75073-56-2Relevant academic research and scientific papers
Novel, potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors as potential therapeutics for osteoporosis with dual human and mouse activities
Perspicace, Enrico,Cozzoli, Liliana,Gargano, Emanuele M.,Hanke, Nina,Carotti, Angelo,Hartmann, Rolf W.,Marchais-Oberwinkler, Sandrine
, p. 317 - 337 (2014/07/21)
17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) is responsible for the oxidation of the highly active estradiol (E2) and testosterone (T) into the less potent estrone (E1) and Δ4-androstene-3,17-dione (Δ4-AD), respectively. As 17β-HSD2 is present in bones and as estradiol and testosterone are able to induce bone formation and repress bone resorption, inhibition of this enzyme could be a new promising approach for the treatment of osteoporosis. Herein, we describe the design, the synthesis and the biological evaluation of 24 new 17β-HSD2 inhibitors in the 5-substituted thiophene-2-carboxamide class. Structure-activity and structure-selectivity relationships have been explored by variation of the sulfur atom position in the central core, exchange of the thiophene by a thiazole, substitution of the amide group with a larger moiety, exchange of the N-methylamide group with bioisosteres like N-methylsulfonamide, N-methylthioamide and ketone, and substitutions at positions 2 and 3 of the thiophene core with alkyl and phenyl groups leading to 2,3,5-trisubstituted thiophene derivatives. The compounds were evaluated on human and mouse enzymes. From this study, a novel highly potent and selective compound in both human and mouse 17β-HSD2 enzymes was identified, compound 21 (IC 50(h17β-HSD2) = 235 nM, selectivity factor toward h17β-HSD1 = 95, IC50 (m17β-HSD2) = 54 nM). This new compound 21 could be used for an in vivo proof of principle to demonstrate the true therapeutic efficacy of 17β-HSD2 inhibitors in osteoporosis. New structural insights into the active sites of the human and mouse enzymes were gained.
Synthesis and biological evaluation of β-chloro vinyl chalcones as inhibitors of TNF-α and IL-6 with antimicrobial activity
Bandgar, Babasaheb P.,Patil, Sachin A.,Korbad, Balaji L.,Nile, Shivraj H.,Khobragade, Chandrahase N.
scheme or table, p. 2629 - 2633 (2010/07/09)
A series of β-chloro vinyl chalcones have been synthesized by Claisen-Schmidt condensation. β-chloro vinyl aldehyde has been synthesized by the Vilsmayer-Hack formylation reaction. The structures of the newly synthesized compounds were confirmed by 1H NMR, IR and Mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-α and IL-6) and antimicrobial (antibacterial and antifungal) activity. Compounds 5a, 5d, 5e, 5g and 5i exhibited promising activity against IL-6 with 58-83% inhibition at 10 μM concentration. None of the compound was found to be cytotoxic in CCK-8 cells at 10 μM concentration. Whereas compounds 5b, 5d, 5e and 5i showed very good antibacterial activity and compounds 5a, 5b, 5e and 5i showed good antifungal activity.
Heteroaromatic Rings as Substituents. Part 5. Evaluation of ? and ?- Constants of 2-Selenienyl and 2-Tellurienyl Groups
Fringuelli, Francesco,Serena, Bernardino,Taticchi, Aldo
, p. 971 - 975 (2007/10/02)
p- and m-2-selenienyl- and 2-tellurienyl-anisoles, p- and m-2-selenienyl- and 2-tellurienyl-phenols, and four 2,5-disubstituted tellurophens were synthesized and their structures established by 1H n.m.r. and mass spectra.The ?- and ? constants
