Pyrazolo pyrimidine triazoles

Variation of the ring portion of acyclovir has been achieved. Compounds include monocyclic (isocytosine, triazole, imidazole), bicyclic (adenine, 8-azapurine, pyrrolo[2,3-c/]-pyrimidine, pyrazolo[3,4-[Pg.131]

Pyrazolo[l,5-fc]-l,2,4-triazole 154 " and l,2,4-triazolo[l,5-a]pyridine 156 ring systems were successfully obtained from the corresponding formamidoximes or related ami-doximes 153 and 155, respectively, and acylating agent (TsCl or TFAA) (equations 67 and 68). Similarly, l,2,4-triazolo[l,5-a]pyrimidines were obtained from pyrimidine formamidoximes . 

When the synthesis of a heterocyclic system containing a diazole fused onto l,2,3-triazin-4-one (e.g., imidazo[4,5-i [l,2,3]tnazin-4-one (Section 10.13.9.1.l(i)) and pyrazolo[3,4-rf [l,2,3]triazin-4-one (Section 10.13.9.1.1(ii))) or 1,2,3-triazole fused onto pyrimidin-4(7)-(di)one (e.g., [l,2,3]triazolo[4,5-rf pyrimidin-4(7)-(di)one (Section 10.13.9.1.l(iv))) is required, the synthesis of the six-membered ring is the most reliable method. There are several recent accounts of six-membered annulations onto 1,2,3-triazoles to give [l,2,3]triazolo[4,5-r/ pyrimidines (Section 10.13.9.1.l(iv)), which are valuable alternatives to 1,2,3-triazole annulation using nitrosation techniques <1996CHEC-II(7)489>. 

Alternatively, (217) react with activated methylene synthons in the presence of potassium bicarbonate to afford transient C=N adducts (218) which revert to the 4-amino-5-(/ ,/ -di substituted vinyl)triazoles (219) or (220). Recyclization of these products (219) or (220) affords (215). Similar transformations of l-substituted-l/7-pyrazolo[3,4-J]pyrimidines (77CPB535), pyrido[2,3-t/]py-rimidines (75CPB2939, 78CPB3242), and quinazolines <79CPB286l> have also been reported. 

Two groups of compounds appear to show the most promise as selective xanthine oxidase inhibitors those based on a pyrazolo[l,5-a]pyrimidine nucleus, which show mixed or non-competitive inhibition and substituted triazoles, which are competitive inhibitors [192, 193]. The 3-position of the pyrazolo[l,5-a]pyrimidines (48) is spatially equivalent to the 9-position of purine, and 3-aryl-substituted compounds were found to be 30-160-times better inhibitors than allopurinol (Table 3.8) [ 194]. In contrast, the hetero-rings in the potent substituted triazole inhibitors (49) are no longer fused, but those compounds with substituted aryl groups in the 3-position have the highest levels of intrinsic activity (Table 3.8) [195]. 

The formamide reaction has been successfully used to convert a 2-amino-pyridine-3-carboxamide to pyrido[2,3-d]pyrimidin-4-ones (see 3)220 3-aminopyrazole-4-carboxamide (see 15) to pyrazolo[3,4-rf ] pyrimidin-4-ones (see 16)118 4-aminopyrazole-3-carboxamide to pyrazolo[4,3-d]pyrimi-din-7-ones (see 17)221 many 4-amino-1,2,3-triazole-5-carboxamides (see 20) to 8-azapurin-6-ones (see 21)157,217-222—226 and 4-aminoimidazole-5-car-boxamides (see 18) to purin-6-ones (see 19).124-202-227 228 Secondary amines are suitable starting materials, as in the conversion of 4-amino-l,2,3-triazole-5-(jV-methyl)carboxamide and its 3-benzyl63 and... 

Thiourea has been used similarly to prepare, at 175°C (3 hr) up to 205°C (20 min), good yields of annelated 2-thioxopyrimidin-4-ones such as 8-methyl-2-thioxo-8-azapurin-6-one (156) from 4-amino-1,2,3-triazole-5-car-boxamides (see 20),254 as well as pyrazolo[4,3-d]- and pyrazolo[3,4-d]pyri-midinediones from the appropriate aminopyrazolecarboxamides (see 15) 24,221 and thieno[2,3-d]pyrimidine-2,4-diones (see 12) from 2-amino-thiophene-3-carboxamide.25 5... 

Aryl-6-phenyl-2-methylthio/secondary amino substituted-4(3//)-pyrimidinones were derived from a reaction of N-arylamino substituted 1,3-diaza-1,3-butadienes with substituted ketenes that was analyzed by computational methods <97T13829>. 1,3-Diazines related to 6-amino-4-chloro-5-cyano-2-(dimethylamino)pyrimidine were prepared in one-pot fashion from 1,1-diamino-2,2-dicyanoethylene and phosgeniminium chloride <97SC1223>. Pyrazolo[3,4- /]pyrimidines were derived from 4-substituted 5-aminopyrazole-l-carbothioamides <97JCR(S)352>. Amino-5-(trifluoromethyl)-l,2,4-triazole gave polysubstituted 2-... 

H. Behbehani, H.M. Ibrahim, S. Makhseed, H. Mahmoud, Applications of 2-aryIhydrazononitriles in synthesis preparation of new indole containing 1,2,3-triazole, pyrazole and pyrazolo[l,5-a]pyrimidine derivatives and evaluation of their antimicrobial activities, Eur. J. Med. Chem. 46 (2011) 1813-1820. 

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