4-[2-(4-bromophenyl)-1,3-dioxolan-2-yl]-piperidine | 203186-02-1

• 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: 4-[2-(4-bromophenyl)-1,3-dioxolan-2-yl]-piperidine
• 英文别名: 4-[2-(4-Bromophenyl)-1,3-dioxolan-2-yl]piperidine
• CAS: 203186-02-1
• 化学式: C₁₄H₁₈BrNO₂
• 分子量: 312.206
• InChiKey: RKCFVYYSKVELRI-UHFFFAOYSA-N

物化性质

• 沸点：
  391.7±42.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[2-(4-bromophenyl)-1,3-dioxolan-2-yl]-piperidine 在 titanium(IV) isopropylate 、 盐酸 、 sodium tetrahydroborate 、 甲基溴化镁 、 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 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 54.0h， 生成 [4-[4-[(4-Bromophenyl)-hydroxy-methyl]-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：

  在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 生成 4-[2-(4-bromophenyl)-1,3-dioxolan-2-yl]-piperidine
  参考文献：
  名称：

  MUSCARINIC ANTAGONISTS

  摘要：

  公开号：

  EP1214299B1

文献信息

• Chemokine receptor binding compounds
  申请人：Zhou Yuanxi

  公开号：US20050277670A1

  公开（公告）日：2005-12-15

  The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. These compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  本发明涉及化学因子受体结合化合物、制药组合物及其使用。更具体地，本发明涉及化学因子受体活性调节剂，优选为CCR5的调节剂。这些化合物表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护作用。
• PIPERIDINE DERIVATIVES USEFUL AS CCR5 ANTAGONISTS
  申请人：SCHERING CORPORATION

  公开号：EP1175402B1

  公开（公告）日：2005-07-20
• Design and synthesis of pyridin-2-yloxymethylpiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic (R5) HIV-1 replication
  作者：Renato Skerlj、Gary Bridger、Yuanxi Zhou、Elyse Bourque、Jonathan Langille、Maria Di Fluri、David Bogucki、Wen Yang、Tongshuang Li、Letian Wang、Susan Nan、Ian Baird、Markus Metz、Marilyn Darkes、Jean Labrecque、Gloria Lau、Simon Fricker、Dana Huskens、Dominique Schols

  DOI：10.1016/j.bmcl.2011.02.058

  日期：2011.4

  A novel series of CCR5 antagonists were identified based on the redesign of Schering C. An SAR was established based on inhibition of CCR5 (RANTES) binding and these compounds exhibited potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of 4-[(<i>Z</i>)-(4-Bromophenyl)- (ethoxyimino)methyl]-1‘-[(2,4-dimethyl-3- pyridinyl)carbonyl]-4‘-methyl-1,4‘- bipiperidine <i>N</i>-Oxide (SCH 351125):  An Orally Bioavailable Human CCR5 Antagonist for the Treatment of HIV Infection
  作者：Anandan Palani、Sherry Shapiro、John W. Clader、William J. Greenlee、Kathleen Cox、Julie Strizki、Michael Endres、Bahige M. Baroudy

  DOI：10.1021/jm015526o

  日期：2001.10.1

  Structure-activity studies on piperidino-piperidine 3 led to the discovery of SCH 351125 (1), a selective CCR5 antagonist with potent activity against RANTES binding (K-i = 2 nM), which possesses subnanomolar activity in blocking viral entry and has excellent antiviral potency versus a panel of primary HIV-1 viral isolates. Compound 1, which has good oral bioavailability in rats, dogs, and monkeys, is proposed as a potential therapeutic agent for the treatment of HIV-1 and has entered human clinical trials.
• Isopropyl amide derivatives of potent and selective muscarinic M2 receptor antagonists
  作者：Anandan Palani、Sundeep Dugar、John W. Clader、William J. Greenlee、Vilma Ruperto、Ruth A. Duffy、Jean E. Lachowicz

  DOI：10.1016/j.bmcl.2004.01.033

  日期：2004.4

  Low molecular weight amide derivatives were synthesized and evaluated as M-2 receptor antagonists for the treatment of Alzheimer's disease. Isopropyl amides 19 and 31 are highly potent, selective and low molecular weight M-2 receptor antagonists with structural features different from our clinical candidate 1. (C) 2004 Elsevier Ltd. All rights reserved.