(4,6-Dimethyl-pyrimidin-5-yl)-(4-methyl-4-{(S)-3-methyl-4-[(S)-2-phenyl-1-(4-trifluoromethyl-phenyl)-ethyl]-piperazin-1-yl}-piperidin-1-yl)-methanone | 696600-46-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (4,6-Dimethyl-pyrimidin-5-yl)-(4-methyl-4-{(S)-3-methyl-4-[(S)-2-phenyl-1-(4-trifluoromethyl-phenyl)-ethyl]-piperazin-1-yl}-piperidin-1-yl)-methanone
• 英文别名: (4,6-dimethylpyrimidin-5-yl)-[4-methyl-4-[(3S)-3-methyl-4-[(1S)-2-phenyl-1-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1-piperidyl]methanone；(4,6-dimethylpyrimidin-5-yl)-[4-methyl-4-[(3S)-3-methyl-4-[(1S)-2-phenyl-1-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]piperidin-1-yl]methanone
• CAS: 696600-46-1
• 化学式: C₃₃H₄₀F₃N₅O
• 分子量: 579.709
• InChiKey: IOAZQBRQOPSGMR-IADCTJSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4,6-Dimethyl-pyrimidin-5-yl)-(4-methyl-4-{(S)-3-methyl-4-[(S)-2-phenyl-1-(4-trifluoromethyl-phenyl)-ethyl]-piperazin-1-yl}-piperidin-1-yl)-methanone 在 盐酸 作用下， 生成
  参考文献：
  名称：

  Piperazine derivatives useful as CCR5 antagonists

  摘要：

  公开了使用CCR5拮抗剂的公式，其中 R是可选择的取代苯基，吡啶基，噻吩基或萘基; R1是氢或烷基; R2是取代苯基，取代杂环基，萘基，芴基，二苯甲基或可选择的取代苯基或杂环基烷基; R3是氢，烷基，烷氧基烷基，环烷基，环烷基烷基，或可选择的取代苯基，苯基烷基，萘基，萘基烷基，杂环基或杂环基烷基; R4，R5和R7是氢或烷基; R6是氢，烷基或烯基; 用于治疗HIV，固体器官移植排斥，移植物宿主病，关节炎，类风湿关节炎，炎症性肠病，特应性皮炎，牛皮癣，哮喘，过敏或多发性硬化症的方法，以及包含它们的新化合物，包含它们的药物组合物，以及CCR5拮抗剂与抗HIV治疗中有用的抗病毒剂或与治疗炎症性疾病中有用的药物的组合。

  公开号：

  US06391865B1
• 作为产物：
  描述：

  (S)-4-N-叔丁氧羰基-2-甲基哌嗪 在 titanium(IV) isopropylate 、 sodium hexamethyldisilazane 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 magnesium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 23.0h， 生成 (4,6-Dimethyl-pyrimidin-5-yl)-(4-methyl-4-{(S)-3-methyl-4-[(S)-2-phenyl-1-(4-trifluoromethyl-phenyl)-ethyl]-piperazin-1-yl}-piperidin-1-yl)-methanone
  参考文献：
  名称：

  Piperazine-Based CCR5 Antagonists as HIV-1 Inhibitors. IV. Discovery of 1-[(4,6-Dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-{2-methoxy-1(R)-4-(trifluoromethyl)phenyl}ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a Potent, Highly Selective, and Orally Bioavailable CCR5 Antagonist

  摘要：

  The nature and the size of the benzylic substituent are shown to be the key to controlling receptor selectivity (CCR5 vs M1, M2) and potency in the title compounds. Optimization of the lead benzylic methyl compound 3 led to the methoxymethyl analogue 30, which had excellent receptor selectivity and oral bioavailability in rats and monkeys. Compound 30 (Sch-417690/Sch-D), a potent inhibitor of HIV-1 entry into target cells, is currently in clinical trials.

  DOI：

  10.1021/jm0304515

文献信息

• PIPERIDINE DERIVATIVES USEFUL AS CCR5 ANTAGONISTS
  申请人：Baroudy Bahige M.

