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CHEMICAL CHAPERONINS AS NOVEL MOLECULAR MODULATORS OF BETA PROTEIN AGGREGATION PRESENT IN CONFORMATIONAL DISEASES

机译:化学伴侣蛋白作为顺应性疾病中贝塔蛋白凝集的新型分子调节剂

摘要

This invention relates to chemistry and biochemistry applied to the field of medicine and is referred to a new method of prevention and therapeutic treatment of conformational diseases (CD), in particular to amyloid origin diseases by administrating an effective amount of one or more compounds, salts, prodrugs or solvates, which are considered herein as chemical chaperonins, of Formula I, Where: R1: -alkylenyl-C(O)NH-alkylenyl-R3, -alkylenyl-C(O)OR4; R3: COOH, OH, SH, NH2, NH-alkyl-, NH-dithiocarbamate-alkyl, N-alkyl-dithiocarbamate alkaline earth metal salts. R4: succinimidyl group. R2: H, -alkyl; wherein the term alkyl is characterized by a linear or branched aliphatic chain, hydrogen and saturated carbon atoms, comprising a methyl, ethyl, n-propyl, iso-propyl, n-butyl or iso-butyl groups. Wherein, the term alkylenyl refers to a divalent analog of a linear or branched alkyl group, preferably ethylenyl (CH2CH2) or butylenyl (CH2CH2CH2CH2) radicals. These compounds are neutral, lipophilic, and have low molecular weight. The present invention provides a novel method for CD prevention and therapeutic treatment, by inhibition, reduction and breakdown of prefibril, protofibril, amyloid fiber and plaque structures, all of them characterized by presenting cross--toxic structures (e.g. Alzheimer disease (AD), Parkinson's disease (PD), Diabetes Mellitus Type II (DM2), etc.), through the administration of the Formula I compounds, which are considered herein as chemical chaperonins, in any acceptable pharmaceutical composition of one or more compounds or salts thereof, prodrug or solvate, that are capable of inhibiting, reducing, removing, etc., the formation of these structures which cause a protein misfolding, as well as to disaggregate fibers already formed.
机译:本发明涉及应用于医学领域的化学和生物化学,并且涉及通过施用有效量的一种或多种化合物,盐来预防和治疗构象性疾病(CD),特别是淀粉样蛋白源性疾病的新方法。 ,式I的前药或溶剂化物,在本文中被认为是化学伴侣蛋白,其中:R 1:-亚烷基-C(O)NH-亚烷基-R 3,-亚烷基-C(O)OR 4; R 3:COOH,OH,SH,NH 2,NH-烷基-,NH-二硫代氨基甲酸酯-烷基,N-烷基-二硫代氨基甲酸酯碱土金属盐。 R4:琥珀酰亚胺基。 R 2:H,-烷基;其中术语烷基的特征在于直链或支链的脂族链,氢和饱和碳原子,其包含甲基,乙基,正丙基,异丙基,正丁基或异丁基。其中,术语亚烷基是指直链或支链烷基的二价类似物,优选为亚乙基(CH 2 CH 2)或亚丁基(CH 2 CH 2 CH 2 CH 2)基团。这些化合物是中性的,亲脂的并且具有低分子量。本发明提供了一种通过抑制,减少和分解原纤维,原纤维,淀粉样蛋白纤维和噬斑结构来预防和治疗CD的新方法,所有这些特征均表现出交叉毒性结构(例如阿尔茨海默氏病(AD),通过在一种或多种化合物或其盐,前药的任何可接受的药物组合物中施用式I化合物(在本文中被视为化学伴侣蛋白)来治疗帕金森氏病(PD),II型糖尿病(DM2)等)或溶剂化物,它们能够抑制,减少,去除等导致蛋白质错折叠以及分解已经形成的纤维的这些结构的形成。

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