Recent Advances in the Synthesis of 1,3-Azoles.

The 1,3-azole motif is a common and integral feature of many clinical drugs. Due to their wide-ranging applications, the development of 1,3-azoles as therapeutic agents is an ongoing focus of medicinal chemists. This review highlights the recent approaches towards the assembly of 1,3-oxazole, 1,3-thiazole and 1,3-imidazole motifs.

Synthesis, pharmacological studies and molecular modeling of some tetracyclic 1,3-diazepinium chlorides.

Seven new 1,3-diazepinium chlorides exhibiting some structural similarities to the 1,4-benzodiazepines were synthesized. In a Hippocratic screen using mice, three of these salts, 3-methoxy-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8a), 3-methoxy-9-methyl-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8c) and 3-methoxy-11-methyl-6-oxo-7,13-dihydro-6H-benzofuro[2,3-e]pyrido[1,2-a][1,3]diazepin-12-ium chloride (8e) were examined for their effect on the central nervous system, and their activities compared to that of diazepam. On their own, salts 8a, 8c and 8e solicited no sedative effects on the behaviour of the animals. However, they elicited significant effects in combination with diazepam on diazepam-induced activities such as decreased motor activity, ataxia and loss of righting reflex. Compounds 8a and 8c were fitted into the pharmacophore/receptor model developed by Cook et al. with interaction at the L(1), H(1) and A(2) sites indicating that they are potential inverse agonists of the Bz receptor. The compounds displayed some affinity for the alpha1 isoform of the GABA(A)/BzR (L(Di) interaction) but are non-selective for alpha5 (no L(2) interaction). Results of binding affinity studies showed that compound 8a is mildly selective for the alpha1 receptor although not very potent (K(i)=746.5nM). The significant potentiation of diazepam-induced ataxia and decreased motor activity by compounds 8a and 8c in the Hippocratic screen may be associated with alpha1 selectivity.

Synthesis of benzothiazoles via ipso substitution of ortho-methoxythiobenzamides.

An efficient route to the synthesis of benzothiazoles from ortho-methoxythiobenzamides via the ipso substitution of an aromatic methoxy group is presented, and the mechanism of the Jacobson synthesis of benzothiazoles is further investigated.

Synthesis of 9-methyl-1H-[1,4]thiazino[3,2-g]quinoline-2,5,10(3H)-trione, the B,C,D ring core of the shermilamine alkaloids.

Synthesis of 9-methyl-1H-[1,4]thiazino[3,2-g]quinoline-2,5,10(3H)-trione (4), from N-(4-bromo-2,5-dimethoxyphenyl)acetamide (23) is described. Oxidative cyclisation of 2,2'-disulfanediylbis[N-(2,5-dimethoxyphenyl)acetamide] (19) to 5,8-dimethoxy-2H-1,4-benzothiazin-3(4H)-one (7b) is also reported.

Thiophene isosteres of 9,10-dithioanthraquinone.

[reaction: see text] The preparation of 1,3,5,7-tetramethyl-4,8-dihydrobenzo[1,2-c:4,5-c']dithiophene-4,8-dione and its conversion to the corresponding mono- and dithione are described.