(S)-2-(3-羟基-9H-黄嘌呤-9-基)-2-甲基丙酸 | 1008118-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: (S)-2-(3-羟基-9H-黄嘌呤-9-基)-2-甲基丙酸
• 英文名称: (S)-2-(3-hydroxy-9H-xanthen-9-yl)-2-methylpropanoic acid
• 英文别名: 2-[(9S)-3-hydroxy-9H-xanthen-9-yl]-2-methylpropanoic acid
• CAS: 1008118-88-4
• 化学式: C₁₇H₁₆O₄
• 分子量: 284.312
• InChiKey: UVPPHBSOVDNXAW-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氨基-1,3,4-噻二唑 、 (S)-2-(3-羟基-9H-黄嘌呤-9-基)-2-甲基丙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以66%的产率得到(S)-2-(3-hydroxy-9H-xanthen-9-yl)-2-methyl-N-(1,3,4-thiadiazol-2-yl)propanamide
  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：

  (S)-2-(3-methoxy-9H-xanthen-9-yl)-2-methylpropanoic acid 在 potassium carbonate 、 2-氨基苯硫醇 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 1.5h， 以70%的产率得到(S)-2-(3-羟基-9H-黄嘌呤-9-基)-2-甲基丙酸
  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

• 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。
• US8034940B2
  申请人：——

  公开号：US8034940B2

  公开（公告）日：2011-10-11
• [EN] MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF<br/>[FR] MODULATEURS DU RÉCEPTEUR DE GLUCOCORTICOÏDE, DE L'ACTIVITÉ DU AP-1 ET/OU DU NF-KB ET LEUR UTILISATION
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2008021926A2

  公开（公告）日：2008-02-21

  [EN] Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-KB 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 R₅, R₆, R₇, and R₈; J₁, J₂, and J3 are at each occurrence the same or different and are independently -A₁QA₂-; Q is a bond, O, S, S(O), or S(O)2; A₁ and A₂ are the same or different and are at each occurrence independently selected from a bond, C1-3alkylene, substituted C₁
  [FR] L'invention concerne de nouveaux composés non stéroïdiens utiles pour le traitement de maladies associées à la modulation du récepteur de glucocorticoïde, de l'activité du AP-1 et/ou du NF-KB, y compris des maladies inflammatoires et immunitaires, ayant la structure de la formule (I), un de leurs énantiomères, diastéréoisomères ou tautomères, ou un de leurs promédicaments, ou un de leurs sels pharmaceutiquement acceptables, dans laquelle : Z est un hétérocyclo ou hétéroaryle ; A est un cycle carbocyclique ayant de 5 à 8 éléments ou un cycle hétérocyclique ayant de 5 à 8 éléments ; B est un cycle cycloalkyle, cycloalcényle, aryle, hétérocyclo ou hétéroaryle, chaque cycle étant fusionné au cycle A sur des atomes adjacents et éventuellement substitué par un à quatre groupements qui sont identiques ou différents et sont choisis indépendamment parmi R₅, R₆, R₇ et R₈; J₁, J₂ et J3 sont à chaque occurrence identiques ou différents et représentent indépendamment -A₁QA₂- ; Q représente une liaison, O, S, S(O) ou S(O)2 ; A₁ et A₂ sont identiques ou différents et sont à chaque occurrence choisis indépendamment parmi une liaison, un alkylène en C1-3, un alkylène en C1-3 substitué, un alcénylène en C2-4 et un alcénylène en C2-4 substitué, à condition que A₁ et A₂ soient choisis de manière à ce que le cycle A soit un cycle carbocyclique ou hétérocyclique ayant de 5 à 8 éléments ; R₁ à R₁₁ sont tels que définis dans le présent document. L'invention concerne également des compositions pharmaceutiques et des procédés de traitement de maladies inflammatoires ou immunitaires et de l'obésité et du diabète en utilisant de tels composés.
• Dimethyl-diphenyl-propanamide Derivatives As Nonsteroidal Dissociated Glucocorticoid Receptor Agonists
  作者：Bingwei V. Yang、David S. Weinstein、Lidia M. Doweyko、Hua Gong、Wayne Vaccaro、Tram Huynh、Hai-yun Xiao、Arthur M. Doweyko、Lorraine Mckay、Deborah A. Holloway、John E. Somerville、Sium Habte、Mark Cunningham、Michele McMahon、Robert Townsend、David Shuster、John H. Dodd、Steven G. Nadler、Joel C. Barrish

  DOI：10.1021/jm100957a

  日期：2010.12.9

  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.