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A series of new benzothiazole derivatives 6a-h have been synthesized, in five steps, from substituted phenols via the 1,3,4-oxadiazole-2-thiones 5a-h. The in vitro antitumor activity of the compounds obtained was investigated and the benzothiazol derivatives 6d and 6e showed strong effects on leukaemia cell lines CCRF-CEM (CC50=12+/-2 micromol L(-1), 8+/-1 micromol L(-1), respectively). These compounds are leading candidates for further development. The title compounds were tested against representatives of several virus families containing single stranded RNA genomes, either positive-sense (ssRNA+), or negativesense (RNA-), and against double-stranded RNA genomes (dsRNA), as well as some Flaviviridae viruses

The synthetic routes of 1,2,4-triazole compounds as well as their pharmacological properties have been described. The review focuses intensively on two methods: cycloaddition reaction in the syntheses of various 1,5-dialky-1H-1,2,4-triazole derivatives from the reactive cumulenes with the nitrile precursors as well as the microwave irradiation method.

The family of nitric oxide synthases (NOS) catalyzes the conversion of l-arginine to l-citrulline and nitric oxide (NO), an important cellular messenger molecule which has been implicated in the pathophysiology of septic shock and inflammatory and neurodegenerative disease states. NOS can be maximally activated by the ubiquitous cofactor, (6R)-5,6,7,8-tetrahydrobiopterin (H4Bip), and antagonists of H4Bip may be of therapeutic importance to inhibit pathologically high NO formation. The 4-amino substituted analogue of H4Bip was reported to be a potent NOS inhibitor. Therefore, we developed a series of novel 4-amino pteridine derivatives, anti-pterins, to pharmacologically target the neuronal isoform of nitric oxide synthase (NOS-I). To functionally characterize the pterin/anti-pterin interaction and establish a structure−activity relationship (SAR), we systematically altered the substituents in the 2-, 4-, 5-, 6-, and 7-position of the pteridine nucleus. Varying the substitution pattern in the 2-, 5-, and 7-position resulted in no significant inhibitory effect on enzyme activity. In contrast, bulky substituents in the 6-position, such as phenyl, markedly increased the inhibitory potency of the reduced 4-amino-5,6,7,8-tetrahydropteridines, possibly as a consequence of hydrophobic interactions within NOS-I. However, this was not the case for the aromatic 4-amino pteridines. Interestingly, chemical modification of the 4-amino substituent by dialkyl/diaralkylation together with 6-arylation of the aromatic 2,4-diamino pteridine resulted in potent and efficacious inhibitors of NOS-I, suggesting possible hydrophilic and hydrophobic interactions within NOS-I. This SAR agrees with (a) the recently published crystal structure of the oxygenase domain of the inducible NOS isoform (NOS-II) and (b) the comparative molecular field analysis of selected NOS-I inhibitors, which resulted in a 3D-QSAR model of the pterin binding site interactions. Further optimization should be possible when the full length structure of NOS-I becomes available.

5-substituted 4-(4-chlorophenyl)- 4H-1,2,4-triazol-3-thiones 3 and 2-substituted 5-(4-chlorophenylamino)-1,3,4-thiadiazoles 4 were prepared from the intermediate thiosemicarbazides 2 under basic and acidic conditions, respectively. The thiosemicarbazides, in turn, were prepared by the reaction of hydrazides 1 with 4-chlorophenylisothiocyanate in MeOH. Some of the new synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. All the compounds were inactive except 3f, which showed an EC 50 value of 23.9 µg/mL and 9.9 µg/mL against HIV-1 and HIV-2 with a therapeutic index of 3 and 7, respectively. It means that compound 3f was cytotoxic to MT-4 cells at CC 50 of 72.7 µg/mL in both strains. C 2007 Wiley Periodicals, Inc.

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