- Regio- and Stereoselective Rhodium(II)-Catalyzed C–H Functionalization of Cyclobutanes
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Recent developments in controlled C–H functionalization transformations continue to inspire new retrosynthetic disconnections. One tactic in C–H functionalization is the intermolecular C–H insertion reaction of rhodium-bound carbenes. These intermediates can undergo highly selective transformations through the modulation of the ligand framework of the rhodium catalyst. This work describes our continued efforts toward differentiating C–H bonds in the same molecule by judicious catalyst choice. Substituted cyclobutanes that exist as a mixture of interconverting conformers and possess neighboring C–H bonds within a highly strained framework are the targets herein for challenging the current suite of catalysts. Although most C–H functionalization tactics focus on generating 1,2-disubstituted cyclobutanes via substrate-controlled directing-group methods, the regiodivergent methods discussed in this paper provide access to chiral 1,1-disubstituted and cis-1,3-disubstituted cyclobutanes simply by changing the catalyst identity, thus permitting entry to novel chemical space. This study shows how to control site selectivity in C–H functionalization by simply using the correct catalyst. Cyclobutanes were used as the scaffold to illustrate the impact of catalyst control because the core unit is incorporated into various structures of biomedical interest. The catalysts control whether the chemistry occurs at C1 or C3 of the cyclobutane. Traditional synthetic strategies have viewed most C–H bonds as chemically inert and utilize functional groups for transformations. C–H functionalization is an attractive alternative strategy for the synthesis of complex organic molecules because it leads to the possibility of rapidly accessing novel chemical space. To fully develop this alternative approach, it is necessary to identify ways for reacting at specific C–H bonds even when a number of similar C–H bonds may exist in a substrate molecule. It would be particularly beneficial if a collection of catalysts were available, each with a preference for reaction at a specific C–H bond. Over the past few years, we have developed such a collection of catalysts for C–H functionalization chemistry of rhodium-bound carbenes. In this paper, we illustrate how these catalysts can be applied to the selective functionalization of cyclobutanes, leading to the formation of pharmaceutically relevant chiral building blocks.
- Garlets, Zachary J.,Wertz, Benjamin D.,Liu, Wenbin,Voight, Eric A.,Davies, Huw M.L.
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p. 304 - 313
(2020/01/08)
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- HCV POLYMERASE INHIBITORS
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The invention provides compounds of the formula:wherein B is a nucleobase selected from the groups (a) to (d):and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
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Page/Page column 64
(2020/02/14)
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- DIOXOLANE ANALOGUES OF URIDINE FOR THE TREATMENT OF CANCER
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The invention provides compounds of formula (I), wherein: R1 is OR11, or NR5R5'; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(=O)R6, O(C=O)R6 or O(C=O)OR6; R5′ is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.
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Page/Page column 37
(2016/03/22)
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- HCV POLYMERASE INHIBITORS
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The invention provides compounds of the formula:(I) wherein B is a nucleobase selected from the groups (a) to (d) and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
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Page/Page column 54
(2015/03/28)
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- HCV POLYMERASE INHIBITORS
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The invention provides compounds of the formula (I) wherein B is a nucleobase selected from the groups (a) to (d): and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
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Page/Page column 56
(2015/05/05)
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- NOVEL COMPOUNDS, ISOMER THEREOF, OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF AS VANILLOID RECEPTOR ANTAGONIST AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
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This present invention relates to novel compounds, isomer thereof or pharmaceutically acceptable salts thereof as vanilloid receptor (Vanilloid Receptor 1; VR1; TRPV1) antagonist; and a pharmaceutical composition containing the same. The present invention provides a pharmaceutical composition for preventing or treating a disease such as pain, migraine, arthralgia, neuralgia, neuropathies, nerve injury, skin disorder, urinary bladder hypersensitiveness, irritable bowel syndrome, fecal urgency, a respiratory disorder, irritation of skin, eye or mucous membrane, stomach-duodenal ulcer, inflammatory diseases, ear disease, heart disease and so on.
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Page/Page column 94-95
(2010/04/03)
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