4-[hydroxy-(3-methoxyphenyl)methyl]-N,N-dimethylbenzamide | 1027738-04-0

• 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-[hydroxy-(3-methoxyphenyl)methyl]-N,N-dimethylbenzamide
• CAS: 1027738-04-0
• 化学式: C₁₇H₁₉NO₃
• 分子量: 285.343
• InChiKey: BAEWNXXFNFGCPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[hydroxy-(3-methoxyphenyl)methyl]-N,N-dimethylbenzamide 在 盐酸 作用下， 以 氯仿 、 水 为溶剂， 反应 12.0h， 以99%的产率得到4-[chloro-(3-methoxyphenyl)methyl]-N,N-dimethylbenzamide
  参考文献：
  名称：

  具有二氮杂三环癸烷骨架的新型δ（δ）阿片受体配体的合成与生物学评价。

  摘要：

  考虑到δ（δ）选择性阿片样物质激动剂化合物SNC-80的有趣的药理学特征，合成了包含两个二氮杂三环癸烷环系统代替二甲基哌嗪核心基序的受构象约束的类似物。 这些化合物表现出亚纳摩尔或低纳摩尔δ阿片受体结合亲和力。取决于二氮杂三环癸烷环上的取代基，这些化合物对δ阿片受体的选择性高于对μ和κ受体的选择性。 在新化合物中，与SNC-80相比，1Aa具有更有趣的生物学特性，具有更高的δ亲和力和选择性。使用离体（分离的小鼠输精管）和体内（甩尾）测定法确认了1Aa的δ受体激动剂谱和抗伤害感受活性。

  DOI：

  10.1016/j.ejmech.2013.09.014
• 作为产物：
  描述：

  4-(3’-甲氧基苯甲酰基)苯甲酸 在 sodium tetrahydroborate 、 氯化亚砜 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 9.0h， 生成 4-[hydroxy-(3-methoxyphenyl)methyl]-N,N-dimethylbenzamide
  参考文献：
  名称：

  具有二氮杂三环癸烷骨架的新型δ（δ）阿片受体配体的合成与生物学评价。

  摘要：

  考虑到δ（δ）选择性阿片样物质激动剂化合物SNC-80的有趣的药理学特征，合成了包含两个二氮杂三环癸烷环系统代替二甲基哌嗪核心基序的受构象约束的类似物。 这些化合物表现出亚纳摩尔或低纳摩尔δ阿片受体结合亲和力。取决于二氮杂三环癸烷环上的取代基，这些化合物对δ阿片受体的选择性高于对μ和κ受体的选择性。 在新化合物中，与SNC-80相比，1Aa具有更有趣的生物学特性，具有更高的δ亲和力和选择性。使用离体（分离的小鼠输精管）和体内（甩尾）测定法确认了1Aa的δ受体激动剂谱和抗伤害感受活性。

  DOI：

  10.1016/j.ejmech.2013.09.014

文献信息

• PHARMACEUTICAL COMPOUNDS
  申请人：LAZZARI Paolo

  公开号：US20110152238A1

  公开（公告）日：2011-06-23

  Diazapolycyclic compounds having affinity for the opioidergic receptors, preferably for the delta opioidergic receptors, with central and/or peripheral activity, having formula: A 1 -D 1 -T 1 (I) wherein: A 1 is a group of formula (II): wherein: R 1 is phenyl wherein one of the ring hydrogen atoms is substituted with a group selected from C(O)R′, C(O)OR′, C(O)NHR′ or C(O)NR 3 R 4 , R′, R 3 and R 4 , being as defined in the application; R 2 is phenyl, optionally substituted D 1 is a diazapolycyclic group T 1 is a group selected from H, alkyl, alkenyl, alkynyl and from the following optionally substituted groups: cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl or heteroarylalkyl, and their hydrates and solvates and pharmaceutically acceptable salts.

