2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[2-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyrimidin-5-yl]-isobutyramide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[2-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyrimidin-5-yl]-isobutyramide
• 英文别名: 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(2-(4-methylpiperazin-1-yl)-4-o-tolylpyrimidin-5-yl)propanamide；2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]propanamide
• 化学式: C₂₉H₃₁F₆N₅O
• 分子量: 579.588
• InChiKey: XBFMATCYYBERSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-(3,5-bis-trifluoromethyl-phenyl)-N-(2-methanesulfonyl-4-o-tolyl-pyrimidin-5-yl)-N-methyl-isobutyramide 、 1,4-二氧六环 在 二氯甲烷 、 magnesium sulfate 、 SiO2 、 Dichloromethane methanol ammonium hydroxide 作用下， 反应 16.0h， 以to give 0.37 g (71%) 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[2-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyrimidin-5-yl]-isobutyramide as a colorless solid, m.p. 149°151°, MS (ISP)的产率得到2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[2-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyrimidin-5-yl]-isobutyramide
  参考文献：
  名称：

  4-phenyl-pyrimidine derivatives

  摘要：

  该发明提供了化合物的公式，其中R1为氢或卤素；R2为氢、卤素、低碳基或低氧基；R1和R2可以一起是—CH═CH—CH═CH—，其中R1和R2与它们连接的两个碳环原子一起形成一个融合环；R3为卤素、三氟甲基、低碳基或低氧基；R4/R4′各自独立地为氢或低碳基；R5为低碳基、低氧基、氨基、苯基、羟基-低碳基、氰基-低碳基、氨基甲酰-低碳基、吡啶基、嘧啶基、—(CH2)n-哌嗪基，该基团可以选择性地被一个或两个低碳基或羟基-低碳基取代，—(CH2)n-吗啉基，—(CH2)n-哌啶基，—(CH2)n+1-咪唑基，低碳基硫醇基，低碳基磺酰基，苄氨基，—NH—(CH2)n+1N(R4″)2，—(CH2)n+1N(R4″)2，—O—(CH2)n+1-吗啉基，—O—(CH2)n+1-哌啶基或—O—(CH2)n+1N(R4″)2，其中R4″为氢或低碳基；n为0-2；X为—C（O）N（R4″）—或—N（R4″）C（O）—；以及其药学上可接受的酸加盐。已经证明，这些化合物具有良好的NK-1受体亲和力，因此可以用于治疗与该受体相关的疾病。

  公开号：

  US06274588B1

文献信息

• NOVEL TETRAHYDROCARBAZOLE DERIVATIVES AS LIGANDS OF G-PROTEIN COUPLED RECEPTORS
  申请人：SCHUSTER Tilmann

  公开号：US20120122763A1

  公开（公告）日：2012-05-17

  The present invention provides novel tetrahydrocarbazole compounds according to formula (I) as ligands of G-protein coupled receptors (GPCR) which are useful in the treatment and/or prophylaxis of physiological and/or pathological conditions in mammals mediated by GPCR or of physiological and/or pathological conditions which can be treated by modulation of these receptors.

  本发明提供了新型四氢咔唑化合物，其符合公式（I），作为G蛋白偶联受体（GPCR）的配体，可用于治疗和/或预防哺乳动物由GPCR介导的生理和/或病理状况，或可以通过调节这些受体来治疗的生理和/或病理状况。
• Novel Tetrahydrocarbazole Derivatives as Ligands of G-protein Coupled Receptors
  申请人：Æterna Zentaris GmbH

  公开号：EP1988098A1

  公开（公告）日：2008-11-05

  The present invention provides novel tetrahydrocarbazole derivatives according to formula (I) as ligands of G-protein coupled receptors (GPCR). The compounds of the invention are useful in the treatment and/or prophylaxis of physiological and/or pathological conditions in mammals, preferably humans, which are mediated by GPCR or of physiological and/or pathological conditions which can be treated by modulation of these receptors. The present invention further provides LHRH receptor antagonists that can be used for the modulation of these receptors and are useful for treating above conditions, in particular prostate cancer, breast cancer, uterine cancer, endometrial cancer, cervical cancer, ovarian cancer, benign prostate hyperplasia (BPH), endometriosis, uterine fibroids, uterine myomas, endometrium hyperplasia, dysmenorrhoea, dysfunctional uterine bleeding (menorrhagia, metrorrhagia), pubertas praecox, hirsutism, polycystic ovary syndrome, hormone-dependent tumor diseases, HIV infections or AIDS, neurological or neurodegenerative disorders, ARC (AIDS related complex), Kaposi sarcoma, tumors originating from the brain and/or nervous system and/or meninges, dementia, Alzheimer's disease, nausea and vomiting, pain, inflammations, rheumatic and arthritic pathological states.

  本发明提供了公式（I）的新型四氢咔唑衍生物，作为G蛋白偶联受体（GPCR）的配体。本发明的化合物可用于治疗和/或预防哺乳动物，尤其是人类的生理和/或病理状况，这些状况是由GPCR介导的或可以通过调节这些受体来治疗的生理和/或病理状况。本发明还提供了LHRH受体拮抗剂，可用于调节这些受体，对于治疗上述疾病，特别是前列腺癌、乳腺癌、子宫癌、子宫内膜癌、宫颈癌、卵巢癌、良性前列腺增生（BPH）、子宫内膜异位症、子宫肌瘤、子宫内膜增生、痛经、功能性子宫出血（月经过多、子宫出血）、早发性青春期、多毛症、多囊卵巢综合征、激素依赖性肿瘤疾病、HIV感染或艾滋病、神经或神经退行性疾病、ARC（艾滋病相关综合征）、卡波西肉瘤、起源于大脑和/或神经系统和/或脑膜的肿瘤、痴呆症、阿尔茨海默病、恶心和呕吐、疼痛、炎症、风湿和关节病理状态都很有用。
• Brain, spinal, and nerve injury treatment
  申请人：EUSTRALIS PHARMACEUTICALS LIMITED

  公开号：US10201568B2

  公开（公告）日：2019-02-12

  A treatment for brain, spinal and nerve injury comprising use of a substance P receptor antagonist optionally in combination with a magnesium compound. There is also provided a formulation for use in this treatment comprising a substance P receptor antagonist and a magnesium compound.

  一种治疗脑、脊柱和神经损伤的方法，包括使用一种 P 物质受体拮抗剂（可选择与一种镁化合物结合使用）。还提供了一种用于这种治疗的制剂，包括一种 P 物质受体拮抗剂和一种镁化合物。
• Brain, spinal and nerve injury treatment
  申请人：Nimmo John Alan

  公开号：US20050107380A1

  公开（公告）日：2005-05-19

  A treatment for brain, spinal and nerve injury comprising use of a substance P receptor antagonist optionally in combination with a magnesium compound. There is also provided a formulation for use in this treatment comprising a substance P receptor antagonist and a magnesium compound.

  一种治疗脑、脊柱和神经损伤的方法，包括使用一种 P 物质受体拮抗剂（可选择与一种镁化合物结合使用）。还提供了一种用于这种治疗的制剂，包括一种 P 物质受体拮抗剂和一种镁化合物。
• 4-PHENYL-PYRIMIDINE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1187815A1

  公开（公告）日：2002-03-20