Optimization of a 2,4-diaminopyrimidine HTS hit using a combination of parallel synthesis and X-ray crystallography afforded lead compound 16 IC50 = 655 nM [73,74]. The 1-(3-methoxypropyl)-1,2,3,4-tetrahydroquinoline moiety of 16 was shown to occupy the S3 and Ss3p pockets of renin. Using NMR techniques, small molecules that could bind to the S2 pocket were identified and linked to 16 to give 17 IC50 = 1 nM [75]. Further synthesis lead to 18 IC50 = 1nM, %F = 8), 19 (IC50 = 48 nM, %F = 74) and 20 (IC50 = 2nM, %F = 34) [76,77].

20 R = NHCO2Me

Was this article helpful?

0 0
Anxiety Away

Anxiety Away

The strategies revealed within Anxiety Away are fast acting, simple and guaranteed to work even if you have suffered from anxiety for a long time!

Get My Free Ebook

Post a comment