R116301 | 336884-84-5

• 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: R116301
• 英文别名: 2-[4-[(2R,4S)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)piperidin-4-yl]piperazin-1-yl]-N-(2,6-dimethylphenyl)acetamide；2-[4-[(2R,4S)-2-benzyl-1-[3,5-bis(trifluoromethyl)benzoyl]piperidin-4-yl]piperazin-1-yl]-N-(2,6-dimethylphenyl)acetamide
• CAS: 336884-84-5
• 化学式: C₃₅H₃₈F₆N₄O₂
• 分子量: 660.703
• InChiKey: KHOXGPDKCIQOOR-XZWHSSHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  47
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.9
• 氢给体数：
  1
• 氢受体数：
  10

制备方法与用途

R116031是一种具有生物活性的化学物质。

反应信息

• 作为反应物：
  描述：

  R116301 、 L-苹果酸 反应 0.5h， 生成 [11C]-R 116301
  参考文献：
  名称：

  Process Development of the Synthetic Route to R116301

  摘要：

  We describe in this paper the synthesis of compound 1 (R116301), which was developed to prepare pilot scale quantities (20-50 kg) of drug substance. The synthesis involves the (BuLi)-Bu-s deprotonation of Boc-protected piperidone acetal 2, followed by benzaldehyde addition and ring closure to cyclic carbamate 4. Piperidine acetal 5 is resolved with Brown's acid and acylated. The ketone obtained after piperidine acetal deprotection undergoes reductive amination with N-benzyl piperazine, the most critical step in the synthesis. After debenzylation, final coupling and salt formation, compound 1 is obtained over 10 steps with 4% overall yield.

  DOI：

  10.1021/op700086d
• 作为产物：
  描述：

  4,4-(乙烯二氧基)-1-叔丁氧羰基哌啶 在 titanium(IV) isopropylate 、 四甲基乙二胺 、 5%-palladium/activated carbon 、 potassium tert-butylate 、 氢气 、 仲丁基锂 、 sodium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙醚 、 异丙醇 为溶剂， -70.0~100.0 ℃ 、100.0 kPa 条件下， 反应 48.75h， 生成 R116301
  参考文献：
  名称：

  Process Development of the Synthetic Route to R116301

  摘要：

  We describe in this paper the synthesis of compound 1 (R116301), which was developed to prepare pilot scale quantities (20-50 kg) of drug substance. The synthesis involves the (BuLi)-Bu-s deprotonation of Boc-protected piperidone acetal 2, followed by benzaldehyde addition and ring closure to cyclic carbamate 4. Piperidine acetal 5 is resolved with Brown's acid and acylated. The ketone obtained after piperidine acetal deprotection undergoes reductive amination with N-benzyl piperazine, the most critical step in the synthesis. After debenzylation, final coupling and salt formation, compound 1 is obtained over 10 steps with 4% overall yield.

  DOI：

  10.1021/op700086d

文献信息

• Pharmaceutical compositions comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water soluble and respectively base
  申请人：Vandecruys Petrus Gerebern Roger

  公开号：US20060078609A1

  公开（公告）日：2006-04-13

  The invention provides a novel pharmaceutical composition comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water-soluble acid respectively base characterized in that the acid respectively base:drug compound ratio is at least 1:1 by weight.

  本发明提供了一种新型的药物组合物，包括一种碱性或酸性药物化合物、表面活性剂和生理耐受性的水溶性酸或碱，其特征在于酸或碱与药物化合物的比例至少为1：1（重量比）。
• 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。
• Pharmaceutical compositions comprising a basic drug compound, vitamin E TPGS and a physiologically tolerable water-soluble acid
  申请人：Janssen Pharmaceutica NV

  公开号：EP1567134B1

  公开（公告）日：2019-11-06
• COMBINATION OF OPIOIDS AND A PIPERAZINE DERIVATIVE FOR THE TREATMENT OF PAIN
  申请人：Janssen Pharmaceutica NV

  公开号：EP1635833B1

  公开（公告）日：2008-05-14