2β-formyl-3β-(4-chlorophenyl)tropane | 152426-04-5

• 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-formyl-3β-(4-chlorophenyl)tropane
• 英文别名: 3beta-(4-Chlorophenyl)-2beta-formyltropane；(1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbaldehyde
• CAS: 152426-04-5
• 化学式: C₁₅H₁₈ClNO
• 分子量: 263.767
• InChiKey: HOVSGEDRYGNHHA-LJISPDSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2β-formyl-3β-(4-chlorophenyl)tropane 在 platinum on activated charcoal 正丁基锂 、 氢气 作用下， 以 环己烷 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 17.0h， 生成 2β-(2-phenylethyl)-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 草酰氯 、 二异丁基氢化铝 、 二甲基亚砜 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 2β-formyl-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 analogs
  申请人：Mayo Foundation for Medical Education and Research

  公开号：US05268480A1

  公开（公告）日：1993-12-07

  Bioactive cocaine analogs of the general formulae: ##STR1## are provided wherein X' is H or (C.sub.1 -C.sub.5)alkyl, X is H, halo, alkyl, alkoxy, perfluoroalkyl, nitro, alkoxycarbonyl, dialkoxyphosphonyl, acyl, perfluoroacyl, azido (substituted)silyl or (substituted)thio, and Y is H, halo, nitro, amino or (substituted)amino, alkoxycarbonyl, carboxy, alkyl or alkoxy; and the pharmaceutically acceptable salts thereof.

  提供了一些通式为##STR1##的生物活性可卡因类似物，其中X'是H或(C.sub.1-C.sub.5)烷基，X是H，卤素，烷基，烷氧基，全氟烷基，硝基，烷氧羰基，二烷氧基磷酰基，酰基，全氟酰基，偶氮基（取代）硅烷基或（取代）硫代基，Y是H，卤素，硝基，氨基或（取代）氨基，烷氧羰基，羧基，烷基或烷氧基；以及其药学上可接受的盐。
• 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.
• 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
• US5268480A
  申请人：——

  公开号：US5268480A

  公开（公告）日：1993-12-07
• US5391744A
  申请人：——

  公开号：US5391744A

  公开（公告）日：1995-02-21