- GLUCOPYRANOSE DERIVATIVES USEFUL AS SGLT2 INHIBITORS
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The present invention is directed to glucopyranose derivatives of formula (I), pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by SGLT2 activity. More particularly, the compounds of the present invention are useful in the treatment of for example, Type II diabetes mellitus, Syndrome X, and complications and symptoms associated with said disorders.
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Page/Page column 59
(2020/06/10)
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- GLUCOPYRANOSE DERIVATIVES USEFUL AS SGLT2 INHIBITORS
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The present invention is directed to glucopyranose derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by SGLT2 activity. More particularly, the compounds of the present invention are useful in the treatment of for example, Type II diabetes mellitus, Syndrome X, and complications and symptoms associated with said disorders.
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Page/Page column 59
(2020/06/10)
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- Modular Tuning of Electrophilic Reactivity of Iridium Nitrenoids for the Intermolecular Selective α-Amidation of β-Keto Esters
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We report herein an Ir-catalyzed intermolecular amino group transfer to β-keto esters (amides) to access α-aminocarbonyl products with excellent chemoselectivity. The key strategy was to engineer electrophilicity of the putative Ir-nitrenoids by tuning electronic property of the κ2-N,O chelating ligands, thus facilitating nucleophilic addition of enol π-bonds of 1,3-dicarbonyl substrates.
- Lee, Minhan,Jung, Hoimin,Kim, Dongwook,Park, Jung-Woo,Chang, Sukbok
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supporting information
p. 11999 - 12004
(2020/08/06)
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- Ligustrazine derivative, and preparation method and applications thereof
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The invention provides a ligustrazine derivative, and a preparation method and applications thereof. The ligustrazine derivative is capable of treating IAA induced hypoxic injury, promoting neuron cell proliferation, promoting cell synapsis lengthening, and can be used for treating stroke and neurodegenerative diseases.
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Paragraph 0047; 0081; 0110; 0111; 0112
(2019/08/12)
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- MATRIX METALLOPROTEINASE (MMP) INHIBITORS AND METHODS OF USE THEREOF
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Hydantoin based compounds useful as inhibitors of matrix metalloproteinases (MMPs), particularly macrophage elastase (MMP-12) are described. Also described are related compositions and methods of using the compounds to inhibit MMP-12 and treat diseases mediated by MMP-12, such as asthma, chronic obstructive pulmonary disease (COPD), emphysema, acute lung injury, idiopathic pulmonary fibrosis (IPF), sarcoidosis, systemic sclerosis, liver fibrosis, nonalcoholic steatohepatitis (NASH), arthritis, cancer, heart disease, inflammatory bowel disease (IBD), acute kidney injury (AKI), chronic kidney disease (CKD), Alport syndrome, and nephritis.
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Paragraph 0532-0533
(2019/12/02)
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- α-Amino-β-carboxymuconate-?-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of de Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis
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NAD+ has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Although the beneficial effects of boosting NAD+ on mitochondrial fitness, metabolism, and lifespan are well established, to date, no therapeutic enhancers of de novo NAD+ biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22), the first potent and selective inhibitor of human ACMSD (IC50 = 0.013 μM) that increases NAD+ levels in cellular systems. The results of physicochemical-property, ADME, and safety profiling, coupled with in vivo target-engagement studies, support the hypothesis that ACMSD inhibition increases de novo NAD+ biosynthesis and position 22 as a first-class molecule for the evaluation of the therapeutic potential of ACMSD inhibition in treating disorders with perturbed NAD+ supply or homeostasis.
- Pellicciari, Roberto,Liscio, Paride,Giacchè, Nicola,De Franco, Francesca,Carotti, Andrea,Robertson, Janet,Cialabrini, Lucia,Katsyuba, Elena,Raffaelli, Nadia,Auwerx, Johan
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p. 745 - 759
(2018/02/17)
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- 3-chloro methyl benzoyl chloride synthetic method
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The present invention relates to a 3-chloro methyl benzoyl chloride synthetic method, and the specific method is as follows: 3-chloro methyl benzoyl chloride is synthesized from benzenyl trichloride and paraformaldehyde in a solvent in aluminium trichloride, ferric chloride and other Lewis acid catalysts. The synthetic method is a one-step reaction, and is simple and easy to control, mild in reaction condition, and high in finished product yield, starting materials are cheap and readily available, production cost is low, the synthetic method is less in waste, the waste can be harmlessly processed, and the synthetic method is clean and environmentally-friendly.
