Low density lipoprotein receptor up-regulation

Practical Synthesis of Low-Density Lipoprotein Receptor Upregulator, N-[1-(3-Phenylpropane-1-yl)piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4- carboxamide

“…Found: C, 68.93; H, 6.36; N, 13.51; S, 7.80. 1 H NMR (CDCl 3 , δ, 300 MHz) 1.45−1.51 (2H, m), 1.77−1.85 (2H, m), 1.91−1.95 (2H, m), 2.03−2.12 (2H, m), 2.35 (2H, t, J = 7.9 Hz), 2.62 (2H, t, J = 7.8 Hz), 2.80−2.85 (2H, m), 3.78−3.81 (1H, m), 5.68 (1H, d, J = 7.7 Hz), 5.75−5.78 (1H, m), 6.58−6.67 (3H, m), 7.02 (1H, s), 7.15−7.30 (5H, m) (lit 1b. (CDCl 3 , δ, 200 MHz) 1.41−1.64 (2H, m), 1.75−2.21 (6H, m), 2.31−2.47 (2H, m), 2.63 (2H, t, J = 7.7 Hz), 2.79−2.96 (2H, m), 3.72−3.92 (1H, m), 5.75−5.80 (2H, m), 6.57−6.69 (3H, m), 7.03 (1H, s), 7.16−7.32 (5H, m)).…”

“…In the search for new therapeutic drugs for hyperlipidemia, 5-thia-1,8 b -diazaacenaphthylene derivatives were found to reduce plasma total- and low-density lipoprotein (LDL) cholesterol . In particular, N -[1-(3-phenylpropane-1-yl)piperidin-4-yl]-5-thia-1,8 b -diazaacenaphthylene-4-carboxamide ( 4 ) 1 was found to be especially effective.…”

“…Hence, the preparation of 4 on a large scale was required to support toxicological evaluation. The route for synthesizing 4 from a carboxylic acid derivative ( 1 ), 1a,b reported by Takatani et al, is shown in Scheme . However, this procedure had several limitations for large-scale preparation, for example, the requirement of a protective and deprotective process, multisteps, and tedious chromatographic methods.…”