2-(2-phenyl-1H-imidazol-5-yl)acetonitrile | 52353-66-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2-phenyl-1H-imidazol-5-yl)acetonitrile
• 英文别名: 2-(2-phenyl-1H-imidazol-4-yl)acetonitrile
• CAS: 52353-66-9
• 化学式: C₁₁H₉N₃
• 分子量: 183.213
• InChiKey: MFFNKNXNXZWFQL-UHFFFAOYSA-N

物化性质

• 沸点：
  449.6±20.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  52.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-phenyl-1H-imidazol-5-yl)acetonitrile 在 氢溴酸 、 盐酸 作用下， 以 乙醇 为溶剂， 反应 25.5h， 以43%的产率得到4(5)-(carboxymethyl)-2-phenylimidazole hydrochloride
  参考文献：
  名称：

  5-Substituted Imidazole-4-acetic Acid Analogues:  Synthesis, Modeling, and Pharmacological Characterization of a Series of Novel γ-Aminobutyric Acid_C Receptor Agonists

  摘要：

  A series of ring-substituted analogues of imidazole-4-acetic acid (IAA, 4), a partial agonist at both GABA(A) and GABA(C) receptors (GABA = gamma-aminobutyric acid), have been synthesized. The synthesized compounds 8a-1 have been evaluated as ligands for the alpha(1)beta(2)gamma(2S) GABA(A) receptors and the rho(1) GABA(C) receptors using the FLIPR membrane potential (FMP) assay and by electrophysiology techniques. None of the tested compounds displayed activity at the GABA(A) receptors at concentrations up to 1000 mu M. However, the 5-Me, 5-Ph, 5-p-Me-Ph, and 5-p-F-Ph IAA analogues, 8a,c,f,g, displayed full agonist activities at the rho(1) receptors in the FMP assay (EC50 in the range 22-420 mu M). Ligand-protein docking identified the Thr129 in the alpha(1) subunit and the corresponding Ser168 residue in rho(1) as determinants of the selectivity displayed by the 5-substituted IAA analogues. The fact that GABA, 4, and 8a displayed decreased agonist potencies at a rho(1)Ser168Thr mutant compared to the WT rho(1) receptor strongly supported this hypothesis. However, in contrast to GABA and 4, which exhibited increased agonist potencies at a alpha(1)(Thr129Ser)beta(2)gamma(2) mutant compared to WT GABA(A) receptor, the data obtained for 8a at the WT and mutant receptors were nonconclusive.

  DOI：

  10.1021/jm070447j
• 作为产物：
  描述：

  4-羟基甲基-2-苯基-1H-咪唑 在 氯化亚砜 作用下， 以 二甲基亚砜 为溶剂， 生成 2-(2-phenyl-1H-imidazol-5-yl)acetonitrile
  参考文献：
  名称：

  Highly Potent Geminal Bisphosphonates. From Pamidronate Disodium (Aredia) to Zoledronic Acid (Zometa)

  摘要：

  Bisphosphonates (BP) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED50 of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.

  DOI：

  10.1021/jm020819i

文献信息

• Mutant IDH1 inhibitors useful for treating cancer
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICE

  公开号：US10703746B2

  公开（公告）日：2020-07-07

  Compounds of Formula I and Formula II and the pharmaceutically acceptable salts thereof are disclosed The variables A, B, Y, Z, X1, X2, R1-4 and R13-18 are disclosed herein. The compounds are useful for treating cancer disorders, especially those involving mutant IDH1 enzymes. Pharmaceutical compositions containing compounds of Formula I or Formula II and methods of treatment comprising administering compounds of Formula I and Formula II are also disclosed.

  公开了式 I 和式 II 的化合物及其药学上可接受的盐 本文公开了变量 A、B、Y、Z、X1、X2、R1-4 和 R13-18。这些化合物可用于治疗癌症疾病，特别是涉及突变 IDH1 酶的疾病。还公开了含有式 I 或式 II 化合物的药物组合物以及包括施用式 I 和式 II 化合物的治疗方法。
• [EN] MUTANT IDH1 INHIBITORS USEFUL FOR TREATING CANCER<br/>[FR] INHIBITEURS D'IDH1 MUTANTS UTILES POUR TRAITER LE CANCER
  申请人：US HEALTH

  公开号：WO2016106331A8

  公开（公告）日：2016-09-29
• Discovery and Optimization of 2<i>H</i>-1λ²-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer
  作者：Jason M. Rohde、Surendra Karavadhi、Rajan Pragani、Li Liu、Yuhong Fang、Weihe Zhang、Andrew McIver、Hongchao Zheng、Qingyang Liu、Mindy I. Davis、Daniel J. Urban、Tobie D. Lee、Dorian M. Cheff、Melinda Hollingshead、Mark J. Henderson、Natalia J. Martinez、Kyle R. Brimacombe、Adam Yasgar、Wei Zhao、Carleen Klumpp-Thomas、Sam Michael、Joseph Covey、William J. Moore、Gordon M. Stott、Zhuyin Li、Anton Simeonov、Ajit Jadhav、Stephen Frye、Matthew D. Hall、Min Shen、Xiaodong Wang、Samarjit Patnaik、Matthew B. Boxer

  DOI：10.1021/acs.jmedchem.1c00019

  日期：2021.4.22
• CYCLOPROPANECARBOXYLIC ACID DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2548872B1

  公开（公告）日：2016-09-28
• MUTANT IDH1 INHIBITORS USEFUL FOR TREATING CANCER
  申请人：The United States of America, as represented by The Secretary, Department of Health and Human Services

  公开号：EP3237385B1

  公开（公告）日：2021-11-24