Stable carteolol hydrochloride, preparation method thereof and eye medicine combination

Abstract

The invention relates to stable carteolol hydrochloride, a preparation method thereof and an eye medicine combination, in particular to a method for preparing carteolol hydrochloride. The method comprises the following steps of preparing 3-amino-2-cyclohexenone, tetrahydro-2,5(1H, 6H)-quinolinone, 5-hydroxy-3,4-dihydro-2(1H)-carbostyril and 5-(2,3-epoxypropoxy)-3,4-dihydro-2(1H)-carbostyril, and then the carteolol hydrochloride is obtained. Furthermore, the invention provides the carteolol hydrochloride crude medicine obtained according to the method, the eye medicine combination prepared by using the obtained carteolol hydrochloride as the crude medicine, and applications of the obtained carteolol hydrochloride to preparation of drugs for treating or preventing glaucoma or ocular hypertension. The method has excellent pharmaceutical characteristics, for example, the obtained crude medicine and a preparation has excellent stability.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a beta-adrenergic receptor blocker, its preparation method and eye drop pharmaceutical composition containing it, in particular to carteolol hydrochloride, its preparation method and its containing Eye drops pharmaceutical composition. The carteolol hydrochloride prepared by the invention has excellent medicinal properties. Background technique [0002] Carteolol (Carteolol), clinically used as its hydrochloride, also known as carteolol, is a β-adrenergic receptor blocker developed by Otsuka Pharmaceutical Company of Japan. Launched under the trade name Milelan. On January 22, 1997, with the approval of the State Food and Drug Administration, China Otsuka Pharmaceutical Co., Ltd. began to produce carteolol hydrochloride eye drops with the trade name "Mekailang". So far, the domestic clinical use is mainly the carteolol hydrochloride eye drops produced by China Otsuka Pharmaceut...

AI Technical Summary

Problems solved by technology

5-Hydroxy-3,4-dihydro-2(1H)-quinolone can be obtained by amination of 1,3-cyclohexanedione, condensation with allyl acid, and dehydroaromatization [Shono T, Matsumura Y, Kashimura S.A new practical synthesis of 5-hydroxy-3,4-dihydrocarbostyril and 5-hydroxycarbostyril[J].J Org Chem,1981,46(18):3719-3721; Tamura Y,Terashima M,Higuchi Y,et al.Synthesis of 5-hydroxy and alkoxy-3,4-dihydrocarbostyils[J].Chem Ind(London), 1970,7(45):1435], the operating conditions of this method are relatively harsh, and it is necessary to use liquid ammonia for ammoniation and noble metal catalysts for high temperature removal Hydroaromatization, and easily over-dehydrogenated to obtain by-products

There are literature [Huang YH, Hartmann RW.The improved preparation of 7,8-dihydroquinoline-5(6H)-one and 6,7-dihydro-5H-1-pyrindin-5-one[J].Synth Commun,1998,28 (7): 1197-1200] Using 1,3-cyclohexanedione and ammonium acetate to reflux ammoniation in benzene can avoid the use of liquid ammonia, but the solvent is highly toxic; it was later reported [Wang GW, MiaoCB. Environmentally benign one -pot multi-component approaches to the synthesis of novel unsymmetrical 4-arylacridinediones [J]. Green Chem, 2006, 8: 1080-1085] changed to hydrogenation and dehydroaromatization under solvent-free conditions, which simplifies the operation , but will generate imine products that are not easy to remove

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