- TYROSINE KINASE NON-RECEPTOR 1 (TNK1) INHIBITORS AND USES THEREOF
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Provided herein is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g, X11, X22, R11, R22, R33, R44, R55, R66, R77, R88, m, n) are as described herein. Compounds of Formula I, pharmaceutically acceptable salts thereof, pharmaceutical compositions of either of the foregoing, and combinations of any of the foregoing can be used to treat tyrosine kinase non- receptor 1 (TNK1)-mediated diseases, disorders and conditions.
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Paragraph 00299
(2021/01/23)
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- Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach
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Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily on MPS1 to cope with the stress arising from abnormal numbers of chromosomes and centrosomes and are thus more sensitive to MPS1 inhibition than normal cells. We report the discovery and optimization of a series of new pyrido[3,4-d]pyrimidine based inhibitors via a structure-based hybridization approach from our previously reported inhibitor CCT251455 and a modestly potent screening hit. Compounds in this novel series display excellent potency and selectivity for MPS1, which translates into biomarker modulation in an in vivo human tumor xenograft model.
- Innocenti, Paolo,Woodward, Hannah L.,Solanki, Savade,Naud, Sébastien,Westwood, Isaac M.,Cronin, Nora,Hayes, Angela,Roberts, Jennie,Henley, Alan T.,Baker, Ross,Faisal, Amir,Mak, Grace Wing-Yan,Box, Gary,Valenti, Melanie,De Haven Brandon, Alexis,O'Fee, Lisa,Saville, Harry,Schmitt, Jessica,Matijssen, Berry,Burke, Rosemary,Van Montfort, Rob L. M.,Raynaud, Florence I.,Eccles, Suzanne A.,Linardopoulos, Spiros,Blagg, Julian,Hoelder, Swen
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supporting information
p. 3671 - 3688
(2016/05/19)
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- SULFONAMIDE DERIVATIVE AND MEDICINAL USE THEREOF
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Provided are sulfonamide derivatives of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action.
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Paragraph 1292-1293
(2015/02/25)
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- INHIBITOR COMPOUNDS
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The present invention relates to compounds of formula (I), wherein R, R, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 - also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them
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Paragraph 00265; 00266
(2014/03/26)
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- MACROCYCLIC FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
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The present invention relates generally to novel macrocycles of Formula (I): or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, thereof, wherein the variables A, B, L, M, W, Z, R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein. These compounds are selective inhibitors of the serine protease coagulation factor VIIa which can be used as medicaments.
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Page/Page column 209
(2008/06/13)
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- NOVEL AMIDINE COMPOUNDS FOR TREATING MICROBIAL INFECTIONS
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Novel amidine and diamidine compounds are useful in the treatment of microbial infections, including mycobacterial, fungal and protozoal infections. Pharmaceutical formulations comprising these compounds can be used in methods of treating microbial infect
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Page/Page column 41
(2010/02/11)
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- Detection of inhibition of bovine viral diarrhea virus by aromatic cationic molecules
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Bovine viral diarrhea virus (BVDV) is an economically significant pathogen of cattle and a problematic contaminant in the laboratory. BVDV is often used as an in vitro model for hepatitis C virus during drug discovery efforts. Aromatic dicationic molecule
- Givens, M. Daniel,Dykstra, Christine C.,Brock, Kenny V.,Stringfellow, David A.,Kumar, Arvind,Stephens, Chad E.,Goker, Hakan,Boykin, David W.
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p. 2223 - 2230
(2007/10/03)
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