Michael Brands

Dihydropyrimidinones—A New Class of Anti-Staphylococcal Antibiotics

We report the synthesis and pharmacological evaluation of new derivatives of natural dipeptide antibiotic TAN-1057 A, B. In the course of this program, we identified novel analogues of the natural product that display similar antibacterial activity and showed improved tolerability.

Pyrimidinone antibiotics--heterocyclic analogues with improved antibacterial spectrum.

We report the synthesis and pharmacological evaluation of new derivatives of the natural dipeptide antibiotic TAN 1057 A,B containing heterocycles either in the beta-amino acid side chain or as mimics of the urea function. In the course of this program, we identified novel analogues that display activity towards a broader panel of Gram-positive bacteriae.

Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer

Selective inhibition of exclusively transcription‐regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY‐958, lead optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification of the orally available clinical candidate atuveciclib (BAYu20051143572). Structurally characterized by an unusual benzyl sulfoximine group, BAYu20051143572 exhibited the best overall profile inu2005vitro and inu2005vivo, including high efficacy and good tolerability in xenograft models in mice and rats. BAYu20051143572 is the first potent and highly selective PTEFb/CDK9 inhibitor to enter clinical trials for the treatment of cancer.