Survey of Published QSAR on Factor Xa Inhibitors

Survey of Published QSAR on Factor Xa Inhibitors Diaryloxypyridines 

N-dimethylamide and the imidazolinyl ring seemed to be good alternatives for the second amidine. 

Aminophenol was used as a potent and selective scaffold [73] since it was more synthetically accessible than the benzimidazole template. For a set of aminophenol-based inhibitors (5-8), the correlation obtained was as shown by Eq. 8. In this equation, 

Ih-b was used with a value of 1 for the possibility of existence of a hydrogen bond at the R2 substituent and MR-R4 was the molar refractivity for the R4 group. The positive coefficient of MR-R4 indicated that the larger and more polarizable is the R4-substituent the more would be the inhibitory activity. The negative sign with Ir b showed that the presence of a hydrogen bond results in lower activity. Equation 8 [72] also exhibits the importance of hy-drophilicity of the compounds for the inhibition of FXa. 

Most of the nonpeptide FXa inhibitors reported in the literature were compounds with two basic groups [74]. To date very few monobasic FXa inhibitors have been reported. Ellis and co-workers [74] have reported their effort on synthesizing a series of bisbenzamidine isoxazoline derivatives and a series of monobasic substituted biaryl isoxazoline derivatives (9-12). For these compounds, Eq. 9 was derived [72]. In Eq. 9, Ipyr was used to take values 

---