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In the framework of investigating the role of heteroatoms in pyridinyl-substituted 5-membered (hetero)cycles as potential p38alpha MAP kinase inhibitor scaffolds, cyclopentene, pyrrole, furan, and imidazole analogues were synthesized and tested with respect to their ability to inhibit p38alpha MAP kinase. The vicinal pyridine/4-fluorophenyl pharmacophore was conserved, such as in the prototypical imidazole inhibitor SB203580. The strength of the HB interaction was calculated and compared to the biological data.

New chiral mono-and bicyclic b-sultams, valuable building blocks for drug synthesis, have been prepared from l-Ala, l-Val, l-Leu, l-Ile, l-Phe, l-Cys, l-Ser, l-Thr, and d-penicillamine by transformation of the COOH group into a methylsulfonyl chloride function, followed by cyclization under basic conditions. Selected properties, derivatives, and reactions of the b-sultams are described.Introduction. ± 1,2-Thiazetidine 1,1-dioxide (b-sultam) is a sulfone analogue (bioisoster) of the b-lactam moiety found in many important drugs [1]. It is known that the sultam ring is much more reactive than the b-lactam ring [2], and that b-sultams can interact with serine proteases such as elastase [3]. Therefore, b-sultams might be useful building blocks for new synthetic drugs and, therefore, should be available not only as racemic or diastereoisomeric mixtures, but as pure isomers [4]. Here, we report the synthesis and properties of chiral, stereochemically pure mono and bicyclic 3-substituted 1,2-thiazetidine 1,1-dioxides and their substitution products.A few examples of chiral b-sultams have been described in the literature [5]. For example, (R)-1,2-thiazetidine-3-carboxylic acid was obtained from l-Cys, and (R)-1,2-thiazetidine-3-methanol from l-Ser. In both cases, compounds from the natural −chiral pool× were used as starting materials, a general approach that has also been followed in the present paper.