- IMIDAZOTRIAZINONE COMPOUNDS
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The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.
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Paragraph 0639; 0640; 0641
(2013/10/08)
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- The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis
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Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described.
- De Savi, Chris,Pape, Andrew,Cumming, John G.,Ting, Attilla,Smith, Peter D.,Burrows, Jeremy N.,Mills, Mark,Davies, Chris,Lamont, Scott,Milne, David,Cook, Calum,Moore, Peter,Sawyer, Yvonne,Gerhardt, Stefan
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scheme or table
p. 1376 - 1381
(2011/04/23)
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- SOLUBLE EPOXIDE HYDROLASE INHIBITORS AND METHODS OF USING SAME
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Disclosed are compounds active against soluble epoxide hydrolase (sEH), compositions thereof and methods of using and making same.
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Page/Page column 92-93
(2008/06/13)
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- Aryl sulfonamide and sulfonyl compounds as modulators of PPAR and methods of treating metabolic disorders
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Aryl sulfonamide and sulfonyl compounds as modulators of peroxisome proliferator activated receptors, pharmaceutical compositions comprising the same, and methods of treating disease using the same are disclosed.
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Page/Page column 64
(2010/02/14)
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- N-substituted nonaryl-heterocyclic NMDA/NR2B antagonists
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Compounds represented by Formula (I): 1or pharmaceutically acceptable salts thereof, are effective as NMDA NR2B antagonists useful for relieving pain.
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- Synthesis and anxiolytic activity of N-substituted cyclic imides (1R*,2S*3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3-b icyclo[2.2.1]heptanedicarboxime (Tandospirone) and related compounds
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A series of cyclic imides bearing a ω-(4-aryl and 4-heteroaryl-1-piperazinyl)alkyl moieties was synthesized and tested in vivo for anxiolytic activity. The in vitro binding affinities of these compounds were also examined for 5-HT(1A) receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, (1R*,2S*,3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (1: tandospirone), was found to be equipotent with buspirone in its anxiolytic activity and more anxio-selective than buspirone and diazepam. Tandospirone (1) is currently undergoing clinical evaluation as a selective anxiolytic agent.
- Ishizumi,Kojima,Antoku
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p. 2288 - 2300
(2007/10/02)
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- A NEW ROUTE TO THE SYNTHESIS OF 5-FLUOROURACIL
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Starting from tetrafluoropyrimidine (1), selective fluorine/chlorine exchange reactions and selective hydrogenolysis of the chlorine substituents are described.Combination of these methods, together with a subsequent hydrolysis reaction, provides a new route to the synthesis of 5-fluorouracil via 4,6-dichloro-2,5-difluoropyrimidine and 4-chloro-2,5-difluoropyrimidine.
- Baasner, B.,Klauke, E.
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p. 417 - 430
(2007/10/02)
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- Chemoselectivity and Regoselectivity in Reactions of Pyrimidines
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Selective nucleophilic substitution and hydrogenolysis reactions in pyrimidines are discussed.Stepwise oxidation reactions of pyrimidine sulfides and HPLC studies of these are reported.
- Gacek, Michel,Undheim, Kjell
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p. 691 - 696
(2007/10/02)
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