苯甲酸,4-[[(1,4-二氢-2-甲基-4-羰基-6-喹唑啉基)甲基]-2-炔丙基氨基]- | 112888-70-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 苯甲酸,4-[[(1,4-二氢-2-甲基-4-羰基-6-喹唑啉基)甲基]-2-炔丙基氨基]-
• 英文名称: 4--N-prop-2-ynylamino>benzoic acid
• 英文别名: p-[N-(2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzoic acid；p-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzoic acid；4-[(2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]benzoic acid
• CAS: 112888-70-7
• 化学式: C₂₀H₁₇N₃O₃
• 分子量: 347.373
• InChiKey: GPKDXPDXMCBSIS-UHFFFAOYSA-N

物化性质

• 沸点：
  614.6±65.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯甲酸,4-[[(1,4-二氢-2-甲基-4-羰基-6-喹唑啉基)甲基]-2-炔丙基氨基]- 在 diethyl cyanophosphoridate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (S)-2-[(S)-4-Carboxy-4-((S)-4-carboxy-4-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyrylamino)-butyrylamino]-pentanedioic acid; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Syntheses and thymidylate synthase inhibitory activity of the poly-.gamma.-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates

  摘要：

  Thirteen poly-gamma-glutamates derived from several novel antifolates have been synthesized by a convergent route. The syntheses of poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (8) (ICI D1694), 2-desamino-N10-propargyl-5,8-dideazafolic acid (6), 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (7), 2-desamino-2-methyl-N10-propargyl-2'-fluoro-5,8-dideazafolic acid (9), and 2-desamino-2-methyl-4-chloro-N10-propargyl-2'-fluoro-3,5,8-trideazafolic acid (11) are described. A key step in the route involves coupling of an alpha-tert-butyl-protected poly-gamma-glutamate of the required chain length to the appropriate 5,8-dideazapteroic acid, obtained by carboxypeptidase G2 cleavage of the parent monoglutamate, if available, or by chemical synthesis. Deprotection with trifluoroacetic acid in the final step gave the desired poly-gamma-glutamyl antifolates as their trifluoroacetate salts. As inhibitors of thymidylate synthase, these polyglutamates were more potent in every case than the corresponding non-polyglutamylated drug.

  DOI：

  10.1021/jm00083a008
• 作为产物：
  描述：

  N-p-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzoyl-L-glutamic acid 在 Tris buffer (tris(hydroxymethyl)aminomethane, ZnCl₂, aq. HCl, pH 7.3) 作用下， 反应 1.5h， 以99%的产率得到苯甲酸,4-[[(1,4-二氢-2-甲基-4-羰基-6-喹唑啉基)甲基]-2-炔丙基氨基]-
  参考文献：
  名称：

  Syntheses and thymidylate synthase inhibitory activity of the poly-.gamma.-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates

  摘要：

  Thirteen poly-gamma-glutamates derived from several novel antifolates have been synthesized by a convergent route. The syntheses of poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (8) (ICI D1694), 2-desamino-N10-propargyl-5,8-dideazafolic acid (6), 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (7), 2-desamino-2-methyl-N10-propargyl-2'-fluoro-5,8-dideazafolic acid (9), and 2-desamino-2-methyl-4-chloro-N10-propargyl-2'-fluoro-3,5,8-trideazafolic acid (11) are described. A key step in the route involves coupling of an alpha-tert-butyl-protected poly-gamma-glutamate of the required chain length to the appropriate 5,8-dideazapteroic acid, obtained by carboxypeptidase G2 cleavage of the parent monoglutamate, if available, or by chemical synthesis. Deprotection with trifluoroacetic acid in the final step gave the desired poly-gamma-glutamyl antifolates as their trifluoroacetate salts. As inhibitors of thymidylate synthase, these polyglutamates were more potent in every case than the corresponding non-polyglutamylated drug.

  DOI：

  10.1021/jm00083a008

文献信息

• Anti-tumor compounds
  申请人：Imperial Chemical Industries PLC

  公开号：US05280027A1

  公开（公告）日：1994-01-18

  The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumour activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 includes hydrogen, amino and alkyl or alkoxy each of up to 4 carbon atoms; R.sup.2 includes hydrogen, alkyl, hydroxyalkyl and halogenoalkyl each of up to 4 carbon atoms; R.sup.3 is hydrogen or alkyl or up to 3 carbon atoms; Ar is phenylene or heterocyclene; L is a group of the formula --CO.NH--, --NH.CO--, --CO.NR.sup.4 --, --NR.sup.4.CO--, --CH.dbd.CH-- or --CO.O--, wherein R.sup.4 is alkyl of up to 4 carbon atoms; and Y is a branched alkyl group bearing substituents Y.sup.2 and Y.sup.3 the definition of each independently including hydroxy, cyano, aryl and heteroaryl, and the definition of Y.sup.3 also optionally including sulpho, N-phenylsulphonylcarbamoyl and 5-tetrazolyl; or a pharmaceutically-acceptable salt thereof.

