Brimonidine tartrate, AGN-190342-LF, UK-14304-18, Alphagan P, Alphagan

5-溴-6-(2-咪唑林-2-乙氨基)喹喲沙林D-酒石酸盐 溴莫尼定 布林莫尼定酒石酸盐Chemical Name: 5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline D-tartrate; 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine D-tartrate
CAS No. 79570-19-7, 59803-98-4 (free base), 59803-99-5 (L-tartrate)
项目整合开发状态: Launched-1996
项目研究机构: Pfizer (Originator), Allergan (Licensee), Kyorin (Licensee), Senju (Licensee)
合成路线:Several degradation products and metabolites of brimonidine have been synthesized:1) The reaction of 5-bromoquinoxalin-6-amine (I) with cyanamide (II) and HCl in refluxing dioxane gives N2-(5-bromoquinoxalin-6-yl)guanidine (AGN-191383).2) The reaction of AGN-191383 with 1,1'-oxalyldiimidazole (III) and dimethylaminopyridine (DMAP) in pyridine yields 2-(5-bromoquinoxalin-6-ylimino)imidazolidine-4,5-dione (AGN-192597).3) The reaction of AGN-191383 with sodium iodoacetate (IV) in DMSO and then acidification with HCl affords 2-[N2-(5-bromoquinoxalin-6-yl)guanidino]acetic acid (AGN-192614).

合成路线:4) The reaction of amine (I) with phenyl cyanate (V) and KH in THF gives N-(5-bromoquinoxalin-6-yl)cyanamide (VI),which is cyclized with ethyl glycinate (VII) in refluxing ethanol to yield 2-(5-bromoquinoxalin-6-imino)imidazolidin-4-one (AGN-192119).5) The reaction of cyanamide (VI) with 2-aminoacetaldehyde diethyl acetal (VIII) affords N1-(5-bromoquinoxalin-6-yl)-N3-(2,2-diethoxyethyl)guanidine (IX),which is cyclized by means of HCl to the hydroxyimidazoline (X).Finally,this compound is treated with NaOH to afford 5-bromo-6-(2-imidazolylamino)quinoxaline (AGN-192076).

合成路线:6) The reaction of amine (I) with phenyl chloroformate (XI) in pyridine gives N-(5-bromoquinoxalin-6-yl)carbamic acid phenyl ester (XII),which is then treated with ethylenediamine (XIII) to afford N-(2-aminoethyl)-N'-(5-bromoquinoxalin-6-yl)urea (AGN-192170)).

合成路线:7) The oxidation of brimonidine (AGN-190342) with H2O2 and HCl yields 5-bromo-6-(imidazolidin-2-ylideneamino)-1,2,3,4-tetrahydroquinoxaline-2,3-dione (AGN-191858).