，可用于治疗受试者的代谢性疾病，例如，具有一般式I或一般式III的化合物，其中变量的定义在此提供。本发明还提供了包括这些化合物的组合物，并使用这些化合物制备药物和治疗代谢性疾病，例如2型糖尿病的方法。
• CONFORMATIONALLY CONSTRAINED CARBOXYLIC ACID DERIVATIVES USEFUL FOR TREATING METABOLIC DISORDERS
  申请人：Amgen, Inc

  公开号：EP2260017A1

  公开（公告）日：2010-12-15
• US8450522B2
  申请人：——

  公开号：US8450522B2

  公开（公告）日：2013-05-28
• Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles
  作者：Yingcai Wang、Jiwen (Jim) Liu、Paul J. Dransfield、Liusheng Zhu、Zhongyu Wang、Xiaohui Du、Xianyun Jiao、Yongli Su、An-rong Li、Sean P. Brown、Annie Kasparian、Marc Vimolratana、Ming Yu、Vatee Pattaropong、Jonathan B. Houze、Gayathri Swaminath、Thanhvien Tran、Khanh Nguyen、Qi Guo、Jane Zhang、Run Zhuang、Frank Li、Lynn Miao、Michael D. Bartberger、Tiffany L. Correll、David Chow、Simon Wong、Jian Luo、Daniel C.-H. Lin、Julio C. Medina

  DOI：10.1021/ml300427u

  日期：2013.6.13

  GPR40 (FFAR1 or FFA1) is a target of high interest being pursued to treat type II diabetes due to its unique Mechanism leading to :little risk of hypoglycemia. We recently reported the discovery of AM-1638 (2), a potent full agonist. GPR40. In this report, we present the discovery Of GPR40 full agonists containing conformationally constrained tricyclic spirocycles and their structure- activity relationships leading to More potent agonists such as AM-5262 (26) with improved rat PK profile and general selectivity profile. AM-5262 enhanced glucose stimulated insulin secretion (mouse and human islets) and improved glucose homeostasis in vivo (OGTT in HF/STZ mice) when compared to AM-1638.,