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Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship.
Eur J Med Chem. 2013 Apr; 62:597-604.EJ

Abstract

In this study, starting from a lead compound discovered by virtual screening, a series of novel heterocyclic substituted benzenesulfonamides were designed and synthesized as new carbonic anhydrase IX (CA IX) inhibitors. Some compounds exhibited potent inhibitory effects against CA IX (in the low nanomolar range) as well as high selectivity against other carbonic anhydrase isozymes (CA I and CA II). The most potent and selective compound 27 could inhibit CA IX in the subnanomolar level with IC50 of 0.48 nM, which increased the potency by about 40-fold against CA IX compared with the lead compound 26, and presented more than 10(3) fold selectivity over CA I and CA II. The structure-activity relationship (SAR) based on the docking experiments further elucidated the effects of the compounds on the bioactivity and selectivity.

Authors+Show Affiliations

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, Shanghai 200237, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23429054

Citation

Gao, Rui, et al. "Optimization of Heterocyclic Substituted Benzenesulfonamides as Novel Carbonic Anhydrase IX Inhibitors and Their Structure Activity Relationship." European Journal of Medicinal Chemistry, vol. 62, 2013, pp. 597-604.
Gao R, Liao S, Zhang C, et al. Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship. Eur J Med Chem. 2013;62:597-604.
Gao, R., Liao, S., Zhang, C., Zhu, W., Wang, L., Huang, J., Zhao, Z., Li, H., Qian, X., & Xu, Y. (2013). Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship. European Journal of Medicinal Chemistry, 62, 597-604. https://doi.org/10.1016/j.ejmech.2013.01.030
Gao R, et al. Optimization of Heterocyclic Substituted Benzenesulfonamides as Novel Carbonic Anhydrase IX Inhibitors and Their Structure Activity Relationship. Eur J Med Chem. 2013;62:597-604. PubMed PMID: 23429054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship. AU - Gao,Rui, AU - Liao,Sha, AU - Zhang,Chen, AU - Zhu,Weilong, AU - Wang,Liyan, AU - Huang,Jin, AU - Zhao,Zhenjiang, AU - Li,Honglin, AU - Qian,Xuhong, AU - Xu,Yufang, Y1 - 2013/02/04/ PY - 2012/11/21/received PY - 2013/01/19/revised PY - 2013/01/24/accepted PY - 2013/2/23/entrez PY - 2013/2/23/pubmed PY - 2013/10/18/medline SP - 597 EP - 604 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 62 N2 - In this study, starting from a lead compound discovered by virtual screening, a series of novel heterocyclic substituted benzenesulfonamides were designed and synthesized as new carbonic anhydrase IX (CA IX) inhibitors. Some compounds exhibited potent inhibitory effects against CA IX (in the low nanomolar range) as well as high selectivity against other carbonic anhydrase isozymes (CA I and CA II). The most potent and selective compound 27 could inhibit CA IX in the subnanomolar level with IC50 of 0.48 nM, which increased the potency by about 40-fold against CA IX compared with the lead compound 26, and presented more than 10(3) fold selectivity over CA I and CA II. The structure-activity relationship (SAR) based on the docking experiments further elucidated the effects of the compounds on the bioactivity and selectivity. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/23429054/Optimization_of_heterocyclic_substituted_benzenesulfonamides_as_novel_carbonic_anhydrase_IX_inhibitors_and_their_structure_activity_relationship_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(13)00058-5 DB - PRIME DP - Unbound Medicine ER -