  本发明涉及喹唑啉衍生物，或其药用可接受的盐，这些衍生物具有抗肿瘤活性；提供它们的制造过程；以及含有它们的药物组合物。本发明提供了一种喹唑啉的公式：##STR1##其中，R.sup.1 包括氢、氨基和每个碳原子最多4个的烷基或烷氧基；R.sup.2 包括氢、烷基、羟烷基和卤代烷基，每个碳原子最多4个；R.sup.3 是氢或最多3个碳原子的烷基；Ar是苯基或杂环基；L是以下公式之一的基团：--CO.NH--，--NH.CO--，--CO.NR.sup.4 --，--NR.sup.4.CO--，--CH.dbd.CH--或--CO.O--，其中R.sup.4是碳原子最多4个的烷基；Y是带有取代基Y.sup.2和Y.sup.3的支链烷基，每个定义独立包括羟基、氰基、芳基和杂芳基，Y.sup.3的定义还可选包括磺酸基、N-苯磺酰氨基甲酰基和5-四唑基；或其药用可接受的盐。
• Quinazoline derivatives possessing anti-tumor activity
  申请人：Imperial Chemical Industries PLC

  公开号：US05089499A1

  公开（公告）日：1992-02-18

  The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumor activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: ##STR1## wherein R.sup.1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R.sup.1 is substituted alkyl or alkoxy each of up to 3 carbon atoms; R.sup.2 is hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, halogenoalkyl or cyanoalkyl each of up to 6 carbon atoms; Ar is phenylene or heterocyclene; L is a group of the formula --CO.NH--, --NH.CO--, --CO.NR.sup.3 --, --NR.sup.3. CO--, --CH.dbd.CH--, --CH.sub.2 O--, --OCH.sub.2, --CH.sub.2 S--, --SCH.sub.2 --, --CO.CH.sub.2 --, --CH.sub.2.CO-- or --CO.O--, wherein R.sup.3 is alkyl of up to 6 carbon atoms; and Y is aryl or heteroaryl or a hydrogenated derivative thereof: or Y is a group of the formula --A--Y.sup.1 in which A is alkylene, cycloalkylene, alkenylene or alkynylene each of up to 6 carbon atoms and Y.sup.1 is aryl or heteroaryl or a hydrogenated derivative thereof; or a pharmaceutically-acceptable salt thereof.

  该发明涉及喹唑啉衍生物或其药用盐，具有抗肿瘤活性；以及其制备方法；以及含有它们的药物组合物。 该发明提供了一种喹唑啉的结构式：其中R.sup.1是氢或氨基，或每个最多6个碳原子的烷基或烷氧基；或R.sup.1是取代的每个最多3个碳原子的烷基或烷氧基；R.sup.2是氢，烷基，烯基，炔基，羟基烷基，卤代烷基或氰基烷基，每个最多6个碳原子；Ar是苯基或杂环烯；L是下式的基团：--CO.NH--，--NH.CO--，--CO.NR.sup.3--，--NR.sup.3.CO--，--CH.dbd.CH--，--CH.sub.2O--，--OCH.sub.2--，--CH.sub.2S--，--SCH.sub.2--，--CO.CH.sub.2--，--CH.sub.2.CO--或--CO.O--，其中R.sup.3是最多6个碳原子的烷基；Y是芳基或杂芳基或其氢化衍生物：或Y是下式的基团：--A--Y.sup.1，其中A是烷基，环烷基，烯基或炔基，每个最多6个碳原子，Y.sup.1是芳基或杂芳基或其氢化衍生物；或其药用盐。
• New γ-fluoromethotrexates modified in the pteridine ring: synthesis and in vitro immunosuppressive activity
  作者：Yoshitsugu Kokuryo、Takuji Nakatani、Makoto Kakinuma、Mikio Kabaki、Kyozo Kawata、Akira Kugimiya、Kenji Kawada、Mitsunobu Matsumoto、Ryuji Suzuki、Mitsuaki Ohtani

  DOI：10.1016/s0223-5234(00)00147-1

  日期：2000.5

  Our continuing program to develop new antifolate drugs useful against rheumatoid arthritis led us to modify the pteridine ring of gamma-fluoromethotrexate. Pyrrolopyrimidine derivatives 1e and 1t were found to exhibit potent suppressive effects on the responses of both T and B cells to mitogens, although tetrahydropyridopyrimidine derivatives 2e and 2t and quinazoline derivatives 3e, 3t and 4e showed

  我们不断开发可用于治疗类风湿性关节炎的抗叶酸药物的计划使我们修改了γ-氟代甲氨蝶呤的蝶啶环。尽管四氢吡啶并嘧啶衍生物2e和2t以及喹唑啉衍生物3e，3t和4e显示出非常弱的抑制活性，但发现吡咯并嘧啶衍生物1e和1t对T和B细胞对促细胞分裂剂的反应均显示出强抑制作用。因此，γ-氟代甲氨蝶呤的蝶啶环向吡咯并嘧啶环的转化导致了新的潜在的抗风湿性化合物。
• HOUGHES, LESILE RICHARD;OIDFIELD, JOHN;PEGG, STEPHEN JOHN
  作者：HOUGHES, LESILE RICHARD、OIDFIELD, JOHN、PEGG, STEPHEN JOHN

  DOI：——

  日期：——
• DIPEPTIDYLQUINAZOLONES AS ANTI-CANCER AGENTS
  申请人：BRITISH TECHNOLOGY GROUP LIMITED

  公开号：EP0631576A1

  公开（公告）日：1995-01-04