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Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases.

ABSTRACT: 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 ?M). 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.

SUBMITTER: Siles R

PROVIDER: S-EPMC3159800 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases.

Siles Rogelio R Kawasaki Yuko Y Ross Patrick P Freire Ernesto E

Bioorganic & medicinal chemistry letters 20110714 18

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 ...[more]

PMID: 21807511

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