Djigoue G.B.,Chu Of Quebec Research Center Chul T |
Djigoue G.B.,Laval University |
Kenmogne L.C.,Chu Of Quebec Research Center Chul T |
Kenmogne L.C.,Laval University |
And 3 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2013
Spiromorpholinone derivatives were synthesized from androsterone or cyclohexanone in 6 or 3 steps, respectively, and these scaffolds were used for the introduction of a hydrophobic group via a nucleophilic substitution. Non-steroidal spiromorpholinones are not active as inhibitors of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3), but steroidal morpholinones are very potent inhibitors. In fact, those with (S) stereochemistry are more active than their (R) homologues, whereas N-benzylated compounds are more active than their non substituted precursors. The target compounds exhibited strong inhibition of 17β-HSD3 in rat testis homogenate (87-92% inhibition at 1 μM). © 2013 Elsevier Ltd. All rights reserved.