N-aryl-N′-ureido-O-sulfamates: Potent and selective inhibitors of the human Carbonic Anhydrase VII isoform with neuropathic pain relieving properties

被引：15

作者：

Bozdag, Murat ^{[1
]}

Poli, Giulio ^{[2
]}

Angeli, Andrea ^{[1
]}

Lucarini, Elena ^{[3
]}

Tuccinardi, Tiziano ^{[2
]}

Mannelli, Lorenzo Di Cesare ^{[3
]}

Sellerri, Silvia ^{[1
]}

Ghelardini, Carla ^{[3
]}

Winum, Jean-Yves ^{[4
]}

Carta, Fabrizio ^{[1
]}

Supuran, Claudiu T. ^{[1
]}

机构：

[1] Univ Florence, NEUROFARBA Dept, Sez Sci Farmaceut & Nutraceut, Via Ugo Schiff 6, I-50019 Florence, Italy

[2] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56126 Pisa, Italy

[3] Univ Florence, NEUROFARBA Dept, Sez Farmacol & Tossicol, Viale Gaetano Pieraccini 6, I-50139 Florence, Italy

[4] Univ Montpellier, ENSCM, UMR 5247 CNRS, IBMM, 240 Ave Prof Emile Jeanbrau, F-34296 Montpellier 05, France

来源：

BIOORGANIC CHEMISTRY | 2019年 / 89卷

关键词：

Carbonic Anhydrase; Neuropathic pain; Carbonic Anhydrase Inhibitors; N-aryl-N '-ureido-O-sulfamates; MECHANISM; COUMARINS; DESIGN; SHOW; IX; DISCOVERY; AFFINITY; SYSTEM; GROWTH;

D O I：

10.1016/j.bioorg.2019.103033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Herein we report for the first time an efficient synthetic procedure for the preparation of N-aryl-N'-ureido-O-sulfamates (AUSs) as a new class of Carbonic Anhydrase Inhibitors (CAIs). The compounds were tested for the inhibition of several human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) isoforms. Interesting inhibition activity and high selectivity against CA VII and XII versus CA I and II, with K(I)s in the low nanomolar range, were observed. Molecular modeling studies allowed us to decipher the structural features underpinning the selective inhibitory profile of AUSs towards isoforms CAs VII and XII. A selection of sulfamates showed promising neuropathic pain modulating effects in an in vivo animal model of oxaliplatin induced pain.

引用

页数：10

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