Inhibitors of lipoprotein(a) assembly

Karen E Sexton; Helen T Lee; Mark Massa; Janak Padia; William C Patt; Peggy Liao; Jason K Pontrello; Bruce D Roth; Mark A Spahr; Randy Ramharack

doi:10.1016/j.bmc.2002.04.001

Inhibitors of lipoprotein(a) assembly

Bioorg Med Chem. 2003 Nov 3;11(22):4827-45. doi: 10.1016/j.bmc.2002.04.001.

Authors

Karen E Sexton¹, Helen T Lee, Mark Massa, Janak Padia, William C Patt, Peggy Liao, Jason K Pontrello, Bruce D Roth, Mark A Spahr, Randy Ramharack

Affiliation

¹ Department of Medicinal Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.

PMID: 14556799
DOI: 10.1016/j.bmc.2002.04.001

Abstract

Compounds of the general structure A and B were investigated for their activity as lipoprotein(a), [Lp(a)], assembly (coupling) inhibitors. SAR around the amino acid derivatives (structure A) gave compound 14-6 as a potent coupling inhibitor. Oral dosing of compound 14-6 to Lp(a) transgenic mice and cymologous monkeys resulted in a>30% decrease in plasma Lp(a) levels after 1-2 weeks of treatment at 100 mg/kg/day.

MeSH terms

Amino Acids / chemistry
Amino Acids / pharmacology*
Animals
Cell Line
Dose-Response Relationship, Drug
Haplorhini
Humans
Inhibitory Concentration 50
Lipoprotein(a) / antagonists & inhibitors*
Lipoprotein(a) / biosynthesis
Lipoprotein(a) / blood
Mice
Mice, Transgenic
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Amino Acids
Lipoprotein(a)
Sulfonamides