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Synlett 2014; 25(10): 1443-1447
DOI: 10.1055/s-0033-1341258
letter
© Georg Thieme Verlag Stuttgart · New York

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

Koen Muylaert
a   Department 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
a   Department 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
b   Drug 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
a   Department 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
c   XStruct, Department of Inorganic and Physical Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281, S3, 9000 Gent, Belgium
,
Hans Loones
a   Department 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
b   Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, O&N II, Herestraat 49 – Box 921, 3000 Leuven, Belgium
,
Daniel García
a   Department 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
a   Department 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
b   Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, O&N II, Herestraat 49 – Box 921, 3000 Leuven, Belgium
,
Christian V. Stevens*
a   Department 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
› Author Affiliations
Further Information

Publication History

Received: 14 March 2014

Accepted after revision: 27 March 2014

Publication Date:
12 May 2014 (online)

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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

Supporting Information

    for this article is available online at http://www.thieme-connect.com/products/ejournals/journal/ 10.1055/s-00000083.
  • Supporting Information
 

  • References and Notes

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