- Synthesis and Antimicrobial Activity of 1,3,4-Oxadiazole-2(3H)-thione and Azidomethanone Derivatives Based on Quinoline-4-carbohydrazide Derivatives
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A new series compounds of quinoline derivatives were synthesized by reaction of 3-(carboxymethyl)-2-arylquinoline-4-carboxylic acids 1a, 1b, 1c with different nucleophiles. The structures of the new compounds were elucidated on the basis of FTIR,1/s
- Mohamed, Mansoura I.,Kandile, Nadia G.,Zaky, Howida T.
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- TRPV4 ANTAGONISTS
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The present invention relates to quinoline analogs, pharmaceutical compositions containing them and their use as TRPV4 antagonists.
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Page/Page column 50
(2011/10/13)
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- Quinoline derivatives as neurokinin receptor antagonists
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The present invention relates to substituted quinoline hydrazides of Formula (I): wherein R1, R2, R3, R4, R5, X, Y and Z are defined herein, pharmaceutical compositions comprising them and their use in treating diseases mediated by neurokinin-2 and/or neurokinin-3 (NK-3) receptors. These compounds can thus be used in methods of treatment to suppress and treat such disorders.
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Page/Page column 14
(2009/04/24)
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- QUINOLINE DERIVATIVES AS NEUROKININ RECEPTOR ANTAGONISTS
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The present invention relates to substituted quinoline-4-carboxylic acid hydrazides defined herein, pharmaceutical compositions comprising them and their use in treating diseases mediated by neurokinin-2 and/or neurokinin-3 (NK-3) receptors.
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Page/Page column 29
(2008/06/13)
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- QUINOLINE 4-CARBOXAMIDE DERIVATIVES AND THEIR USE AS NEUROKININ 3 (NK-3) RECEPTOR ANTAGONISTS
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The invention relates to novel quinoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments particularly in treating disorders of the central nervous system (CNS).
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Page/Page column 27
(2010/02/10)
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- Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase
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A series of 2-phenyl quinoline-4-carboxylic acid derivatives related to brequinar, an inhibitor of human dihydroorotate dehydrogenase (DHODH), has been prepared and evaluated as inhibitors of DHODH from the malaria parasite Plasmodium falciparum. Brequinar was essentially inactive against PfDHODH (IC50 880 μM) whereas several members of the series inhibited PfDHODH. Unexpectedly, replacement of the carboxylic acid required for brequinar to inhibit hDHODH was not essential in the diisopropylamides that inhibited PfDHODH.
- Boa, Andrew N.,Canavan, Shane P.,Hirst, Paul R.,Ramsey, Christopher,Stead, Andrew M.W.,McConkey, Glenn A.
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p. 1945 - 1967
(2007/10/03)
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- N-type calcium channel antagonists for the treatment of pain
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Compounds useful for the treatment of pain in accord with the following structural diagram, wherein R1, R2, R3, R4 and R5 are any of a number of groups as defined in the specification, A and D are as
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- Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3- hydroxy-2-phenylquinoline-4-carboxamide (SB 223412)
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Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SB 223412, hNK- 3-CHO binding K(i) = 1.4 nM) and 55 (3-NH2, hNK-3-CHO binding K(i) = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 μM. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vive this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy- 2-phenylquinoline-4-carboxamide (53, SB 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.
- Giardina, Giuseppe A. M.,Raveglia, Luca F.,Grugni, Mario,Sarau, Henry M.,Farina, Carlo,Medhurst, Andrew D.,Graziani, Davide,Schmidt, Dulcie B.,Rigolio, Roberto,Luttmann, Mark,Cavagnera, Stefano,Foley, James J.,Vecchietti, Vittorio,Hay, Douglas W. P.
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p. 1053 - 1065
(2007/10/03)
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- Synthesis of substituted quinoline-4-carboxylic acids
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A high yielding synthesis of a variety of quinoline-4-carboxylic acids has been accomplished using a modified Pfitzinger approach involving the condensation of a ketone with an isatin derivative employing aqueous acid conditions. A convenient synthesis of
- Lackey,Sternbach
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p. 993 - 997
(2007/10/02)
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