- PLASMA KALLIKREIN INHIBITORS AND USES THEREOF
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The present invention provides compounds and compositions thereof which are useful as inhibitors of plasma kallikrein and which exhibit desirable characteristics for the same.
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Paragraph 0911; 0912
(2021/03/19)
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- Achieving High 1H Nuclear Hyperpolarization Levels with Long Lifetimes in a Range of Tuberculosis Drug Scaffolds
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Despite the successful use of isoniazid, rifampicin, pyrazinamide and ethambutol in the treatment of tuberculosis (TB), it is a disease of growing global concern. We illustrate here a series of methods that will dramatically improve the magnetic resonance imaging (MRI) detectability of nineteen TB-relevant agents. We note that the future probing of their uptake and distribution in vivo would be expected to significantly enhance their efficacy in disease treatment. This improvement in detectability is achieved by use of the parahydrogen based SABRE protocol in conjunction with the 2H-labelling of key sites within their molecular structures and the 2H-labelling of the magnetization transfer catalyst. The T1 relaxation times and polarization levels of these agents are quantified under test conditions to produce a protocol to identify structurally optimized motifs for future detection. For example, deuteration of the 6-position of a pyrazinamide analogue leads to a structural form that exhibits T1 values of 144.5 s for 5-H with up to 20 % polarization. This represents a >7-fold extension in relaxation time and almost 10-fold improvement in polarization level when compared to its unoptimized structure.
- Norcott, Philip,Rayner, Peter J.,Green, Gary G. R.,Duckett, Simon B.
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supporting information
p. 16990 - 16997
(2017/11/20)
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- PHTALAZINONE DERIVATIVES AS MPEGS -1 INHIBITORS
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The present patent application is directed to bicyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are theref
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Page/Page column 55
(2013/06/05)
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- Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors
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A series of 2-amino-isoxazolopyridines was designed and synthesized as Polo-like kinase (Plk) inhibitors. Key SAR and crystallographic data are discussed. More advanced analogues inhibit Plk1 with good enzymatic activity and modest cell-based activity. Differential selectivity among the three Plk isoforms is observed.
- Hanan, Emily J.,Fucini, Raymond V.,Romanowski, Michael J.,Elling, Robert A.,Lew, Willard,Purkey, Hans E.,VanderPorten, Erica C.,Yang, Wenjin
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scheme or table
p. 5186 - 5189
(2009/05/07)
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- VIRAL POLYMERASE INHIBITORS
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The present invention relates to viral polymerase inhibitors, in particular inhibitors of viral polymerases within the Flaviviridae family such as hepatitis C virus (HCV), processes for their preparation and their use in the treatment of infections.
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Page/Page column 83
(2009/01/20)
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- SUBSTITUTED PYRROLE DERIVATIVE
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The present invention provides a novel pyrrole derivative having excellent androgen receptor antagonism, which is represented by the formula (I): wherein R1represents a hydrogen atom, a cyano group or a group represented by the formula COORA (wherein RA represents an optional substituted C1-6 alkyl group), R2 and R4 are the same or different, and each represents a hydrogen atom, a C1-6 alkyl group, a C3-6 cycloalkyl group, a trifluoromethyl group, an amino-C1-6 alkyl group, a mono-or di-substituted amino-C1-6 alkyl group, an optionally halogenated C1-6 alkyl group substituted with an optionally substituted hydroxyl group, a C2-6 alkenyl group substituted with an optionally substituted hydroxyl group, a C1-6 alkyl group substituted with an optionally substituted and optionally oxidized thiol group, an optionally substituted with and optionally oxidized thiol group, a cyano group, an acyl group, an optionally substituted oxazolyl group or a 1,3-dioxolan-2-yl group, R3 represents a group represented by the formula (a): (wherein X represents a halogen atom, Y represents a carbon atom or a nitrogen atom, Alk represents an optionally substituted C 1-4 alkylene group, and RB represents a hydrogen atom or an acyl group), and R5 represents a phenyl group which has a cyano group at a 4-position or a 3-position thereof, and may be further substituted, or a salt thereof. The present invention also provides an androgen receptor antagonist containing the pyrrole derivative, or a salt thereof.
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Page/Page column 92
(2010/11/08)
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