3-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole
• 英文别名: 3-methyl-1-[3-nitro-5-(trifluoromethyl)phenyl]pyrazole
• 化学式: C₁₁H₈F₃N₃O₂
• 分子量: 271.199
• InChiKey: HUJWOURUMMYETH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole 在 钯 氢气 、 甲醇 、 crude product 、 乙酸乙酯 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以to afford pure product 3-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)aniline (300 mg, 1.045 mmol, 94% yield)的产率得到3-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)aniline
  参考文献：
  名称：

  Pyridine derivatives as rearranged during transfection (RET) kinase inhibitors

  摘要：

  本发明涉及新型化合物，其为重排转录（RET）激酶的抑制剂，涉及含有它们的制药组合物，制备它们的过程，以及它们在治疗中的使用，单独或联合使用，用于规范胃肠敏感性、动力和/或分泌以及/或腹部疾病或疾病相关的治疗，包括但不限于所有分类的肠易激综合症（IBS），包括腹泻型、便秘型或交替排便模式，功能性腹胀、功能性便秘、功能性腹泻、未指定的功能性肠道疾病、功能性腹痛综合征、慢性特发性便秘、功能性食管障碍、功能性胃十二指肠障碍、功能性肛门疼痛、炎症性肠病、增殖性疾病，如非小细胞肺癌、肝细胞癌、结直肠癌、髓样甲状腺癌、滤泡性甲状腺癌、间变性甲状腺癌、乳头状甲状腺癌、脑肿瘤、腹膜腔癌、实体肿瘤、其他肺癌、头颈癌、胶质瘤、神经母细胞瘤、Von Hippel-Lindau综合症和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、移行细胞癌、前列腺癌、食管和胃食管交界处癌、胆管癌、腺癌以及任何具有增加RET激酶活性的恶性肿瘤。

  公开号：

  US09382238B2
• 作为产物：
  描述：

  3-甲基吡唑 、 3-氟-5-硝基三氟甲苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以42.1%的产率得到3-methyl-1-(3-nitro-5-(trifluoromethyl)phenyl)-1H-pyrazole
  参考文献：
  名称：

  [EN] PYRIDINE DERIVATIVES AS REARRANGED DURING TRANSFECTION (RET) KINASE INHIBITORS
  [FR] DÉRIVÉS PYRIDINE UTILISÉS COMME INHIBITEURS DE LA KINASE RÉARRANGÉE AU COURS DE LA TRANSFECTION (RET)

  摘要：

  这项发明涉及一种新型化合物，它们是重排基因转位（RET）激酶的抑制剂，包括含有它们的药物组合物，它们的制备方法，以及它们在治疗中的使用，单独或结合使用，用于规范胃肠敏感性、蠕动和/或分泌以及/或腹部紊乱或疾病的治疗，或与与RET功能障碍相关的疾病相关的治疗，或者调节RET活性可能具有治疗益处的治疗，包括但不限于所有分类的肠易激综合征（IBS），包括以腹泻为主、以便秘为主或交替排便模式、功能性腹胀、功能性便秘、功能性腹泻、未特指的功能性肠道障碍、功能性腹痛综合征、慢性特发性便秘、功能性食管障碍、功能性胃十二指肠障碍、功能性肛门疼痛、炎症性肠病、非小细胞肺癌、肝细胞癌、结肠癌、髓样甲状腺癌、滤泡性甲状腺癌、间变性甲状腺癌、乳头状甲状腺癌、脑肿瘤、腹腔癌、实体肿瘤、其他肺癌、头颈癌、神经胶质瘤、神经母细胞瘤、冯·希普-林道综合征和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、移行细胞癌、前列腺癌、食管和胃食管交界处癌症、胆道癌、腺癌，以及任何具有增加RET激酶活性的恶性肿瘤。

