3-(5,5-二甲基-2-氧代-2-[1,3,2]二氧杂磷杂环己基) -4-(3-硝基苯基)-丁-3-烯-2-酮 | 111011-78-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(5,5-二甲基-2-氧代-2-[1,3,2]二氧杂磷杂环己基) -4-(3-硝基苯基)-丁-3-烯-2-酮
• 中文别名: 3-(5,5-二甲基-2-氧代-2-[1,3,2]二氧杂磷杂环己基)-4-(3-硝基苯基)-丁-3-烯-2-酮
• 英文名称: 2-<1-acetyl-2-(3-nitrophenyl)ethenyl>-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan
• 英文别名: 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane；2-<1-acetyl-2-(3-nitrophenyl)ethenyl>-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane；3-(5,5-Dimethyl-2-oxo-1,3,2lambda5-dioxaphosphinan-2-yl)-4-(3-nitrophenyl)but-3-en-2-one；3-(5,5-dimethyl-2-oxo-1,3,2λ5-dioxaphosphinan-2-yl)-4-(3-nitrophenyl)but-3-en-2-one
• CAS: 111011-78-0
• 化学式: C₁₅H₁₈NO₆P
• 分子量: 339.285
• InChiKey: UMECHLASJBPFHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P501,P270,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313,P301+P312+P330
• 危险性描述：
  H302,H315,H319

反应信息

• 作为反应物：
  描述：

  3-(5,5-二甲基-2-氧代-2-[1,3,2]二氧杂磷杂环己基) -4-(3-硝基苯基)-丁-3-烯-2-酮 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 4.83h， 生成 (S)-2-ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-1-methoxymethyl-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate
  参考文献：
  名称：

  Synthesis and Crystal Structure of Optically Active 2-(Benzyl(phenyl)amino)ethyl 5-(5,5-Dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate(NZ-105).

  摘要：

  (S)-2-[苄基(苯基)氨基]乙基 5-(5, 5-二甲基-2-氧代-1, 3, 2-二氧磷杂膦-2-基)-1, 4-二氢-2, 6-通过分级结晶合成4-(3-硝基苯基)-3-吡啶甲酸二甲酯((S)-NZ-105)和R异构体(S)-2-甲氧基-2-苯乙基 5-(5, 5-二甲基-2-氧代-1, 3, 2-二氧磷杂膦-2-基)-1, 4-二氢-2, 6-二甲基-4 -(3-硝基苯基)-3-吡啶甲酸。单晶X射线衍射分析发现钙拮抗活性存在于S异构体中

  DOI：

  10.1248/cpb.40.2377
• 作为产物：
  描述：

  2-甲氧基-5,5-二甲基-1,3,2-二氧磷杂环己烷 在 哌啶 、 溶剂黄146 作用下， 以 乙醚 、 苯 为溶剂， 反应 13.5h， 生成 3-(5,5-二甲基-2-氧代-2-[1,3,2]二氧杂磷杂环己基) -4-(3-硝基苯基)-丁-3-烯-2-酮
  参考文献：
  名称：

  Synthesis of 1,4-Dihydropyridine-5-phosphonates and Their Calcium-Antagonistic and Antihypertensive Activities. Novel Calcium-Antagonist 2-(Benzyl(phenly)amino)ethyl 5-(5,5-Dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate Hydrochloride Ethanol(NZ-105) and Its Crystal Structure.

  摘要：

  研究了3-羧酸酯变体在2,2-二甲基三甲基烯-3-烷氧羰基-4-芳基-1,4-二氢-2,6-二甲基-5-吡啶膦酸酯(1)中与钙拮抗和降压活性相关的影响：合成了含有不超过12个碳的烷基和羧酸酯部分含有氨基功能团的类似物，以检测其生物活性。其中，2-[苄基(苯基)氨基]乙基5-(5,5-二甲基-2-氧-1,3,2-二氧膦杂环己烷-2-基)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3-吡啶羧酸酯盐酸盐乙醇(NZ-105)显示出特别有益的活性，并被选中进行进一步的药理学研究和临床开发。描述了通过X射线晶体学分析获得的NZ-105的结构-活性关系和固态结构的一些方面。

  DOI：

  10.1248/cpb.40.2362

文献信息

• Syntheses and antihypertensive activities of 1,4-dihydropyridine-5-phosphonate derivatives. III.
  作者：IWAO MORITA、Yuko HARUTA、TOSHIO TOMITA、MASAMI TSUDA、KAZUHISA KANDORI、MASAHIRO KISE、KIYOSHI KIMURA

  DOI：10.1248/cpb.35.4819

  日期：——

  Various 1-and 2-substituted and 1, 2-fused 1, 4-dihydropyridine-5-phosphonate derivatives were designed and synthesized as analogues of 1, 4-dihydropyridine-3, 5-dicarboxylate, and their antihypertensive activities were examined. Several compounds proved to be equal or superior to nifedipine in lowering blood pressure in normotensive and spontaneously hypertensive rats. Among these compounds, 1-substituted 1, 4-dihydropyridine derivatives showed potent antihypertensive activities. The structure-activity relationships are discussed.

