8-(p-chlorophenyl-sulfonamido)-4-[3-(pyridin-3-yl)propyl]octanenitrile | 134163-84-1

• 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: 8-(p-chlorophenyl-sulfonamido)-4-[3-(pyridin-3-yl)propyl]octanenitrile
• 英文别名: 8-(p-chlorophenylsulfonamido)-4-[3-(pyridin-3-yl)propyl]-octanenitrile；8-(p-chlorophenylsulfonamido)-4-[3-(3-pyridyl)propyl]-octanenitrile；8-(p-chlorophenylsulfonamido)-4[3-(3-pyridyl)propyl]octanenitrile；4-chloro-N-[5-(2-cyanoethyl)-8-pyridin-3-yloctyl]benzenesulfonamide
• CAS: 134163-84-1
• 化学式: C₂₂H₂₈ClN₃O₂S
• 分子量: 434.002
• InChiKey: XYPWKMFMWCHDIF-UHFFFAOYSA-N

物化性质

• 沸点：
  626.1±65.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(p-chlorophenyl-sulfonamido)-4-[3-(pyridin-3-yl)propyl]octanenitrile 在 tri-n-butyltin azide 作用下， 以 四氢呋喃 为溶剂， 反应 64.0h， 以39%的产率得到1-<<(4-chlorophenyl)sulfonyl>amino>-5-<2-(tetrazol-5-yl)ethyl>-8-(3-pyridinyl)octane
  参考文献：
  名称：

  Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-[3-(3-pyridinyl)propyl]octanoic acid and analogs

  摘要：

  The title compound (10a) and its analogs were synthesized and found to possess two activities, the inhibition of the biosynthesis of thromboxane A2 and antagonism of its receptors. The in vitro and in vivo profile of these compounds as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) is described. 10a and its analogs displayed very potent TxRA activity in human washed platelets (IC50 almost-equal-to 10(-7)-10(-9) M) and dog saphenous vein (pA2 almost-equal-to 9) and also potent TxSI activity (IC50 almost-equal-to 10(-9) M). The good bioavailability and the long duration of action of some of these compounds was demonstrated using ex vivo measurement of the TxRA activity upon oral administration to guinea pigs. Compounds 10a, 20, and 33 potently inhibited arachidonic acid induced bronchoconstriction in guinea pigs.

  DOI：

  10.1021/jm00101a015
• 作为产物：
  描述：

  8-[(4-氯苯基)磺酰氨基]-4-(3-吡啶-3-基丙基)辛酸 在 吡啶 、 氯化亚砜 、 氨 、 三氟乙酸酐 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 8-(p-chlorophenyl-sulfonamido)-4-[3-(pyridin-3-yl)propyl]octanenitrile
  参考文献：
  名称：

  Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-[3-(3-pyridinyl)propyl]octanoic acid and analogs

  摘要：

  The title compound (10a) and its analogs were synthesized and found to possess two activities, the inhibition of the biosynthesis of thromboxane A2 and antagonism of its receptors. The in vitro and in vivo profile of these compounds as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) is described. 10a and its analogs displayed very potent TxRA activity in human washed platelets (IC50 almost-equal-to 10(-7)-10(-9) M) and dog saphenous vein (pA2 almost-equal-to 9) and also potent TxSI activity (IC50 almost-equal-to 10(-9) M). The good bioavailability and the long duration of action of some of these compounds was demonstrated using ex vivo measurement of the TxRA activity upon oral administration to guinea pigs. Compounds 10a, 20, and 33 potently inhibited arachidonic acid induced bronchoconstriction in guinea pigs.

  DOI：

  10.1021/jm00101a015

文献信息

• Certain (arylsulfonamido- and imidazolyl-)-substituted carboxylic acids
  申请人：Ciba-Geigy Corporation

  公开号：US05153214A1

  公开（公告）日：1992-10-06

  The present invention is concerned with compounds of formula I ##STR1## wherein A, B, M, R, Ar and Het are as defined in the specification, pharmaceutically acceptable ester and amide derivatives thereof; N-oxides thereof, tetrazole derivatives thereof, and salts thereof. These compounds have valuable pharmacological activities, especially as inhibitors of thromboxane synthetase and as receptor antagonists of thromboxane A.sub.2 and prostaglandin H.sub.2.

