TY - JOUR
T1 - Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases
AU - Siles, Rogelio
AU - Kawasaki, Yuko
AU - Ross, Patrick
AU - Freire, Ernesto
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health ( GM56550 and GM57144 ) and the National Science Foundation ( MCB0641252 ).
PY - 2011/9/15
Y1 - 2011/9/15
N2 - A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (K i = 880 nM) and significant selectivity against other human related serine proteases like trypsin (K i = 729 μM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development.
AB - A small library of 25 triazole/tetrazole-based sulfonamides have been synthesized and further evaluated for their inhibitory activity against thrombin, trypsin, tryptase and chymase. In general, the triazole-based sulfonamides inhibited thrombin more efficiently than the tetrazole counterparts. Particularly, compound 26 showed strong thrombin inhibition (K i = 880 nM) and significant selectivity against other human related serine proteases like trypsin (K i = 729 μM). Thrombin binding affinity of the same compound was determined by ITC and demonstrated that the binding of this new triazole-based scaffold is enthalpically driven, making it a good candidate for further development.
KW - Isothermal titration calorimetry
KW - Sulfonamide synthesis
KW - Thrombosis or thrombin inhibition
KW - Triazole and tetrazole scaffolds
KW - Trypsin selectivity
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U2 - 10.1016/j.bmcl.2011.07.023
DO - 10.1016/j.bmcl.2011.07.023
M3 - Article
C2 - 21807511
AN - SCOPUS:80051918474
VL - 21
SP - 5305
EP - 5309
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 18
ER -