Pyrimidine-5-carbonitriles II: synthesis and antimicrobial activity of novel 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles.

New series of 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 6-alkyl-2-thiouracil-5-carbonitriles 4c,d, 6-alkyl-2-arylmethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 5a-p, 6-alkyl-2-(2-methoxyethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 6a-d, 6-alkyl-2-benzyloxymethylsulfanyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 7a-c, 6-alkyl-2-(5-nitrofuran-2-ylmethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 8a-d, 6-alkyl-4-arylthio-2-(benzylsulfanyl)pyrimidine-5-carbonitriles 10a, b and 2-benzylsulfanyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-6-pentylpyrimidine-5-carbonitrile 11, were synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 4d, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5 l, 5p, 7a, 7b, 7c, 8a, 8b, 8c, 8d and 11 -displayed marked antibacterial activity particularly against the tested Gram-positive bacteria. Meanwhile, none of these compounds were proved to be active against Candida albicans.

Synthesis of certain 5-substituted 2-thiohydantoin derivatives as potential cytotoxic and antiviral agents.

A convenient route is reported for the synthesis of certain series of 2-thiohydantoins carrying various heterocyclic substituents such as 5-bromothienylidene 3a,b, 5-(2-carboxyphenylthio)-2-thienylidene 4a,b and 4H-thieno[2,3-b][1]benzothiopyran-4-one 5a,b. Glycosylation of these thiohydantoins afforded the S-glycosyl derivatives 10a-d. The synthesized compounds were tested for their activity against HIV-1 virus and as antitumor agents.

Synthesis and antiinflammatory activity of certain thienopyrimidine derivatives.

Interaction of ethyl 2-amino-4,5,6, 7-tetrahydrobenzo[b]thiophene-3-carboxylate 1 with 2-thiophene carbonyl chloride 2 afforded ethyl 2-(2-thenoylamino)-4, 5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 3 which upon cyclization yielded 2-(2-thienyl)-5,6,7, 8-tetrahydrobenzo[b]-thieno[2,3-d]-4H-3, 1-oxazin-4-one 4 and 2(2-thienyl)-3-amino-5, 6,7,8-tetrahydrobenzo-[b]thieno[2,3-d]-3,4-dihydropyrimidin-4-one 6. Some of the prepared compounds were screened for their antiinflammatory activity, compound 7c and 9b showed significant activity.

Synthesis of an AZT-HEPT hybrid and homologous AzddU derivatives.

3'-Azido-2',3'-dideoxyuridines 6 and their corresponding alpha anomers 5 were synthesized by condensation of silylated 6-alkyl and 5,6-dialkyl substituted uracils 2 with methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-alpha, beta-D-erythro-pentofuranoside (4). Compounds 5 and 6 were treated with tetrabutylammonium fluoride to obtain the deprotected nucleosides 7 and 8, respectively.

Synthesis and anti-inflammatory and analgesic activity of some 3-(1-adamantyl)-4-substituted-5-mercapto-1,2,4-triazoles.

The synthesis of a series of 4,5-disubstituted-3-(1-adamantyl)- 1,2,4-triazoles is described. The compounds 3-(1-adamantyl)4-methyl, ethyl and benzyl-5-mercapto-1,2,4-triazoles (3a, 3b and 3f) produced a high dose-dependent anti-inflammatory activity against carrageenin-induced paw oedema in rats. The analgesic activity of these active compounds correlated with their anti-inflammatory activities.

Percentages of the deuterium retained after para-hydroxylation of (R)(+)4-2H-phenytoin and (S)(-) 4-2H-phenytoin in rat.

(R)(+) and (S)(-) 4-2H-phenytoin have been used as substrates for the determination of the percentage of deuterium retention (NIH shift) after para-hydroxylation of the substrates in rat. By using GC-MS analyses, the percentages of deuterium retention were found to be 69% and 70% for the (R) and (S) phenyl rings, respectively. The results add additional evidence for the involvement of arene oxide in the oxidation of the pro (R) and pro (S) phenyls of phenytoin. The oxidation process of each ring could be mediated by independent enzyme systems, a rapid oxidative enzyme for the pro (S) phenyl and a slow oxidative enzyme for the pro (R) phenyl.

Comparative study on the para-metabolic oxidation of phenytoin and decadeuteriophenytoin.

The in-vivo metabolic conversion of equal mixture of phenytoin and decadeuteriophenytoin to the para-hydroxy metabolite in rat was investigated in order to verify a possible role of an insertion or abstraction mechanisms in the hydroxylation process. Determination of kH/k2H values of urine samples at 2 h intervals for 24 h indicated that there was no isotope effect during in-vivo para-hydroxylation of phenytoin. This gives evidence of the arene oxide intermediacy possibly being the sole pathway for para-hydroxylation of phenytoin.

Synthesis and biological testing of certain 2-(5-substituted-2-thienylthio)benzoic acid derivatives.

The syntesis of a number of 2-(5-substituted-2-thienylthio)benzoic acid derivatives is described. The synthesized compounds were screened for their muscle relaxant and parasympatholytic activities and the results are reported.