- EIF4E-INHIBITING 4-OXO-3,4-DIHYDROPYRIDO[3,4-D]PYRIMIDINE COMPOUNDS
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The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. For Formula I compounds X1, X2, X3, X4, X5, X6, Q, L1, L2, Y, R1, R2, R3, R4, R5, R6, R7, R8 and rings A, B and C are as defined in the specification. The inventive Formula I compounds are inhibitors of eIF4e and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.
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Paragraph 0311-0312; 0360
(2021/01/23)
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- POTASSIUM CHANNEL MODULATORS
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Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with potassium channels. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with potassium channels.
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Paragraph 0398; 0400
(2018/01/14)
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- AMINOPYRAZINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES
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Disclosed are compounds of Formula A and Formula A-1, or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof; wherein "R1", "RA-1", "R2", "R3", and "Het" are defined herein above, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.
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- Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazines as GABAA receptor agonists at the α3 subunit
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We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the 0.3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for 57). Although most analogues showed no selectivity in terms of efficacy, some did show partial agonism at α1 and antagonism at α3 (e.g., 25 and 75). However, two analogues tested (93 and 96), both with triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series.
- Russell, Michael G. N.,Carling, Robert W.,Atack, John R.,Bromidge, Frances A.,Cook, Susan M.,Hunt, Peter,Isted, Catherine,Lucas, Matt,McKernan, Ruth M.,Mitchinson, Andrew,Moore, Kevin W.,Narquizian, Robert,Macaulay, Alison J.,Thomas, David,Thompson, Sally-Anne,Wafford, Keith A.,Castro, José L.
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p. 1367 - 1383
(2007/10/03)
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- Preparation of cyanopyridines by direct cyanation
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After pretreatment with nitric acid and trifluoroacetic anhydride, aqueous potassium cyanide converted pyridines 1a-1 into their corresponding 2-cyano derivatives 4a-1 in an average yield of 52%. Georg Thieme Verlag Stuttgart.
- Katritzky, Alan R.,Scriven, Eric F. V.,Majumder, Suman,Tu, Hongbin,Vakulenko, Anatoliy V.,Akhmedov, Novruz G.,Murugan, Ramiah
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p. 993 - 997
(2007/10/03)
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