4-(5-((2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propyl)amino)pentyl)benzene-1,2-diol | 1612146-64-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-(5-((2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propyl)amino)pentyl)benzene-1,2-diol
• 英文别名: 4-(5-((2-Amino-4,5,6,7-tetrahydrobenzo [d]thiazol-6-yl)(propyl)amino)pentyl)benzene-1,2-diol；4-[5-[(2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)-propylamino]pentyl]benzene-1,2-diol
• CAS: 1612146-64-1
• 化学式: C₂₁H₃₁N₃O₂S
• 分子量: 389.562
• InChiKey: CVHFBMSYCSPBIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-(4-hydroxy-3-methoxyphenyl)pentanal 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 43.0h， 生成 4-(5-((2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propyl)amino)pentyl)benzene-1,2-diol
  参考文献：
  名称：

  Novel multifunctional dopamine D 2 /D 3 receptors agonists with potential neuroprotection and anti-alpha synuclein protein aggregation properties

  摘要：

  Our ongoing drug development endeavor to design compounds for symptomatic and neuroprotective treatment of Parkinson's disease (PD) led us to carry out a structure activity relationship study based on dopamine agonists pramipexole and 5-OHDPAT. Our goal was to incorporate structural elements in these agonists in a way to preserve their agonist activity while producing inhibitory activity against aggregation of alpha-synuclein protein. In our design we appended various catechol and related phenol derivatives to the parent agonists via different linker lengths. Structural optimization led to development of several potent agonists among which (-)-8a, (-)-14 and (-)-20 exhibited potent neuroprotective properties in a cellular PD model involving neurotoxin 6-OHDA. The lead compounds (-)-8a and (-)-14 were able to modulate aggregation of alpha-synuclein protein efficiently. Finally, in an in vivo PD animal model, compound (-)-8a exhibited efficacious anti-parkinsonian effect. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.08.021

文献信息

• [EN] NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] AGENTS NEUROPROTECTEURS POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：UNIV WAYNE STATE

  公开号：WO2014085600A1

  公开（公告）日：2014-06-05

  A compound having formula I is useful for treating a neurodegenerative disease: I, R1 is an C1-12 organyl group; is a C1-12 heterocyclic ring system containing 5 to 12 ring atoms and up to three heteroatoms individually selected from the group consisting of N, O, S, and Se; R2 are C1-12 organyl groups; R7, R8 are each independently, hydrogen (H), hydroxyl, oxo (i.e., carbonyl), C1-8 alkyl, C1-8 alkoxyl, C2-8 alkenyl, C2-10 alkynyl, C5-7 cycloalkyl, C5-7 cycloalkenyl, halo, C1-4 aldehyde, or -NR4q where R4 is H, C1-8 alkyl, C2-8 alkenyl, C4-8 cycloalkyl, C4-8 cycloalkenyl, or C6-10 aryl; o is 0, 1, 2, 3, or 4; A is a C6-12 aryl group, C5-12 heteroaryl group, or an optionally substituted 3-hydroxypyridin- 4(1H)-one; p is an integer from 1 to 6; and Zm is absent or a divalent linking moiety; and m is an integer representing the number of time Z is repeated.

  化合物I的化学式对治疗神经退行性疾病有用：I，其中R1是一个C1-12有机基团；是一个含有5到12个环原子和最多三个异原子（分别选自N、O、S和Se）的C1-12杂环环系统；R2是C1-12有机基团；R7、R8分别独立地是氢（H）、羟基、羰基（即酮基）、C1-8烷基、C1-8烷氧基、C2-8烯基、C2-10炔基、C5-7环烷基、C5-7环烯基、卤素、C1-4醛基，或-NR4q，其中R4是H、C1-8烷基、C2-8烯基、C4-8环烷基、C4-8环烯基或C6-10芳基；o为0、1、2、3或4；A是一个C6-12芳基、C5-12杂芳基，或一个可选择地取代的3-羟基吡啶-4(1H)-酮；p是一个从1到6的整数；Zm不存在或是一个二价连接基团；m是表示Z重复次数的整数。
• NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：WAYNE STATE UNIVERSITY

  公开号：US20150299180A1

  公开（公告）日：2015-10-22

  A compound having formula I is useful for treating a neurodegenerative disease: R 1 is an C 1-12 organyl group; is a C 1-12 heterocyclic ring system containing 5 to 12 ring atoms and up to three heteroatoms individually selected from the group consisting of N, O, S, and Se; R 2 are C 1-12 organyl groups; R 7 , R 8 are each independently, hydrogen (H), hydroxyl, oxo (i.e., carbonyl), C 1-8 alkyl, C 1-8 alkoxyl, C 2-8 alkenyl, C 2-10 alkynyl, C 5-7 cycloalkyl, C 5-7 cycloalkenyl, halo, C 1-4 aldehyde, or —NR 4 q where R 4 is H, C 1-8 alkyl, C 2-8 alkenyl, C 4-8 cycloalkyl, C 4-8 cycloalkenyl, or C 6-10 aryl; o is 0, 1, 2, 3, or 4; A is a C 6-12 aryl group, C 5-12 heteroaryl group, or an optionally substituted 3-hydroxypyridin-4(1H)-one; p is an integer from 1 to 6; and Z m is absent or a divalent linking moiety; and m is an integer representing the number of time Z is repeated.

