4-chloro-2-(7-bromoheptyl)-5-<4-<2-(2-methoxyphenoxy)ethyl>-1-piprazinyl>-3(2H)-pyridazinone | 234090-67-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-chloro-2-(7-bromoheptyl)-5-<4-<2-(2-methoxyphenoxy)ethyl>-1-piprazinyl>-3(2H)-pyridazinone
• 英文别名: 2-(7-Bromoheptyl)-4-chloro-5-[4-[2-(2-methoxyphenoxy)ethyl]piperazin-1-yl]pyridazin-3-one
• CAS: 234090-67-6
• 化学式: C₂₄H₃₄BrClN₄O₃
• 分子量: 541.916
• InChiKey: GUUCQLWFEKBTON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2-乙氧基苯基)哌嗪 、 4-chloro-2-(7-bromoheptyl)-5-<4-<2-(2-methoxyphenoxy)ethyl>-1-piprazinyl>-3(2H)-pyridazinone 在 sodium carbonate 作用下， 以 异戊醇 为溶剂， 以45%的产率得到4-Chloro-2-{7-[4-(2-ethoxy-phenyl)-piperazin-1-yl]-heptyl}-5-{4-[2-(2-methoxy-phenoxy)-ethyl]-piperazin-1-yl}-2H-pyridazin-3-one
  参考文献：
  名称：

  Alpha1-肾上腺素受体拮抗剂。6.哒嗪酮-芳基哌嗪的结构优化。研究对哒嗪酮环上的环状取代基和芳基哌嗪部分上的烷氧基的亲和力和选择性的影响。

  摘要：

  在继续寻找选择性的α（1）-肾上腺素能受体（AR）拮抗剂时，我们合成了新的烷氧基芳基哌嗪基烷基吡啶并嗪酮衍生物。测试了新化合物对α（1）-和α（2）-AR以及对5-HT（1A）受体的亲和力。alpha（1）-AR亲和力数据在亚纳摩尔范围内，其中3表示亲和力为0.052 nM，比哌唑嗪高约5倍。没有一个研究的化合物被发现是具有alpha（1）/ alpha（2）选择性的，但是8个化合物显示出有趣的5-HT（1A）/ alpha（1）亲和比为119。

  DOI：

  10.1021/jm0307842
• 作为产物：
  描述：

  1-[2-(2-甲氧基苯氧基)乙基]哌嗪 在 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 37.0h， 生成 4-chloro-2-(7-bromoheptyl)-5-<4-<2-(2-methoxyphenoxy)ethyl>-1-piprazinyl>-3(2H)-pyridazinone
  参考文献：
  名称：

  Alpha1-肾上腺素受体拮抗剂。6.哒嗪酮-芳基哌嗪的结构优化。研究对哒嗪酮环上的环状取代基和芳基哌嗪部分上的烷氧基的亲和力和选择性的影响。

  摘要：

  在继续寻找选择性的α（1）-肾上腺素能受体（AR）拮抗剂时，我们合成了新的烷氧基芳基哌嗪基烷基吡啶并嗪酮衍生物。测试了新化合物对α（1）-和α（2）-AR以及对5-HT（1A）受体的亲和力。alpha（1）-AR亲和力数据在亚纳摩尔范围内，其中3表示亲和力为0.052 nM，比哌唑嗪高约5倍。没有一个研究的化合物被发现是具有alpha（1）/ alpha（2）选择性的，但是8个化合物显示出有趣的5-HT（1A）/ alpha（1）亲和比为119。

  DOI：

  10.1021/jm0307842

文献信息

• α1-Adrenoceptor antagonists. 5. Pyridazinone-arylpiperazines. Probing the influence on affinity and selectivity of both ortho-Alkoxy groups at the arylpiperazine moiety and cyclic substituents at the pyridazinone nucleus
  作者：Laura Betti、Monia Floridi、Gino Giannaccini、Fabrizio Manetti、Giovannella Strappaghetti、Andrea Tafi、Maurizio Botta

  DOI：10.1016/s0960-894x(02)00932-0

  日期：2003.1

  Our previous work on pyridazinone-arylpiperazine derivatives suggested some structural features that a compound should have to show high affinity and good selectivity for alpha(1) adrenoceptors (AR) with respect to alpha(2)-AR. Accordingly, two classes of new alkoxyphenylpiperazinylheptylpyridazinones were designed and synthesized to evaluate the effect of the alkoxy substituent on affinity and selectivity. As expected, affinity increased with larger alkoxy groups. Affinity values are all comparable with that of the reference compound (prazosin), with the exception of compound 1c found 4.5-fold more active than prazosin. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis of new pyridazinone derivatives and their affinity towards α1–α2-adrenoceptors
  作者：Stefano Corsano、Giovannella Strappaghetti、Roberta Barbaro、Gino Giannaccini、Laura Betti、Antonio Lucacchini

  DOI：10.1016/s0968-0896(99)00046-2

  日期：1999.5

  A series of 3(2H)-pyridazinone derivatives was evaluated for their affinity in vitro towards alpha(1)-alpha(2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha(1)-adrenoceptor (with K-i values in the subnanomolar range), and a gradual increase in affinity was observed by increasing the polymethylene chain length of this series up to a maximum of six and seven carbon atoms, when the fragment 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl is linked in 5 position of the 3(2H)-pyridazinone ring, while a slight decrease was found for the higher homologues. Increasing the chain length when the 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl group is linked in 6 position of the 3(2H)-pyridazinone ring, had a different effect: there is the highest affinity when the polymethylene chain is of four carbon atoms. The alkylic chain, a spacer between the two major constituents of the molecule, can influence the affinity and the selectivity. (C) 1999 Elsevier Science Ltd. All rights reserved.
• α₁-Adrenoceptor Antagonists. 6. Structural Optimization of Pyridazinone−Arylpiperazines. Study of the Influence on Affinity and Selectivity of Cyclic Substituents at the Pyridazinone Ring and Alkoxy Groups at the Arylpiperazine Moiety
  作者：Laura Betti、Federico Corelli、Monia Floridi、Gino Giannaccini、Laura Maccari、Fabrizio Manetti、Giovannella Strappaghetti、Maurizio Botta

  DOI：10.1021/jm0307842

  日期：2003.7.1

  compounds were tested for their affinity toward alpha(1)- and alpha(2)-AR and toward the 5-HT(1A) receptor. alpha(1)-AR affinity data are in the subnanomolar range, with 3 showing an affinity of 0.052 nM, about 5-fold higher than prazosin. None of the studied compounds was found to be alpha(1)/alpha(2) selective, but 8 showed an interesting 5-HT(1A)/alpha(1) affinity ratio of 119.

  在继续寻找选择性的α（1）-肾上腺素能受体（AR）拮抗剂时，我们合成了新的烷氧基芳基哌嗪基烷基吡啶并嗪酮衍生物。测试了新化合物对α（1）-和α（2）-AR以及对5-HT（1A）受体的亲和力。alpha（1）-AR亲和力数据在亚纳摩尔范围内，其中3表示亲和力为0.052 nM，比哌唑嗪高约5倍。没有一个研究的化合物被发现是具有alpha（1）/ alpha（2）选择性的，但是8个化合物显示出有趣的5-HT（1A）/ alpha（1）亲和比为119。