دورية أكاديمية
Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists.
| العنوان: | Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists. |
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| المؤلفون: | Thompson WJ; Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486., Anderson PS, Britcher SF, Lyle TA, Thies JE, Magill CA, Varga SL, Schwering JE, Lyle PA, Christy ME, et. al. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 1990 Feb; Vol. 33 (2), pp. 789-808. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print Cited Medium: Print ISSN: 0022-2623 (Print) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Anticonvulsants/*chemical synthesis , Aspartic Acid/*analogs & derivatives , Imines/*chemical synthesis , Polycyclic Compounds/*chemical synthesis , Receptors, Neurotransmitter/*drug effects, Animals ; Aspartic Acid/antagonists & inhibitors ; Binding, Competitive ; Cerebral Cortex/metabolism ; Chemical Phenomena ; Chemistry ; Drug Design ; Imines/pharmacology ; In Vitro Techniques ; Ion Channels/drug effects ; Models, Molecular ; N-Methylaspartate ; Polycyclic Compounds/pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, N-Methyl-D-Aspartate ; Thermodynamics |
| مستخلص: | A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested. |
| المشرفين على المادة: | 0 (Anticonvulsants) 0 (Imines) 0 (Ion Channels) 0 (Polycyclic Compounds) 0 (Receptors, N-Methyl-D-Aspartate) 0 (Receptors, Neurotransmitter) 30KYC7MIAI (Aspartic Acid) 6384-92-5 (N-Methylaspartate) |
| تواريخ الأحداث: | Date Created: 19900201 Date Completed: 19900309 Latest Revision: 20190709 |
| رمز التحديث: | 20240627 |
| DOI: | 10.1021/jm00164a052 |
| PMID: | 1688947 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 0022-2623 |
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| DOI: | 10.1021/jm00164a052 |