187752-79-0Relevant academic research and scientific papers
Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin
Hanessian, Stephen,Ersmark, Karolina,Wang, Xiaotian,Del Valle, Juan R.,Blomberg, Niklas,Xue, Yafeng,Fjellstroem, Ola
, p. 3480 - 3485 (2008/02/09)
Based on X-ray crystallographic data of complexes of chlorodysinosin A with the enzyme thrombin, a series of analogs were synthesized varying the nature of the P1, P2, and P3 pharmacophoric sites and the central octahydroindole carboxyamide core. In general, introduction of a hydrophobic substituent on the d-leucine amide residue dramatically improved the inhibition of the enzyme. This is rationalized based on a better fit of the P3 subunit in the hydrophobic S3 enzyme site. Single digit nanomolar inhibition expressed as IC50 was observed for several analogs.
