- KCNT1 INHIBITORS AND METHODS OF USE
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The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
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- Novel betrixaban intermediate and preparation method and application thereof
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The invention discloses a novel betrixaban intermediate and a preparation method and application thereof. The structure of the intermediate is shown in formula I. The intermediate can achieve efficient and high-yield construction of an N,N-dimethylcarbamimidoyl structure fragment in the betrixaban structure through a bio-enzyme catalysis method, and has the advantages of being green and environmentally friendly.
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- Novel Human Aminopeptidase N Inhibitors: Discovery and Optimization of Subsite Binding Interactions
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Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues that are potent inhibitors of the APN homologue from the malarial parasite Plasmodium falciparum M1 aminopeptidase (PfA-M1). Herein, we describe the rationale that underpins the repurposing of PfA-M1 inhibitors as novel APN inhibitors. A series of novel hydroxamic acid analogues were developed using a structure-based design approach and evaluated their inhibition activities against APN. N-(2-(Hydroxyamino)-2-oxo-1-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-4-yl)ethyl)-4-(methylsulfonamido)benzamide (6ad) proved to be an extremely potent inhibitor of APN activity in vitro, selective against other zinc-dependent enzymes such as matrix metalloproteases, and possessed limited cytotoxicity against Ad293 cells and favorable physicochemical and metabolic stability properties. The combined results indicate that compound 6ad may be a useful lead for the development of anticancer agents.
- Lee, Jisook,Vinh, Natalie B.,Drinkwater, Nyssa,Yang, Wei,Kannan Sivaraman, Komagal,Schembri, Luke S.,Gazdik, Michelle,Grin, Peter M.,Butler, Georgina S.,Overall, Christopher M.,Charman, Susan A.,McGowan, Sheena,Scammells, Peter J.
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supporting information
p. 7185 - 7209
(2019/08/28)
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- NOVEL PIPERAZINE ANALOGS AS BROAD-SPECTRUM INFLUENZA ANTIVIRALS
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A compound of Formula (I) is set forth, including pharmaceutically acceptable salts thereof, wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar
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Page/Page column 63
(2012/03/27)
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- Acidity of benzoic acids bearing the (CO)5Cr=CN(CH 3)2 group
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Benzoic acids 2a and 2b, bearing the (CO)5Cr=CN(CH 3)2 group in the p- and m-position, and the corresponding benzoic acids 2c and 2d, in which the rotation of the aminocarbene moiety was blocked by the presence of a methyl group, were prepared together with the corresponding N,N-dimethylamido acids 3a-d. The measurement of pKa values in EtOH and DMF revealed that the (CO)5Cr=CN(CH 3)2 group is a very weak electron acceptor (δp = 0; δm = 0.14). The restriction of the rotation of the aminocarbene moiety did not significantly influence its electronic properties. The obtained results are in accordance with earlier findings that the relatively strong acidity of carbene complexes bearing hydrogens at the ±-position to the carbene atom is due to the resonance stabilization of the anion.
- Parik, Patrik,Kulhanek, Jiri,Ludwig, Miroslav,Wagner, Roman,Rotrekl, Ivan,Drahonovsky, Dusan,Meca, Ludek,Smidkova, Marketa,Tobrman, Tomas,Dvorak, Dalimil
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experimental part
p. 4135 - 4138
(2011/01/03)
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- AMINOISOQUINOLINE DERIVATIVES
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Aminoisoquinoline derivatives represented by formulae (I and II), analogs thereof or pharmaceutically acceptable salts of the same. Because of having excellent inhibitory effects on activated blood coagulation factor X, these compounds are useful as active ingredients in anticoagulants or preventives/remedies for thrombosis or embolism.
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- BENZAMIDINE DERIVATIVES
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Benzamidine derivatives of the following formulae or analogs thereof, i. e., pharmaceutically acceptable salts thereof, are provided. These compounds or salts thereof have a blood-coagulation inhibiting effect based on an excellent effect of inhibiting the action of activated blood coagulation factor X, and they are useful as anticoagulants.
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