53484-27-8Relevant academic research and scientific papers
Benzimidazole derivatives as potent and isoform selective tumor-associated carbonic anhydrase IX/XII inhibitors
?al??kan, Burcu,Banoglu, Erden,Gür Maz, Tu??e,Nocentini, Alessio,Supuran, Claudiu T.,Uslu, Azize Gizem
, (2020)
We describe the synthesis of a series of 2-arylbenzimidazole derivatives bearing sulfonamide functionality (4a–d, 7a–c and 10) as well as hydroxamic acid (15a–b), carboxylic acid (16a–b), carboxamide (17a–b) and boronic acid (22a–b and 26) functionalities, which act as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. The newly synthesized benzimidazole derivatives were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IX, and XII), and especially the sulfonamide-containing benzimidazoles demonstrated intriguing inhibitory activity against tumor associated CA IX and XII with KI values in the range of 5.2–29.3 nM and 9.9–41.7 nM, respectively. Notably, compound 4c was the most potent and selective CA IX (KI = 6.6 nM) and XII (KI = 9.9 nM) inhibitor with a significant selectivity ratio over cytosolic CA I and II isoforms in the range of 3.4–25.2. In addition, compounds having hydroxamic acid (15a-b) or carboxylic acid (16a-b) functionalities resulted in greater selectivity ratios for CA IX/XII over CAI/II in the range of 4.1–121.5 although with KI values in lower micromolar potency (KIs = 0.36–0.85 μM for CA IX/XII).
REACTION OF 2,4-DISUBSTITUTED CHLOROBENZENES WITH 3-ALKYLAMINO- AND 3-DIALKYLAMINOPROPIONITRILES
Plakidin, Val. L.,Vostrova, V. N.
, p. 295 - 303 (2007/10/02)
The reaction of 2,4-disubstituted chlorobenzenes with 3-dialkylaminopropionitriles at 65-170 deg C leads to the formation of 2,4-disubstituted N,N-dialkylanilines, and the reaction with 3-alkylaminopropionitriles at 20-130 deg C leads to the formation of 2,4-disubstituted N-alkyl-N-β-cyanoethylanilines.In addition, in the latter case at high temperature (130 deg C) the cyanoethyl group is removed from the substituted N-alkyl-N-β-cyanoethylaniline with the formation of the 2,4-disubstituted N-alkylaniline.
