P1,P3 Truncated Analogs of Oscillarin and their Inhibitory Activity against Blood Coagulation Factors

Based on modeling and available X-ray co-crystal structure data of oscillarin with the enzyme thrombin, a series of P1,P3 truncated analogs were prepared using the azabicyclic octahydroindole carboxamide core as a scaffold. The P1 subunit of the original natural product was replaced by a 4-amidinobe...

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Bibliographic Details
Published inChimia Vol. 61; no. 6
Main Authors Stephen Hanessiana, Sébastien Guillemette, Karolina Ersmark
Format Journal Article
LanguageEnglish
Published Swiss Chemical Society 27.06.2007
Subjects
Aeruginosin mimics
Sulfonamide
Thrombin inhibition
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Summary:Based on modeling and available X-ray co-crystal structure data of oscillarin with the enzyme thrombin, a series of P1,P3 truncated analogs were prepared using the azabicyclic octahydroindole carboxamide core as a scaffold. The P1 subunit of the original natural product was replaced by a 4-amidinobenzamide group, and the P3 subunit was simulated by N-benzylsulfonyl glycine amide or an N-acetyl D-phenylalanine amide. Single digit micromolar inhibition was found against trypsin, thrombin, Factor Xa, and Factor XIa for some analogs.
ISSN:0009-4293
2673-2424
DOI:10.2533/chimia.2007.361