- METHYL SULFANYL PYRMIDMES USEFUL AS ANTIINFLAMMATORIES, ANALGESICS, AND ANTIEPILEPTICS
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The present invention relates to pyrimidine derivatives of Formula (Ia) and (Ib) (including tautomers, isomers, prodrugs, and pharmaceutically acceptable salts thereof). Said compounds are useful in the treatment of pain (such as neuropathic pain), inflammation, and epilepsy (by acting as anticonvulsants). Methods of medical treatment making use of said compounds, as well as additional compounds of Formula (IIa) and (IIb), are also disclosed.
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Page/Page column 87
(2010/12/18)
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- COMPOUNDS
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The invention provides an optically active form of the compound of formula (I), or a pharmaceutically acceptable ester, amide, solvate or salt thereof, including a salt of such an ester or amide, and a solvate of such an ester, amide or salt; uses of the
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Page/Page column 34-35
(2010/11/26)
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- 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. structure-activity relationships for chromophore modification and phenyl ring substitution
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High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]-carbazole-1,3(2H,6H)- dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2′-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.
- Palmer, Brian D.,Thompson, Andrew M.,Booth, R. John,Dobrusin, Ellen M.,Kraker, Alan J.,Lee, Ho H.,Lunney, Elizabeth A.,Mitchell, Lorna H.,Ortwine, Daniel F.,Smaill, Jeff B.,Swan, Leesa M.,Denny, William A.
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p. 4896 - 4911
(2007/10/03)
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- Synthesis and Biological Activity of 1,2-Dithiolanes and 1,2-Dithianes Bearing a Nitrogen-containing Substituent
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A series of 1,2-dithiolanes, 1,2-dithianes and related compounds bearing a nitrogen-containing substituent were synthesized and their pesticidal activity was tested.A new general synthetic route to 1,2-dithiolanes was established from 1,3-diols.A variation in the position and character of the nitrogen atom is shown to be allowable to some extent for promoting insecticidal activity, unlike the case of sulfur atoms.Most compounds showed acaricidal activity, the strongest being displayed by cis-3,5-bis(dimethylaminomethyl)-1,2-dithiolane.
- Uneme, Hideki,Mitsudera, Hiroyuki,Kamikado, Toshiya,Kono, Yoshiaki,Manabe, Yukiaki,Numata, Mitsuo
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p. 2023 - 2033
(2007/10/02)
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