Novel 21-aminosteroids that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma
| Autor: | E J, Jacobsen, J M, McCall, D E, Ayer, F J, Van Doornik, J R, Palmer, K L, Belonga, J M, Braughler, E D, Hall, D J, Houser, M A, Krook |
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| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_treatment Central nervous system Drug Evaluation Preclinical Alpha (ethology) Pharmacology Antioxidants Steroid Lipid peroxidation chemistry.chemical_compound Mice Structure-Activity Relationship Drug Discovery medicine Structure–activity relationship Animals Craniocerebral Trauma Amines IC50 Pregnatrienes Chemistry Head injury Biological activity medicine.disease Rats medicine.anatomical_structure Biochemistry Spinal Injuries Molecular Medicine Steroids Lipid Peroxidation |
| Zdroj: | Journal of medicinal chemistry. 33(4) |
| ISSN: | 0022-2623 |
| Popis: | 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 microM. 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]-16 alpha- 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. |
| Databáze: | OpenAIRE |
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