  本发明涉及以下式I的化合物 ##STR1## 其中A、B、M、R、Ar和Het如规范中所定义，其药学上可接受的酯和酰胺衍生物；其N-氧化物，四唑衍生物和盐。这些化合物具有有价值的药理活性，特别是作为血栓素合酶的抑制剂和血栓素A.sub.2和前列腺素H.sub.2的受体拮抗剂。
• (Arylsulfonamido- and pyridyl-)-substituted carboxylic acids and
  申请人：Ciba-Geigy Corporation

  公开号：US05025025A1

  公开（公告）日：1991-06-18

  Disclosed are the compounds of formula ##STR1## wherein A represents lower alkylene; B represents oxygen, sulfur, lower alkylene, lower alkylene interrupted by oxygen, sulfur, sulfinyl or sulfonyl, (oxy-, sulfinyl-, sulfonyl- or thio)-lower alkylene, lower alkenylene, phenylene or a direct bond; M represents lower alkylene, lower alkylene interrupted by oxygen, sulfur, sulfinyl or sulfonyl, (oxy-, sulfinyl, sulfonyl- or thio)-lower alkylene, lower alkenylene or a direct bond; or one of A, B and M represents lower alkylidenylene and the other two independently represent lower alkylene; R represents hydrogen unless A, B or M represents lower alkylidenylene in which case R represents the second bond to the adjacent aklylidenylene unsaturated carbon atom; Het represents 1-imidazolyl, 3-pyridyl, or 1-imidazolyl or 3-pyridyl substituted by lower alkyl; Ar represents carbocyclic or heterocyclic aryl; pharmaceutically acceptable ester and amide derivatives thereof; the N-oxides of said compounds wherein Het represents optionally substituted pyridyl; the said compounds of formula I wherein COOH is replaced by 5-tetrazolyl; and the pharmaceutically acceptable salts; which are useful as thromboxane synthetase inhibitors and thromboxane receptor antagonists.

  本发明涉及的化合物的式子为##STR1##其中，A代表低级烷基；B代表氧、硫、低级烷基、被氧、硫、亚磺酰基或磺酰基中断的低级烷基，(氧、亚磺酰基、磺酰基或硫)-低级烷基、低级烯基、苯基或直接键；M代表低级烷基、被氧、硫、亚磺酰基或磺酰基中断的低级烷基，(氧、亚磺酰基、磺酰基或硫)-低级烷基、低级烯基或直接键；或者A、B和M中的一个代表低级烷基，另外两个分别独立地代表低级烷基；R代表氢，除非A、B或M代表低级烷基，此时R代表相邻烷基亚烯基不饱和碳原子的第二个键；Het代表1-咪唑基、3-吡啶基，或者被低级烷基取代的1-咪唑基或3-吡啶基；Ar代表环状碳氢基或杂环状芳基；药学上可接受的酯和酰胺衍生物；其中Het代表可选取代的吡啶基的N-氧化物；式I中COOH被5-四氮唑基取代的化合物；以及药学上可接受的盐。这些化合物可用作血栓素合酶抑制剂和血栓素受体拮抗剂。
• Certain (arylsulfonamido- and pyridyl- or imidazolyl-)-substituted carboxylic acids and derivatives thereof
  申请人：CIBA-GEIGY AG

  公开号：EP0405391A1

  公开（公告）日：1991-01-02

  The present invention is concerned with compounds of formula I wherein A, B, M, R, Ar and Het are as defined in the specification, pharmaceutically acceptable ester and amide derivatives thereof; N-oxides thereof, tetrazole derivatives thereof, and salts thereof. These compounds have valuable pharmacological activities, especially as inhibitors of thromboxane synthetase and as receptor antagonists of thromboxane A₂ and prostaglandin H₂. They are prepared in a manner known per se.

  本发明涉及式 I 化合物（其中 A、B、M、R、Ar 和 Het 如说明书中所定义）、其药学上可接受的酯和酰胺衍生物、其 N-氧化物、其四唑衍生物及其盐类。 这些化合物具有重要的药理活性，特别是作为血栓素合成酶的抑制剂和血栓素 A₂及前列腺素 H₂的受体拮抗剂。 它们的制备方法本身是已知的。
• US5025025A
  申请人：——

  公开号：US5025025A

  公开（公告）日：1991-06-18
• US5153214A
  申请人：——

  公开号：US5153214A

  公开（公告）日：1992-10-06