- HETEROARYL-CARBOXYLIC ACIDS AS HISTONE DEMETHYLASE INHIBITORS
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The invention relates to heteroaryl-carboxylic acids as described herein, useful as histone demethylase inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds and to their use in therapy, including e.g., in the treatment of cancer.
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Page/Page column 131; 132
(2018/01/17)
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- COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND USES AS GLUTAMINASE INHIBITORS FOR TREATING CANCERS THEREOF
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Provided are compounds of formula (I), wherein X, Y, Z, W, m, n, o, p, R1, R2 and R6 are defined as in the description. Pharmaceutical compositions and uses as glutaminase inhibitors for treating cancers thereof are also provided.
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Page/Page column 148-149; 160-161
(2014/06/11)
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- HETEROCYCLIC COMPOUND AND HEMATOPOIETIC STEM CELL AMPLIFIER
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An expansion agent for hematopoietic stem cells and/or hematopoietic progenitor cells useful for improvement in the efficiency of gene transfer into hematopoietic stem cells for gene therapy useful for treatment of various disorders is provided. An expansion agent for hematopoietic stem cells and/or hematopoietic progenitor cells containing a compound represented by the formula (I) (wherein X, Y, Z, Ar1, R1, R2, R3, R4, R5, R6 and R7 are as defined in the description), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof, which can expand hematopoietic stem cells and/or hematopoietic progenitor cells.
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Page/Page column 60
(2012/04/23)
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- 6-ARYLALKYLAMINO- 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES AS 5-HT2C RECEPTOR AGONISTS
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The present invention provides 6-substituted 2,3,4,5-tetrahydro-lH- benzo[d]azepines of Formula (I) as selective 5-HT2c receptor agonists for the treatment of 5-HT2c associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety, where, R6 is -NR10R11, where R10 is substituted phenylalkyl or substituted pyridylalkyl and other substituents are as defined in the specification.
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Page/Page column 116
(2010/11/26)
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- 4,6-DISUBSTITUTED PYRIMIDINES AND THEIR USE AS PROTEIN KINASE INHIBITORS
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The invention relates to novel pyrimidine derivatives of Formula (I), which are efficacious inhibitors of protein kinases, in particular of one or more isoforms of the protein kinase B/Akt.
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Page/Page column 55
(2008/06/13)
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- Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity
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Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.
- Le Bourdonnec, Bertrand,Ajello, Christopher W.,Seida, Pamela R.,Susnow, Roberta G.,Cassel, Joel A.,Belanger, Serge,Stabley, Gabriel J.,DeHaven, Robert N.,DeHaven-Hudkins, Diane L.,Dolle, Roland E.
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p. 2647 - 2652
(2007/10/03)
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- Sulfonylamino phenylacetamide derivatives and methods of their use
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Sulfonylamino phenylacetamide derivatives of the general formula are disclosed. Pharmaceutical compositions containing the compounds and methods for their use are also disclosed. In certain embodiments, the compounds of the invention that, preferably: (1) bind with high affinity to κ opioid receptors; (2) display good opioid receptor selectivity of κ versus μ and κ versus δ; and (3) do not substantially inhibit cytochrome P450 enzymatic activity, in particular CYP2D6, CYP2C9 and CYP3A4.
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- Potent dipeptide inhibitors of the pp60(c-src) SH2 domain
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The design, synthesis, and evaluation of dipeptide analogues as ligands for the pp60(c-src) SH2 domain are described. The critical binding interactions between Ac-Tyr-Glu-N(n-C5H11)2 (2) and the protein are established and
- Pacofsky, Gregory J.,Lackey, Karen,Alligood, Krystal J.,Berman, Judd,Charifson, Paul S.,Crosby, Renae M.,Dorsey Jr., George F.,Feldman, Paul L.,Gilmer, Tona M.,Hummel, Conrad W.,Jordan, Steven R.,Mohr, Christopher,Shewchuk, Lisa M.,Sternbach, Daniel D.,Rodriguez, Marc
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p. 1894 - 1908
(2007/10/03)
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- Effect of Conformational Mobility and Hydrogen-Bonding Interactions on the Selectivity of Some Guanidinoaryl-Substituted Mechanism-Based Inhibitors of Trypsin-like Serine Proteases
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Previously, we had reported that some guanidino-substituted α- and β-aryl enol lactones I and II behaved as selective, mechanism-based inhibitors of some trypsin-like proteases (Rai, R.; Katzenellenbogen.J.A.J.Med.Chem., submitted).In this study, we describe the synthesis and kinetic evaluation of some related, guanidino-substituted enol lactones having greater conformational mobility and affording additional hydrogen-bonding sites at the active site.The α-aryl-substituted lactones 1 and 2, which have greater conformational mobility in the guanidinoaryl linkage than I, selectively inhibited the trypsin-like enzymes, and they were relatively poor inactivators of α-chymotrypsin and human neutrophil elastase (HNE).The iodo enol lactone 2 permanently inactivated trypsin, urokinase, tissue plasminogen activator, and plasmin, showing exceptionally high specificity in its interaction with trypsin and urokinase.The selectivity pattern exhibited by the closely related, conformationally less mobile α-aryl-substituted iodo lactone Ib, which was previously shown to be a selective suicide substrate of urokinase and plasmin, provides an interesting comparison.The α-benzamido-substituted lactones 3 and 4, which afford an additional site for active-site hydrogen bonding, were found to be very potent alternate substrate inhibitors of trypsin and urokinase.In addition, the iodo lactone 4 permanently inactivated α-chymotropsin.The importance of secondary interactions in increasing the specificities in the case of α-chymotrypsin is discussed.
- Rai, Roopa,Katzenellenbogen, John A.
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p. 4297 - 4305
(2007/10/02)
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