close

Вход

Забыли?

вход по аккаунту

?

код для вставки
2005
Carboxylic amides
Q 0490
Potent and Selective P2—P3 Ketoamide Inhibitors of Cathepsin K with Good
Properties via Favorable P1', P 1, and/or P3 Substitutions. — The
01- 080 Pharmacokinetic
ketoamides are prepared by different routes. Ketoamide (VI) is synthesized applying
an acyl cyanophosphorane oxidative cleavage and amine coupling procedure. Based on
molecular modelling studies, achiral P2—P3 substituents are incorporated, providing
good inhibitory activity vs. cathepsin K. In addition, modifications of the P1', P1, and P3
moieties lead to an improvement of the pharmacokinetic profile. The resulting inhibitors display good to excellent selectivity vs. cathepsins B, H, and L. Of particular notice, ketoamide (VI) is an extremely potent cathepsin K inhibitor demonstrating good
oral bioavailability. — (CATALANO*, J. G.; et al.; Bioorg. Med. Chem. Lett. 14
(2004) 19, 4897-4902; Dep. Med. Chem., GlaxoSmithKline Res. Dev., Research
Triangle Park, NC 27709, USA; Eng.) — H. Hoennerscheid
Документ
Категория
Без категории
Просмотров
0
Размер файла
19 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа