- Preparation process of amantadine nitrate derivative
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The invention discloses a preparation process of an amantadine nitrate derivative, and the amantadine nitrate derivative is prepared from substituted or unsubstituted adamantane as a raw material by the following steps: (1) synthesizing of adamantanol; (2) carboxylation of the adamantanol; (3) amidation of adamantane acid; (4) reduction; (5) hydrolysis of acylamino adamantanol and boc protection of amino; (6) crystallization of Boc-protected amantadine alcohol; (7) nitric acid esterification of Boc-protected amantadine alcohol; (8) refining of a nitric acid esterification product; (9) amino deprotection and salt formation; and (10) refinement of amantadine nitrate. The amantadine amine nitrate derivative is as shown in the specification, wherein R1 and R2 are same or different, and are respectively hydrogen, a linear or branched alkyl group, a substituted or unsubstituted aryl group and a hetero aryl group. The preparation process is efficient, economic, green, safe and reliable and issuitable for industrial production.
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- 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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p. 135 - 147
(2017/02/05)
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