Synthesis and Early ADME Evaluation of a Novel Scaffold, Tetrahydro-6H-pyrido[3,2-b]azepin-6-one

Muylaert, Koen; Jatczak, Martyna; Wuyts, Benjamin; De Coen, Laurens M; Van Hecke, Kristof; Loones, Hans; Keemink, Janneke; Garcia, Daniel; Mangelinckx, Sven; Annaert, Pieter; Stevens, Christian V

doi:10.1055/s-0033-1341258

Synthesis and Early ADME Evaluation of a Novel Scaffold, Tetrahydro-6H-pyrido[3,2-b]azepin-6-one

Author:

Muylaert, Koen

Jatczak, Martyna ; Wuyts, Benjamin ; De Coen, Laurens M ; Van Hecke, Kristof ; Loones, Hans ; Keemink, Janneke ; Garcia, Daniel ; Mangelinckx, Sven ; Annaert, Pieter ; Stevens, Christian V

Keywords:

Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, bioorganic chemistry, fluorine, fused-ring systems, pyridines, ring expansion, HUMAN INTESTINAL FLUIDS, HIV PROTEASE INHIBITORS, PRIVILEGED STRUCTURES, COMBINATORIAL LIBRARIES, MEDICINAL CHEMISTRY, DRUG SOLUBILITY, ANALOGS, 2,4-METHANOPROLINE, SUBSTRUCTURES, PREDICTION, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, Organic Chemistry, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

The synthesis and preliminary ADME evaluation of -novel 4-(trifluoromethyl)-5,7,8,9-tetrahydro-6H-pyrido[3,2-b]azepin-6-ones is presented. The key step is a ring expansion of 4-(trifluoromethyl)-7,8- dihydroquinolin-5(6H)-ones via a Beckmann rearrangement. The rearrangement opens up possibilities to access novel unexplored scaffolds for medicinal chemistry. The biopharmaceutical profiling revealed a strong structural dependency of the druglike properties. © Georg Thieme Verlag Stuttgart . New York.