Synthesis of 16α-amino-pregnenolone derivatives via ionic liquid-catalyzed aza-Michael addition and their evaluation as C17,20-lyase inhibitors

Eszter Szánti-Pintér; Lilla Maksó; Ágnes Gömöry; Johan Wouters; Bianka Edina Herman; Mihály Szécsi; Gábor Mikle; László Kollár; Rita Skoda-Földes

doi:10.1016/j.steroids.2017.05.006

Synthesis of 16α-amino-pregnenolone derivatives via ionic liquid-catalyzed aza-Michael addition and their evaluation as C_17,20-lyase inhibitors

Steroids. 2017 Jul:123:61-66. doi: 10.1016/j.steroids.2017.05.006. Epub 2017 May 11.

Authors

Eszter Szánti-Pintér¹, Lilla Maksó¹, Ágnes Gömöry², Johan Wouters³, Bianka Edina Herman⁴, Mihály Szécsi⁴, Gábor Mikle⁵, László Kollár⁵, Rita Skoda-Földes⁶

Affiliations

¹ University of Pannonia, Institute of Chemistry, Department of Organic Chemistry, Egyetem u. 10 (P.O. Box 158), H-8200 Veszprém, Hungary.
² Hungarian Academy of Sciences, Research Centre for Natural Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary.
³ University of Namur, Department of Chemistry, Rue de Bruxelles 61, B-5000 Namur, Belgium.
⁴ 1st Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720 Szeged, Hungary.
⁵ University of Pécs, Department of Inorganic Chemistry and MTA-PTE Research Group for Selective Chemical Syntheses, Ifjúság u. 6 (P.O. Box 266), H-7624 Pécs, Hungary.
⁶ University of Pannonia, Institute of Chemistry, Department of Organic Chemistry, Egyetem u. 10 (P.O. Box 158), H-8200 Veszprém, Hungary. Electronic address: skodane@almos.uni-pannon.hu.

PMID: 28502863
DOI: 10.1016/j.steroids.2017.05.006

Abstract

Aza-Michael addition of 16-dehydropregnenolone was studied in the presence of a basic ionic liquid, [DBU][OAc] as catalyst and solvent. The reaction was carried out using different primary and secondary amines as N-nucleophiles. The products were obtained in moderate to good yields and were characterized by ¹H and ¹³C NMR, MS and IR. The ionic liquid was found to be an efficient and recyclable catalyst that was reused five times. The products were investigated for the inhibition of in vitro C_17,20-lyase activity and displayed moderate inhibitory effect.

Keywords: 16-Dehydropregnenolone; Aza-Michael addition; DBU; Ionic liquid; P450(17α) inhibitors.

Publication types

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

MeSH terms

Animals
Catalysis
Chemistry Techniques, Synthetic
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Ionic Liquids / chemistry*
Lyases / antagonists & inhibitors*
Models, Molecular
Molecular Conformation
Pregnenolone / analogs & derivatives
Pregnenolone / chemical synthesis*
Pregnenolone / chemistry
Pregnenolone / pharmacology*
Rats

Substances

Enzyme Inhibitors
Ionic Liquids
16-dehydropregnenolone
Pregnenolone
Lyases