Brimonidine tartrate, AGN-190342-LF, UK-14304-18, Alphagan P, Alphagan-药物合成数据库

【药物名称】Brimonidine tartrate, AGN-190342-LF, UK-14304-18, Alphagan P, Alphagan

化学结构式(Chemical Structure):

参考文献No.	352232
标题:	Synthesis and characterization of degradation products and metabolites of brimonidine - A potent alpha2 adrenergic agonist
作者:	Tang-Liu, D.; Burke, J.; Garst, M.; Harcourt, D.; Acheampong, A.; Breau, A.; Munk, S.A.; Wong, H.; Lai, R.; Wheeler, L.
来源:	211th ACS Natl Meet (March 24-28, New Orleans) 1996,Abst MEDI 021

合成路线图解说明: 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).

合成路线图解说明: 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).

合成路线图解说明: 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)).

合成路线图解说明: 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).