NOVEL 21-AMINOSTEROIDS THAT INHIBIT IRON-DEPENDENT LIPID-PEROXIDATION AND PROTECT AGAINST CENTRAL-NERVOUS-SYSTEM TRAUMA

被引：100

作者：

JACOBSEN, EJ ^{[1
]}

MCCALL, JM ^{[1
]}

AYER, DE ^{[1
]}

VANDOORNIK, FJ ^{[1
]}

PALMER, JR ^{[1
]}

BELONGA, KL ^{[1
]}

BRAUGHLER, JM ^{[1
]}

HALL, ED ^{[1
]}

HOUSER, DJ ^{[1
]}

KROOK, MA ^{[1
]}

RUNGE, TA ^{[1
]}

机构：

[1] UPJOHN CO,CHEM RES PREPARAT,KALAMAZOO,MI 49001

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 04期

关键词：

D O I：

10.1021/jm00166a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 μM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant improvement in the 1 h post-head-injury neurological status (grip test score) by as much as 168.6% of the control has been observed. The most efficacious compound in this assay (30) showed an increase in the 1-week survival of 78.6% as compared to 27.3% for the vehicle-treated mice in the head-injury model. Based on its biological profile, 21-[4-(2,6-di-1- pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16α-methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (30) was selected for further evaluation and is currently entering phase I clinical trials for the treatment of head and spinal trauma. © 1990, American Chemical Society. All rights reserved.

引用

页码：1145 / 1151

页数：7

共 45 条

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