期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 155, 期 -, 页码 545-551出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.06.021
关键词
1,2,3-Triazoles; Benzenesulfonamide; Carbonic anhydrase isoforms I, II, IV, IX; Acetazolamide; Enaminones
资金
- University Grants Commission, New Delhi, India
In a quest to discover new biologically active compounds, a series of twenty novel heterocyclic derivatives substituted at position 5 with-H (7a-7j) or -CF3 (8a-8j), bearing benzenesulfonamide at N-1 position and various aroyl groups at position 4 of the 1,2,3-triazole ring was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibition potential against four human (h) isoforms hCA I, II, IV and IX. All the compounds (7a-7j and 8a-8j) were synthesized via [3+2] cycloaddition reaction from 4-azidobenzenesulfonamide. Interestingly, compounds 7a-7j were prepared in one pot manner via enaminone intermediate using novel methodology. All the newly synthesized compounds (7a-7j & 8a-8j) were found to be excellent inhibitors of edema related isoform hCA I with their inhibition constant (KO ranging from 30.1 to 86.8 nM as compared to standard drug acetazolamide (AAZ) with K-i = 250 nM. Further it was found that most of tested compounds were weaker inhibitors of isoform, hCA II although compounds 7b, 7d-7e, 8a, 8d-8f, 81 (mostly with electron withdrawing substituents) have shown better inhibition potential (K-i < 50 nM). Against glaucoma associated hCA IV, compound 7d was found to be better inhibitor (K-i = 52.4 nM) than AAZ (K-i = 74 nM) while against tumor associated hCA IX, all the compounds have shown moderate inhibition potential. Present study have added one more step in exploring the 1,2,3-triazlole moiety in the medicinal field. (C) 2018 Elsevier Masson SAS. All rights reserved.
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