  化合物I的化学式对治疗神经退行性疾病有用：R1是C1-12有机基团；是含有5到12个环原子和最多三个异原子（选自N、O、S和Se的群体）的C1-12杂环环系统；R2是C1-12有机基团；R7、R8各自独立地是氢（H）、羟基、氧代（即羰基）、C1-8烷基、C1-8烷氧基、C2-8烯基、C2-10炔基、C5-7环烷基、C5-7环烯基、卤素、C1-4醛基或—NR4q，其中R4是H、C1-8烷基、C2-8烯基、C4-8环烷基、C4-8环烯基或C6-10芳基；o为0、1、2、3或4；A是C6-12芳基、C5-12杂芳基或可选地取代的3-羟基吡啶-4（1H）-酮；p为1到6的整数；Zm是缺席或二价连接基；m是代表Z重复次数的整数。
• Neuroprotective agents for treatment of neurodegenerative diseases
  申请人：WAYNE STATE UNIVERSITY

  公开号：US10125127B2

  公开（公告）日：2018-11-13

  A compound having formula I is useful for treating a neurodegenerative disease: R1 is an C1-12 organyl group; is a C1-12 heterocyclic ring system containing 5 to 12 ring atoms and up to three heteroatoms individually selected from the group consisting of N, O, S, and Se; R2 are C1-12 organyl groups; R7, R8 are each independently, hydrogen (H), hydroxyl, oxo (i.e., carbonyl), C1-8 alkyl, C1-8 alkoxyl, C2-8 alkenyl, C2-10 alkynyl, C5-7 cycloalkyl, C5-7 cycloalkenyl, halo, C1-4 aldehyde, or —NR4q where R4 is H, C1-8 alkyl, C2-8 alkenyl, C4-8 cycloalkyl, C4-8 cycloalkenyl, or C6-10 aryl; o is 0, 1, 2, 3, or 4; A is a C6-12 aryl group, C5-12 heteroaryl group, or an optionally substituted 3-hydroxypyridin-4(1H)-one; p is an integer from 1 to 6; and Zm is absent or a divalent linking moiety; and m is an integer representing the number of time Z is repeated.

  具有式 I 的化合物可用于治疗神经退行性疾病： R1 是一个 C1-12 的羰基； 是含有 5 至 12 个环原子和最多三个杂原子的 C1-12 杂环系统，这些杂原子单独选自 N、O、S 和 Se 组成的组； R2 是 C1-12 烯丙基基团； R7、R8 各自独立地为氢（H）、羟基、氧代（即羰基）、C1-8 烷基、C1-8 烷氧基、C2-8 烯基、C2-10 炔基、C5-7 环烷基、C5-7 环烯基、卤代、C1-4 醛或 -NR4q 其中 R4 为 H、C1-8 烷基、C2-8 烯基、C4-8 环烷基、C4-8 环烯基或 C6-10 芳基； o 是 0、1、2、3 或 4； A 是 C6-12 芳基、C5-12 杂芳基或任选取代的 3-羟基吡啶-4(1H)-酮； p 是 1 至 6 的整数；以及 Zm 不存在或为二价连接基团；以及 m 是代表 Z 重复次数的整数。
• NEUROPROTECTIVE AGENTS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Wayne State University

  公开号：EP2925755B1

  公开（公告）日：2021-09-08
• Novel multifunctional dopamine D 2 /D 3 receptors agonists with potential neuroprotection and anti-alpha synuclein protein aggregation properties
  作者：Dan Luo、Horrick Sharma、Deepthi Yedlapudi、Tamara Antonio、Maarten E.A. Reith、Aloke K. Dutta

  DOI：10.1016/j.bmc.2016.08.021

  日期：2016.11

  Our ongoing drug development endeavor to design compounds for symptomatic and neuroprotective treatment of Parkinson's disease (PD) led us to carry out a structure activity relationship study based on dopamine agonists pramipexole and 5-OHDPAT. Our goal was to incorporate structural elements in these agonists in a way to preserve their agonist activity while producing inhibitory activity against aggregation of alpha-synuclein protein. In our design we appended various catechol and related phenol derivatives to the parent agonists via different linker lengths. Structural optimization led to development of several potent agonists among which (-)-8a, (-)-14 and (-)-20 exhibited potent neuroprotective properties in a cellular PD model involving neurotoxin 6-OHDA. The lead compounds (-)-8a and (-)-14 were able to modulate aggregation of alpha-synuclein protein efficiently. Finally, in an in vivo PD animal model, compound (-)-8a exhibited efficacious anti-parkinsonian effect. (C) 2016 Elsevier Ltd. All rights reserved.