L-790,070 | 189442-43-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: L-790,070
• 英文别名: (S)-4-[5-(2-(1-Phenylethylamino)-PYRIDIN-4-yl)-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine；4-[3-methyl-2-piperidin-4-yl-5-[3-(trifluoromethyl)phenyl]imidazol-4-yl]-N-[(1S)-1-phenylethyl]pyridin-2-amine
• CAS: 189442-43-1
• 化学式: C₂₉H₃₀F₃N₅
• 分子量: 505.586
• InChiKey: ZLQKJFNLHHGAQF-IBGZPJMESA-N

物化性质

• 沸点：
  640.7±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  54.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(三氟甲基)苯甲酰氯 在 palladium on activated charcoal 乙酸铵 、 盐酸 、 亚硝酸特丁酯 、 titanium(III) chloride 、 氢气 、 caesium carbonate 、 溶剂黄146 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， -78.0~150.0 ℃ 、101.33 kPa 条件下， 反应 134.83h， 生成 L-790,070
  参考文献：
  名称：

  Design and Synthesis of Potent, Selective, and Orally Bioavailable Tetrasubstituted Imidazole Inhibitors of p38 Mitogen-Activated Protein Kinase

  摘要：

  Novel potent and selective diarylimidazole inhibitors of p38 MAP (mitogen-activated protein) kinase are described which have activity in both cell-based assays of tumor necrosis factor-alpha (TNF-alpha) release and an animal model of rheumatoid arthritis; The SAR leading to the development of selectivity against c-Raf and JNK2 alpha 1 kinases is presented, with key features being substitution of the 4-aryl ring with m-trifluoromethyl and substitution of the 5-heteroaryl ring with a a-amino substituent. Cell-based activity was significantly enhanced by incorporation of a 4-piperidinyl moiety at the 2-position of the imidazole which also enhanced aqueous solubility. In general, oral bioavailability of this class of compounds was found to be poor unless the imidazole was methylated on nitrogen. This work led to identification of 48, a potent (p38 MAP kinase inhibition IC50 0.24 nM) and selective p38 MAP kinase inhibitor which inhibits lipopolysaccharide-stimulated release of TNF-alpha from human blood with an IC50 2.2 nM, shows good oral bioavailability in rat and rhesus monkey, and demonstrates significant improvement in measures of disease progression in a rat adjuvant-induced arthritis model.

  DOI：

  10.1021/jm9805236

文献信息

• COMPOUNDS AND METHODS FOR TREATING INFLAMMATORY AND FIBROTIC DISORDERS
  申请人：Kossen Karl

  公开号：US20090318455A1

  公开（公告）日：2009-12-24

  Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system.

  公开了用于治疗炎症和纤维化疾病的化合物和方法，包括用活性化合物调节应激活化蛋白激酶（SAPK）系统的方法，其中活性化合物对p38 MAPK的抑制效力较低；并且其中接触是在SAPK调节浓度下进行的，该浓度对化合物抑制p38 MAPK的抑制浓度百分比较低。还公开了吡非尼酮的衍生物和类似物，它们可用于调节应激活化蛋白激酶（SAPK）系统。
• An efficient synthesis of tetrasubstituted imidazoles from N-(2-Oxo)-amides
  作者：Christopher F. Claiborne、Nigel J. Liverton、Kevin T. Nguyen

  DOI：10.1016/s0040-4039(98)02058-9

  日期：1998.12

  N-(2-Oxo)-amides were efficiently converted to tri- and tetra- substituted imidazoles under neutral reaction conditions upon treatment with neat ammonium trifluoroacetate.

  用纯净的三氟乙酸铵处理后，在中性反应条件下，N-（2-Oxo）-酰胺可有效地转化为三和四取代的咪唑。
• METHOD OF MODULATING STRESS-ACTIVATED PROTEIN KINASE SYSTEM
  申请人：Blatt Lawrence M.

  公开号：US20120258924A1

  公开（公告）日：2012-10-11

  Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system.

  本发明涉及使用活性化合物调节应激激活蛋白激酶（SAPK）系统的方法，其中该活性化合物对至少一种p38 MAPK抑制的效力较低；并且该接触是在该化合物对至少一种p38 MAPK的抑制浓度低百分比的SAPK调节浓度下进行的。本发明还涉及吡非尼酮的衍生物，这些衍生物可以调节应激激活蛋白激酶（SAPK）系统。
• Method of modulating stress-activated protein kinase system
  申请人：InterMune, Inc.

  公开号：US10010536B2

  公开（公告）日：2018-07-03

  Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system.

  公开了用活性化合物调节应激活化蛋白激酶（SAPK）系统的方法，其中活性化合物对抑制至少一种p38 MAPK表现出较低的效力；并且接触是在SAPK调节浓度下进行的，该浓度是化合物抑制至少一种p38 MAPK的低百分比抑制浓度。还公开了吡非尼酮的衍生物。这些衍生物可以调节应激活化蛋白激酶（SAPK）系统。
• SUBSTITUTED IMIDAZOLES HAVING ANTI-CANCER AND CYTOKINE INHIBITORY ACTIVITY
  申请人：Merck & Co., Inc.

  公开号：EP0854870B1

  公开（公告）日：2009-06-10