close

Вход

Забыли?

вход по аккаунту

?

код для вставки
2004
Fused pyrimidine derivatives
R 0515
Optimization of 3-Phenylpyrazolo[1,5-a]pyrimidines as Potent CorticotropinFactor-1 Antagonists with Adequate Lipophilicity and Water Solubility.
46- 151 Releasing
— To identify CRF1 antagonists possessing more hydrophilicity, several positions of
the core structure of potent CRF1 antagonists are endowed with polar groups. The syntheses of the title compounds start from phenylacetonitriles such as (I) and involve two
subsequent cyclizations as the key steps. The syntheses are accomplished by alkylamination of chloropyrimidine derivative (VII). The 5-position bearing the optimal methyl
group is very sensitive to any replacement while other positions tolerate small hydrophilic groups with slight reduction in binding affinity. Pyrazolopyrimidine (IXb) possesses good binding affinity, potent functional antagonistic activity, and suitable lipophilicity. Moreover, (IXb) possesses good plasma and brain exposure after oral administration. — (CHEN*, C.; WILCOXEN, K. M.; HUANG, C. Q.; MCCARTHY, J. R.;
CHEN, T.; GRIGORIADIS, D. E.; Bioorg. Med. Chem. Lett. 14 (2004) 14,
3669-3673; Dep. Med. Chem., Neurocrine Biosci., Inc., San Diego, CA 92121, USA;
Eng.) — H. Hoennerscheid
Документ
Категория
Без категории
Просмотров
0
Размер файла
19 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа