4-(trifluoromethyl)thiophene-2-carbaldehyde | 1367866-60-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(trifluoromethyl)thiophene-2-carbaldehyde
• CAS: 1367866-60-1
• 化学式: C₆H₃F₃OS
• 分子量: 180.15
• InChiKey: BRJDFNMABHVXNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  45.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(trifluoromethyl)thiophene-2-carbaldehyde 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.17h， 以37%的产率得到[4-(trifluoromethyl)thiophen-2-yl]methanol
  参考文献：
  名称：

  Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel non-basic 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives and mitigation of mutagenicity in Ames test

  摘要：

  To develop non-basic melanin-concentrating hormone receptor 1 (MCHR1) antagonists with a high probability of target selectivity and therapeutic window, we explored neutral bicyclic motifs that could replace the previously reported imidazo[1,2-a]pyridine or 1H-benzimidazole motif. The results indicated that the binding affinity of a chemically neutral 2H-indazole derivative 8a with MCHR1 (hMCHR1: IC50 = 35 nM) was comparable to that of the imidazopyridine and benzimidazole derivatives (1 and 2, respectively) reported so far. However, 8a was positive in the Ames test using TA1537 in S9- condition. Based on a putative intercalation of 8a with DNA, we introduced a sterically-hindering cyclopropyl group on the indazole ring to decrease planarity, which led to the discovery of 1-(2-cyclopropyl-3-methyl-2H-indazol- 5-yl)-4-{[5-(trifluoromethyl)thiophen-3-yl]methoxy} pyridin-2(1H)-one 8l without mutagenicity in TA1537. Compound 8l exerted significant antiobesity effects in diet-induced obese F344 rats and exhibited promising safety profile. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.013
• 作为产物：
  描述：

  2,2,6,6-四甲基哌啶 、 3-(三氟甲基)噻吩 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 4-(trifluoromethyl)thiophene-2-carbaldehyde
  参考文献：
  名称：

  Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel non-basic 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives and mitigation of mutagenicity in Ames test

  摘要：

  To develop non-basic melanin-concentrating hormone receptor 1 (MCHR1) antagonists with a high probability of target selectivity and therapeutic window, we explored neutral bicyclic motifs that could replace the previously reported imidazo[1,2-a]pyridine or 1H-benzimidazole motif. The results indicated that the binding affinity of a chemically neutral 2H-indazole derivative 8a with MCHR1 (hMCHR1: IC50 = 35 nM) was comparable to that of the imidazopyridine and benzimidazole derivatives (1 and 2, respectively) reported so far. However, 8a was positive in the Ames test using TA1537 in S9- condition. Based on a putative intercalation of 8a with DNA, we introduced a sterically-hindering cyclopropyl group on the indazole ring to decrease planarity, which led to the discovery of 1-(2-cyclopropyl-3-methyl-2H-indazol- 5-yl)-4-{[5-(trifluoromethyl)thiophen-3-yl]methoxy} pyridin-2(1H)-one 8l without mutagenicity in TA1537. Compound 8l exerted significant antiobesity effects in diet-induced obese F344 rats and exhibited promising safety profile. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.013

文献信息

• [EN] INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE<br/>[FR] INHIBITEURS DE LA PROTÉINE KINASE I INTERAGISSANT AVEC LE RÉCEPTEUR POUR LE TRAITEMENT D'UNE MALADIE
  申请人：UNIV TEXAS

  公开号：WO2021173917A1

  公开（公告）日：2021-09-02

  Disclosed herein are compounds which inhibit RIPK1, pharmaceutical compositions, and methods of treatment of RIPK1-mediated diseases, such as neurodegenerative disorders, inflammatory disorders, and cancer.

  公开了抑制RIPK1的化合物，药物组合物以及治疗RIPK1介导的疾病的方法，如神经退行性疾病，炎症性疾病和癌症。
• PHENOXYFLUORPYRIMIDINE
  申请人：BAYER AG

  公开号：EP1194417A1

  公开（公告）日：2002-04-10
• [DE] PHENOXYFLUORPYRIMIDINE<br/>[EN] PHENOXY FLUOROPYRIMIDINES<br/>[FR] PHENOXYFLUOROPYRIMIDINES
  申请人：BAYER AG

  公开号：WO2000078733A1

  公开（公告）日：2000-12-28

  Die Erfindung betrifft neue Phenoxyfluorpyrimidine, mehrere Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel.
• Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel non-basic 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives and mitigation of mutagenicity in Ames test
  作者：Hideyuki Igawa、Masashi Takahashi、Minoru Ikoma、Hiromi Kaku、Keiko Kakegawa、Asato Kina、Jumpei Aida、Shoki Okuda、Yayoi Kawata、Toshihiro Noguchi、Natsu Hotta、Syunsuke Yamamoto、Masaharu Nakayama、Yasutaka Nagisa、Shizuo Kasai、Tsuyoshi Maekawa

  DOI：10.1016/j.bmc.2016.04.013

  日期：2016.6

  To develop non-basic melanin-concentrating hormone receptor 1 (MCHR1) antagonists with a high probability of target selectivity and therapeutic window, we explored neutral bicyclic motifs that could replace the previously reported imidazo[1,2-a]pyridine or 1H-benzimidazole motif. The results indicated that the binding affinity of a chemically neutral 2H-indazole derivative 8a with MCHR1 (hMCHR1: IC50 = 35 nM) was comparable to that of the imidazopyridine and benzimidazole derivatives (1 and 2, respectively) reported so far. However, 8a was positive in the Ames test using TA1537 in S9- condition. Based on a putative intercalation of 8a with DNA, we introduced a sterically-hindering cyclopropyl group on the indazole ring to decrease planarity, which led to the discovery of 1-(2-cyclopropyl-3-methyl-2H-indazol- 5-yl)-4-[5-(trifluoromethyl)thiophen-3-yl]methoxy} pyridin-2(1H)-one 8l without mutagenicity in TA1537. Compound 8l exerted significant antiobesity effects in diet-induced obese F344 rats and exhibited promising safety profile. (C) 2016 Elsevier Ltd. All rights reserved.