Novel type of plasmin inhibitors: providing insight into P1 moiety

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Hiroshima International University
• Principal Investigator: TENO Naoki 広島国際大学, 医療栄養学部, 教授 (00535586)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: プラスミン阻害剤 / ピロロピリミジン / ヒダントイン / scaffold / Warhead

Outline of Final Research Achievements

Plasmin is suggested to be involved in physiological processes that are linked to the risk of carcinoma formation. Plasmin inhibitors could be perceived as a promising new principle in the treatment of diseases triggered by plasmin. On the basis of the peptidic sequence derived from the synthetic plasmin substrate, the peptidic inhibitor complexed with plasmin reveal that the P2 residue makes favorable contacts with the open binding pocket comprising the S2 and S3 subsites of plasmin.
Otherwise, as the non-peptidic inhibitors, a novel chemotype, pyrrolopyrimidine scaffold possessing two motifs, a hydantoin-containing P4 moiety and a warhead-containing P1 moiety, is uncovered. A unique feature of the new line of the plasmin inhibitors is that the interaction between the plasmin inhibitors and key subsites in plasmin can be controlled by a spacer like hydantoin. The application of the novel chemotype provides further evidence on the importance of hydantoin as the spacer.

Free Research Field

創薬化学