KF-15570

Chemical Name: 5-Butyl-1-methyl-4,5-dihydro-1H-imidazo[4,5-c]quinolin-4-one
CAS No. 133305-92-7
项目整合开发状态: Preclinical
项目研究机构: Kyowa Hakko (Originator)
合成路线:KF15570 is prepared as follows:1-Butylisatoic anhydride (I) (3) was reacted with anion of ethylnitroacetate to give 1-butyl-4-hydroxy-3-nitroquinolin-2(1H)-one.Without purification,the hydroxy group was chlorinated with phosphorus oxychloride under reflux to give (II).The chlorine in (II) was readily replaced by methyl amino group in THF to provide (III).Hydrogenation of the nitro group in (III),followed by cyclization in refluxing triethylorthoformate,afforded KF15570 (IV).
📌 参考资料/链接:
参考文献标题:Imidazoquinoline derivs
文献作者:Suzuki,F.; Kuroda,T.; Nakazato,Y.; Manabe,H.; Ohmori,K.(Kyowa Hakko Kogyo Co.,Ltd.)
参考来源:EP 0386722; JP 1991264585; US 4994468

📄 详细内容


合成路线:KF15570 is prepared as follows:1-Butylisatoic anhydride (I) (3) was reacted with anion of ethylnitroacetate to give 1-butyl-4-hydroxy-3-nitroquinolin-2(1H)-one.Without purification,the hydroxy group was chlorinated with phosphorus oxychloride under reflux to give (II).The chlorine in (II) was readily replaced by methyl amino group in THF to provide (III).Hydrogenation of the nitro group in (III),followed by cyclization in refluxing triethylorthoformate,afforded KF15570 (IV).

参考文献标题:KF15570
文献作者:Suzuki,F.
参考来源:Drugs Fut 1992,17(10),873


合成路线:A new synthesis for KF-15570 has been described:The oxidation of 1-methyl-1H-imidazo[4,5-c]quinoline (I) with H2O2 in hot acetic acid gives 4-hydroxy-1-methyl-1H-imidazo[4,5-c]quinoline (II),which is then alkylated with butyl iodide and NaH in hot DMF.Compound was much more potent than theophylline in inhibiting Schulz-Dale reaction-induced tracheal contractions (ID50 = 0.25 mcM) and showed similar acute toxicity in mice (minimal lethal dose > 300 mg/kg i.v.).It was more effective than aminophylline in inhibiting antigen-induced bronchoconstriction in anesthetized guinea pigs (ED50 = 0.42 mg/kg i.v.),but showed fewer cardiac and CNS side effects than theophylline.

参考文献标题:New bronchodilators.1.1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones
文献作者:Suzuki,F.; Kuroda,T.; Nakasato,Y.; Manabe,H.; Ohmori,K.; Kitamura,S.; Ichikawa,S.; Ohno,T.
参考来源:J Med Chem 1992,35(22),4045


合成路线:KF15570 is prepared as follows:1-Butylisatoic anhydride (I) (3) was reacted with anion of ethylnitroacetate to give 1-butyl-4-hydroxy-3-nitroquinolin-2(1H)-one.Without purification,the hydroxy group was chlorinated with phosphorus oxychloride under reflux to give (II).The chlorine in (II) was readily replaced by methyl amino group in THF to provide (III).Hydrogenation of the nitro group in (III),followed by cyclization in refluxing triethylorthoformate,afforded KF15570 (IV).
参考文献标题:New bronchodilators.1.1,5-Substituted 1H-imidazo[4,5-c]quinolin-4(5H)-ones
文献作者:Suzuki,F.; Kuroda,T.; Nakasato,Y.; Manabe,H.; Ohmori,K.; Kitamura,S.; Ichikawa,S.; Ohno,T.
参考来源:J Med Chem 1992,35(22),4045-53


产品链接: CAS No. 133305-92-7››