- Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases
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A series of memantine nitrate derivatives, as dual functional compounds with neuroprotective and vasodilatory activity for neurodegenerative diseases, was designed and synthesized. These compounds combined the memantine skeleton and a nitrate moiety, and thus inhibited the N-methyl-d-aspartic acid receptor and released NO in the central nervous system. The biological evaluation results revealed that the new memantine nitrates were effective in protecting neurons against glutamate-induced injury in vitro. Moreover, memantine nitrates dilated aortic rings against phenylephrine-induced contraction. The structure-activity relationships of neuroprotection and vasodilation were both analyzed. In further studies, compound MN-05 significantly protected cortical neurons by inhibiting Ca2+ influx, reducing free radical production and maintaining the mitochondrial membrane potential. Further research on MN-05 is warranted.
- Liu, Zheng,Yang, Si,Jin, Xiaoyong,Zhang, Gaoxiao,Guo, Baojian,Chen, Haiyun,Yu, Pei,Sun, Yewei,Zhang, Zaijun,Wang, Yuqiang
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supporting information
p. 135 - 147
(2017/02/05)
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- AMINO ADAMANTANE DERIVATIVES, METHODS FOR THE PRODUCTION AND USE THEREOF
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The invention relates to 1-amino adamantane derivatives and 3-amino adamantane-1-carboxylic acid derivatives, wherein the 5th and/or 7th position of the adamantane base frame can be substituted in any particular manner. The invention also relates to methods for the production of said inventive compounds, in addition to methods for linking the thus obtained monomer 3-amino adamantane-1-carboxylic acid derivatives in order to form oligomers. The inventive compounds are suitable for use as anti-viral active substances, artificial ion channels and for the therapy, diagnosis and prophylaxis of diseases, wherein a defect of the GA-BA-system occurs.
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Page/Page column 54-55
(2010/02/15)
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- Contribution a l'etude des reactions d'alkylation et de polyalkylation de l'adamantane et de ses homologues
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A method for preparing alkyl derivatives of cage-structure compounds is proposed.It relies on the use of Grignard reactions with a high boiling point solvent.The reactions take place at atmospheric pressure.Methylation of adamantane, diamantane, and homoadamantane occurs with quantitative yield.With other primary alkyl groups, yields are better than 60percent.Competition between alkylation and secondary reactions is discussed on the basis of a free radical mechanism.
- Molle, G.,Dubois, J. E.,Bauer, P.
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p. 2428 - 2433
(2007/10/02)
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- Structure-Anti-Parkinson Activity Relationships in the Aminoadamantanes. Influence of Bridgehead Substitution
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A limited series of bridgehead alkyl-, dialkyl- and trialkyl-substituted amantadines was synthesized and tested for potential anti-Parkinson activity as dopamine (DA) agonists.The compounds were evaluated using a battery of three murine bioassays, including stimulation of locomotor activity, induction of circling in animals with unilateral striatal lesions, and reversal of reserpine/α-methyltyrosine induced akinesia.Apparent mechanistic differences were seen between the methyl-substituted series and the ethyl-substituted series.While activities in both series increase with increasing liphophilicity, the methyl series (1b-d), as well as amantadine itself (1a) exhibits only indirect DA agonist activity, as evidenced by ipsilateral rotation in the circling model and no significant difference from control in reversal of akinesia.The ethyl series (1e,f) exhibits weak but reprodicible direct DA agonist activity, as shown by contralateral rotation in the circling assay for 1e and reversal of akinesia by 1e and 1f.The 3-n-propyl derivative (1g) was devoid of any DA agonist activity.
- Henkel, James G.,Hane, Jeffrey T.,Gianutsos, Gerald
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