- AMIDE COMPOUND AND PHARMACEUTICAL COMPRISING SAME
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Provided is a novel compound which has an excellent Aβ aggregation inhibitory effect and is useful as a pharmaceutical. An amide compound represented by the formula (1) or a salt thereof, wherein Z represents CH or N; A and B are the same or different and each represents —CH2—, —O—, —S—, or —NH—; R1 and R2 are the same or different and each represents a branched alkyl group, a branched alkenyl group, an optionally substituted aromatic hydrocarbon group, an optionally substituted aralkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aromatic heterocyclic group; and R3 represents a branched alkyl group, a branched alkenyl group, an optionally substituted cycloalkyl group, or an optionally substituted aralkyl group.
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- Rational design and identification of a non-peptidic aggregation inhibitor of amyloid-β based on a pharmacophore motif obtained from cyclo[-Lys-Leu-Val-Phe-Phe-]
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Inhibition of pathogenic protein aggregation may be an important and straightforward therapeutic strategy for curing amyloid diseases. Small-molecule aggregation inhibitors of Alzheimer's amyloid-β (Aβ) are extremely scarce, however, and are mainly restricted to dye- and polyphenol-type compounds that lack drug-likeness. Based on the structure-activity relationship of cyclic Aβ16-20 (cyclo-[KLVFF]), we identified unique pharmacophore motifs comprising side-chains of Leu2, Val3, Phe4, and Phe5 residues without involvement of the backbone amide bonds to inhibit Aβ aggregation. This finding allowed us to design non-peptidic, small-molecule aggregation inhibitors that possess potent activity. These molecules are the first successful non-peptidic, small-molecule aggregation inhibitors of amyloids based on rational molecular design.
- Arai, Tadamasa,Araya, Takushi,Sasaki, Daisuke,Taniguchi, Atsuhiko,Sato, Takeshi,Sohma, Youhei,Kanai, Motomu
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p. 8236 - 8239
(2014/08/18)
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- Herbicidal carboxamide derivatives
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The invention provides compounds of the general formula in whichR1 represents a hydrogen or halogen atom or an alkyl or haloalkyl group;the or each group X independently represents a halogen atom or an optionally substituted alkyl or alkoxy group or an alkenyloxy, alkynyloxy, cyano, carboxy, alkoxycarbonyl, (alkylthio)carbonyl, alkylcarbonyl, amido, alkylamido, nitro, alkylthio, haloalkylthio, alkenylthio, alkynylthio, alkylsulphinyl, alkylsulphonyl, alkyloximinoalkyl or alkenyloximinoalkyl group;n is 0 or an integer from 1 to 5; andL is an alkoxy group.
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