4.6- Diamino-1,2-dihydro-1,3,5-triazines

Base-catalyzed Dimroth rearrangements of l-aryl-4,6-diamino-1,3,5-triazines or triflic acid-induced decomposition of 6-anilino-1,3,5-triazines led to the formation of the corresponding substituted 1,2-dihydro-l,3,5-triazines, whose structure was established on the basis of H NMR spectra (93JHC849). 

Scheme 6.266 Synthesis of 4,6-diamino-2,2-dimethyl-l,2-dihydro-l-phenyl-l, 3,5-triazines.

Studies have recently become available concerning the kinetics and mechanism of the isomerisation, in dilute aqueous solution, of dihydrotriazines of this type (e.g. 4,6-diamino-l-(3,5-dichlorophenyl)-l,2-dihydro-2,2-dimethyl-l,3,5-triazine), and of their degradation to substituted biguanides 683). 

Biguanides [H2NC( = NH)NHC( = NH)NH2] react with lactones, amides, ortho esters, esters, acid anhydrides and acid chlorides to produce a wide range of 6-substituted 2,4-diamino-1,3,5-triazines (515) (59HC(l3)i). Biguanides with carbodiimides, isothiocyanates and ketones give corresponding melamines, thiones and dihydro derivatives, respectively. 

Amino-l,2,4-triazine-5,6-diones (534), 4-amino-4,5-dihydro-1,2,4-triazines (535), 4-amino-5-imino-l,2,4-triazines (536) and 4,6-diamino-1,2,4-triazin-5-ones (537) were prepared by reaction of hydrazidines (526) with oxalates, a-bromo ketones, acyl cyanides (485) and thioxamidates, respectively (80UP21900). 

Reaction of the oxazolium salts (591) with methylhydrazine led to the isolation of 6-hydroxytetrahydro-l,2,4-triazines (592) (74ZOR2429), while the oxazolium or thiazolium salts (593 X = 0,S) with hydrazine gave dihydro-1,2,4-triazines (594) (78HC(33)189, p.576). 2-Amino-3-phenacyloxadiazolium salts (595) and hydrazine afforded the 3,4-diamino compounds (596) (71LA(749)125>. 

Diamino-l-(4-chlorophenyl)-2,2-dimethyl-l,2-dihydro-l,3,5-triazine is the active antimalarial metabolite of the British antimalarial Paludrine (or proguanil) (210) (B-61MI22000, p. 717). 

The role of drug-membrane interactions in overcoming, or at least in reducing, resistance will be discussed using two examples of antibacterials. A series of 5-(substituted) benzyl-2,4-diaminopyrimidines and 4,6-diamino-l,2-dihydro-2,2-dimethyl-l-(3-substituted)phenyl-s-triazines, inhibitors of dihydrofolate reductase (DHFR), were tested against sensitive and resistant E. coli cell cultures as well as against E. coli-derived DHFR [55] and compared with the effect on sensitive and resistant murine tu-... 

An efficient synthesis of l-aryl-4,6-diamino-l,2-dihydro-l,3,5-triazines from an acid-catalyzed reaction between the corresponding arylbiguanidine and carbonyl compounds has been reported <02SC2089>. A new family of functionalized terpyridine-like ligands containing a central 1,3,5-triazine, (8a) and (8b) has been synthesized. These compounds exhibit room-temperature luminiscence as their Ru(II) complexes (9a), (9b) and (9c) <02CC1356>. 

A review by Modest summarizes methods developed for use of the reagent for the synthesis of aromatic triazines (2)° and of 4,6-diamino-l-aryl-l,2-dihydro-s-triazines (4). ... 

Similarly prepared from l,2-diamino-3-chlorocyclopropenylium ions 9 and 4,6-disubstituted 5-dialkylamino-l,2,3-triazincs 10 were the derivatives of l,2-diamino-3-(l,2,3-triazinium-2-yl)cyclopropcnylium dications 11, which upon hydrolysis gave the 1,2-diamino-3-(5-oxo-2,5-dihydro-l,2,3-triazin-2-yl)cyclopropenylium ions 12. " °... 

The use of antifolates in the treatment of coccidiosis in domestic animals has also been established. It has been found that compounds derived from 2,4-diamino-pyrimidines and 2,2-dialkyl-l-aryl-4,6-diamino-l,2-dihydro-s-triazines exhibit promising anticoccidial activity. The noteworthy compounds of this class were found to be pyrimethamine (33), diaverdine (35) and ormetoprim (36) [59]. The metabolites 31a,b of proguanil and chlorproguanil also exhibit marked activity against coccidiosis [60]. 

Diamino-l,2,4-triazines (317) and ortho-esters afforded imidazo[4,5-e]-l,2,4-triazines (6-aza-purines) (318) <86JCS(P2)93l, 90LA631>. With glyoxal and substituted glyoxals in methanol dihydro-and tetrahydro-pyrazino[2,3-e]-l,2,4-triazines (319) (azapteridine systems) were obtained. In one case the pyrazino[2,3-e]-l,2,4-triazine (320) was obtained, by dehydration of the dihydroxy-tetra-hydro intermediate (Scheme 57) <83JHC1123,86JHC33,93H(36)2577>. 

Methiotriazamine, l,6-Dihydro.6.6.dimethyl-I-[4-(methylthio pkenytJ-l,3tS-triazine-2,4-diamine 4.6-di-amino-I,2-dihydrO-2,2-dimetbyl l-[p-[Pg.943]

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