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

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

doi:10.1055/s-0033-1341258

Synlett, Table of Contents

Synlett 2014; 25(10): 1443-1447
DOI: 10.1055/s-0033-1341258

letter

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

Koen Muylaert

^aDepartment of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: Chris.Stevens@UGent.be

,

Martyna Jatczak

^aDepartment of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: Chris.Stevens@UGent.be

,

Benjamin Wuyts

^bDrug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, O&N II, Herestraat 49 – Box 921, 3000 Leuven, Belgium

,

Laurens M. De Coen

^aDepartment of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: Chris.Stevens@UGent.be

,

Kristof Van Hecke

^cXStruct, Department of Inorganic and Physical Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281, S3, 9000 Gent, Belgium

,

Hans Loones

^aDepartment of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: Chris.Stevens@UGent.be

,

Janneke Keemink

^bDrug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, O&N II, Herestraat 49 – Box 921, 3000 Leuven, Belgium

,

Daniel García

^aDepartment of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: Chris.Stevens@UGent.be

,

Sven Mangelinckx

^aDepartment of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: Chris.Stevens@UGent.be

,

Pieter Annaert

^bDrug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, O&N II, Herestraat 49 – Box 921, 3000 Leuven, Belgium

,

Christian V. Stevens*

^aDepartment of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium Fax: +32(9)2646221 Email: Chris.Stevens@UGent.be

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Abstract

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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.

Key words

bioorganic chemistry - fluorine - fused-ring systems - pyridines - ring expansion

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References

References and Notes
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