- PYRIDAZINONES AND METHODS OF USE THEREOF
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Disclosed are therapeutic methods, e.g., of treating kidney diseases, using compounds of Formula (A) in combination with a second therapeutic agent.
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Page/Page column 136; 137
(2020/10/09)
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- PYRIDAZINONES AND METHODS OF USE THEREOF
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Disclosed are compounds according to Formula (A), and related tautomers and pharmaceutical compositions. Also disclosed are therapeutic methods, e.g., of treating kidney diseases, using the compounds of Formula (A).
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Page/Page column 522
(2019/04/11)
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- HETEROCYCLIC COMPOUNDS AND THEIR USES
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Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.
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Page/Page column 27
(2011/07/06)
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- Syntheses of aza and fluorine-substituted 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-ones
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A practical and expedient synthesis of the title compounds is described. They were prepared by Stille reaction of nitro halopyridines 4 or nitro fluro-halobenzenes 10, followed by Michael addition of tert-butyl 4-aminopiperidine-1-carboxylate to the resulting activated vinyl compounds 5 and 11, hydrogenation (-NO2→-NH2), cyclic urea formation, Boc removal, and HCl salt formation. However, N3 and F1 analogs could not be made by this general strategy. Activated vinyl compounds 5a and 5d when reacted with tert-butyl 4-aminopiperidine-1-carboxylate did not stop at the desired Michael addition stage; but proceeded to produce azaindolines 8 and 9. Michael addition did not occur to compound 11d; instead, the fluorine atom was displaced.
- Han, Xiaojun,Civiello, Rita L.,Mercer, Stephen E.,Macor, John E.,Dubowchik, Gene M.
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scheme or table
p. 386 - 388
(2009/05/07)
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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 52
(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 155
(2010/11/29)
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- CONSTRAINED COMPOUNDS AS CGRP-RECEPTOR ANTAGONISTS
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The invention encompasses constrained bicyclic and tricyclic CGRP-receptor antagonists, methods for identifying them, pharmaceutical compositions comprising them, and methods for their use in therapy for treatment of migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.
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Page/Page column 117
(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 53
(2008/06/13)
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- Thrombin inhibitors
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Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein b is NY or O; c is CY2or N; d is CY3or N; e is CY4or N; f is CY5or N; g is CY6or N; Y4, Y5, and Y6are independently hydrogen, C1-4alkyl, or halogen; Y1and Y2are independently hydrogen, C1-4alkyl, C3-7cycloalkyl, halogen, NH2, OH or C1-4alkoxy, and Y3is hydrogen, C1-4alkyl, C3-7cycloalkyl, halogen, —CN, NH2, OH or C1-4alkoxy; A is and W, W1, R1, R3, R4, R5, X and Z are defined in the specification.
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- Suzuki cross-coupling reactions of potassium alkenyltrifluoroborates
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(formula presented) The palladium-catalyzed coupling reaction of potassium alkenyltrifluoroborates with aryl or alkenyl halides or triflates proceeds readily with good yields. The trifluoroborates are air-and moisture-stable solids that can be stored indefinitely. The cross-coupling can be effected using PdCl2(dppf)-CH2Cl2 as the catalyst in n-PrOH in the presence of Et3N. A variety of functional groups are tolerated. ? Dedicated to Professor Herbert C. Brown on the occasion of his 90th birthday.
- Molander, Gary A.,Rivero, Marta Rodriguez
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p. 107 - 109
(2007/10/03)
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- Efficient synthesis of ribonucleotide reductase inhibitors 3- aminopyridine-2-carboxaldehyde thiosemicorbazone (3-AP) and 3-amino-4- methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) via palladium mediated cross-coupling reactions
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An efficient synthesis of potent ribonucleotide reductases inhibitors 3- amino-pyridine-2-carboxaldehyde thiosemicarbazone (3-AP) end 3-amino-4- methyl-pyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) is described. The synthesis of 3-AP and 3-AMP was achieved in 4 and 5 steps, with overall yields of 61% and 39%, respectively. The synthesis featured a convergent approach utilizing a Stille coupling strategy to prepare vinylpyridine derivatives. A more economic way to synthesize vinylpyridine using Heck reaction was also discussed.
- Li, Jun,Chen, Shu-Hui,Li, Xiuyan,Niu, Chuansheng,Doyle, Terrence W.
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p. 393 - 400
(2007/10/03)
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