Tags

Type your tag names separated by a space and hit enter

Carbonic anhydrase inhibitors. Regioselective synthesis of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII.
Eur J Med Chem. 2010 Sep; 45(9):3656-61.EJ

Abstract

A series of 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamide (2-16) have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is the cytosolic ubiquitous CA I and II, and cancer-associated isozymes CA IX and XII. Against the human isozymes hCA I the new compounds showed inhibition constants in the range of 1.09-12.1 microM, against hCA II in the range of 50.5-172 nM, against hCA IX in the range of 5.2-118 nM, and against hCA XII in the range of 8.7-381 nM, respectively. Compounds 2, 3, 5-9, 11, 13 and 14 showed excellent hCA IX inhibitory efficacy, with K(I)s = 5.2-11.0 nM, being much more effective as compared to the clinically used sulfonamides AAZ, MZA, EZA, DCP and IND (K(I)s = 24-50 nM). Compounds 2, 3, 5-9, 11 and 13 were also very effective hCA XII inhibitors (K(I)s = 8.7-45.2 nM) which are comparable or more effective than those clinically used EZA and DCP (K(I)s = 22 and 50 nM), respectively.

Authors+Show Affiliations

Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.No 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

20554082

Citation

Brzozowski, Zdzisław, et al. "Carbonic Anhydrase Inhibitors. Regioselective Synthesis of Novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and Their Inhibition of the Human Cytosolic Isozymes I and II and Transmembrane Cancer-associated Isozymes IX and XII." European Journal of Medicinal Chemistry, vol. 45, no. 9, 2010, pp. 3656-61.
Brzozowski Z, Sławiński J, Innocenti A, et al. Carbonic anhydrase inhibitors. Regioselective synthesis of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII. Eur J Med Chem. 2010;45(9):3656-61.
Brzozowski, Z., Sławiński, J., Innocenti, A., & Supuran, C. T. (2010). Carbonic anhydrase inhibitors. Regioselective synthesis of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII. European Journal of Medicinal Chemistry, 45(9), 3656-61. https://doi.org/10.1016/j.ejmech.2010.05.011
Brzozowski Z, et al. Carbonic Anhydrase Inhibitors. Regioselective Synthesis of Novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and Their Inhibition of the Human Cytosolic Isozymes I and II and Transmembrane Cancer-associated Isozymes IX and XII. Eur J Med Chem. 2010;45(9):3656-61. PubMed PMID: 20554082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carbonic anhydrase inhibitors. Regioselective synthesis of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII. AU - Brzozowski,Zdzisław, AU - Sławiński,Jarosław, AU - Innocenti,Alessio, AU - Supuran,Claudiu T, Y1 - 2010/05/12/ PY - 2010/03/20/received PY - 2010/05/04/revised PY - 2010/05/05/accepted PY - 2010/6/18/entrez PY - 2010/6/18/pubmed PY - 2010/12/14/medline SP - 3656 EP - 61 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 45 IS - 9 N2 - A series of 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamide (2-16) have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is the cytosolic ubiquitous CA I and II, and cancer-associated isozymes CA IX and XII. Against the human isozymes hCA I the new compounds showed inhibition constants in the range of 1.09-12.1 microM, against hCA II in the range of 50.5-172 nM, against hCA IX in the range of 5.2-118 nM, and against hCA XII in the range of 8.7-381 nM, respectively. Compounds 2, 3, 5-9, 11, 13 and 14 showed excellent hCA IX inhibitory efficacy, with K(I)s = 5.2-11.0 nM, being much more effective as compared to the clinically used sulfonamides AAZ, MZA, EZA, DCP and IND (K(I)s = 24-50 nM). Compounds 2, 3, 5-9, 11 and 13 were also very effective hCA XII inhibitors (K(I)s = 8.7-45.2 nM) which are comparable or more effective than those clinically used EZA and DCP (K(I)s = 22 and 50 nM), respectively. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/20554082/Carbonic_anhydrase_inhibitors__Regioselective_synthesis_of_novel_1_substituted_14_dihydro_4_oxo_3_pyridinesulfonamides_and_their_inhibition_of_the_human_cytosolic_isozymes_I_and_II_and_transmembrane_cancer_associated_isozymes_IX_and_XII_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(10)00350-8 DB - PRIME DP - Unbound Medicine ER -