1067237-01-7Relevant academic research and scientific papers
Factor VIIa inhibitors: Target hopping in the serine protease family using X-ray structure determination
Shiraishi, Takuya,Kadono, Shojiro,Haramura, Masayuki,Kodama, Hirofumi,Ono, Yoshiyuki,Iikura, Hitoshi,Esaki, Tohru,Koga, Takaki,Hattori, Kunihiro,Watanabe, Yoshiaki,Sakamoto, Akihisa,Yoshihashi, Kazutaka,Kitazawa, Takehisa,Esaki, Keiko,Ohta, Masateru,Sato, Haruhiko,Kozono, Toshiro
scheme or table, p. 4533 - 4537 (2009/04/08)
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. Compound 1 was discovered from focused screening of serine protease-directed compounds from our internal collection. Using parallel synthesis supported by structure-based drug design, we identified peptidemimetic FVIIa/TF inhibitors (compounds 4-11) containing l-Gln or l-Met as the P2 moiety. However, these compounds lacked the selectivity of other serine proteases in the coagulation cascade, especially thrombin. Further optimization of these compounds was carried out with a focus on the P4 moiety. Among the optimized compounds, 12b-f showed improved selectivity.
