2Q1L

Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors

Summary for 2Q1L

• Entry DOI: 10.2210/pdb2q1l/pdb
• Descriptor: 3-hydroxy-3-methylglutaryl-coenzyme A reductase, (3R,5R)-7-[5-(ANILINOCARBONYL)-3,4-BIS(4-FLUOROPHENYL)-1-ISOPROPYL-1H-PYRROL-2-YL]-3,5-DIHYDROXYHEPTANOIC ACID (3 entities in total)
• Functional Keywords: oxidoreductase, cholesterol biosynthesis, hmg-coa, nadph, statin
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: P04035
• Total number of polymer chains: 4
• Total formula weight: 192224.72

Authors

Pavlovsky, A.,Pfefferkorn, J.A.,Harris, M.S.,Finzel, B.C. (deposition date: 2007-05-24, release date: 2007-07-17, Last modification date: 2024-02-21)

Primary citation

Pfefferkorn, J.A.,Song, Y.,Sun, K.L.,Miller, S.R.,Trivedi, B.K.,Choi, C.,Sorenson, R.J.,Bratton, L.D.,Unangst, P.C.,Larsen, S.D.,Poel, T.J.,Cheng, X.M.,Lee, C.,Erasga, N.,Auerbach, B.,Askew, V.,Dillon, L.,Hanselman, J.C.,Lin, Z.,Lu, G.,Robertson, A.,Olsen, K.,Mertz, T.,Sekerke, C.,Pavlovsky, A.,Harris, M.S.,Bainbridge, G.,Caspers, N.,Chen, H.,Eberstadt, M.
Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors.
Bioorg.Med.Chem.Lett., 17:4538-4544, 2007

PubMed Abstract: This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.

PubMed: 17574412
DOI: 10.1016/j.bmcl.2007.05.096

Experimental method

X-RAY DIFFRACTION (2.05 Å)