Mark H. Stefaniak

Green chemistry tools to influence a medicinal chemistry and research chemistry based organisation

Influencing and improving the environmental performance of a large multi-national pharmaceutical company can be achieved with the help of electronic education tools, backed up by site champions and strong site teams. This paper describes the development of two of those education tools.

Nucleophilic SN2 displacements on penicillin-6- and cephalosporin-7- triflates; 6β-iodopenicillanic acid, a new β-lactamase inhibitor

Abstract Triflate or nonaflate esters of alkyl 6α (or β) hydroxypenicillanates are substituted (with inversion) by the soft nucleophiles iodide, bromide, chloride, azide, arylselenoxide, 1 thiocyanate, thiols, and thiolacids; carbon nucleophiles fail. Methoxide (hard) attacks the lactam bond, opening both rings to give a known 11 1,4 thiazine. Iodide substitutes 7α-trifloxycephalosporins, giving 7β-iodocephalosporins.

A new class of selective and potent inhibitors of neuronal nitric oxide synthase.

The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity.

Synthesis of 5-Heterocyclic Substituted Quinazolin-4-ones via 2-Aminobenzonitrile Derivatives

Two routes to prepare a series of six 5-heterocyclic substituted 2-chloro-7-methoxyquinazolin-4-ones are described, where the heterocycle is a substituted or unsubstituted 1-pyrazolyl, 5-pyrazolyl or 2-thiazolyl group. Both routes proceeded via key 2-aminobenzonitrile intermediates.

Penicillin and cephalosporin sulphoximines

Abstract Penicillin N -cyanosulphoximines are obtained by permanganate oxidation of the sulphilimines. Phthalimidosulphoximines are obtained from penicillin or cephalosporin sulphoxides are phthalimidonitrene (from N -aminophthalimide with lead tetraacetate).