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CHEMICAL CHAPERONINS AS NOVEL MOLECULAR MODULATORS OF BETA PROTEIN AGGREGATION PRESENT IN CONFORMATIONAL DISEASES
专利权人:
发明人:
MARQUIZA SABLON CARRAZANA,Chrislayne RODRIGUEZ-TANTY,Myriam Marlene ALTAMIRANO BUSTAMANTE,Fernand Vedrenne GUTIERREZ,Suchitil RIVERA MARRERO,Isaac Gomez FERNANDEZ,Rosa Maria LOPEZ BARROSO,Lina Andrea
申请号:
US14771144
公开号:
US20160106691A1
申请日:
2013.12.30
申请国别(地区):
US
年份:
2016
代理人:
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)O—R4 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-β-toxic structures (e.g. Alzheimer disease (AD), Parkinsons 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.
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