- Discovery of triazole aminopyrazines as a highly potent and selective series of PI3Kδ inhibitors
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A novel class of potent PI3Kδ inhibitors with >1000-fold selectivity against other class I PI3K isoforms is described. Optimization of the substituents on a triazole aminopyrazine scaffold, emerging from an in-house PI3Kα program, turned moderately selective PI3Kδ compounds into highly potent and selective PI3Kδ inhibitors. These efforts resulted in a series of aminopyrazines with PI3Kδ IC50???1?nM in the enzyme assay, some of the most selective PI3Kδ inhibitors published to date, with a cell potency in a JeKo-cell assay of 20–120?nM.
- Terstiege, Ina,Perry, Matthew,Petersen, Jens,Tyrchan, Christian,Svensson, Tor,Lindmark, Helena,?ster, Linda
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Read Online
- 5,6-BISARYL-2-PYRIDINE-CARBOXAMIDE DERIVATIVES, PREPARATION AND APPLICATION THEREOF IN THERAPEUTICS AS UROTENSIN II RECEPTOR ANTAGONISTS
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The present invention relates to derivatives of 5,6-bisaryl-2-pyridine-carboxamide, their preparation and their application in therapeutics as antagonists of urotensin II receptors.
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Page/Page column 27
(2009/12/28)
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- Anti-cancer agents and uses thereof
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The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3-R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
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Page/Page column 39
(2008/12/08)
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- ANTI-CANCER AGENTS ANS USES THEREOF
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The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula (I): and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3 R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6- 10 carbons in the ring portion, an optionally-substituted 6- membered heteroaryl group having 1- 3 nitrogen atoms in the ring portion, an optionally-substituted 5- membered heteroaryl group having 0- 4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6- membered ring is fused either to a 5- membered ring or to a 6- membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
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Page/Page column 112
(2010/11/29)
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- Substituted piperazines as metabotropic glutamate receptor antagonists
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The invention relates to compounds of formula I or pharmaceutically acceptable salts or solvates thereof: where Ar1, Ar2, Hy, L, R1, m and n are as defined in the description. The invention also includes pharmaceutical compositions and uses thereof, processes for making the compounds, as well as methods for the medical treatment of mGluR5-mediated disorders.
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Page/Page column 14-15
(2008/06/13)
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- HETEROARYL UREA DERIVATIVES USEFUL FOR INHIBITING CHKl
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Substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division, also are disclosed.
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Page/Page column 77
(2008/06/13)
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- Anti-cancer agents and uses thereof
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The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3—R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, non-small cell lung and colon.
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Page/Page column 40
(2008/06/13)
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- Urea kinase inhibitors
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Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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(2008/06/13)
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- Urea kinase inhibitors
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Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Studies on Pyrazines. 16. Palladium-Catalyzed Cyanation of 2-Amino-5-bromopyrazines
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We report here a synthesis of 2-amino-5-cyano- 3 and 2-amino-3,5-dicyanopyrazines 4 by palladium(0)-catalyzed cyanation of the corresponding pyrazine amino bromides 1 and 2.
- Sato, Nobuhiro,Suzuki, Masakazu
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p. 1371 - 1372
(2007/10/02)
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