4-(2-chlorophenyl)2-iodo-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | 67860-41-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻烯杂卓类
• 英文名称: 4-(2-chlorophenyl)2-iodo-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
• 英文别名: 4-(2-chlorophenyl)-2-iodo-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine；7-(2-chlorophenyl)-4-iodo-13-methyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene
• CAS: 67860-41-7
• 化学式: C₁₅H₁₀ClIN₄S
• 分子量: 440.695
• InChiKey: KJZJHABCRCESGN-UHFFFAOYSA-N

物化性质

• 熔点：
  254-256 °C
• 沸点：
  581.4±60.0 °C(Predicted)
• 密度：
  1.95±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  71.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-chlorophenyl)2-iodo-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine 在 copper(l) iodide 、 palladium diacetate 、 三乙胺 、 间氯过氧苯甲酸 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 5-[3-[7-(2-Chlorophenyl)-13-methyl-8-oxido-3-thia-1,11,12-triaza-8-azoniatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-4-yl]prop-2-ynyl]phenanthridin-6-one
  参考文献：
  名称：

  Triazolobenzo- and triazolothienodiazepines as potent antagonists of platelet activating factor

  摘要：

  A series of [1,2,4]triazolo[4,3-alpha][1,4]benzodiazepines bearing an ethynyl functionality at the 8-position and the isosteric thieno[3,2-f][1,2,4]triazolo[4,3-alpha][1,4]diazepines were prepared and evaluated as antagonists of platelet activating factor. The effects of substitution were explored in in vitro and in vivo test systems designed to measured PAF-antagonistic activity. Results are discussed and compared with previously published data. Many of the compounds had activity superior to WEB 2086, compound 1. In general, the thieno analogues exhibited better oral activity than the corresponding benzodiazepines. The duration of activity upon oral administration was modulated by the substitution on the acetylenic side chain. Compounds 71 and 81 were selected for further pharmacological evaluation as a result of their good oral potency and exceptionally long duration of action.

  DOI：

  10.1021/jm00107a048
• 作为产物：
  描述：

  5-(2-氯苯基)-3,4-二氢噻吩并[3,2-f][1,4]二氮杂卓-2-酮 在 tetraphosphorus decasulfide 、 sodium acetate 、 一氯化碘 、 碳酸氢钠 、 对甲苯磺酸 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 二乙二醇二甲醚 、 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 3.25h， 生成 4-(2-chlorophenyl)2-iodo-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
  参考文献：
  名称：

  Triazolobenzo- and triazolothienodiazepines as potent antagonists of platelet activating factor

  摘要：

  A series of [1,2,4]triazolo[4,3-alpha][1,4]benzodiazepines bearing an ethynyl functionality at the 8-position and the isosteric thieno[3,2-f][1,2,4]triazolo[4,3-alpha][1,4]diazepines were prepared and evaluated as antagonists of platelet activating factor. The effects of substitution were explored in in vitro and in vivo test systems designed to measured PAF-antagonistic activity. Results are discussed and compared with previously published data. Many of the compounds had activity superior to WEB 2086, compound 1. In general, the thieno analogues exhibited better oral activity than the corresponding benzodiazepines. The duration of activity upon oral administration was modulated by the substitution on the acetylenic side chain. Compounds 71 and 81 were selected for further pharmacological evaluation as a result of their good oral potency and exceptionally long duration of action.

  DOI：

  10.1021/jm00107a048

文献信息

• Triazolo(4,3-A)(1,4)benzodiazepines and thieno
  申请人：Hoffmann-La Roche Inc.

  公开号：US04959361A1

  公开（公告）日：1990-09-25

  The invention relates to compounds of the formula ##STR1## wherein X is --CH.dbd.CH-- or S; R.sub.1 is lower alkyl, lower alkoxy or trifluoromethyl; R.sub.2 is hydrogen, lower alkyl, lower alkoxy, hydroxy or alkanoyloxy; R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy; s is an integer from 0 to 1, provided that when s is 1, R.sub.2 cannot be hydroxy, lower alkoxy or alkanoyloxy; R.sub.5 is a radical of the formula R.sub.6 --(CH.sub.2).sub.n -- or R.sub.7 --O--(CH.sub.2).sub.m -- wherein R.sub.6 and R.sub.7 are aryl or a heterocyclic radical, n is an integer of from 0 to 2 and m is an integer of from 1 to 2, provided that, when n is 0, R.sub.6 must be attached through a carbon to carbon bond, and provided that R.sub.7 is always attached through a carbon to oxygen bond, and, when at least one asymmetric carbon is present, its enantiomers and racemates, and pharmaceutically acceptable acid addition salts thereof. The compounds of formula I exhibit activity as platelet activating factor (PAF) antagonists and are, therefore, useful in disease states characterized by excess platelet activating factor or for the prevention and treatment of cardiovascular diseases, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shock or transplant rejection.

  本发明涉及通式##STR1##的化合物，其中X为--CH=CH--或S；R1为低级烷基、低级烷氧基或三氟甲基；R2为氢、低级烷基、低级烷氧基、羟基或烷酰氧基；R3和R4各自独立地为氢、氯、氟、低级烷基或低级烷氧基；s为0至1的整数，但当s为1时，R2不能为羟基、低级烷氧基或烷酰氧基；R5为通式R6--(CH2)n--或R7--O--(CH2)m--的基团，其中R6和R7为芳基或杂环基团，n为0至2的整数，m为1至2的整数，但当n为0时，R6必须通过碳-碳键连接，且R7始终通过碳-氧键连接，当存在至少一个不对称碳时，包括其对映体和外消旋体，以及药学上可接受的酸加成盐。通式I的化合物表现出作为血小板活化因子（PAF）拮抗剂的活性，因此可用于治疗以过量血小板活化因子为特征的疾病状态，或用于预防和治疗心血管疾病、肺部疾病、免疫紊乱、炎症性疾病、皮肤病、休克或移植排斥反应。
• Thienotriazolodiazepines as platelet-activating factor antagonists. Steric limitations for the substituent in position 2
  作者：Armin Walser、Thomas Flynn、Carl Mason、Herman Crowley、Catherine Maresca、Margaret O'Donnell

  DOI：10.1021/jm00108a031

  日期：1991.4

  substituted ethynyl group at the 2-position, and the corresponding cis-olefins and fully saturated analogues are described. The compounds were evaluated as potential antagonists of platelet-activating factor (PAF) in in vitro and in vitro test models. The new thienotriazolodiazepines are compared with known related compounds such as WEB 2086 (compound 6) and the phenylethyl derivatives 27 and 28.

  描述了在2-位带有取代的乙炔基的噻吩并氮杂二氮杂卓的制剂，以及相应的顺式烯烃和完全饱和的类似物。在体外和体外测试模型中，将这些化合物评估为血小板活化因子（PAF）的潜在拮抗剂。将新的噻吩并氮杂二氮杂卓与已知的相关化合物如WEB 2086（化合物6）和苯乙基衍生物27和28进行了比较。
• J. Med. Chem. 1991, 34, 1209-1221
  作者：

  DOI：——

  日期：——
• WALSER, ARMIN;FLYNN, THOMAS;MASON, CARL;CROWLEY, HERMAN;MARESCA, CATHERIN+, J. MED. CHEM., 34,(1991) N, C. 1209-1221
  作者：WALSER, ARMIN、FLYNN, THOMAS、MASON, CARL、CROWLEY, HERMAN、MARESCA, CATHERIN+

  DOI：——

  日期：——
• WALSER, ARMIN
  作者：WALSER, ARMIN

  DOI：——

  日期：——