2β-(hydroxymethyl)-3β-(4-chlorophenyl)tropane | 150583-23-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 2β-(hydroxymethyl)-3β-(4-chlorophenyl)tropane
• 英文别名: 2β-hydroxymethyl-3β-(4-chlorophenyl)tropane；3β-(4-chlorophenyl)-2β-hydroxymethyltropane；3β-[4-Chlorophenyl]-2β-hydroxymethyltropane；[(1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl]methanol
• CAS: 150583-23-6
• 化学式: C₁₅H₂₀ClNO
• 分子量: 265.783
• InChiKey: HPEJYVLWXPBTEG-LJISPDSOSA-N

物化性质

• 沸点：
  362.6±42.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2β-(hydroxymethyl)-3β-(4-chlorophenyl)tropane 在 正丁基锂 、 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 2β-vinyl-3β-(4-chlorophenyl)tropane
  参考文献：
  名称：

  Chemistry and Biology of the 2.beta.-Alkyl-3.beta.-phenyl Analogs of Cocaine: Subnanomolar Affinity Ligands That Suggest a New Pharmacophore Model at the C-2 Position

  摘要：

  A series of 2 beta-alkyl-3 beta-phenyltropanes (i.e., the 2 beta-alkyl analogues of the WIN series) were prepared as analogues of cocaine and tested for their ability to displace [H-3]mazindol binding and to inhibit high-affinity dopamine uptake into striatal nerve endings (synaptosomes). These 2 beta-alkyl analogues were readily prepared in optically pure form starting from cocaine by proceeding through the 2 beta-phenyl-bearing aldehyde 6 as a key intermediate. Wittig reaction of 6 with the appropriate phosphorane and hydrogenation delivered the final products. Ah new compounds with the exception of 8e were found to exhibit nanomolar or subnanomolar affinity for the cocaine binding site in the rat striatum. These results are in apparent opposition to the binding model previously proposed which suggests a hydrogen bond donor-acceptor interaction to be present in the vicinity of the C-2 substituent. Taken together with our previous reports and recent findings from other laboratories, we suggest a new pharmacophore model in which 2 beta-substituents lacking H-bond accepters enhance affinity to the binding site through hydrophobic interactions. The new SAR data contained herein may be relevant to the design of possible cocaine antagonists.

  DOI：

  10.1021/jm00016a012
• 作为产物：
  描述：

  脱水芽子碱甲基酯甲磺酸盐 在 二异丁基氢化铝 作用下， 以 乙醚 、 正己烷 、 甲苯 为溶剂， 反应 2.5h， 生成 2β-(hydroxymethyl)-3β-(4-chlorophenyl)tropane
  参考文献：
  名称：

  Chemistry and Biology of the 2.beta.-Alkyl-3.beta.-phenyl Analogs of Cocaine: Subnanomolar Affinity Ligands That Suggest a New Pharmacophore Model at the C-2 Position

  摘要：

  A series of 2 beta-alkyl-3 beta-phenyltropanes (i.e., the 2 beta-alkyl analogues of the WIN series) were prepared as analogues of cocaine and tested for their ability to displace [H-3]mazindol binding and to inhibit high-affinity dopamine uptake into striatal nerve endings (synaptosomes). These 2 beta-alkyl analogues were readily prepared in optically pure form starting from cocaine by proceeding through the 2 beta-phenyl-bearing aldehyde 6 as a key intermediate. Wittig reaction of 6 with the appropriate phosphorane and hydrogenation delivered the final products. Ah new compounds with the exception of 8e were found to exhibit nanomolar or subnanomolar affinity for the cocaine binding site in the rat striatum. These results are in apparent opposition to the binding model previously proposed which suggests a hydrogen bond donor-acceptor interaction to be present in the vicinity of the C-2 substituent. Taken together with our previous reports and recent findings from other laboratories, we suggest a new pharmacophore model in which 2 beta-substituents lacking H-bond accepters enhance affinity to the binding site through hydrophobic interactions. The new SAR data contained herein may be relevant to the design of possible cocaine antagonists.

