N-[3-(5-fluoro-pyridin-3-yl)acryloyl]-4-(4-diphenylmethyl-1-piperazinyl)butylamine | 118420-35-2

• 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: N-[3-(5-fluoro-pyridin-3-yl)acryloyl]-4-(4-diphenylmethyl-1-piperazinyl)butylamine
• 英文别名: N-[3-(5-fluoro-3-pyridyl)acryloyl]-4-(4-diphenylmethyl-1-piperazinyl)butylamine；(E)-N-[4-(4-benzhydrylpiperazin-1-yl)butyl]-3-(5-fluoropyridin-3-yl)prop-2-enamide
• CAS: 118420-35-2
• 化学式: C₂₉H₃₃FN₄O
• 分子量: 472.606
• InChiKey: JCNMFOILUYLFQB-BUHFOSPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氟烟酰肼 在 哌啶 、 吡啶 、 氯甲酸乙酯 、 sodium carbonate 作用下， 以 吡啶 、 乙二醇 为溶剂， 生成 N-[3-(5-fluoro-pyridin-3-yl)acryloyl]-4-(4-diphenylmethyl-1-piperazinyl)butylamine
  参考文献：
  名称：

  Acrylamide derivatives as antiallergic agents. 2. Synthesis and structure activity relationships of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acrylamides

  摘要：

  A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (3-pyridyl)acrylamide] against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase. Particularly, (E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (6-methyl-3-pyridyl)acrylamide (17p) showed an ED50 value of 3.3 mg/kg po in the rat PCA test, which was one-fifth of ketotifen and oxatomide. As compared with ketotifen and oxatomide, compound 17p (AL-3264) possessed a better balance of antiallergic properties due to inhibition of chemical mediator release, inhibition of 5-lipoxygenase, and antagonism of histamine.

  DOI：

  10.1021/jm00123a012

文献信息

• .omega.-(3-pyridyl)alkenamide derivatives and anti-allergenic
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04778796A1

  公开（公告）日：1988-10-18

  Compounds of the formula: ##STR1## wherein X is alkylene or --(CR.sub.6 .dbd.CR.sub.7).sub.r -- wherein R.sub.6 is H, alkyl or phenyl, R.sub.7 is H, alkyl, cyano or phenyl, and r is 1 or 2; A is alkylene or alkylene interrupted by at least one double bond; R.sub.1 is H, halogen, alkyl, alkoxy, alkylthio, cycloalkyloxy, cycloalkylthio, alkoxycarbonyl, carboxy, phenyl, phenoxy, phenylthio, 3-pyridyloxy or 3-pyridylthio; R.sub.2 is H, hydroxy, alkanoyloxy or alkoxycarbonyloxy, or adjacent R.sub.1 and R.sub.2 may combine to form tetramethylene or --CH.sub.2 OCR.sub.8 R.sub.9 O-- (R.sub.8 and R.sub.9 are alkyl); R.sub.3 is H, alkyl or hydroxyalkyl; R.sub.4 is H or alkyl; R.sub.5 is phenyl, heteroaryl or --(CH.sub.2).sub.m --CHR.sub.10 R.sub.11 (R.sub.10 is H or phenyl, R.sub.11 is phenyl or pyridyl and m is 0 to 2); p is 0 or 1; and q is 2 or 3; the phenyl group or moiety being optionally substituted, and a salt thereof, process for the preparation thereof, and pharmaceutical composition containing the same. Said compounds and salts thereof show excellent antiallergic activity mainly through 5-lipoxygenase inhibiting activity, antihistamine activity and/or inhibitory activity against chemical mediator release and useful for treatment of allergic diseases.

  该公式化合物为：其中X为烷基或--(CR6.dbd.CR7)r--，其中R6为H、烷基或苯基，R7为H、烷基、氰基或苯基，r为1或2；A为烷基或至少有一个双键中断的烷基；R1为H、卤素、烷基、烷氧基、烷基硫基、环烷氧基、环烷硫基、烷氧羰基、羧基、苯基、苯氧基、苯硫基、3-吡啶氧基或3-吡啶硫基；R2为H、羟基、烷酰氧基或烷氧羰氧基，或相邻的R1和R2可结合形成四亚甲基或--CH2OCR8R9O--（R8和R9为烷基）；R3为H、烷基或羟基烷基；R4为H或烷基；R5为苯基、杂环芳基或--(CH2)m--CHR10R11（R10为H或苯基，R11为苯基或吡啶基，m为0至2）；p为0或1；q为2或3；苯基或基团可选择性地被取代，以及其盐，以及制备方法和含有该化合物的药物组合物。所述化合物及其盐主要通过5-脂氧合酶抑制活性、抗组胺活性和/或抑制化学介质释放活性表现出优异的抗过敏活性，对于治疗过敏性疾病具有用处。
• Pyridine compounds, process for the preparation thereof and pharmaceutical composition containing the same
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP0210782B1

  公开（公告）日：1991-04-17
• US4778796A
  申请人：——

  公开号：US4778796A

  公开（公告）日：1988-10-18
• Acrylamide derivatives as antiallergic agents. 2. Synthesis and structure activity relationships of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acrylamides
  作者：Yoshinori Nishikawa、Tokuhiko Shindo、Katsumi Ishii、Hideo Nakamura、Tatsuya Kon、Hitoshi Uno

  DOI：10.1021/jm00123a012

  日期：1989.3

  A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (3-pyridyl)acrylamide] against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase. Particularly, (E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (6-methyl-3-pyridyl)acrylamide (17p) showed an ED50 value of 3.3 mg/kg po in the rat PCA test, which was one-fifth of ketotifen and oxatomide. As compared with ketotifen and oxatomide, compound 17p (AL-3264) possessed a better balance of antiallergic properties due to inhibition of chemical mediator release, inhibition of 5-lipoxygenase, and antagonism of histamine.