6-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin-3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]-3-methylpyridin-2(1H)-one | 1189757-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin-3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]-3-methylpyridin-2(1H)-one
• 英文别名: 6-[(4S,5S)-5-(4-fluorophenyl)-5-(6-fluoropyridin-3-yl)-4-methyl-1,4-dihydroimidazol-2-yl]-3-methyl-1H-pyridin-2-one
• CAS: 1189757-78-5
• 化学式: C₂₁H₁₈F₂N₄O
• 分子量: 380.397
• InChiKey: SEMWMDKBYYETPU-ZSEKCTLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(benzyloxy)-6-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin-3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]-3-methylpyridine 在 三氟乙酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 48.0h， 以61%的产率得到6-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin-3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]-3-methylpyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of pyridone-containing imidazolines as potent and selective inhibitors of neuropeptide Y Y5 receptor

  摘要：

  A series of 2-pyridone-containing imidazoline derivatives was synthesized and evaluated as neuropeptide Y Y5 receptor antagonists. Optimization of the 2-pyridone structure on the 2-position of the imidazoline ring led to identification of 1-(difluoromethyl)-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin- 3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl] pyridin-2(1H)-one (7m). Compound 7m displayed statistically significant inhibition of food intake in an agonist-induced food intake model in SD rats and no adverse cardiovascular effects in anesthetized dogs. In addition, markedly higher brain penetrability and a lower plasma Occ90 value were observed in P-gp-deficient mdr1a (-/-) mice compared to mdr1a (+/+) mice after oral administration of 7m. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.069

文献信息

• Novel pyridone derivatives
  申请人：Sato Nagaaki

  公开号：US20050154025A1

  公开（公告）日：2005-07-14

  A compound of the formula (I): wherein R 1 is hydrogen, halogen, cyano, lower alkyl, halo-lower alkyl, hydroxy, lower alkoxy or aralkyloxy; R 2 and R 3 are each independently hydrogen, halogen or halo-lower alkyl; and R 4 and R are each independently hydrogen or halogen, is useful as a pharmaceutical composition for the treatment of various diseases related to NPY, for example, cardiovascular disorders such as angina, acute or congestive heart failure, myocardial infarction, hypertension, nephropathy, electrolyte abnormality, vasospasm, etc., nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, memory impairment, sleep disorders, cognitive impairment, etc., metabolic diseases such as obesity, diabetes, hormone abnormality, gout, fatty liver, etc., genital or reproductive disorders such as infertility, preterm labor, sexual dysfunction, etc., gastro-intestinal disorders, respiratory disorders, inflammatory diseases or glaucoma, and the like.

  式(I)的化合物：其中R1为氢、卤、氰、低碳基、卤代低碳基、羟基、低烷氧基或芳基氧基；R2和R3各自独立地为氢、卤或卤代低碳基；R4和R各自独立地为氢或卤。该化合物可用作药物组合物，用于治疗与NPY相关的各种疾病，例如心血管疾病（如心绞痛、急性或充血性心力衰竭、心肌梗死、高血压、肾病、电解质异常、血管痉挛等）、神经系统疾病（如贪食症、抑郁症、焦虑症、癫痫、失智症、疼痛、酗酒、戒毒、昼夜节律紊乱、精神分裂症、记忆障碍、睡眠障碍、认知障碍等）、代谢性疾病（如肥胖症、糖尿病、激素异常、痛风、脂肪肝等）、生殖系统疾病（如不孕症、早产、性功能障碍等）、胃肠道疾病、呼吸系统疾病、炎症性疾病或青光眼等。
• NOVEL PYRIDONE DERIVATIVE
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1486497A1

  公开（公告）日：2004-12-15

  A compound of the formula (I): wherein R1 is hydrogen, halogen, cyano, lower alkyl, halo-lower alkyl, hydroxy, lower alkoxy or aralkyloxy; R2 and R3 are each independently hydrogen, halogen or halo-lower alkyl; and R4 and R5 are each independently hydrogen or halogen, is useful as a pharmaceutical composition for the treatment of various diseases related to NPY, for example, cardiovascular disorders such as angina, acute or congestive heart failure, myocardial infarction, hypertension, nephropathy, electrolyte abnormality, vasospasm, etc., nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, memory impairment, sleep disorders, cognitive impairment, etc. , metabolic diseases such as obesity, diabetes, hormone abnormality, gout, fatty liver, etc., genital or reproductive disorders such as infertility, preterm labor, sexual dysfunction, etc., gastro-intestinal disorders, respiratory disorders, inflammatory diseases or glaucoma, and the like.

  式（I）的化合物： 其中 R1 是氢、卤素、氰基、低级烷基、卤代低级烷基、羟基、低级烷氧基或芳氧基；R2 和 R3 各自独立地是氢、卤素或卤代低级烷基；以及 R4 和 R5 各自独立地是氢或卤素，可作为药物组合物用于治疗与 NPY 有关的各种疾病，例如心绞痛、急性或充血性心力衰竭、心肌梗塞、高血压、肾病、电解质异常、血管痉挛等心血管疾病、神经系统疾病，如暴食症、抑郁症、焦虑症、癫痫发作、癫痫、痴呆症、疼痛、酒精中毒、药物戒断、昼夜节律紊乱、精神分裂症、记忆障碍、睡眠障碍、认知障碍等； - 代谢性疾病，如肥胖症、高血压、肾病、电解质异常、血管痉挛等。代谢性疾病，如肥胖、糖尿病、激素异常、痛风、脂肪肝等；生殖系统疾病，如不孕不育、早产、性功能障碍等；胃肠道疾病；呼吸系统疾病；炎症性疾病或青光眼等。
• US7119107B2
  申请人：——

  公开号：US7119107B2

  公开（公告）日：2006-10-10
• Discovery of pyridone-containing imidazolines as potent and selective inhibitors of neuropeptide Y Y5 receptor
  作者：Makoto Ando、Nagaaki Sato、Tsuyoshi Nagase、Keita Nagai、Shiho Ishikawa、Hirobumi Takahashi、Norikazu Ohtake、Junko Ito、Mioko Hirayama、Yuko Mitobe、Hisashi Iwaasa、Akira Gomori、Hiroko Matsushita、Kiyoshi Tadano、Naoko Fujino、Sachiko Tanaka、Tomoyuki Ohe、Akane Ishihara、Akio Kanatani、Takehiro Fukami

  DOI：10.1016/j.bmc.2009.05.069

  日期：2009.8

  A series of 2-pyridone-containing imidazoline derivatives was synthesized and evaluated as neuropeptide Y Y5 receptor antagonists. Optimization of the 2-pyridone structure on the 2-position of the imidazoline ring led to identification of 1-(difluoromethyl)-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin- 3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl] pyridin-2(1H)-one (7m). Compound 7m displayed statistically significant inhibition of food intake in an agonist-induced food intake model in SD rats and no adverse cardiovascular effects in anesthetized dogs. In addition, markedly higher brain penetrability and a lower plasma Occ90 value were observed in P-gp-deficient mdr1a (-/-) mice compared to mdr1a (+/+) mice after oral administration of 7m. (C) 2009 Elsevier Ltd. All rights reserved.