2-(2,4-dichlorophenyl)-3-(dimethylamino)acrolein

• 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: 2-(2,4-dichlorophenyl)-3-(dimethylamino)acrolein
• 英文别名: 2-(2,4-chlorophenyl)-3-(dimethylamino)acrolein；(Z)-2-(2,4-dichlorophenyl)-3-(dimethylamino)-2-propenal；(Z)-2-(2,4-dichlorophenyl)-3-(dimethylamino)prop-2-enal
• 化学式: C₁₁H₁₁Cl₂NO
• 分子量: 244.12
• InChiKey: AMURNPAKOWBJIB-SOFGYWHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 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：

  纳曲酮 、 2-(2,4-dichlorophenyl)-3-(dimethylamino)acrolein 在 乙酸铵 、 溶剂黄146 作用下， 反应 20.0h， 以27%的产率得到17-(cyclopropylmethyl)-6,7-didehydro-3,14-dihydroxy-4,5α-epoxy-5'-(2,4-dichlorophenyl)pyrido[2',3':6,7]morphinan
  参考文献：
  名称：

  Novel ligands for the opioid receptors: synthesis and structure–activity relationships among 5′-aryl and 5′-heteroaryl 17-cyclopropylmethyl-4,5α-epoxypyrido[2′,3′:6,7]morphinans

  摘要：

  A series of pyridomorphinans possessing an aryl (10a-s) or heteroaryl (11a-h) substituent at the 5'-position of the pyridine ring of 17-cyclopropylmethyl-4,5alpha-epoxypyrido[2,3:6,7]morphinan was synthesized and evaluated for binding and functional activity at the opioid delta, mu, and kappa receptors. All of these pyridomorphinans bound with higher affinity at the delta site than at mu or kappa sites. The binding data on isomeric compounds revealed that there exists greater bulk tolerance for substituents placed at the o-position of the phenyl ring than at m- or p-positions. Among the ligands examined, the 2-chlorophenyl (101), 2-nitrophenyl (10n), 2-pyridyl (11a), and 4-quinolinyl (11g) compounds bound to the delta receptor with subnanomolar affinity. Compound 10c with the p-tolyl substituent displayed the highest mu/delta selectivity (ratio = 42) whereas compound 101 with the 2-chlorophenyl substituent displayed the highest kappa/delta selectivity (ratio 23). At 10 muM concentration, the in vitro functional activity determined using [S-35]GTP-gamma-S binding assays showed that all of the compounds were antagonists devoid of any significant agonist activity at the delta, mu, and kappa receptors. Antagonist potency determinations of three selected ligands revealed that the p-tolyl compound 10c is a potent 6 selective antagonist. In the [S-35]GTP-7-S assays this compound had a functional antagonist K-i value of 0.2, 4.52, and 7.62 nM at the delta, mu, and kappa receptors, respectively. In the smooth muscle assays 10c displayed delta antagonist potency with a K-e value of 0.88 nM. As an antagonist, it was 70-fold more potent at the 6 receptors in the MVD than at the mu receptors in the GPI. The in vitro delta antagonist profile of this pyridomorphinan 10c resembles that of the widely used delta selective antagonist ligand naltrindole. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00432-2

文献信息

• Identification of Opioid Ligands Possessing Mixed μ Agonist/δ Antagonist Activity among Pyridomorphinans Derived from Naloxone, Oxymorphone, and Hydropmorphone
  作者：Subramaniam Ananthan、Naveen K. Khare、Surendra K. Saini、Lainne E. Seitz、Jeffrey L. Bartlett、Peg Davis、Christina M. Dersch、Frank Porreca、Richard B. Rothman、Edward J. Bilsky

  DOI：10.1021/jm030311v

  日期：2004.3.1

  profile of mixed micro agonist/delta antagonist activity in vitro and in vivo. In a repeated administration paradigm in which the standard micro agonist morphine produces significant tolerance, repeated administration of the micro agonist/delta antagonist ligand 7h produced no tolerance. These results indicate that appropriate molecular manipulations of the morphinan templates could provide ligands with

  合成了一系列衍生自纳洛酮，羟吗啡酮和氢吗啡酮（7a-k）的吡啶基吗啡喃，并使用放射性配体结合测定法评估了在脑膜中阿片样物质δ，微和κ受体上的结合亲和力，并在体外使用[[ 35）S]GTP-γ-S在脑组织中的结合测定以及使用豚鼠回肠（GPI）和小鼠输精管（MVD）平滑肌制备物的生物测定。具有羟吗啡酮和氢吗啡酮骨架的吡啶环未取代的吡啶基吗啡喃在微和δ受体上显示出几乎相等的结合亲和力。它们在κ位点的亲和力比它们在微位点和δ位点的结合亲和力小近10倍。在5'处引入芳基取代基 吡啶环上的α-位改善了δ位点的结合亲和力，同时降低了微位点的结合亲和力。几乎所有在吗啡喃部分的17位具有N-甲基，在吗啡喃部分的14位具有或不具有羟基的配体在微受体上均表现出激动剂活性，具有不同的效能和功效。在[（35）S]GTP-γ-S结合试验中，大多数这些吡啶基吗啡喃在δ和κ受体上没有任何显着的激动剂活性，但在δ受体上表现
• PYRIDOMORPHINANS, PYRIDAZINOMORPHINANS AND USE THEREOF
  申请人：Southern Research Institute

  公开号：EP1660088A2

  公开（公告）日：2006-05-31
• EP1660088A4
  申请人：——

  公开号：EP1660088A4

  公开（公告）日：2009-04-29
• Pyridomorphinans, Pyridazinomorphinans and Use Thereof
  申请人：Ananthan Subramaniam

  公开号：US20080194568A1

  公开（公告）日：2008-08-14

  Compounds represented by formula (I) wherein R is C 1-6 cycloalkylalkyl; or C 3-6 alkenyl; R′ is H or C 1-6 alkyl; X is H or OH; Y is alkyl, cycloalkyl, aryl, heteroaryl or aroyl; and Z is CH or N; provided that X is H, when Z is CH and R is C 4 cycloalkylalkyl or C 4 alkenyl; prodrugs thereof; and pharmaceutically acceptable salts thereof are provided. Compounds of the above formula are useful as analgesics for treating pain; as immunomodulators, to modulate the behavioral effects of drugs of abuse and to modulate the development of tolerance and dependence of μ agonists.
• US7541364B2
  申请人：——

  公开号：US7541364B2

  公开（公告）日：2009-06-02