2-(3-methoxy-9H-xanthen-9-yl)-2-methylpropanoic acid | 1008118-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-(3-methoxy-9H-xanthen-9-yl)-2-methylpropanoic acid
• CAS: 1008118-76-0
• 化学式: C₁₈H₁₈O₄
• 分子量: 298.339
• InChiKey: QTOLGDYJCNLLNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-methoxy-9H-xanthen-9-yl)-2-methylpropanoic acid 在 Chiralpak-AD 作用下， 生成 (R)-2-(3-methoxy-9H-xanthen-9-yl)-2-methylpropanoic acid 、 (S)-2-(3-methoxy-9H-xanthen-9-yl)-2-methylpropanoic acid
  参考文献：
  名称：

  Dimethyl-diphenyl-propanamide Derivatives As Nonsteroidal Dissociated Glucocorticoid Receptor Agonists

  摘要：

  A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed.

  DOI：

  10.1021/jm100957a
• 作为产物：
  描述：

  2-(9-Hydroxy-3-methoxyxanthen-9-yl)-2-methylpropanoic acid 在 三乙基硅烷 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 生成 2-(3-methoxy-9H-xanthen-9-yl)-2-methylpropanoic acid
  参考文献：
  名称：

  Dimethyl-diphenyl-propanamide Derivatives As Nonsteroidal Dissociated Glucocorticoid Receptor Agonists

  摘要：

  A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed.

  DOI：

  10.1021/jm100957a

文献信息

• [EN] IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR<br/>[FR] DÉRIVÉS IMIDE ET ACYLURÉE UTILISÉS COMME MODULATEURS DU RÉCEPTEUR DE GLUCOCORTICOÏDES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015027021A1

  公开（公告）日：2015-02-26

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-KB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-KB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、二对映体或互变异构体，或其药用可接受盐，其中变量如规范中所定义。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Weinstein David S.

  公开号：US20090075995A1

  公开（公告）日：2009-03-19

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R 5 , R 6 , R 7 , and R 8 ; J 1 , J 2 , and J 3 are at each occurrence the same or different and are independently -A 1 QA 2 -; Q is a bond, O, S, S(O), or S(O) 2 ; A 1 and A 2 are the same or different and are at each occurrence independently selected from a bond, C 1-3 alkylene, substituted C 1-3 alkylene, C 2-4 alkenylene, and substituted C 2-4 alkenylene, provided that A 1 and A 2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R 1 to R 11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

  提供了一系列新颖的非甾体化合物，这些化合物在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病中很有用，包括炎性和免疫疾病，具有以下结构式（I）： 其对应的光学异构体、对映异构体或互变异构体，或其前药酯，或其药用可接受盐，其中： Z是杂环或杂芳基； A是一个5至8成员的碳环或一个5至8成员的杂环； B是一个环烷基、环烯基、芳基、杂环或杂芳基环，其中每个环都与A环上的相邻原子融合，并且可以选择性地被一个到四个独立选自R5、R6、R7和R8的相同或不同的组取代； J1、J2和J3每次出现时相同或不同，独立地选自-A1QA2-；Q是键、O、S、S(O)或S(O)2；A1和A2相同或不同，每次出现时独立地选自键、C1-3烷基、取代的C1-3烷基、C2-4烯基和取代的C2-4烯基，前提是A1和A2的选择使得环A是一个5至8成员的碳环或杂环； R1至R11如本文所述定义。 还提供了使用这些化合物的药物组合物和治疗炎性疾病、免疫相关疾病、肥胖和糖尿病的方法。
• IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160185776A1

  公开（公告）日：2016-06-30

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF- K B activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.
• US8034940B2
  申请人：——

  公开号：US8034940B2

  公开（公告）日：2011-10-11
• US9593113B2
  申请人：——

  公开号：US9593113B2

  公开（公告）日：2017-03-14