Synthesis and biological evaluation of thieno[3,2-d]- pyrimidinones, thieno[3,2-d]pyrimidines and quinazolinones: conformationally restricted 17b-hydroxysteroid dehydrogenase type 2 (17b-HSD2) inhibitors

Enrico Perspicace; Sandrine Marchais-Oberwinkler; Rolf W Hartmann

doi:10.3390/molecules18044487

Synthesis and biological evaluation of thieno[3,2-d]- pyrimidinones, thieno[3,2-d]pyrimidines and quinazolinones: conformationally restricted 17b-hydroxysteroid dehydrogenase type 2 (17b-HSD2) inhibitors

Molecules. 2013 Apr 16;18(4):4487-509. doi: 10.3390/molecules18044487.

Authors

Enrico Perspicace¹, Sandrine Marchais-Oberwinkler, Rolf W Hartmann

Affiliation

¹ Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, D-66123 Saarbrücken, Germany.

Abstract

In this study, a series of conformationally restricted thieno[3,2-d]pyrimidinones, thieno[3,2-d]pyrimidines and quinazolinones was designed and synthesized with the goal of improving the biological activity as 17b-hydroxysteroid dehydrogenase type 2 inhibitors of the corresponding amidothiophene derivatives. Two moderately active compounds were discovered and this allowed the identification of the biologically active open conformer as well as the extension of the enzyme binding site characterisation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Female
Humans
Hydroxysteroid Dehydrogenases / antagonists & inhibitors
Hydroxysteroid Dehydrogenases / metabolism
Molecular Conformation
Placenta / enzymology
Pregnancy
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology
Pyrimidinones / chemical synthesis*
Pyrimidinones / pharmacology
Quinazolinones / chemical synthesis*
Quinazolinones / pharmacology
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Pyrimidines
Pyrimidinones
Quinazolinones
Hydroxysteroid Dehydrogenases