A series of novel N,N ''-diaryl cyanoguanidines were synthesized by reacting diphenyl N-cyanocarbonimidate with sulfanilamide followed by treatment of the obtained cyano-O-phenylisourea with substituted aromatic amines. The newly prepared N,N ''-diaryl cyanoguanidines showed a very interesting inhibition profile against four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, hCA I and hCA II (cytosolic), hCA IV (membrane-bound), and hCA IX (transmembrane). All these compounds showed a potent inhibition against isoform hCA II,with inhibition constants in the low nanomolar range, as well as a high selectivity for hCA II over hCA I, IV and IX. Since hCA II is an important drug target for antiglaucoma agents, these isoform-selective inhibitors may be considered of interest for further medicinal/pharmacologic studies. (C) 2018 Elsevier Inc. All rights reserved.

Synthesis and biological evaluation of novel N,N'-diaryl cyanoguanidines acting as potent and selective carbonic anhydrase II inhibitors / Akocak, Suleyman; Lolak, Nabih; Bua, Silvia; Turel, Idris; Supuran, Claudiu T. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - ELETTRONICO. - 77:(2018), pp. 0-0. [10.1016/j.bioorg.2018.01.022]

Synthesis and biological evaluation of novel N,N'-diaryl cyanoguanidines acting as potent and selective carbonic anhydrase II inhibitors

Bua, Silvia;Supuran, Claudiu T
2018

Abstract

A series of novel N,N ''-diaryl cyanoguanidines were synthesized by reacting diphenyl N-cyanocarbonimidate with sulfanilamide followed by treatment of the obtained cyano-O-phenylisourea with substituted aromatic amines. The newly prepared N,N ''-diaryl cyanoguanidines showed a very interesting inhibition profile against four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, hCA I and hCA II (cytosolic), hCA IV (membrane-bound), and hCA IX (transmembrane). All these compounds showed a potent inhibition against isoform hCA II,with inhibition constants in the low nanomolar range, as well as a high selectivity for hCA II over hCA I, IV and IX. Since hCA II is an important drug target for antiglaucoma agents, these isoform-selective inhibitors may be considered of interest for further medicinal/pharmacologic studies. (C) 2018 Elsevier Inc. All rights reserved.
2018
77
0
0
Akocak, Suleyman; Lolak, Nabih; Bua, Silvia; Turel, Idris; Supuran, Claudiu T
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1308199
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 30
social impact