- Quinoline formamide compound as well as preparation method and application thereof
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The invention discloses quinoline formamide compounds as well as a preparation method and application thereof. Specifically, the invention relates to a compound represented by a formula (I) as shown in the specification or a tautomer, a meso-racemate, a r
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Paragraph 0130-0135; 0148-0153
(2020/11/25)
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- GLUCOSE TRANSPORT INHIBITORS
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The present invention relates to chemical compounds that selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for
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Page/Page column 129; 130; 157; 158
(2015/07/07)
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- Selective inhibitors of fibroblast activation protein (FAP) with a (4-quinolinoyl)-glycyl-2-cyanopyrrolidine scaffold
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Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp2 hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>10 3) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory.
- Jansen, Koen,Heirbaut, Leen,Cheng, Jonathan D.,Joossens, Jurgen,Ryabtsova, Oxana,Cos, Paul,Maes, Louis,Lambeir, Anne-Marie,De Meester, Ingrid,Augustyns, Koen,Van Der Veken, Pieter
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supporting information
p. 491 - 496
(2013/07/19)
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- Facile and efficient synthesis of quinoline-4-carboxylic acids under microwave irradiation
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A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under microwave irradiation.
- Zhu, Hui,Yang, Ri Fang,Yun, Liu Hong,Li, Jin
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experimental part
p. 35 - 38
(2010/11/04)
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- Synthesis and in vitro pharmacology of substituted quinoline-2,4-dicarboxylic acids as inhibitors of vesicular glutamate transport
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The vesicular glutamate transport (VGLUT) system selectively mediates the uptake of L-glutamate into synaptic vesicles. Uptake is linked to an H+-ATPase that provides coupling among ATP hydrolysis, an electrochemical proton gradient, and glutamate transport. Substituted quinoline-2,4-dicarboxylic acids (QDCs), prepared by condensation of dimethyl ketoglutaconate (DKG) with substituted anilines and subsequent hydrolysis, were investigated as potential VGLUT inhibitors in synaptic vesicles. A brief panel of substituted QDCs was previously reported (Carrigan et al. Bioorg. Med. Chem. Lett. 1999, 9, 2607-2612)1 and showed that certain substituents led to more potent competitive inhibitors of VGLUT. Using these compounds as leads, an expanded series of QDC analogues were prepared either by condensation of DKG with novel anilines or via aryl-coupling (Suzuki or Heck) to dimethyl 6-bromoquinolinedicarboxylate. From the panel of almost 50 substituted QDCs tested as inhibitors of the VGLUT system, the 6-PhCH=CH-QDC (Ki = 167 μM), 6-PhCH2CH2-QDC (Ki = 143 μM), 6-(4′-phenylstyryl)-QDC (Ki = 64 μM), and 6-biphenyl-4-yl-QDC (Ki=41 μM) were found to be the most potent blockers. A preliminary assessment of the key elements needed for binding to the VGLUT protein based on the structure-activity relationships for the panel of substituted QDCs is discussed herein. The substituted QDCs represent the first synthetically derived VGLUT inhibitors and are promising templates for the development of selective transporter inhibitors.
- Carrigan, Christina N.,Bartlett, Richard D.,Esslinger, C. Sean,Cybulski, Kimberly A.,Tongcharoensirikul, Pakamas,Bridges, Richard J.,Thompson, Charles M.
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p. 2260 - 2276
(2007/10/03)
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- Quinoline-2,4-dicarboxylic acids: Synthesis and evaluation as inhibitors of the glutamate vesicular transport system
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Twenty-six quinoline-2,4-dicarboxylic acids (QDC's) were synthesized by a modified Doebner-von Miller pathway and tested as inhibitors against the glutamate vesicular transport (GVT) protein. The QDC's were active as inhibitors with the most potent QDC's found to contain halogens at the 6-/8-position, a hydroxyl at the 8-position, or a tethered aromatic moiety at the 6- or 7-position of the quinoline.
- Carrigan, Christina N.,Esslinger, C. Sean,Bartlett, Richard D.,Bridges, Richard J.,Thompson, Charles M.
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p. 2607 - 2612
(2007/10/03)
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