SYNTHESIS AND IN-VITRO PROFILE OF A NOVEL SERIES OF CATECHOL BENZIMIDAZOLES - THE DISCOVERY OF POTENT, SELECTIVE PHOSPHODIESTERASE TYPE-IV INHIBITORS WITH GREATLY ATTENUATED AFFINITY FOR THE [H-3] ROLIPRAM BINDING-SITE

被引：37

作者：

CHENG, JB ^{[1
]}

COOPER, K ^{[1
]}

DUPLANTIER, AJ ^{[1
]}

EGGLER, JF ^{[1
]}

KRAUS, KG ^{[1
]}

MARSHALL, SC ^{[1
]}

MARFAT, A ^{[1
]}

MASAMUNE, H ^{[1
]}

SHIRLEY, JT ^{[1
]}

TICKNER, JE ^{[1
]}

UMLAND, JP ^{[1
]}

机构：

[1] PFIZER INC,DIV CENT RES,GROTON,CT 06340

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 17期

关键词：

D O I：

10.1016/0960-894X(95)00334-P

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and biological properties of a novel series of potent and selective phosphodiesterase type IV (PDE IV) inhibitors are described. These catechol benzimidazoles were designed from rolipram and initial compounds reflected a similarly high affinity for the [H-3]rolipram binding site (500 to 1000X greater affinity for the [H-3]rolipram binding site over the PDE IV inhibitory site). However, SAR studies on the 8-alkoxy position revealed that this [H-3]rolipram binding site affinity could be attenuated, while potentiating the PDE IV inhibitory activity. This resulted in the 2-indanyl analog 13 which is a potent, selective PDE IV inhibitor with a 15X differential in favor of PDE IV binding.

引用

页码：1969 / 1972

页数：4

共 6 条

[1]

HARRISON SA, 1986, MOL PHARMACOL, V29, P506

[2] EFFECTS OF NOVEL CATECHOL ETHER IMIDAZOLIDINONES ON CALCIUM-INDEPENDENT PHOSPHODIESTERASE ACTIVITY, [H-3] ROLIPRAM BINDING, AND RESERPINE-INDUCED HYPOTHERMIA IN MICE [J].