3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid | 1143579-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid
• 英文别名: II-B08；3-{1-[3-(biphenyl-4-ylamino)-3-oxopropyl]-1H-1,2,3-triazol-4-yl}-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid；6-hydroxy-1-methyl-3-[1-[3-oxo-3-(4-phenylanilino)propyl]triazol-4-yl]-2-phenylindole-5-carboxylic acid
• CAS: 1143579-78-5
• 化学式: C₃₃H₂₇N₅O₄
• 分子量: 557.608
• InChiKey: RATFAFAWIWHLMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-azido-N-(biphenyl-4-yl)propanamide 、 3-ethynyl-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid 在 copper(ll) sulfate pentahydrate 、 tris(benzyltriazolylmethyl)amine 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 24.0h， 以44%的产率得到3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid
  参考文献：
  名称：

  基于水杨酸的小分子抑制剂，用于含有蛋白质酪氨酸磷酸酶-2 (SHP2) 的致癌 Src 同源-2 域

  摘要：

  Src homology-2 域包含蛋白酪氨酸磷酸酶-2 (SHP2) 在生长因子和细胞因子信号传导中起关键作用。功能获得性 SHP2 突变与 Noonan 综合征、各种白血病和实体瘤有关。因此，人们对 SHP2 作为抗癌和抗白血病治疗的潜在靶点有相当大的兴趣。我们报告了一种基于水杨酸的组合文库方法，旨在结合活性位点和附近独特的亚袋，以提高亲和力和选择性。文库的筛选导致鉴定出具有高效细胞活性的 SHP2 抑制剂 II-B08（化合物9）。化合物9阻断生长因子刺激的 ERK1/2 激活和造血祖细胞增殖，提供支持证据表明 SHP2 的化学抑制可能对抗癌和抗白血病治疗有治疗作用。与9复合的 SHP2 结构的 X 射线晶体学分析揭示了可用于获得更有效和选择性 SHP2 抑制剂的分子决定因素。

  DOI：

  10.1021/jm901645u

文献信息

• Compositions and Methods for the Prevention and Treatment of Osteolysis and Osteoporosis
  申请人：RHODE ISLAND HOSPITAL

  公开号：US20150352131A1

  公开（公告）日：2015-12-10

  This application discloses compositions, devices, and methods for the prevention and treatment of osteolysis and osteoporosis. Treatment or prevention of osteolysis or osteoporosis is carried out by targeting the enzyme, Shp2 (a Src homology 2 (SH2) domain containing non-transmembrane Protein Tyrosine Phosphatase (PTP)), or proteins involved in the Shp2 signaling pathway by administering a Shp2 pathway inhibitor that inhibits fusion of pre-osteoclasts.
• INHIBITORS OF SHP2
  申请人：Bayer Aktiengesellschaft

  公开号：US20210230300A1

  公开（公告）日：2021-07-29

  The present invention is related to an inhibitor or antagonist of SHP2 for the treatment and/or prevention of a neoplastic disease.
• [EN] MATERIALS AND METHODS FOR REGULATING THE ACTIVITY OF PHOSPHATASES<br/>[FR] MATÉRIAUX ET PROCÉDÉS POUR RÉGULER L'ACTIVITÉ DES PHOSPHATASES
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2009049098A2

  公开（公告）日：2009-04-16

  Reported herein are bidentate or tridentate salicylic acid based combinatorial libraries and method of making and using the same to inhibit phosphatases. Generally, these inhibitors include elements that interact with both the active site and a nearby peripheral site of phosphates such as Lyp, SHP2 and mPTPB. These moleuces are used to study, characterize, regulate and inhibit various phosphatases. These molecules and pharmaceutically acceptable salts of them may be use to treat various diseases or conditions that involve the activity of at least one phosphatase.
• [EN] COMPOSITIONS AND METHODS FOR THE PREVENTION AND TREATMENT OF OSTEOLYSIS AND OSTEOPOROSIS<br/>[FR] COMPOSITIONS ET MÉTHODES POUR LA PRÉVENTION ET LE TRAITEMENT DE L'OSTÉOLYSE ET DE L'OSTÉOPOROSE
  申请人：RHODE ISLAND HOSPITAL

  公开号：WO2014113584A1

  公开（公告）日：2014-07-24

  This application discloses compositions, devices, and methods for the prevention and treatment of osteolysis and osteoporosis. Osteoporosis (OP) and periprosthetic osteolysis (PO) are skeletal disorders causing major health and economic burdens worldwide. Roughly half of all women over age 50 will experience an osteoporosis-related bone fracture. About 10 to 20% of total joint arthroplasty patients suffer from PO and require revision procedures. The drugs currently available to treat OP and PO have low efficacy and unpleasant side effects. Treatment or prevention of osteolysis or osteoporosis is carried out by targeting the enzyme, Shp2 (a Src homology 2 (SH2) domain containing non-transmembrane PTP), or proteins involved in the Shp2 signaling pathway.
• Salicylic Acid Based Small Molecule Inhibitor for the Oncogenic Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (SHP2)
  作者：Xian Zhang、Yantao He、Sijiu Liu、Zhihong Yu、Zhong-Xing Jiang、Zhenyun Yang、Yuanshu Dong、Sarah C. Nabinger、Li Wu、Andrea M. Gunawan、Lina Wang、Rebecca J. Chan、Zhong-Yin Zhang

  DOI：10.1021/jm901645u

  日期：2010.3.25

  homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with Noonan syndrome, various kinds of leukemias, and solid tumors. Thus, there is considerable interest in SHP2 as a potential target for anticancer and antileukemia therapy. We report a salicylic acid based combinatorial library approach

  Src homology-2 域包含蛋白酪氨酸磷酸酶-2 (SHP2) 在生长因子和细胞因子信号传导中起关键作用。功能获得性 SHP2 突变与 Noonan 综合征、各种白血病和实体瘤有关。因此，人们对 SHP2 作为抗癌和抗白血病治疗的潜在靶点有相当大的兴趣。我们报告了一种基于水杨酸的组合文库方法，旨在结合活性位点和附近独特的亚袋，以提高亲和力和选择性。文库的筛选导致鉴定出具有高效细胞活性的 SHP2 抑制剂 II-B08（化合物9）。化合物9阻断生长因子刺激的 ERK1/2 激活和造血祖细胞增殖，提供支持证据表明 SHP2 的化学抑制可能对抗癌和抗白血病治疗有治疗作用。与9复合的 SHP2 结构的 X 射线晶体学分析揭示了可用于获得更有效和选择性 SHP2 抑制剂的分子决定因素。