Novel tetrahydrochinoline derived CETP inhibitors

In the course of our efforts to identify orally active cholesteryl ester transfer protein (CETP) inhibitors, we have continued to explore tetrahydrochinoline derivatives. Based on BAY 19-4789 structural modifications led to the discovery of novel cycloalkyl substituted compounds. Thus, example 11b is a highly potent CETP inhibitor both in vitro and in vivo in transgenic mice with favourable pharmacokinetic properties for clinical development.

Variations in the 4-position of 4 led to novel CETP inhibitors. The cyclohexyl group was found to be a suitable replacement for the pF-phenyl substituent. Compound 11b was identified as a potent CETP inhibitor with an excellent in vitro and PK-profile.Figure optionsDownload as PowerPoint slide