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The present invention relates to a N2,N4-diphenylpyrimidin-2,4-diamine derivative, a method for preparing the same, and a pharmaceutical composition for the prevention or treatment of cancer, containing the same as an active ingredient. The derivative shows a relatively weak EGFR activity inhibitory effect on wild-type EGFR, a high inhibitory ability on EGFR mutation, and a high inhibitory ability on even FLT3 and FLT3 mutation, and thus, can be effectively used for the treatment of cancer with EGFR mutation or cancer with FLT3 or a mutation thereof, and the derivative shows a synergy effect at the time of combination administration, and thus can be effectively used for the treatment of combination administration.

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Piperidine – Wikipedia,
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1-[(3- or 4-Benzoylphenyl)-lower-alkyl]-[(CH2)n –N=B]-substituted-piperidines, useful as anti-asthmatic, anti-allergic, anti-cholinergic, bronchodilator and anti-inflammatory agents, are prepared by alkylation of an appropriate substituted piperidine with a (3- or 4-benzoylphenyl)-lower-alkyl halide or tosylate; by reaction of a 1-[2-(3- or 4-lithiophenyl)-lower-alkyl]-[(CH2)n –N=B]-substituted-piperidine with benzonitrile and hydrolysis of the resulting benzimidoyl compound; or by reduction of a 1-[alpha-(3- or 4-benzoylphenyl)-lower-alkanoyl]-[(CH2)n –N=B]-substituted-piperidine. The analogous carbinols are prepared by reduction, with an alkali metal borohydride, of the ketone.

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Inhibition of lysine specific demethylase 1 (LSD1) has been shown to induce the differentiation of leukemia stem cells in acute myeloid leukemia (AML). Irreversible inhibitors developed from the nonspecific inhibitor tranylcypromine have entered clinical trials; however, the development of effective reversible inhibitors has proved more challenging. Herein, we describe our efforts to identify reversible inhibitors of LSD1 from a high throughput screen and subsequent in silico modeling approaches. From a single hit (12) validated by biochemical and biophysical assays, we describe our efforts to develop acyclic scaffold-hops from GSK-690 (1). A further scaffold modification to a (4-cyanophenyl)glycinamide (e.g., 29a) led to the development of compound 32, with a Kd value of 32 nM and an EC50 value of 0.67 muM in a surrogate cellular biomarker assay. Moreover, this derivative does not display the same level of hERG liability as observed with 1 and represents a promising lead for further development.

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Disclosed is a substituted 2H-pyrazole derivative serving as a selective CDK4/6 inhibitor. Specifically, disclosed is a compound of formula (I) or a pharmaceutically acceptable salt thereof which serves as a selective CDK4/6 inhibitor.

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A first aspect of the- invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, (Formula (I)) wherein: R1 is (CH2)mNR11R12;R2 is selected from H, halo, OR13, NuEtaR13, alkyl, alkenyl and alkynyl; R3 is selected from alkyl, alkenyl, alkynyl, aryl, halo, aryloxy, NHCO2R4, NHCONR5R6, NHCOR7, NH-alkyl, NH-alkenyl, NH(CH2);n-aryl, (CH2)p-heteroaryl, (CH2)qCO2R8, (CH2)rCOR9 and NHSO2R10, wherein each alkyl, alkenyl, aryl or heteroaryl moiety in the aforementioned list is optionally further substituted by one or more groups selected from alkyl, halo OH, NH2, alkoxy, aryloxy, alkylamino, arylamino, carboxyl and carboxamide; R4 to R10 and R13 are each independently selected from alkyl, alkenyl and aryl; R11 and R12 are each independently selected from alkyl and alkenyl; or R11 and R:12 are linked together with the nitrogen to which they are attached to form a heterocycloalkyl or heterocycloalkenyl group; n, m, p, q and r are each independently selected from 0, 1, 2,.3. 4, 5 and 6. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing according to the invention.

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A series of 1,3-benzoxazole-4-carbonitriles was synthesized and evaluated for its antifungal activity, solubility, and metabolic stability. Among those compounds, 4-cyano-N,N,5-trimethyl-7-[(3S)-3-methyl-3-(methylamino) pyrrolidin-1-yl]-6-phenyl-1,3-benzoxazole-2-carboxamide (16b) exhibited potent in vitro activity against Candida species, higher water solubility, and improved metabolic stability compared to lead compound 1. Compound 16b showed potent in vivo efficacy against mice Candida infection models and good bioavailability in rats.

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The invention relates to a compound which is an indane according to Formula (I), or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, L, M, ?, n, p, and q are as defined herein. The compounds are useful in the treatment of antibacterial infection either as stand alone antibiotics, or in combination with further antibiotics.

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The present invention belongs to the technical field of medicine, relating in particular to: a fused ring compound as represented by Formula (I) for use as a mineralocorticoid receptor antagonist, a pharmaceutically acceptable salt thereof, and an isomer thereof; a preparation method for these compounds; a pharmaceutical preparation containing these compounds; and an application of these compounds, the pharmaceutically acceptable salt thereof, or the isomers thereof in the preparation of medicants for the treatment and/or prevention of kidney injury, cardiovascular diseases such as hypertension, and/or endocrine disease. The definitions of X, Y1, Y2, Y3, R1, R2a, R2b, R3a, R3b, R4, Cy and n are as presented in the description.

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Gastrointestinal stromal tumors (GISTs) are prototypes of stem cell factor receptor (c-KIT)-driven cancer. Two receptor tyrosine kinases, c-KIT and fms-tyrosine kinase (FLT3), are frequently mutated in acute myeloid leukemia (AML) patients, and these mutations are associated with poor prognosis. In this study, we discovered a multitargeted tyrosine kinase inhibitor, compound 15a, with potent inhibition against single or double mutations of c-KIT developed in GISTs. Moreover, crystal structure analysis revealed the unique binding mode of 15a with c-KIT and may elucidate its high potency in inhibiting c-KIT kinase activity. Compound 15a inhibited cell proliferation and induced apoptosis by targeting c-KIT in c-KIT-mutant GIST cell lines. The antitumor effects of 15a were also demonstrated in GIST430 and GIST patient-derived xenograft models. Further studies demonstrated that 15a inhibited the proliferation of c-KIT- and FLT3-driven AML cells in vitro and in vivo. The results of this study suggest that 15a may be a potential anticancer drug for the treatment of GISTs and AML.

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The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

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