  设计并合成了多种1-和2-取代以及1, 2-融合的1, 4-二氢吡啶-5-膦酸酯衍生物，作为1, 4-二氢吡啶-3, 5-二羧酸盐的类似物，研究了它们的抗高血压活性。几个化合物在降低正常血压和自发性高血压大鼠的血压方面证明与尼非地平相当或更优。在这些化合物中，1-取代的1, 4-二氢吡啶衍生物显示出强效的抗高血压活性。讨论了它们的结构-活性关系。
• Transformation of 1,4-Dihydropyridine Ring of Calcium Antagonist NZ-105 into Cyclohexenone Ring.
  作者：Yoshimasa KAMIKAWAJI、Ryozo SAKODA、Kiyotomo SETO

  DOI：10.1248/cpb.43.315

  日期：——

  On hydrolysis of the calcium antagonist, 2-(N-benzyl-N-phenylamino)ethyl 5-(5, 5-dimethyl-2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)pyridine-3-carboxylate hydrochloride ethanol (NZ-105 1·HCl·EtOH) in 35% hydrochloric acid, the 1, 4-dihydropyridine ring was transformed to a cyclohexeone ring, affording the cyclohexenonephosphonates 2 and 3.

  钙拮抗剂水解后，2-(N-苄基-N-苯基氨基)乙基 5-(5, 5-二甲基-2-氧代-1, 3, 2-二氧磷杂环己烷-2-基)-1, 4-二氢-2, 6-二甲基-4-(3-硝基苯基)吡啶-3-羧酸盐酸盐乙醇（NZ-105 1·HCl·EtOH）在35%盐酸中，1, 4-二氢吡啶环转化为环己酮环，生成环己烯膦酸酯2和3。
• US4839361A
  申请人：——

  公开号：US4839361A

  公开（公告）日：1989-06-13
• Synthesis of 1,4-Dihydropyridine-5-phosphonates and Their Calcium-Antagonistic and Antihypertensive Activities. Novel Calcium-Antagonist 2-(Benzyl(phenly)amino)ethyl 5-(5,5-Dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate Hydrochloride Ethanol(NZ-105) and Its Crystal Structure.
  作者：Ryozo SAKODA、Yoshimasa KAMIKAWAJI、Kiyotomo SETO

  DOI：10.1248/cpb.40.2362

  日期：——

  The effect of the 3-carboxylic-ester variation in 2, 2-dimethyltrimethylene 3-alkoxycarbonyl-4-aryl-1, 4-dihydro-2, 6-dimethyl-5-pyridinephosphonates (1) was investigated with relation to the calcium-antagonistic and antihypertensive activities : the analogs contaning the alkyl groups of not more than 12 carbons and an amino functionality in the carboxylic-ester moiety were synthesized to be examined for biological activities. Among them, 2-[benzyl(phenyl)amino]-ethyl 5(5, 5-dimethyl-2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-phridine-carboxylate hydrochloride ethanol (NZ-105) showed particularly beneficial activities and was selected for further pharmacological studies and clinical development. Some aspects of the structure-activity relationships and solid-state structure of NZ-105 by X-ray crystallographic analysis were described.

  研究了3-羧酸酯变体在2,2-二甲基三甲基烯-3-烷氧羰基-4-芳基-1,4-二氢-2,6-二甲基-5-吡啶膦酸酯(1)中与钙拮抗和降压活性相关的影响：合成了含有不超过12个碳的烷基和羧酸酯部分含有氨基功能团的类似物，以检测其生物活性。其中，2-[苄基(苯基)氨基]乙基5-(5,5-二甲基-2-氧-1,3,2-二氧膦杂环己烷-2-基)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3-吡啶羧酸酯盐酸盐乙醇(NZ-105)显示出特别有益的活性，并被选中进行进一步的药理学研究和临床开发。描述了通过X射线晶体学分析获得的NZ-105的结构-活性关系和固态结构的一些方面。
• Synthesis and Crystal Structure of Optically Active 2-(Benzyl(phenyl)amino)ethyl 5-(5,5-Dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate(NZ-105).
  作者：Ryozo SAKODA、Hiroo MATSUMOTO、Kiyotomo SETO

  DOI：10.1248/cpb.40.2377

  日期：——

  (S)-2-[Benzyl(phenyl)amino]ethyl 5-(5, 5-dimethyl -2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate ((S)-NZ-105) and R isomer were synthesized throuth the fractional crystallization of (S)-2-Methoxy-2-phenylethyl 5-(5, 5-dimethyl-2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate. Calcium antagonism activity was found to reside in the S isomer from single crystal X-ray diffraction analysis

  (S)-2-[苄基(苯基)氨基]乙基 5-(5, 5-二甲基-2-氧代-1, 3, 2-二氧磷杂膦-2-基)-1, 4-二氢-2, 6-通过分级结晶合成4-(3-硝基苯基)-3-吡啶甲酸二甲酯((S)-NZ-105)和R异构体(S)-2-甲氧基-2-苯乙基 5-(5, 5-二甲基-2-氧代-1, 3, 2-二氧磷杂膦-2-基)-1, 4-二氢-2, 6-二甲基-4 -(3-硝基苯基)-3-吡啶甲酸。单晶X射线衍射分析发现钙拮抗活性存在于S异构体中