  公开号：US20080188485A1

  公开（公告）日：2008-08-07

  The use of CCR 5 antagonists of the formula or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R 1 is hydrogen or alkyl; R 2 is substituted phenyl, substituted heteroaryl, naphthyl fluorenyl, diphenylmethyl or optionally substituted phenyl- or heteroarylalkyl; R 3 is hydrogen, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, or optionally substituted phenyl, phenylalkyl, naphthyl, naphthylalkyl, heteroaryl or heteroarylalkyl; R 4 , R 5 and R 7 are hydrogen or alkyl; R 6 is hydrogen, alkyl or alkenyl; for the treatment of HIV, solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis is disclosed, as well as novel compounds, pharmaceutical compositions comprising them, and the combination of CCR5 antagonists of the invention in combination with antiviral agents useful in the treatment of HIV or agents useful in the treatment of inflammatory diseases.

  本发明涉及CCR5拮抗剂的使用，其化学式为或其药学上可接受的盐，其中R是可选的取代苯基、吡啶基、噻吩基或萘基；R1是氢或烷基；R2是取代苯基、取代杂环芳基、萘基、芴基、二苯甲基或可选取代的苯基或杂环芳基烷基；R3是氢、烷基、烷氧基烷基、环烷基、环烷基烷基或可选取代的苯基、苯基烷基、萘基、萘基烷基、杂环芳基或杂环芳基烷基；R4、R5和R7是氢或烷基；R6是氢、烷基或烯基；用于治疗HIV、固体器官移植排斥、移植物抗宿主病、关节炎、类风湿性关节炎、炎症性肠病、特应性皮炎、牛皮癣、哮喘、过敏或多发性硬化症，以及新型化合物、包含它们的药物组合物，以及本发明的CCR5拮抗剂与用于治疗HIV或治疗炎症性疾病的抗病毒药物的组合。
• US7384944B2
  申请人：——

  公开号：US7384944B2

  公开（公告）日：2008-06-10
• US7825121B2
  申请人：——

  公开号：US7825121B2

  公开（公告）日：2010-11-02
• US8114879B2
  申请人：——

  公开号：US8114879B2

  公开（公告）日：2012-02-14
• Piperazine derivatives useful as CCR5 antagonists
  申请人：Schering Corporation

  公开号：US06391865B1

  公开（公告）日：2002-05-21

  The use of CCR5 antagonists of the formula or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R1 is hydrogen or alkyl; R2 is substituted phenyl, substituted heteroaryl, naphthyl, fluorenyl, diphenylmethyl or optionally substituted phenyl- or heteroaryl-alkyl; R3 is hydrogen, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, or optionally substituted phenyl, phenylalkyl, naphthyl, naphthylalkyl, heteroaryl or heteroarylalkyl; R4, R5 and R7 are hydrogen or alkyl; R6 is hydrogen, alkyl or alkenyl; for the treatment of HIV, solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis is disclosed, as well as novel compounds, pharmaceutical compositions comprising them, and the combination of CCR5 antagonists of the invention in combination with antiviral agents useful in the treatment of HIV or agents useful in the treatment of inflammatory diseases.

  公开了使用CCR5拮抗剂的公式，其中 R是可选择的取代苯基，吡啶基，噻吩基或萘基; R1是氢或烷基; R2是取代苯基，取代杂环基，萘基，芴基，二苯甲基或可选择的取代苯基或杂环基烷基; R3是氢，烷基，烷氧基烷基，环烷基，环烷基烷基，或可选择的取代苯基，苯基烷基，萘基，萘基烷基，杂环基或杂环基烷基; R4，R5和R7是氢或烷基; R6是氢，烷基或烯基; 用于治疗HIV，固体器官移植排斥，移植物宿主病，关节炎，类风湿关节炎，炎症性肠病，特应性皮炎，牛皮癣，哮喘，过敏或多发性硬化症的方法，以及包含它们的新化合物，包含它们的药物组合物，以及CCR5拮抗剂与抗HIV治疗中有用的抗病毒剂或与治疗炎症性疾病中有用的药物的组合。