9-carbethoxy-2-(2-fluorophenyl)-7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]-triazolo[1,5-c]pyrimidin-5-(6H)one | 108442-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 9-carbethoxy-2-(2-fluorophenyl)-7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]-triazolo[1,5-c]pyrimidin-5-(6H)one
• 英文别名: Ethyl 4-(2-fluorophenyl)-7-oxo-3,5,6,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4-triene-12-carboxylate；ethyl 4-(2-fluorophenyl)-7-oxo-3,5,6,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),2,4-triene-12-carboxylate
• CAS: 108442-25-7
• 化学式: C₁₇H₁₆FN₅O₃
• 分子量: 357.344
• InChiKey: XWOTVUPMCFQMCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-carbethoxy-2-(2-fluorophenyl)-7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]-triazolo[1,5-c]pyrimidin-5-(6H)one 在 盐酸 、 sodium hydroxide 作用下， 生成 2-(2-fluorophenyl)-7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)one
  参考文献：
  名称：

  Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones

  摘要：

  Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo-[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e]?? [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.

  DOI：

  10.1021/jm00113a032
• 作为产物：
  描述：

  双(2-氰基乙基)胺 在 三正丙胺 、 potassium tert-butylate 、 sodium ethanolate 、 碳酸氢钠 作用下， 以 乙醇 、 乙二醇甲醚 、 丁酮 、 叔丁醇 为溶剂， 反应 20.0h， 生成 9-carbethoxy-2-(2-fluorophenyl)-7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]-triazolo[1,5-c]pyrimidin-5-(6H)one
  参考文献：
  名称：

  Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones

  摘要：

  Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo-[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e]?? [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.

  DOI：

  10.1021/jm00113a032

文献信息

• 2-Substituted-e-fused-[1,2,4]-triazolo[1,5-c] pyrimidines, pharmaceutical compositions, and uses thereof
  申请人：CIBA-GEIGY AG

  公开号：EP0263071A1

  公开（公告）日：1988-04-06

  Compounds of the formula wherein R1 is optionally substituted phenyl, pyridyl, thienyl, furyl, pyrrolyl, thiazolyl, or ribofuranosyl; X is oxygen, NR, or sulfur: R is hydrogen, lower alkyl, lower alkenyl, or lower alkynyl; and ring A is a) an optionally substituted 5-8 membered monocycloalken-1,2-diyl; b) an optionally substituted carbob- icyclic ring of the formula. wherein n and m are each independently one or two; or c) an optionally substituted 5-6 membered heterocycle having one or two heteroatoms, the atoms of which are selected from carbon, oxygen, nitrogen, and sulfur. Also disclosed are tautomers of the above and pharmaceutically acceptable salts; compositions thereof; and methods of using the compounds, tautomer, or salts.

  式中的化合物 其中 R1 是任选取代的苯基、吡啶基、噻吩基、呋喃基、吡咯基、噻唑基或呋喃核糖基；X 是氧、NR 或硫：R 是氢、低级烷基、低级烯基或低级炔基；以及环 A 是 a）任选取代的 5-8 位单环烯-1,2-二基；b）式中任选取代的碳冰环。 其中 n 和 m 各自独立地为一个或两个；或 c) 具有一个或两个杂原子的任选取代的 5-6 分子杂环，这些杂原子选自碳、氧、氮和硫。还公开了上述化合物的同系物和药学上可接受的盐；其组合物；以及使用这些化合物、同系物或盐的方法。
• FRANCIS, JOHN E.
  作者：FRANCIS, JOHN E.

  DOI：——

  日期：——
• US4831013A
  申请人：——

  公开号：US4831013A

  公开（公告）日：1989-05-16
• [EN] 2-SUBSTITUTED-E-FUSED-(1,2,4)TRIAZOLO(1,5-C)PYRIMIDINES PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
  申请人：CIBA-GEIGY AG

  公开号：WO1988002370A1

  公开（公告）日：1988-04-07

  (EN) Compounds of formula (I), wherein R1 is optionally substituted phenyl, pyridyl, thienyl, furyl, pyrrolyl, thiazolyl, or ribofuranosyl; X is oxygen, NR, or sulfur; R is hydrogen, lower alkyl, lower alkenyl, or lower alkynyl; and ring A is a) an optionally substituted 5-8 membered monocycloalken-1,2-diyl; b) an optionally substituted carbobicyclic ring of formula (II), wherein n and m are each independently one or two; or c) an optionally substituted 5-6 membered heterocycle having one or two heteroatoms, the atoms of which are selected from carbon, oxygen, nitrogen, and sulfur. Also disclosed are tautomers of the above and pharmaceutically acceptable salts; compositions thereof; and methods of using the compounds, tautomer, or salts.(FR) Composés présentant la formule (I) dans laquelle R1 est, au choix, un phényle substitué, un pyridyle, un thiényle, un furyle, un pyrrolyle, un thiazolyle ou un ribofuranosyle; X est l'oxygène, NR ou le soufre; R est l'hydrogène, un alkyle inférieur, un alcynyle inférieur ou alkyle inférieur; et le cycle A est a) un monocycloalcène-1,2-diyle à 5 à 8 côtés, éventuellement substitué; b) un cycle carbobicyclique, éventuellement substitué, de formule (II) dans laquelle n et m représentent indépendamment 1 ou 2; ou c) un hétérocycle de 5 à 6 côtés éventuellement substitué comprenant un ou deux hétéro-atomes, et dont les atomes sont choisis parmi le carbone, l'oxygène, l'azote et le soufre. Sont également décrits des tautomères de ces composés ainsi que des sels pharmaceutiques; compositions comprenant ces composés et procédés utilisant les composés, leurs tautomères ou leurs sels.
• Anxiolytic properties of certain annelated [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones
  作者：John E. Francis、Debra A. Bennett、James L. Hyun、Stephen L. Rovinski、Caryl L. Amrick、Patricia S. Loo、Deborah Murphy、Robert F. Neale、Douglas E. Wilson

  DOI：10.1021/jm00113a032

  日期：1991.9

  Modification of the benzodiazepine (BZ) receptor binding template 2-aryl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one by replacement of the annelated benzene ring with various alicyclic and heterocyclic moieties led to novel structures with potent BZ receptor binding affinity. High affinity was found in some cycloalkyl-annelated [1,2,4]triazolo-[1,5-c]pyrimidin-5(6H)-ones and in some 7,8,9,10-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones, in which the degree of activity was strongly dependent on the N-substituent in the 9-position. Nine compounds with BZ receptor IC50 binding affinity values equal or superior to diazepam were evaluated in secondary screening. One of these, 9-benzyl-2-phenyl-7,8,9,10-tetrahydropyrido[3,4-e]?? [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one, showed good activity in rats as a potential anxiolytic agent without sedative liability. However, it increased the rotorod deficit produced by ethanol at anxiolytic doses, an indication of alcohol interaction. Thus, none of the compounds showed an advantage over CGS 9896 (Yokoyama et al. J. Med. Chem. 1982, 25, 337-339), which is free of sedative and alcohol interaction potential as measured by the test procedures described.