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Paragraph 0037; 0038
(2016/10/07)
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- NOVEL COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) inhibitory activity, isomers thereof, or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions comprising the same, a method of treating disease using the composition, and methods for preparing the novel compounds. The novel compounds according to the present invention have histone deacetylase 6 (HDAC6) inhibitory activity, and are effective for the prevention or treatment of HDAC6-associated diseases, including cancer, inflammatory diseases, autoimmune diseases, neurological diseases and neurodegenerative disorders.
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Paragraph 1751; 1752
(2015/10/05)
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- Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors
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A new class of colchicine derivatives were designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluations of these hybrids included the inhibitory activity of HDAC, tubulin polymerization analysis, in vitro cell cycle analysis in HCT-116 cells and cytotoxicity against different cancer cell lines. Hybrid 6d behaved as potent HDAC-tubulin dual inhibitor and showed comparable cytotoxicity with colchicine. Compound 11a exhibited powerful tubulin inhibitory activity, moderate anti-HDAC activity and the most potent cytotoxicity (IC50 Combining double low line 2-105 nM).
- Zhang, Xuan,Kong, Yannan,Zhang, Jie,Su, Mingbo,Zhou, Yubo,Zang, Yi,Li, Jia,Chen, Yi,Fang, Yanfen,Zhang, Xiongwen,Lu, Wei
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p. 127 - 135
(2015/04/14)
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- Synthesis and structure-activity relationships of novel, potent, orally active hypoxia-inducible factor-1 inhibitors
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Hypoxia-inducible factor-1 (HIF-1) is the chief transcription factor regulating hypoxia-driven gene expression. HIF-1 overexpression is associated with poor prognosis in several cancers and therefore represents an attractive target for novel antitumor agents. We explored small molecule inhibitors of the HIF-1 pathway. Using high-throughput-screening, we identified benzanilide compound 1 (IC50= 560 nM) as a seed. Subsequent extensive derivatization led to the discovery of compounds 43a and 51d, with anti-HIF-1 activities in vitro (IC50= 21 and 0.47 nM, respectively), and in vivo. Additionally, 43a (12.5-100 mg/kg) also displayed in vivo anti-tumor efficacy, without influencing body weight.
- Nagao, Satoshi,Yamane, Yoshinobu,Funasaka, Setsuo,Tanaka, Keigo,Miyazaki, Kazuki,Kotake, Yoshihiko,Kamata, Jun-Ichi,Watanabe-Miyano, Saori,Toyama, Osamu,Ozawa, Yoichi,Mizui, Yoshiharu,Okamoto, Kiyoshi,Ito, Daisuke
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p. 5513 - 5529
(2014/12/10)
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- NAPHTHYLACETIC ACIDS
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The invention is concerned with the compounds of formula (I) and pharmaceutically acceptable salts and esters thereof, wherein X, Q, and R1-R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Page/Page column 93-94
(2010/06/15)
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- N-Cycloalkanoyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
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A systematic structure-activity relationship investigation of the lead compound 1 resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation.
- Sidduri, Achyutharao,Tilley, Jefferson W,Hull, Kenneth,Lou, Jian Ping,Kaplan, Gerry,Sheffron, Allen,Chen,Campbell, Robert,Guthrie, Robert,Huang, Tai-Nan,Huby, Nicholas,Rowan, Karen,Schwinge, Virginia,Renzetti, Louis M
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p. 2475 - 2478
(2007/10/03)
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- Reactive immunization elicits catalytic antibodies for polyester hydrolysis
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In the search for biocatalysts for degradation of nonnatural polymers, reactive immunization with haptens 7 and 11 was used to prepare catalytic antibodies capable of cleaving short oligomeric esters, as well as the insoluble polyester 25. These antibodies were found to be highly specific and efficient esterases for oligomers. Triester 24 was preferentially hydrolyzed by an endo-cleavage pathway, however, with a higher molecular weight polymer 25 no site specificity could be observed. Catalytic efficiency of the antibodies towards the insoluble polymer 25 was limited due to physical constraints.
- Chen,Kubiak,Ashley,Janda
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p. 2796 - 2803
(2007/10/03)
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