  公开号：

  WO2014141187A1

文献信息

• NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US20160271123A1

  公开（公告）日：2016-09-22

  This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

  本发明涉及一种新型化合物，其为重排转录因子（RET）激酶的抑制剂，以及含有它们的制药组合物，其制备过程和其在治疗中的使用，单独或联合使用，用于正常化胃肠敏感性、运动性和/或分泌以及腹部紊乱或疾病和/或与RET功能障碍相关的治疗或调节RET活性可能具有治疗效益的疾病，包括但不限于所有分类的肠易激综合症（IBS），包括腹泻型、便秘型或交替排便模式，功能性腹胀、功能性便秘、功能性腹泻、未特指的功能性肠道疾病、功能性腹痛综合征、慢性特发性便秘、功能性食管障碍、功能性胃十二指肠障碍、功能性肛门疼痛、炎症性肠病、非小细胞肺癌、肝细胞癌、结直肠癌、髓样甲状腺癌、滤泡性甲状腺癌、间变性甲状腺癌、乳头状甲状腺癌、脑肿瘤、腹腔癌、实体肿瘤、其他肺癌、头颈癌、胶质瘤、神经母细胞瘤、Von Hippel-Lindau综合征和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、移行细胞癌、前列腺癌、食管和胃食管连接处的癌症、胆道癌、腺癌以及任何RET激酶活性增加的恶性肿瘤。
• Pyridine derivatives as rearranged during transfection (RET) kinase inhibitors
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US09382238B2

  公开（公告）日：2016-07-05

  This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

  本发明涉及新型化合物，其为重排转录（RET）激酶的抑制剂，涉及含有它们的制药组合物，制备它们的过程，以及它们在治疗中的使用，单独或联合使用，用于规范胃肠敏感性、动力和/或分泌以及/或腹部疾病或疾病相关的治疗，包括但不限于所有分类的肠易激综合症（IBS），包括腹泻型、便秘型或交替排便模式，功能性腹胀、功能性便秘、功能性腹泻、未指定的功能性肠道疾病、功能性腹痛综合征、慢性特发性便秘、功能性食管障碍、功能性胃十二指肠障碍、功能性肛门疼痛、炎症性肠病、增殖性疾病，如非小细胞肺癌、肝细胞癌、结直肠癌、髓样甲状腺癌、滤泡性甲状腺癌、间变性甲状腺癌、乳头状甲状腺癌、脑肿瘤、腹膜腔癌、实体肿瘤、其他肺癌、头颈癌、胶质瘤、神经母细胞瘤、Von Hippel-Lindau综合症和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、移行细胞癌、前列腺癌、食管和胃食管交界处癌、胆管癌、腺癌以及任何具有增加RET激酶活性的恶性肿瘤。
• US9382238B2
  申请人：——

  公开号：US9382238B2

  公开（公告）日：2016-07-05
• US9789100B2
  申请人：——

  公开号：US9789100B2

  公开（公告）日：2017-10-17
• [EN] PYRIDINE DERIVATIVES AS REARRANGED DURING TRANSFECTION (RET) KINASE INHIBITORS<br/>[FR] DÉRIVÉS PYRIDINE UTILISÉS COMME INHIBITEURS DE LA KINASE RÉARRANGÉE AU COURS DE LA TRANSFECTION (RET)
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2014141187A1

  公开（公告）日：2014-09-18

  This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

  这项发明涉及一种新型化合物，它们是重排基因转位（RET）激酶的抑制剂，包括含有它们的药物组合物，它们的制备方法，以及它们在治疗中的使用，单独或结合使用，用于规范胃肠敏感性、蠕动和/或分泌以及/或腹部紊乱或疾病的治疗，或与与RET功能障碍相关的疾病相关的治疗，或者调节RET活性可能具有治疗益处的治疗，包括但不限于所有分类的肠易激综合征（IBS），包括以腹泻为主、以便秘为主或交替排便模式、功能性腹胀、功能性便秘、功能性腹泻、未特指的功能性肠道障碍、功能性腹痛综合征、慢性特发性便秘、功能性食管障碍、功能性胃十二指肠障碍、功能性肛门疼痛、炎症性肠病、非小细胞肺癌、肝细胞癌、结肠癌、髓样甲状腺癌、滤泡性甲状腺癌、间变性甲状腺癌、乳头状甲状腺癌、脑肿瘤、腹腔癌、实体肿瘤、其他肺癌、头颈癌、神经胶质瘤、神经母细胞瘤、冯·希普-林道综合征和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、移行细胞癌、前列腺癌、食管和胃食管交界处癌症、胆道癌、腺癌，以及任何具有增加RET激酶活性的恶性肿瘤。