193538-78-2Relevant articles and documents
A Series of Thiadiazolyl-Benzenesulfonamides Incorporating an Aromatic Tail as Isoform-Selective, Potent Carbonic Anhydrase II/XII Inhibitors
Banoglu, Erden,Bonardi, Alessandro,Gratteri, Paola,Supuran, Claudiu T.,Vullo, Daniela,Ercanl?, Taner,Gür Maz, Tu??e
, (2022/03/14)
We describe the synthesis of a series of thiadiazolyl-benzenesulfonamide derivatives carrying an aromatic tail linked by an amide linker (12–34), as human carbonic anhydrase (hCA) inhibitors. These thiadiazol derivatives were evaluated against four physiologically relevant CA isoforms (hCA I, II, IX, and XII), and demonstrated intriguing inhibitory activity against CA II with Ki values in the range of 2.4–31.6 nM. Besides hCA II, also hCA XII activity was potently inhibited by some of the derivatives (Ki=1.5–88.5 nM), producing dual inhibitors of both isoforms. Notably, compound 17 was the most potent dual CA II (Ki=3.1 nM) and XII (Ki=1.5 nM) inhibitor with a significant selectivity ratio over CA I and IX isoforms. In conclusion, although all compounds exhibited preferential activity towards hCA II, the nature of the substituents at the tail part of the main scaffold influenced the activity and selectivity toward other isoforms.
6,7-Dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline amides and corresponding ester isosteres as multidrug resistance reversers
Bartolucci, Gianluca,Braconi, Laura,Colabufo, Nicola Antonio,Contino, Marialessandra,Dei, Silvia,Giampietro, Roberta,Manetti, Dina,Perrone, Maria Grazia,Riganti, Chiara,Romanelli, Maria Novella,Teodori, Elisabetta,Chiaramonte, Niccolò
, p. 974 - 992 (2020/04/24)
Aiming to deepen the structure–activity relationships of the two P-glycoprotein (P-gp) modulators elacridar and tariquidar, a new series of amide and ester derivatives carrying a 6,7-dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline scaffold linked to different methoxy-substituted aryl moieties were synthesised. The obtained compounds were evaluated for their P-gp interaction profile and selectivity towards the two other ABC transporters, multidrug-resistance-associated protein-1 and breast cancer resistance protein, showing to be very active and selective versus P-gp. Two amide derivatives, displaying the best P-gp activity, were tested in co-administration with the antineoplastic drug doxorubicin in different cancer cell lines, showing a significant sensitising activity towards doxorubicin. The investigation on the chemical stability of the derivatives towards spontaneous or enzymatic hydrolysis, showed that amides are stable in both models while some ester compounds were hydrolysed in human plasma. This study allowed us to identify two chemosensitizers that behave as non-transported substrates and are characterised by different selectivity profiles.
Nickel-Catalyzed Oxidative Decarboxylative Annulation for the Synthesis of Heterocycle-Containing Phenanthridinones
Honeycutt, Aaron P.,Hoover, Jessica M.
supporting information, p. 7216 - 7219 (2018/11/23)
A nickel-catalyzed oxidative decarboxylative annulation reaction of simple benzamides and (hetero)aromatic carboxylates has been developed. This reaction provides access to a large array of phenanthridinones and their heterocyclic analogues, highlighting the utility and versatility of oxidative decarboxylative coupling strategies for C-C bond formation.