Chymase Inhibitors

He SH, Xie H, Zhang XJ, Wang XJ. Inhibition of histamine release from human mast cells by natural chymase inhibitors. Acta Pharmacol Sin. 2004 25 822-826. 

Diazetidin-2,4-dione has been found to be a chymase inhibitor (IC50 4.0nM). It has been found that 1,3-diazetidin-2,4-dione derivatives possess high activities against bovine pancreatic cr-chrymotrypsin, human cathepsin G, and human neutrophil elastase. Some of the derivatives of l,3-diazetidin-2,4-diones have been shown to be effective as a scaffold for serine protease inhibitors <2001BML1691>. Further, 1,3-diazetidinone containing scaffolds have been found to possess potential antibacterial properties (Section 2.13.7.3). 

In earlier investigations by the authors (1,2), 2-oxo-l,2,3,4-tetrahydropyrazines, (I), and thiazolidine derivatives, (II), respectively, were prepared, which were effective as chymase inhibitors. 

Imidazolidinediones, (HI), prepared by Sakai (3) and 2,4(lH,3H)-quinazolinedione derivatives, (IV), prepared by Fukami (4) were effective as chymase inhibitors and used in the treatment of cardiovascular and inflammatory disorders. 

Arooj M, Thangapandian S, John S, Hwang S, Park JK, Lee KW (2012) Computational studies of novel chymase inhibitors against cardiovaseular and allergic diseases mechanism and inhibition. Chem Biol Drug Des 80(6) 862-875. doi 10.1111/cbdd.12006... 

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