Synthesis of some novel pyridinethione nucleoside of expected chemotherapeutic effect

Research Abstract

The present investigation comprises a survey covering the synthesis and biological importance of many imidazo and oxazolo[4,5-b]pyridines. The thesis involves the preparation of 2,3-diaminopyridine (VIIa) and 2-amino-3-hydroxypyridine (VIIb) and their reaction with p-aminobenzoic to give the imidazo and oxazolopyridines VIIIa,b. The latter were halogenated to afford VIIIc-h. The imidazo and oxazolopyridines VIIIa-h were aceylated with acetyl chloride, chloroacetyl chloride, dichloroacetyl chloride and benzoyl chloride to give the corresponding acylated derivatives IXa-h, XIa-h, XIIa-h and XIIIa-h. The diacetyl derivatives Xa-d were also synthesized. On the other hand, the imidazo and oxazolopyridines VIIIa-h were diazotized and the diazonium salts of VIIIa,b were reacted with diethylmalonate to give XIVa,b. The latter were condensed with two hydrazines to give the cyclized products XVa-d. The intermediates XIVa,b were also reacted with urea and thiourea to give the cyclized derivatives XVIa-d. Moreover, the diazonium salts of VIIIa,b,g and h were reacted with malononitrile to afford the dicyano derivatives XVIIa-d. The latter when condensed with hydrazine afforded compounds XVIIIa-d. In addition a number of azo dyes of imidazo and oxazolopyridines were also, synthesized XIXa-v via coupling of the diazonium salts of VIIIa-h with different phenolic compounds. The azo dyes XIXa,f,o and p were acetylated to give the corresponding acetyl derivatives XXa-d. The investigation comprises also the reaction of VIIIa-h with different aromatic aldehydes to give arylidine derivatives XXIa-v. Some of the latter were reacted with chloroacetyl chloride to yield β-lactam containing derivatives XXIIa-d and with thioglycolic acid to give compounds XXIIIa-d. Additionally some of these new imidazo and oxazolo[4,5-b]pyridine derivatives were subjected to antimicrobial screening and molecular modeling study. The study includes the synthesis of certain unavailable starting and intermediates materials: 1) Ethyl pyridine-3-carboxylate (Ethyl nicotinate) (I). 2) Pyridine-3-carboxhydrazide (Nicotinhydrazide) (II). 3) 3-Ethoxycarbonylaminopyridine (III). 4) 3-Ethoxycarbonylamino-2-nitropyridine (IV). 5) 3-Amino-2-nitropyridine (V). 6) 2,3-Diaminopyridine (VIIa). 7) 3-Hydroxy-2-nitropyridine (VI). 8) 2-Amino-3-hydroxypyridine (VII b). 9) 2-(4-Aminophenyl)imidazo(or oxazolo)[4,5-b]pyridines VIIIa,b. The thesis includes also the synthesis of certain new intermediates and final products: 1) 2-(4-Amino-3-iodophenyl)imidazo(or oxazolo)[4,5-b]pyridines VIIIc,d. 2) 2-(4-Amino-3-chlorophenyl)imidazo(or oxazolo)[4,5-b]pyridines VIIIe,f. 3) 2-(4-Acetamidophenyl)imidazo(or oxazolo)[4,5-b]pyridines IXa,b. 4) 2-(4-Acetamido-3-bromophenyl)imidazo(or oxazolo)[4,5-b]pyridines IXc,d. 5) 2-(4-Amino-3-bromophenyl)imidazo(or oxazolo)[4,5-b]pyridines VIII g,h. 6) 2-(4-Acetamido-3-halophenyl)imidazo(or oxazolo)[4,5-b]pyridines IXe-h. 7) 2-(4-Diacetylaminophenyl)oxazolo[4,5-b]pyridines (Xa-d). 8) 2-(4-Chloroacetamidophenyl)imidazo(or oxazolo)[4,5-b]pyridines XIa-h. 9) 2-(4-Dichloroacetamidophenyl)imidazo(or oxazolo)[4,5-b]pyridines XIIa-h. 10) 2-(4-Benzamidophenyl)imidazo(or oxazolo)[4,5-b]pyridines XIIIa-h. 11) 2-{4-[N2(Bis(ethoxycarbonyl)methylene)hydrazino]phenyl}imidazo (or oxazolo)[4,5-b]pyridines XIVa,b. 12) 2-{4-[N2-(3,5-Dioxopyrazolidin-4-ylidene)hydrazino]phenyl}imidazo (or oxazolo)[4,5-b]pyridines XVa-d. 13) 2-{4-[N2-(2,4,6-Trioxoperhydropyrimidin-5-ylidene)hydrazino]phenyl}imidazo (or oxazolo)[4,5-b]pyridines XVIa,c. 14) 2-{4-[N2-(4,6-Dioxo-2-thioxoperhydropyrimidin-5-ylidene)hydrazino]phenyl} imidazo (or oxazolo )[4,5-b]pyridines XVIb,d. 15) 2-{4-[N2(Bis(cyano)methylene)hydrazino]phenyl}imidazo(or oxazolo) [4,5-b]pyridines XVIIa-d. 16) 2-{4-[N2-(3,5-Diaminopyrazol-4-ylidene)hydrazino]phenyl}imidazo (or oxazolo)[4,5-b]pyridines XVIIIa-d. 17) 2-[4-Arylazophenyl]imidazo(or oxazolo)[4,5-b]pyridines XIXa-v. 18) 2-[4-(4-acetoxyphenyl)azophenyl]imidazo(or oxazolo)[4,5-b]pyridines XXa-d. 19) 2-[4-Arylidenaminophenyl]imidazo(or oxazolo)[4,5-b]pyridines XXIa-v. 20) 2-[4-(3-Chloro-2-oxo-4-substituted phenylazetidin-1-yl)phenyl]imidazo (or oxazolo)[4,5-b]pyridines XXIIa-d. 21) 2-[4-(4-oxo-2-subsituted phenylthiazolidin-3-yl)phenyl]imidazo (or oxazolo)[4,5-b]pyridines XXIIIa-d. The structure of the new compounds was substantiated from elemental analysis as well as IR and in certain cases 1H-NMR and mass spectra.

Research Keywords

Synthesis of some novel pyridinethione nucleoside of expected chemotherapeutic effect