- Discovery and characterization of novel indole and 7-azaindole derivatives as inhibitors of β-amyloid-42 aggregation for the treatment of Alzheimer's disease
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The aggregation of amyloid-β peptides into cytotoxic oligomeric and fibrillary aggregates is believed to be one of the major pathological events in Alzheimer disease. Here we report the design and synthesis of a novel series of indole and 7-azaindole derivatives containing, nitrile, piperidine and N-methyl-piperidine substituents at the 3-position to prevent the pathological self-assembly of amyloid-β. We have further demonstrated that substitution of the azaindole and indole derivatives at the 3 positions is required to obtain compounds with improved physicochemical properties to allow brain penetration.
- Sreenivasachary, Nampally,Kroth, Heiko,Benderitter, Pascal,Hamel, Anne,Varisco, Yvan,Hickman, David T.,Froestl, Wolfgang,Pfeifer, Andrea,Muhs, Andreas
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supporting information
p. 1405 - 1411
(2017/03/08)
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- 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors
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7-Azaindole-1-carboxamides were designed as a new class of PARP-1 inhibitors The compounds displayed a variable pattern of target inhibition profile that, in part, paralleled the antiproliferative activity in cell lines characterized by homologous recombination defects A selected compound (1l; ST7710AA1) showed significant in vitro target inhibition and capability to substantially bypass the multidrug resistance mediated by Pgp In antitumor activity studies against the MX1 human breast carcinoma growth in nude mice, the compound exhibited an effect similar to that of Olaparib in terms of tumor volume inhibition when used at a lower dose than the reference compound Treatment was well tolerated, as no deaths or significant weight losses were observed among the treated animals
- Cincinelli, Raffaella,Musso, Loana,Merlini, Lucio,Giannini, Giuseppe,Vesci, Loredana,Milazzo, Ferdinando M.,Carenini, Nives,Perego, Paola,Penco, Sergio,Artali, Roberto,Zunino, Franco,Pisano, Claudio,Dallavalle, Sabrina
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p. 1089 - 1103
(2014/02/14)
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- ANTICANCER AGENT
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An anticancer agent comprising a compound represented by the formula (I) [R1 represents hydrogen atom, hydroxyl group, a C1-6alkoxy group and the like; R2 and R3 represents hydrogen atom, a halogen atom, a C1-6alkyl group and the like; R4 represents hydrogen atom, a C1-6alkyl group, a C1-6alkylsulfonyl group and the like; R5 represents hydrogen atom or a substituent; .... represents a single bond or a double bond; R6 and R7 represents hydrogen atom, a C1-6alkyl group and the like; R8 represents hydrogen atom, a C1-6alkyl group and the like; A represents -O-, -S-, or - CH2-; D represents -C= or -N=; X represents methylene group, -O-, or -CO-; Q represents -N= or -C(R8)=; and Y represents a heterocyclic group or amino group], which shows a superior inhibitory activity against pim-1 kinase.
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Paragraph 0283
(2013/03/26)
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- NOVEL COMPOUNDS FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS
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The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer?s disease, and of diseases or conditions associated with amyloid-like prote
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Page/Page column 83
(2011/11/01)
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- Novel Compounds for the Treatment of Diseases Associated with Amyloid or Amyloid-Like Proteins
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The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.
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Page/Page column 39
(2011/11/30)
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- Compounds and methods for development of Ret modulators
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Compounds active on Ret are described, as well as methods of using such compounds. Also described are crystal structures of Ret surrogates that were determined using X-ray crystallography. The use of such Ret surrogate crystals and strucural information can, for example, be used for identifying molecular scaffolds and for developing ligands that bind to and modulate Ret and for identifying improved ligands based on known ligands.
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Page/Page column 71-72
(2008/06/13)
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- Regioselective functionalization of 1H-pyrrolo[2,3-b]pyridine via its N-oxide
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Selective functionalization of 1H-pyrrolo[2,3-b]pyridine (7-azaindole) at the 6-position was achieved by Reissert-Henze type reaction. Thus, halogeno (Cl, Br, I), cyano and thiocyanato groups were directly introduced to the pyridine ring of 7-azaindole.
- Minakata,Komatsu,Ohshiro
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p. 661 - 663
(2007/10/02)
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