- Aryl or N-heteroaryl Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands
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The invention relates to aryl or N-heteroaryl substituted methanesulfonamide derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Paragraph 0498; 0499
(2013/04/10)
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- ARYL OR N-HETEROARYL SUBSTITUTED METHANESULFONAMIDE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
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The invention relates to aryl or N-heteroaryl substituted methanesulfonamide derivatives of Formula (I) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Page/Page column 66; 67
(2013/04/13)
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- Amine Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands
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The invention relates to amine substituted methanesulfonamide derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Paragraph 0584; 0585; 0593; 0594
(2013/04/10)
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- AMINE SUBSTITUTED METHANESULFONAMIDE DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
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The invention relates to amine substituted methanesulfonamide derivatives of formula (I) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Page/Page column 80
(2013/04/13)
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- NON-SYSTEMIC TGR5 AGONISTS
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Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.
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Page/Page column 221
(2013/07/05)
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- Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors
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Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto - enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited-marked antiretroviral activity. Here, we show the synthesis and the detailed structure - activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3,3- dimethylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nMin the strand transfer assay and an ED50 of 0.6 nMin the antiviral assay, and 6-(3-chloro-2-fluorobenzyl) -1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid 49, which had an IC50 of 7.2 nMand an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrasecatalyzed strand transfer processes than 3′-processing reactions, as is the case with the keto - enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.
- Sato, Motohide,Kawakami, Hiroshi,Motomura, Takahisa,Aramaki, Hisateru,Matsuda, Takashi,Yamashita, Masaki,Ito, Yoshiharu,Matsuzaki, Yuji,Yamataka, Kazunobu,Ikeda, Satoru,Shinkai, Hisashi
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supporting information; experimental part
p. 4869 - 4882
(2010/03/02)
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- Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl- 3-hydroxy. N-[3'-methyl-4'-(trifluoromethyl)phenyl]propenamide and related compounds
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The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.
- Kuo, Elizabeth A.,Hambleton, Philip T.,Kay, David P.,Evans, Phillip L.,Matharu, Saroop S.,Little, Edward,McDowall, Neil,Jones, C. Beth,Hedgecock, Charles J. R.,Yea, Christopher M.,Chan, A. W. Edith,Hairsine, Peter W.,Ager, Ian R.,Tully, W. Roger,Williamson, Richard A.,Westwood, Robert
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p. 4608 - 4621
(2007/10/03)
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- Formation of Aryliodine(III) Derivatives in the Nitration of Aryl Iodides in Acetic Anhydride
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Nitration of iodobenzene, o-iodotoluene, and p-iodotoluene in acetic anhydride results in reversible oxidation to aryliodine(III) compounds prior to the formation of the expected nitro derivatives. μ-Oxo has been isolated from nitration of iodobenzene and its crystal structure determined.
- Bushnell, Gordon W.,Fischer, Alfred,Ibrahim, Prabha N.
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p. 1281 - 1286
(2007/10/02)
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- Substituent and Ring Size Dependence of the 4J(Me-C-C-H) Coupling Constant
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The magnitude of the 4J proton-proton coupling constant across the fragment CH3-C-C-H (a probe of the bond order between the central sp2-sp2 hybridized carbon atoms) has been found to be essentially independent of substitution on a toluene fragment and the size of the ring containing the ortho-allylic fragment.The coupling constant is sensitive to direct substitution on the ortho-allilyc fragment, especially where the substituent is placed α to methyl group.KEY WORDS - 4J proton-proton coupling constant ortho-benzylic coupling constant ring size dependence substituent dependence
- Collins, M. J.,Hatton, P. M.,Sternbell, S.,Tansey, C. W.
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p. 824 - 828
(2007/10/02)
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