- Preparation technology of 6-hydroxy-bentazone
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The invention discloses a preparation technology of 6-hydroxy-3-isopropyl-1H-benzo[c][1,2,6]thiadiazine-4(3H)-keto-2,2-dioxide. The preparation technology includes subjecting 5-chloro-2-nitrobenzoic acid serving as a raw material to hydrolysis reaction an
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- Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay
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Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC50) and cell culture (EC50) potencies of less than 100 nanomolar.
- Stammers, Timothy A.,Coulombe, Rene,Duplessis, Martin,Fazal, Gulrez,Gagnon, Alexandre,Garneau, Michel,Goulet, Sylvie,Jakalian, Araz,Laplante, Steven,Rancourt, Jean,Thavonekham, Bounkham,Wernic, Dominik,Kukolj, George,Beaulieu, Pierre L.
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p. 6879 - 6885
(2014/01/06)
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- Viral Polymerase Inhibitors
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Compounds of formula I: wherein X, R2, R3, R5 and R6 are defined herein, are useful as inhibitors of the hepatitis C virus NS5B polymerase.
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- Kynurenic acid amides as novel NR2B selective NMDA receptor antagonists
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A novel series of kynurenic acid amides, ring-enlarged derivatives of indole-2-carboxamides, was prepared and identified as in vivo active NR2B subtype selective NMDA receptor antagonists. The synthesis and SAR studies are discussed.
- Borza, Istvan,Kolok, Sandor,Galgoczy, Kornel,Gere, Aniko,Horvath, Csilla,Farkas, Sandor,Greiner, Istvan,Domany, Gyoergy
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p. 406 - 409
(2007/10/03)
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- Total syntheses of the benzodiazepine alkaloids circumdatin F and circumdatin C
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Total syntheses of circumdatin F and circumdatin C, which both possess a 3H-quinazolin-4-one as well as a 1,4-benzodiazepin-5-one moiety, are described. A tripeptide derivative was synthesized as a key intermediate and dehydrated to a benzoxazine by react
- Witt,Bergman
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p. 2784 - 2788
(2007/10/03)
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- Inhibitors of Cyclic AMP Phosphodiesterase. 3. Synthesis and Biological Evaluation of Pyrido and Imidazolyl Analogues of 1,2,3,5-Tetrahydro-2-oxoimidazoquinazoline
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Hybridization of structural elements of 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline ring system common to the cyclic AMP (cAMP) phosphodiesterase (PDE) inhibitors lixazinone (RS-82856,1) and anagrelide (3) with complementary features of other PDE inhibitor cardiotonic agents prompted the design and synthesis of the title compounds 7a-d, 11, 12, and 13a,b.The necessary features of these compounds were determined within the framework of the proposed active-site models for the high affinity form of cAMP PDE inhibited by cGMP (type IV).Evaluation of these targets, both in vitro as inhibitors of platelet or cardiac type IV PDE or in vivo as inotropic agents in the pentobarbital-anesthetized dog model of congestive heart failure, showed that these structure possessed negligibly enhanced activities over the parent heterocyclic system, and remained significantly inferior to 1 in all respects.This difference is ascribed to the absence of the N-cyclohexyl-N-methylbutyramidyl-4-oxy side chain of 1.The proposal that the acidic lactam-type functionality, common to the type IV PDE inhibitor inotropic agents such as 4-6 and 8-10, mimics the polarizable cyclic phosphate moiety of cAMP suggested that the side chain of 1 may function as an effective surrogate for selected characteristics of the adenine portion of cAMP.However, the results of this study show that incorporation of adenine-like hydrogen-bonding functionalities common to other type IV PDE inhibitors into the 1,2,3,5-tetrahydro-2-oxoimidazoquinazoline system did not enhance activity to the levels observed for 1 analogues.These observations, coupled with the kinetic pattern of inhibition of type IV PDE observed for 1 and analogues, suggest that access to a secondary, lipophilic-tolerant binding site, possibly coincident with the adenine binding domain, and adjacent to the catalytic ribose-phosphate binding site of platelet and cardiac type IV PDE, is responsible for the increased potency of these compounds.
- Venuti, Michael C.,Stephenson, Robert A.,Alvarez, Robert,Bruno, John J.,Strosberg, Arthur M.
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p. 2136 - 2145
(2007/10/02)
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