Inhibitors of lipoprotein(a) assembly.
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.
Sexton
Karen E
KE
Department of Medicinal Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
Lee
Helen T
HT
Massa
Mark
M
Padia
Janak
J
Patt
William C
WC
Liao
Peggy
P
Pontrello
Jason K
JK
Roth
Bruce D
BD
Spahr
Mark A
MA
Ramharack
Randy
R
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*
D000596:Amino Acids; D017270:Lipoprotein(a); D013449:Sulfonamides