6-cyano-3-hydroxy-N-(4-methoxyphenyl)-2,2-dimethylchromene-4-carbothioamide | 134122-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-cyano-3-hydroxy-N-(4-methoxyphenyl)-2,2-dimethylchromene-4-carbothioamide
• CAS: 134122-07-9
• 化学式: C₂₀H₁₈N₂O₃S
• 分子量: 366.441
• InChiKey: VONKSNJWXFYOAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-cyano-2,2-dimethyl-2H-1-benzopyran-3-one 、 4-甲氧基苯基 异硫氰酸酯 在 potassium tert-butylate 作用下， 生成 6-cyano-3-hydroxy-N-(4-methoxyphenyl)-2,2-dimethylchromene-4-carbothioamide
  参考文献：
  名称：

  Relaxant activity of 6-cyano-2,2-dimethyl-2H-1-benzopyran-4-carboxamides and -thiocarboxamides and their analogs in guinea pig trachealis

  摘要：

  Structural modifications of the potassium channel activator cromakalim (1) are described in which the amide moiety at C-4 has been replaced by carboxamide and thiocarboxamide functions. Analogues in which the hydroxyl group at C-3 has been oxidized or removed are also disclosed. Such analogues display an interesting profile of smooth muscle relaxant activity in the guinea pig isolated trachea, not all of which appears to result from the opening of potassium channels, but few compounds retain useful in vivo activity. However, one compound in particular, 6-cyano-2,2-dimethyl-N-methyl-2H-1-benzopyran-4-thiocarboxamide (13) was shown to be a potent potassium channel activator in vitro and to provide prolonged protection to guinea pigs from the respiratory effects of inhaled histamine.

  DOI：

  10.1021/jm00112a037

文献信息

• Benzopyran derivatives
  申请人：Beecham Group p.l.c.

  公开号：EP0398665A1

  公开（公告）日：1990-11-22

  A compound of formula (I): or, where appropriate, a pharmaceutically acceptable salt, ester or amide thereof, or a pharmaceutically acceptable solvate thereof wherein: X represents O or S; Y represents N or N⁺-O⁻ or a moiety CR₇ wherein R₇ is as defined below; Z represents O, CH₂, NR, S(O)n or Z represents a bond; R represents hydrogen, alkyl or alkylcarbonyl R₁ and R₂ independently represent hydrogen or alkyl; or R₁ and R₂ together represent a C₂₋₇ polymethylene chain; R₃ represents hydrogen, hydroxy, alkoxy or acyloxy; R₄ is hydrogen; R₅ is hydrogen or R₄ and R₅ together represent a bond; R₆ represents hydrogen, substituted or unsubstituted alkyl, alkoxy, C₃₋₈ cycloalkyl, hydroxy, nitro, cyano, halo, formyl, carboxy, a group of formula RaT¹-, RbRcNT-, RaT²NH-, RdCO.O-, RdCS.O-, Rd(OH)CH-, Rd(SH)CH-, RdC(=N.OH)-, RdC(=N.NH₂)- or alkenyl optionally substituted by alkylcarbonyl, nitro or cyano; when Y represents CR₇, R₇ is independently selected from the variables mentioned above in relation to R₆ providing that at least one of R₆ or R₇ is other than hydrogen; Ra represents Rd or RdO- and Rd represents substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, optional substituents for Rd being up to 3 substituents selected from alkyl, alkoxy, hydroxy, halo, haloalkyl, nitro and cyano; Rb and Rc each independently represent hydrogen, alkyl or alkylcarbonyl; T represents a bond or T¹, T¹ represents -CS- or T² and T² represents -CO-, -SO- or -SO₂- and R₈ represents hydrogen, alkyl or substituted or unsubstituted aryl; R₉ represents hydrogen or alkyl, substituted or unsubstituted aryl or R₈ and R₉ together represent a C₃₋₇ polymethylene group; and n represents 0, 1 or 2; a process for preparing such a compound, a pharmaceutical composition containing such a compound and the use of such a compound or composition in medicine.

  化合物的化学式为（I）：或在适当情况下，其药学上可接受的盐，酯或酰胺，或其药学上可接受的溶剂化合物，其中：X代表O或S；Y代表N或N⁺-O⁻或CR₇基团，其中R₇如下所定义；Z代表O，CH₂，NR，S（O）n或Z代表一个键；R代表氢，烷基或烷基羰基；R₁和R₂独立地代表氢或烷基；或R₁和R₂一起代表一个C₂₋₇多亚甲基链；R₃代表氢，羟基，烷氧基或酰氧基；R₄代表氢；R₅代表氢或R₄和R₅一起代表一个键；R₆代表氢，取代或未取代的烷基，烷氧基，C₃₋₈环烷基，羟基，硝基，氰基，卤素，甲酰基，羧基，公式RaT¹-，RbRcNT-，RaT²NH-，RdCO.O-，RdCS.O-，Rd（OH）CH-，Rd（SH）CH-，RdC（=N.OH）-，RdC（=N.NH₂）-或烯基，可选地用烷基羰基，硝基或氰基取代；当Y代表CR₇时，R₇独立地从上述与R₆有关的变量中选择，前提是R₆或R₇中至少有一个不是氢；Ra代表Rd或RdO-，而Rd代表取代或未取代的烷基，取代或未取代的芳基或取代或未取代的杂环基，Rd的可选取代基包括最多3个从烷基，烷氧基，羟基，卤素，卤代烷基，硝基和氰基中选择的取代基；Rb和Rc各自独立地代表氢，烷基或烷基羰基；T代表一个键或T¹，T¹代表-CS-或T²，T²代表-CO-，-SO-或-SO₂-，而R₈代表氢，烷基或取代或未取代的芳基；R₉代表氢或烷基，取代或未取代的芳基或R₈和R₉一起代表一个C₃₋₇多亚甲基基团；n代表0，1或2；制备这种化合物的方法，含有这种化合物的药物组合物以及这种化合物或组合物在医药中的用途。
• Relaxant activity of 6-cyano-2,2-dimethyl-2H-1-benzopyran-4-carboxamides and -thiocarboxamides and their analogs in guinea pig trachealis
  作者：Jonathan R. S. Arch、Derek R. Buckle、Claire Carey、Hilary Parr-Dobrzanski、Andrew Faller、Keith A. Foster、Catherine S. V. Houge-Frydrych、Ivan L. Pinto、David G. Smith、Stephen G. Taylor

  DOI：10.1021/jm00112a037

  日期：1991.8

  Structural modifications of the potassium channel activator cromakalim (1) are described in which the amide moiety at C-4 has been replaced by carboxamide and thiocarboxamide functions. Analogues in which the hydroxyl group at C-3 has been oxidized or removed are also disclosed. Such analogues display an interesting profile of smooth muscle relaxant activity in the guinea pig isolated trachea, not all of which appears to result from the opening of potassium channels, but few compounds retain useful in vivo activity. However, one compound in particular, 6-cyano-2,2-dimethyl-N-methyl-2H-1-benzopyran-4-thiocarboxamide (13) was shown to be a potent potassium channel activator in vitro and to provide prolonged protection to guinea pigs from the respiratory effects of inhaled histamine.