title: Inhibitors of lipoprotein(a) assembly.
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.
authors.affiliation: Department of Medicinal Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Sexton
authors.forename: Helen T
authors.initials: HT
authors.lastname: Lee
authors.forename: Mark
authors.initials: M
authors.lastname: Massa
authors.forename: Janak
authors.initials: J
authors.lastname: Padia
authors.forename: William C
authors.initials: WC
authors.lastname: Patt
authors.forename: Peggy
authors.initials: P
authors.lastname: Liao
authors.forename: Jason K
authors.initials: JK
authors.lastname: Pontrello
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Roth
authors.forename: Mark A
authors.initials: MA
authors.lastname: Spahr
authors.forename: Randy
authors.initials: R
authors.lastname: Ramharack
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000882:Haplorhini; D006801:Humans; D020128:Inhibitory Concentration 50; D017270:Lipoprotein(a) / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D017270:Lipoprotein(a); D013449:Sulfonamides