5-[2,6-Dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-2-hydroxy-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester | 332934-33-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-[2,6-Dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-2-hydroxy-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester
• 英文别名: 5-[2,6-dichloro-4-(3,5-dioxo-4,5-dihydro-3H-(1,2,4]triazin-2-yl)-phenoxy]-2-hydroxy-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester；(2,5-dioxopyrrolidin-1-yl) 5-[2,6-dichloro-4-(3,5-dioxo-1,2,4-triazin-2-yl)phenoxy]-2-hydroxybenzoate
• CAS: 332934-33-5
• 化学式: C₂₀H₁₂Cl₂N₄O₈
• 分子量: 507.243
• InChiKey: GVZFEPGTNONWAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  环丁基胺 、 5-[2,6-Dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-2-hydroxy-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester 在 TEA 作用下， 以 乙二醇二甲醚 为溶剂， 生成 N-Cyclobutyl-5-[2,6-dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-2-hydroxy-benzamide
  参考文献：
  名称：

  Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TRβ subtype-selective thyromimetics

  摘要：

  In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TRbeta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00947-2
• 作为产物：
  描述：

  5-[2,6-dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-2-methoxy-benzoic acid 在 三氯化硼 、 N,N'-二环己基碳二亚胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 生成 5-[2,6-Dichloro-4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-2-hydroxy-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester
  参考文献：
  名称：

  Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TRβ subtype-selective thyromimetics

  摘要：

  In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TRbeta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00947-2

文献信息

• 6-Azauracil derivatives as thyroid receptor ligands
  申请人：Pfizer, Inc.

  公开号：US06787652B1

  公开（公告）日：2004-09-07

  The present invention provides novel compounds of the Formula I and prodrugs thereof, geometric and optical isomers thereof, and pharmaceutically acceptable salts of such compounds, prodrugs and isomers, wherein R1 to R8 and W are as described herein. Pharmaceutical compositions containing such compounds, prodrugs, isomers or pharmaceutically acceptable salts thereof, and methods, pharmaceutical compositions and kits for treating obesity, overweight condition, hyperlipidemia, thyroid disease, hypothyroidism, thyroid cancer and related disorders and diseases such as diabetes mellitus, atherosclerosis, hypertension, coronary heart disease, hypercholesteremia, depression, osteoporosis, cardiac arrhythmias, glaucoma and congestive heart failure are also provided.

  本发明提供了公式I的新化合物及其前药，几何和光学异构体，以及这些化合物，前药和异构体的药学上可接受的盐，其中R1至R8和W如本文所述。还提供了含有这些化合物，前药，异构体或药学上可接受的盐的制药组合物，以及用于治疗肥胖，超重症，高脂血症，甲状腺疾病，甲状腺功能减退症，甲状腺癌及相关疾病和疾病，如糖尿病，动脉粥样硬化，高血压，冠心病，高胆固醇血症，抑郁症，骨质疏松，心律失常，青光眼和充血性心力衰竭的方法，制药组合物和试剂盒。
• 6-azauracil derivatives as thyroid receptor ligands
  申请人：Pfizer Products Inc.

  公开号：EP1088819B1

  公开（公告）日：2005-06-15
• US6787652B1
  申请人：——

  公开号：US6787652B1

  公开（公告）日：2004-09-07
• US6930107B2
  申请人：——

  公开号：US6930107B2

  公开（公告）日：2005-08-16
• Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent, TRβ subtype-selective thyromimetics
  作者：Robert L. Dow、Steven R. Schneider、Ernest S. Paight、Richard F. Hank、Phoebe Chiang、Peter Cornelius、Eunsun Lee、William P. Newsome、Andrew G. Swick、Josephine Spitzer、Diane M. Hargrove、Terrell A. Patterson、Jayvardhan Pandit、Boris A. Chrunyk、Peter K. LeMotte、Dennis E. Danley、Michele H. Rosner、Mark J. Ammirati、Samuel P. Simons、Gayle K. Schulte、Bonnie F. Tate、Paul DaSilva-Jardine

  DOI：10.1016/s0960-894x(02)00947-2

  日期：2003.2

  In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TRbeta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis. (C) 2002 Elsevier Science Ltd. All rights reserved.