tert-butyl 4-(4-hydroxy-1-piperidyl)-4-methyl-piperidine-1-carboxylate | 438208-24-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(4-hydroxy-1-piperidyl)-4-methyl-piperidine-1-carboxylate
• 英文别名: tert-butyl 4-hydroxy-4'-methyl-1,4'-bipiperidine-1'-carboxylate；tert-butyl 4-(4-hydroxypiperidin-1-yl)-4-methylpiperidine-1-carboxylate
• CAS: 438208-24-3
• 化学式: C₁₆H₃₀N₂O₃
• 分子量: 298.426
• InChiKey: YZDIPJNYADNKAX-UHFFFAOYSA-N

物化性质

• 沸点：
  411.4±40.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-hydroxy-1-piperidyl)-4-methyl-piperidine-1-carboxylate 在 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 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 38.0h， 生成 [4-[4-(4-Bromophenoxy)-1-piperidyl]-4-methyl-1-piperidyl]-(2,6-dimethylphenyl)methanone
  参考文献：
  名称：

  Synthesis, SAR, and Biological Evaluation of Oximino-Piperidino-Piperidine Amides. 1. Orally Bioavailable CCR5 Receptor Antagonists with Potent Anti-HIV Activity

  摘要：

  We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl] -4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our initial lead compound as well as the synthesis and SAR studies directed toward optimization of substitution at the phenyl, oxime, and right-hand side amide groups in the oximino-piperidino-piperidine series. Substitutions (4-Br, 4-CF3, 4-OCF3, 4-SO2Me, and 4-Cl) at the phenyl group are well-tolerated, and small alkyl substitutions (Me, Et, Pr-n, Pr-i, and cyclopropyl methyl) at the oxime moiety are preferred for CCR5 antagonism. The 2,6-dimethylnicotinamide N-oxide moiety is the optimal choice for the right-hand side. Several compounds in this series, including compound 1, exhibited excellent antiviral activity in vitro. Compound 1, which has a favorable pharmacokinetic profile in rodents and primates, excellent oral bioavailability, and potent antiviral activity against a wide range of primary HIV-1 isolates, is a potentially promising new candidate for treatment of HIV-1 infection.

  DOI：

  10.1021/jm0200815
• 作为产物：
  描述：

  4-哌啶酮缩乙二醇 在 titanium(IV) isopropylate 、 盐酸 、 sodium tetrahydroborate 、 甲基溴化镁 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 81.0h， 生成 tert-butyl 4-(4-hydroxy-1-piperidyl)-4-methyl-piperidine-1-carboxylate
  参考文献：
  名称：

  Synthesis, SAR, and Biological Evaluation of Oximino-Piperidino-Piperidine Amides. 1. Orally Bioavailable CCR5 Receptor Antagonists with Potent Anti-HIV Activity

  摘要：

  We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl] -4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our initial lead compound as well as the synthesis and SAR studies directed toward optimization of substitution at the phenyl, oxime, and right-hand side amide groups in the oximino-piperidino-piperidine series. Substitutions (4-Br, 4-CF3, 4-OCF3, 4-SO2Me, and 4-Cl) at the phenyl group are well-tolerated, and small alkyl substitutions (Me, Et, Pr-n, Pr-i, and cyclopropyl methyl) at the oxime moiety are preferred for CCR5 antagonism. The 2,6-dimethylnicotinamide N-oxide moiety is the optimal choice for the right-hand side. Several compounds in this series, including compound 1, exhibited excellent antiviral activity in vitro. Compound 1, which has a favorable pharmacokinetic profile in rodents and primates, excellent oral bioavailability, and potent antiviral activity against a wide range of primary HIV-1 isolates, is a potentially promising new candidate for treatment of HIV-1 infection.

  DOI：

  10.1021/jm0200815

文献信息

• New compounds 966
  申请人：Cheng Yun-Xing

  公开号：US20090076078A1

  公开（公告）日：2009-03-19

  Compounds of Formula I, or pharmaceutically acceptable salts thereof: wherein R 2 , R 3 , X, m and n are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

  公式I的化合物或其药用可接受的盐：其中R2、R3、X、m和n的定义如规范中所述，以及包括这些化合物的盐和药物组合物的制备。它们在治疗中很有用，特别是在疼痛管理中。
• Piperidine derivatives useful as CCR5 antagonists
  申请人：Schering Corporation

  公开号：US20040010008A1

  公开（公告）日：2004-01-15

  The present invention provides a compound of the formula 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 , R 2 , R 3 , R 9 , R 10 , A and B are as defined in the specification. The present invention also provides pharmaceutical compositions containing the compound of this invention, and methods of treatment using the compound of this invention. The invention also relates to the use of a combination of a compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of a compound of this invention, alone or in combination with another agent, in the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis.

  本发明提供了一种具有化学式1的化合物或其药用可接受的盐或溶剂，其中R1、R2、R3、R9、R10、A和B如规范中定义。本发明还提供了含有本发明化合物的药物组合物，以及使用本发明化合物进行治疗的方法。该发明还涉及使用本发明化合物与一种或多种抗病毒或其他在治疗人类免疫缺陷病毒（HIV）中有用的药物的组合。该发明还涉及使用本发明化合物单独或与另一种药物组合在治疗实体器官移植排斥、移植物宿主病、关节炎、类风湿性关节炎、炎症性肠病、特应性皮炎、银屑病、哮喘、过敏或多发性硬化症中。
• MUSCARINIC RECEPTOR AGONISTS, COMPOSITIONS, METHODS OF TREATMENT THEREOF, AND PROCESSES FOR PREPARATION THEREOF 177
  申请人：Cheng Yun-Xing

  公开号：US20090221567A1

  公开（公告）日：2009-09-03

  Compounds of Formula I, or pharmaceutically acceptable salts thereof: wherein Y, X, A, R 1 , R 2 , m, p, and q are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

  式I的化合物，或其药用可接受的盐：其中Y、X、A、R1、R2、m、p和q的定义如规范中所述，以及包括这些化合物的盐和药物组合物已经准备好。它们在治疗中很有用，特别是在疼痛管理中。
• [EN] PIPERIDINE DERIVATIVES AS AGONISTS OF MUSCARINIC RECEPTORS<br/>[FR] DÉRIVÉS DE PIPÉRIDINE EN TANT QU'AGONISTES DE RÉCEPTEURS MUSCARINIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2009034380A1

  公开（公告）日：2009-03-19

  Compounds of Formula (I), or pharmaceutically acceptable salts thereof: wherein R2, R3, X, m and n are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

  化学式(I)的化合物，或其药学上可接受的盐：其中R2、R3、X、m和n的定义如规范中所述，以及包括化合物的盐和制药组合物已经被制备。它们在治疗中有用，特别是在疼痛管理方面。
• CHEMICAL COMPOUNDS
  申请人：Barber Christopher Gordon

  公开号：US20090124635A1

  公开（公告）日：2009-05-14

  The present invention provides compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , m and n are as defined hereinabove. The compounds of the present invention are modulators, especially antagonists, of the activity of chemokine CCR5 receptors. Modulators of the CCR5 receptor may be useful in the treatment of various inflammatory diseases and conditions, and in the treatment of infection by HIV and genetically related retroviruses.

  本发明提供式（I）的化合物，其中R1，R2，R3，R4，R5，m和n如上所定义。本发明的化合物是趋化因子CCR5受体活性的调节剂，特别是拮抗剂。CCR5受体的调节剂可用于治疗各种炎症性疾病和情况，并用于治疗HIV和遗传相关逆转录病毒的感染。