  DOI：

  10.1021/jm00016a012

文献信息

• Cocaine receptor binding ligands
  申请人：Research Triangle Institute

  公开号：US05736123A1

  公开（公告）日：1998-04-07

  Novel compounds useful as intermediates in the synthesis of compounds having high affinity for specific cocaine receptors in the brain have the formula ##STR1## wherein R is (CH.sub.2).sub.n CH.sub.2 Y, and wherein Y is H or F, X is a pharmaceutically acceptable anion, and wherein Sn (R.sup.1, R.sup.2, R.sup.3) is ortho, meta or para and wherein R.sup.1, R.sup.2, R.sup.3 are independently alkyl of 1-6 carbon atoms and n is an integer of 0-5.

  具有高亲和力的化合物在大脑中特定可卡因受体合成中作为中间体有用，其化学式为##STR1##其中R为(CH.sub.2).sub.n CH.sub.2 Y，Y为H或F，X为药用可接受的阴离子，Sn(R.sup.1, R.sup.2, R.sup.3)为邻位、间位或对位，R.sup.1, R.sup.2, R.sup.3独立地为1-6个碳原子的烷基，n为0-5的整数。
• Synthesis and receptor binding properties of 2β-alkynyl and 2β-(1,2,3-triazol)substituted 3β-(substituted phenyl)tropane derivatives
  作者：Chunyang Jin、Hernán A. Navarro、F. Ivy Carroll

  DOI：10.1016/j.bmc.2008.04.008

  日期：2008.5

  A series of 2b-alkynyl and 2b-(1,2,3-triazol) substituted 3b-(substituted phenyl) tropanes were synthesized and evaluated for affinities at dopamine, serotonin, and norepinephrine membrane transporters using competitive radioligand binding assays. All tested compounds were found to exhibit nanomolar or subnanomolar affinity for the dopamine transporter (DAT). One of the most potent and selective compounds in the series was 3b-(4-chlorophenyl)-2b-(4-nitrophenylethynyl) tropane (10c) that possessed an IC50 value of 0.9 nM at the DAT and K-i values of 230 nM and 620 nM at the norepinephrine transporter ( NET) and serotonin transporter (5-HTT), respectively. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxymethyl)-3β-aryltropane Derivatives
  作者：Lifen Xu、Santosh S. Kulkarni、Sari Izenwasser、Jonathan L. Katz、Theresa Kopajtic、Stacey A. Lomenzo、Amy Hauck Newman、Mark L. Trudell

  DOI：10.1021/jm030430a

  日期：2004.3.1

  3beta-Aryltropane analogues wherein the 2-position was substituted with various diarylmethoxy-alkyl groups were synthesized and evaluated for binding at the dopamine transporter (DAT), serotonin transporter (SERT), norepinephrine transporter (NET), and muscarinic (M-1) receptors. The 2beta-analogues 9a-i generally demonstrated high to moderate binding affinities (K-i = 34112 nM) at the DAT with good selectivity over SERT, NET, and M-1 receptors. Alternatively, the 2alpha-isomers 10a-i were 10-fold less potent at the DAT with poor selectivity over SERT. These SAR studies provide further evidence for the varied binding requirements of structurally diverse tropane-based ligands and support future studies to elucidate DAT binding requirements in relation to cocaine-like behavioral endpoints.
• Structure-activity relationship studies of cocaine: replacement of the C-2 ester group by vinyl argues against hydrogen-bonding and provides an esterase-resistant, high-affinity cocaine
  作者：Alan P. Kozikowski、Marinella Roberti、Li Xiang、John S. Bergmann、Patrick M. Callahan、Kathryn A. Cunningham、Kenneth M. Johnson

  DOI：10.1021/jm00103a015

  日期：1992.12
• Cocaine Receptor Binding Ligands
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：EP0644775B1

  公开（公告）日：1999-08-04