当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and structure-activity relationships of 8-substituted-2-aryl-5-alkylaminoquinolines: Potent, orally active corticotropin-releasing factor-1 receptor antagonists.

Synthesis and structure-activity relationships of 8-substituted-2-aryl-5-alkylaminoquinolines: Potent, orally active corticotropin-releasing factor-1 receptor antagonists.

Abstract：

:We previously reported a series of 8-methyl-2-aryl-5-alkylaminoquinolines as a novel class of corticotropin-releasing factor-1 (CRF(1)) receptor antagonists. A critical issue encountered for this series of compounds was low aqueous solubility at physiological pH (pH 7.4). To address this issue, derivatization at key sites (R(2), R(3), R(5), R(5'), and R(8)) was performed and the relationships between structure and solubility were examined. As a result, it was revealed that introduction of a methoxy substituent at the C(8) position had a positive impact on the solubility of the derivatives. Consequently, through in vivo and in vitro biological studies, compound 21d was identified as a potent, orally active CRF(1) receptor antagonist with improved physicochemical properties.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Takeda K,Terauchi T,Hashizume M,Shikata K,Taguchi R,Murata-Tai K,Fujisawa M,Takahashi Y,Shin K,Ino M,Shibata H,Yonaga M

doi

10.1016/j.bmc.2012.09.028

subject

Has Abstract

pub_date

2012-11-15 00:00:00

pages

6559-78

issue

22

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(12)00740-7

journal_volume

20

pub_type

杂志文章

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