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.
Bayer HealthCare AG, Bayer Schering Pharma, Global Drug Discovery, D-42096 Wuppertal, Germany. carsten.schmeck@bayerhealthcare.com
Carsten
C
Schmeck
Heike
H
Gielen-Haertwig
Alexandros
A
Vakalopoulos
Hilmar
H
Bischoff
Volkhart
V
Li
Gabriele
G
Wirtz
Olaf
O
Weber
D000818:Animals; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004285:Dogs; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000737:chemistry
D053480:Cholesterol Ester Transfer Proteins; D000960:Hypolipidemic Agents; D011804:Quinolines; D013764:Tetrahydronaphthalenes; C483909:torcetrapib