(4'-hydroxy-3'-methoxyphenyl)-N-<2-(4-hydroxy-3-methoxyphenyl)ethyl>acetamide | 138645-09-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (4'-hydroxy-3'-methoxyphenyl)-N-<2-(4-hydroxy-3-methoxyphenyl)ethyl>acetamide
• 英文别名: 2-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acetamide
• CAS: 138645-09-7
• 化学式: C₁₈H₂₁NO₅
• 分子量: 331.368
• InChiKey: XBTVSTDRTRTRQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  88
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4'-hydroxy-3'-methoxyphenyl)-N-<2-(4-hydroxy-3-methoxyphenyl)ethyl>acetamide 在 sodium tetrahydroborate 、 potassium carbonate 、 三氯氧磷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 6-methoxy-1-[(3-methoxy-4-propoxyphenyl)methyl]-7-propoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor

  摘要：

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.

  DOI：

  10.1021/cn500330v
• 作为产物：
  描述：

  4-(2-氨基乙基)-2-甲氧基苯酚 、 高香草酸 反应 2.0h， 以59.3%的产率得到(4'-hydroxy-3'-methoxyphenyl)-N-<2-(4-hydroxy-3-methoxyphenyl)ethyl>acetamide
  参考文献：
  名称：

  哺乳动物生物碱：合成和Ö（的-methylation小号） -和（- [R）-3'- hydroxycoclaurine及其Ñ甲基化的类似物与小号-adenosyl -1- [甲基- 14 C]蛋氨酸的存在哺乳动物儿茶酚ö -methyltransferase

  摘要：

  Ó光学活性3'- hydroxycoclaurines的-Methylation图3a和3b中和的Ñ甲基化的类似物5a，5b中与小号-adenosyl -1- [甲基- 14 C]在哺乳动物的存在甲硫氨酸COMT研究了体外。的Ñ -未被取代的（1小号） -和（1 - [R ）-异构体3A和3B，分别得到相应几乎等量Ñ -norreticuline 4和Ñ -nororientaline 19，除了两种未知的副产物（参见图和表1）。所述Ñ甲基化的（1个小号） -异喹啉5a中，在另一方面，在很大程度上得到（小号）-orientaline（（小号） - 19），而几乎等量混合物（[R）-reticuline（图6b）和（- [R ）从（1R）-对映异构体5b获得-原喹啉（（R）-19）。异喹啉3a，b和5a，b通过Bischler-Napieralski环化制备O-苄基保护的异喹啉10（方案1）

  DOI：

  10.1002/hlca.19910740704

文献信息

• [EN] TETRAHYDROPROTOBERBINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS TÉTRAHYDROPROTOBERBINES ET LEURS UTILISATIONS DANS LE TRAITEMENT DE MALADIES NEUROLOGIQUES, PSYCHIATRIQUES ET NEURODÉGÉNÉRATIVES
  申请人：MILLER JAMES JACKSON

  公开号：WO2013020229A1

  公开（公告）日：2013-02-14

  Tetrahydroprotoberbine (THPB) compounds and their use in the treatment of neurological, psychiatric and neurodegenerative diseases is provided. The compounds include d-govadine, l-govadine and racemic govadine, as well as d-THPBs of general formula (I). Enantioselective processes for preparing compounds of formula (I), and d- and l-govadine are also provided.(I)

  提供了Tetrahydroprotoberbine (THPB)化合物及其在治疗神经系统、精神疾病和神经退行性疾病中的用途。这些化合物包括d-govadine、l-govadine和racemic govadine，以及通式(I)的d-THPBs。还提供了制备通式(I)化合物和d-、l-govadine的对映选择性过程。(I)
• TETRAHYDROPROTOBERBINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND NEURODEGENERATIVE DISEASES
  申请人：MILLER James Jackson

  公开号：US20150306092A1

  公开（公告）日：2015-10-29

  Tetrahydroprotoberbine (THPB) compounds and their use in the treatment of neurological, psychiatric and neurodegenerative diseases is provided. The compounds include d-govadine, l-govadine and racemic govadine, as well as d-THPBs of general formula (I). Enantioselective processes for preparing compounds of formula (I), and d- and l-govadine are also provided.(I)
• US9526721B2
  申请人：——

  公开号：US9526721B2

  公开（公告）日：2016-12-27
• Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor
  作者：David A. Perrey、Nadezhda A. German、Ann M. Decker、David Thorn、Jun-Xu Li、Brian P. Gilmour、Brian F. Thomas、Danni L. Harris、Scott P. Runyon、Yanan Zhang

  DOI：10.1021/cn500330v

  日期：2015.4.15

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.
• Mammalian alkaloids: Synthesis andO-methylation of (S)- and (R)-3?-hydroxycoclaurine and theirN-methylated analogues withS-adenosyl-L-[methyl-14C]methionine in presence of mammalian catecholO-methyltransferase
  作者：Xiao-Shu He、Dragana Tadi?、Malgorzata Brzostowska、Arnold Brossi、Maureen Bell、Cyrus Creveling

  DOI：10.1002/hlca.19910740704

  日期：1991.10.30

  3′-hydroxycoclaurines 3a and 3b and of the N-methylated analogs 5a,b with S-adenosyl-L-[methyl-14C]methionine in presence of mammalian COMT was investigated in vitro. The N-unsubstituted (1S)- and (1R )-isomers 3a and 3b, respectively, afforded almost equal amounts of the corresponding N-norreticuline 4 and N-nororientaline 19, besides two unknown by-products (see Fig. and Table 1). The N-methylated (1S)-isoquinoline

  Ó光学活性3'- hydroxycoclaurines的-Methylation图3a和3b中和的Ñ甲基化的类似物5a，5b中与小号-adenosyl -1- [甲基- 14 C]在哺乳动物的存在甲硫氨酸COMT研究了体外。的Ñ -未被取代的（1小号） -和（1 - [R ）-异构体3A和3B，分别得到相应几乎等量Ñ -norreticuline 4和Ñ -nororientaline 19，除了两种未知的副产物（参见图和表1）。所述Ñ甲基化的（1个小号） -异喹啉5a中，在另一方面，在很大程度上得到（小号）-orientaline（（小号） - 19），而几乎等量混合物（[R）-reticuline（图6b）和（- [R ）从（1R）-对映异构体5b获得-原喹啉（（R）-19）。异喹啉3a，b和5a，b通过Bischler-Napieralski环化制备O-苄基保护的异喹啉10（方案1）