2,6-dimethyl-4-(trifluoromethyl)benzeneamine hydrochloride | 1194046-26-8

• 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: 2,6-dimethyl-4-(trifluoromethyl)benzeneamine hydrochloride
• 英文别名: 2,6-Dimethyl-4-(trifluoromethyl)aniline hydrochloride；2,6-dimethyl-4-(trifluoromethyl)aniline;hydrochloride
• CAS: 1194046-26-8
• 化学式: C₉H₁₀F₃N*ClH
• mdl: MFCD16817574
• 分子量: 225.641
• InChiKey: WNBDDEFBRXDLRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  26
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  三光气 、 2,6-dimethyl-4-(trifluoromethyl)benzeneamine hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2,6-dimethyl-4-(trifluoromethyl)phenyl isocyanate
  参考文献：
  名称：

  Novel Pyrrolidine Ureas as C−C Chemokine Receptor 1 (CCR1) Antagonists

  摘要：

  Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1 alpha (MIP-1 alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC50 of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.

  DOI：

  10.1021/jm801416q
• 作为产物：
  描述：

  三甲基环三硼氧烷 、 4-氨基-3,5-二溴三氟甲苯 在 四(三苯基膦)钯 、 potassium carbonate 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 1,4-二氧六环 、 水 为溶剂， 反应 17.17h， 生成 2,6-dimethyl-4-(trifluoromethyl)benzeneamine hydrochloride
  参考文献：
  名称：

  Novel Pyrrolidine Ureas as C−C Chemokine Receptor 1 (CCR1) Antagonists

  摘要：

  Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1 alpha (MIP-1 alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC50 of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.

  DOI：

  10.1021/jm801416q

文献信息

• [EN] SULFONAMIDES AS GPR40- AND GPR120-AGONISTS<br/>[FR] SULFONAMIDES EN TANT QU'AGONISTES DE GPR40 ET GPR120
  申请人：DOMPE FARM SPA

  公开号：WO2018029150A1

  公开（公告）日：2018-02-15

  The invention relates to compounds acting as agonists of G-protein coupled receptor 120 (GPR120) and/or 40 (GPR40), and having formula (I). Said compounds are useful in the treatment of diseases or disorders modulated by GPR120 and/or GPR40 such as diabetes (particularly type 2 diabetes), impaired oral glucose tolerance, insulin resistance, obesity, obesity related disorders, metabolic syndrome, dyslipidemia, elevated LDL, elevated triglycerides, obesity induced inflammation, osteoporosis and obesity related cardiovascular disorders.

  该发明涉及作为G蛋白偶联受体120（GPR120）和/或40（GPR40）激动剂的化合物，其具有化学式（I）。这些化合物在治疗由GPR120和/或GPR40调节的疾病或紊乱方面具有用途，如糖尿病（特别是2型糖尿病）、口服葡萄糖耐量受损、胰岛素抵抗、肥胖、与肥胖相关的疾病、代谢综合征、血脂异常、LDL升高、甘油三酯升高、肥胖诱导的炎症、骨质疏松症和与肥胖相关的心血管疾病。
• SULFONAMIDES AS GPR40- AND GPR120-AGONISTS
  申请人：Dompé farmaceutici S.p.A.

  公开号：EP3281937A1

  公开（公告）日：2018-02-14

  The invention relates to compounds acting as agonists of G-protein coupled receptor 120 (GPR120) and/or 40 (GPR40), and having formula (I): Said compounds are useful in the treatment of diseases or disorders modulated by GPR120 and/or GPR40 such as diabetes (particularly type 2 diabetes), impaired oral glucose tolerance, insulin resistance, obesity, obesity related disorders, metabolic syndrome, dyslipidemia, elevated LDL, elevated triglycerides, obesity induced inflammation, osteoporosis and obesity related cardiovascular disorders.

  本发明涉及作为 G 蛋白偶联受体 120（GPR120）和/或 40（GPR40）的激动剂并具有式（I）的化合物： 所述化合物可用于治疗受 GPR120 和/或 GPR40 调节的疾病或紊乱，如糖尿病（尤其是 2 型糖尿病）、口服葡萄糖耐量受损、胰岛素抵抗、肥胖、肥胖相关紊乱、代谢综合征、血脂异常、低密度脂蛋白升高、甘油三酯升高、肥胖诱发的炎症、骨质疏松症和肥胖相关的心血管紊乱。
• Novel Pyrrolidine Ureas as C−C Chemokine Receptor 1 (CCR1) Antagonists
  作者：J. Robert Merritt、Jinqi Liu、Elizabeth Quadros、Michelle L. Morris、Ruiyan Liu、Rui Zhang、Biji Jacob、Jennifer Postelnek、Catherine M. Hicks、Weiqing Chen、Earl F. Kimble、W. Lynn Rogers、Linda O’Brien、Nicole White、Hema Desai、Shalini Bansal、George King、Michael J. Ohlmeyer、Kenneth C. Appell、Maria L. Webb

  DOI：10.1021/jm801416q

  日期：2009.3.12

  Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1 alpha (MIP-1 alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC50 of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.