NMDA Receptor Antagonists and their use for inhibiting the abnormal hyperphosphorylation of the microtubule Associated Protein Tau

摘要

Compounds that are active aminociclohexano and aminoalquilciclohexano, systemically as NMDA Receptor Antagonists and are effective to inhibit the abnormal hyperphosphorylation of the microtubule Associated Protein Tau, Methods for treating Disorders that are related or associated With the abnormal hyperphosphorylation of the microtubule Associated Protein Tau,,And Pharmaceutical compositions containing same.Claim 1: a method for the Prevention, Treatment or alleviation of a State, a condition, or a condition that results in the hyperphosphorylation of Tau from microtubules, characterized in that the method is useful for: (1) prevent or delay the onset of symptoms And clinical parameters, such as neurodegeneration, disorder or conditionThat develops in a Mammal which may be affected or is susceptible to the State, the disorder or condition, but still not experiencing or showing symptoms and clinical parameters of the State, the disorder or condition, (2) inhibit the State, disorder or condition , i.e.Stop or reduce the development of the disease or at least one clinical sign or a parameter of the same, or (3) to alleviate the disease, that is, cause the regression of the State, the disorder or condition, or at least one of its symptoms and clinical parameters, wherein Said method comprises e The step of administering to a patient in need,A quantity of a aminociclohexano or aminoalquilciclohexano.Claim 2: the method of claim 1, wherein the aminociclohexano or aminoalquilciclohexano is selected from those of formula (1), where R1 is - (a) n - (cr1r2) - nr3r4 m; n + m = 0, 1 or 2; a is selected from the group consisting of Lower alkyl linear or ramif Es (C1 - 6), Lower alquenilos linear or branched (C 6),And alquinilos Lower linear or branched (C2 - 6); R1 and R2 are independently selected from the group consisting of hydrogen, Lower alkyl linear or branched (C1 - 6), Lower alquenilos linear or branched (C 6), Lower and alquinilos linear or branched (R3 and C2 - 6) R4 is independently selected from the group consisting of hydrogen,Lower linear or branched alkyl (C1 - 6), Lower alquenilos linear or branched (C 6), Lower and alquinilos linear or branched (C 6), or together form alquileno (C2 - 10) or alquenileno (2-10), or together with, or form a azacicloalcano azacicloalqueno 3 7 members,Including a azacicloalcano or azacicloalqueno 3 to 7 members (alkyl substituted (C1) and (C2 alquenilo - 6), R5 is selected independently from the group consisting of hydrogen, Lower alkyl linear or branched (C1 - 6), Lower alquenilos linear or branched (C 6), and Quinilos Lower linear or branched (C 6),Or R5 combines with the carbon to which it is United and the next adjacent ring to form a double Bond; MOP, RQ, RR and RS are selected independently from the group consisting of hydrogen, Lower alkyl linear or branched (C1 - 6), linear or branched Lower alquenilos (C 6), Lower alquinilos linear or branched (C 6), cycloalkyl (C3 - 6) and phenyl, or MOP, RQ,RR and RS can be combined together to represent a Lower alquileno Bridge - (CH2) x, where X is 2 to 5, inclusive, where the Bridge alquileno may then be combined to form a Bridge with R5 alquileno additional - Lower and - (CH2), where y is 1 - 3 including, u - V - W - X - y - Z are selected and Mong cyclohexane, ciclohex - 2 - 3 - ciclohex Eno, Eno, ciclohex - 1.4 - 1.5 - diene, ciclohex DieneCiclohex - 2.4 - diene, and ciclohex - 2.5 - diene, and its Optical isomers and Addition salts of Acidic or basic the same acceptable for pharmaceutical use.