- MAXI-K POTASSIUM CHANNEL OPENERS FOR THE TREATMENT OF FRAGILE X ASSOCIATED DISORDERS
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The present invention relates to the compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds provided herein can act as maxi-K potassium channel openers, which makes them suitable for use in therapy, particularly in the treatment or prevention of fragile X associated disorders, such as fragile X syndrome.
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Page/Page column 102-103
(2021/11/26)
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- PYRUVATE KINASE ACTIVATORS FOR USE IN TREATING BLOOD DISORDERS
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Described herein are compounds that activate pyruvate kinase R, pharmaceutical compositions and methods of use thereof. These compounds are represented by Formula (I): Formula (I) wherein R', R2, L', and L2 are as defined herein.
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Page/Page column 4
(2019/03/05)
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- ISOQUINOLINES AS INHIBITORS OF HPK1
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Isoquinoline compounds and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibitng HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the isoquinoline compounds.
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- Modular Route to Azaindanes
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A convergent radical based route to azaindanes is described, relying on the degenerative addition transfer of various substituted S-(pyridylmethyl)-O-ethyl dithiocarbonates (xanthates) to functional alkenes followed by radical cyclization onto the pyridine ring activated by protonation with trifluoroacetic acid. In one case, a richly decorated cyclohepta[b]pyridine could be assembled swiftly by allowing the first adduct to N-phenylmaleimide to undergo addition to N-allylphthalimide prior to cyclization.
- Huang, Qi,Zard, Samir Z.
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p. 3895 - 3898
(2017/07/26)
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- Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists
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Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times.
- Buil, Maria Antonia,Calbet, Marta,Castillo, Marcos,Castro, Jordi,Esteve, Cristina,Ferrer, Manel,Forns, Pilar,González, Jacob,López, Sara,Roberts, Richard S.,Sevilla, Sara,Vidal, Bernat,Vidal, Laura,Vilaseca, Pere
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p. 102 - 133
(2016/03/04)
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- HETEROCYCLIC DERIVED METALLOPROTEASE INHIBITORS
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This invention provides novel heterocyclic derived matrix metalloprotease inhibitors of the formula: and pharmaceutical compositions comprising same, useful for treating disorders ameliorated by antagonizing matrix metalloproteases. This invention also provides therapeutic and prophylactic methods using the instant pharmaceutical compositions.
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Page/Page column 48
(2008/06/13)
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- Pyrazolones as inhibitors of 11B-hydroxysteroid dehydrogenase
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.
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Page/Page column 38-39
(2008/06/13)
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- Identification of MK-944a: A second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors
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Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of α1 acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.
- Dorsey,McDonough,McDaniel,Levin,Newton,Hoffman,Darke,Zugay-Murphy,Emini,Schleif,Olsen,Stahlhut,Rutkowski,Kuo,Lin,Chen,Michelson,Holloway,Huff,Vacca
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p. 3386 - 3399
(2007/10/03)
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