Synthesis of isoxazole-containing sulfonamides with potent carbonic anhydrase II and VII inhibitory properties
Yükleniyor...
Dosyalar
Tarih
2017
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Pergamon-Elsevier Science Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Two series of benzenesulfonamide containing isoxazole compounds were prepared by using conventional and microwave (MW) methods. 5-Amino-3-aryl-N-(4-sulfamoylphenyl)isoxazole-4-carboxamide derivatives were synthesized by the reaction of hydroxymoyl chlorides with 2-cyano-N-(4-sulfamoylphenyl)acetamide in the presence of triethylamine. The synthesized 5-amino isoxazoles were reacted with various benzoyl chlorides in order to obtain 5-amidoisoxazoles. The novel compounds were screened in vitro as inhibitors of four human (h) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1): hCA I, hCA II, hCA IV and hCA VII. The derivatives of the first series were shown to possess excellent inhibitory activity against the cytosolic isoform hCA II, an antiglaucoma drug target, with Kis in the range of 0.5-49.3 nM and hCA VII, a recently validated anti-neuropathic pain target with Kis in the range of 4.3-51.9 nM. (C) 2017 Elsevier Ltd. All rights reserved.
Açıklama
Anahtar Kelimeler
5-Amino Isoxazole, 5-Amidoisoxazole, Carbonic Anhydrase, Sulfonamide, Amide
Kaynak
Bioorganic & Medicinal Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
25
Sayı
4