  Diazapolycyclic化合物具有对阿片受体的亲和力，优选对δ阿片受体具有中枢和/或外周活性，其化学式为：A1-D1-T1(I)其中：A1是式子(II)的一个基团：其中：R1是苯基，其中一个环氢原子被取代为从C(O)R′、C(O)OR′、C(O)NHR′或C(O)NR3R4中选择的基团，R′、R3和R4的定义如申请中所定义；R2是苯基，可选取代D1是一种二氮杂多环基团T1是选择自H、烷基、烯基、炔基和下列可选取代基团的一种：环烷基、杂环烷基、芳基、杂芳基、环烷烷基、杂环烷烷基、芳基烷基或杂芳基烷基，以及它们的水合物、溶剂化合物和药学上可接受的盐。
• Probes for Narcotic Receptor-Mediated Phenomena. 25. Synthesis and Evaluation of <i>N</i>-Alkyl-Substituted (α-Piperazinylbenzyl)benzamides as Novel, Highly Selective δ Opioid Receptor Agonists
  作者：Yousuke Katsura、Xiaoyan Zhang、Koichi Homma、Kenner C. Rice、Silvia N. Calderon、Richard B. Rothman、Henry I. Yamamura、Peg Davis、Judith L. Flippen-Anderson、Heng Xu、Karen Becketts、Eric J. Foltz、Frank Porreca

  DOI：10.1021/jm970106d

  日期：1997.8.1

  A series of N-alkyl- and N,N-dialkyl-4-[alpha-(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl}benzyl]-benzamides were synthesized and evaluated for binding affinities at mu, delta, and kappa opioid receptor subtypes. Several compounds (2e,f,h,i,m) strongly bound to the delta receptor with IC50 values in the nanomolar range. On the other hand, the binding affinities of these compounds for the mu and kappa receptors were in the micromolar or greater range indicating excellent delta opioid receptor subtype selectivities. In this series, two important structure-activity relationships were found for the delta receptor binding affinity. First, the spatial orientation of the alpha-benzylic position influenced the affinities with the alpha R derivatives 2a-n generally showing more than 10-fold greater affinity than the alpha S derivatives 3a-n. Second, the binding affinities were strongly influenced by the number of alkyl substituents on the amide nitrogen. N-Monoalkylbenzamide derivatives 2b-d showed lower affinity than N,N-dialkylbenzamide derivatives 2e-n, and the N-unsubstituted benzamide derivative 2a had the lowest affinity for the delta receptor in the series. The dramatic effect of the amide group substitution pattern on the binding affinity for the delta receptor strongly suggests that the amide function is an important structural element in the interaction of this series of compounds at the delta receptor. Selective compounds in this series were examined for binding affinity in cloned human mu and delta receptors. The results obtained generally paralleled those from the rat brain binding assay. Compounds 2e,f with potent delta binding affinities and high delta selectivities were shown to be delta agonists with high selectivity by studies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Compound 2f was the most selective compound in the rat brain and GPI/MVD assays with 1755- and 958-fold delta vs mu selectivity, respectively.
• Diazacyclic compounds having affinity for opioid receptors
  申请人：Neuroscienze Pharmaness S.C. A R.L.

  公开号：EP2338889B1

  公开（公告）日：2012-08-29
• Synthesis and biological evaluation of novel delta (δ) opioid receptor ligands with diazatricyclodecane skeletons
  作者：Giovanni Loriga、Paolo Lazzari、Stefania Ruiu、Giorgio Marchese、Ilaria Manca、Gian Luca Casu、Christian Dessì、Gérard Aimè Pinna、Battistina Asproni、Gabriele Murineddu

  DOI：10.1016/j.ejmech.2013.09.014

  日期：2013.11

  pharmacological profile of the delta (δ) selective opioid agonist compound SNC-80, conformationally constrained analogs containing two diazatricyclodecane ring systems in place of dimethylpiperazine core motif were synthesized. The compounds showed subnanomolar or low nanomolar δ opioid receptor binding affinity. Depending upon the substituents on the diazatricyclodecane ring, these compounds displayed varying selectivity

  考虑到δ（δ）选择性阿片样物质激动剂化合物SNC-80的有趣的药理学特征，合成了包含两个二氮杂三环癸烷环系统代替二甲基哌嗪核心基序的受构象约束的类似物。 这些化合物表现出亚纳摩尔或低纳摩尔δ阿片受体结合亲和力。取决于二氮杂三环癸烷环上的取代基，这些化合物对δ阿片受体的选择性高于对μ和κ受体的选择性。 在新化合物中，与SNC-80相比，1Aa具有更有趣的生物学特性，具有更高的δ亲和力和选择性。使用离体（分离的小鼠输精管）和体内（甩尾）测定法确认了1Aa的δ受体激动剂谱和抗伤害感受活性。