- Heterocyclic Compound as CDK-HDAC Double-Channel Inhibitor
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The invention provides compounds of formula (I) as shown below, including their possible enantiomers and diastereomers, as well as pharmaceutically acceptable salts, hydrates or solvates thereof. The invention also provides pharmaceutical compositions of
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Paragraph 0141-0142
(2022/02/27)
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- Identification of a novel allosteric GLP-1R antagonist HTL26119 using structure- based drug design
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A series of novel allosteric antagonists of the GLP-1 receptor (GLP-1R), exemplified by HTL26119, are described. SBDD approaches were employed to identify HTL26119, exploiting structural understanding of the allosteric binding site of the closely related Glucagon receptor (GCGR) (Jazayeri et al., 2016) and the homology relationships between GCGR and GLP-1R. The region around residue C3476.36b of the GLP-1R receptor represents a key difference from GCGR and was targeted for selectivity for GLP-1R.
- O'Brien, Alistair,Andrews, Stephen P.,Baig, Asma H.,Bortolato, Andrea,Brown, Alastair J.H.,Brown, Giles A.,Brown, Sue H.,Christopher, John A.,Congreve, Miles,Cooke, Robert M.,De Graaf, Chris,Errey, James C.,Fieldhouse, Charlotte,Jazayeri, Ali,Marshall, Fiona H.,Mason, Jonathan S.,Mobarec, Juan Carlos,Okrasa, Krzysztof,Steele, Kelly N.,Southall, Stacey M.,Teobald, Iryna,Watson, Steve P.,Weir, Malcolm
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supporting information
(2019/09/30)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 001083; 001084
(2015/09/28)
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- BICYCLIC INHIBITORS OF ALK
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The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, wherein R1, X, Y, Z, A, B, G1, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.
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Page/Page column 158
(2012/08/07)
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- PROTEIN KINASE INHIBITORS
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The present invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof which is useful in the treatment of cell proliferative diseases.
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Page/Page column 7
(2010/07/04)
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- Structure-activity studies and analgesic efficacy of N-(3-pyridinyl)- bridged bicyclic diamines, exceptionally potent agonists at nicotinic acetylcholine receptors
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A series of exceptionally potent agonists at neuronal nicotinic acetylcholine receptors (nAChRs) has been investigated. Several N-(3-pyridinyl) derivatives of bridged bicyclic diamines exhibit double-digit-picomolar binding affinities for the α4β2 subtype, placing them with epibatidine among the most potent nAChR ligands described to date. Structure-activity studies have revealed that substitutions, particularly hydrophilic groups in the pyridine 5-position, differentially modulate the agonist activity at ganglionic vs central nAChR subtypes, so that improved subtype selectivity can be demonstrated in vitro. Analgesic efficacy has been achieved across a broad range of pain states, including rodent models of acute thermal nociception, persistent pain, and neuropathic allodynia. Unfortunately, the hydrophilic pyridine substituents that were shown to enhance agonist selectivity for central nAChRs in vitro tend to limit CNS penetration in vivo, so that analgesic efficacy with an improved therapeutic window was not realized with those compounds.
- Bunnelle, William H.,Daanen, Jerome F.,Ryther, Keith B.,Schrimpf, Michael R.,Dart, Michael J.,Gelain, Arianna,Meyer, Michael D.,Frost, Jennifer M.,Anderson, David J.,Buckley, Michael,Curzon, Peter,Cao, Ying-Jun,Puttfarcken, Pamela,Searle, Xenia,Ji, Anguo,Putman, C. Brent,Surowy, Carol,Toma, Lucio,Barlocco, Daniela
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p. 3627 - 3644
(2008/02/11)
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- Pyrrolopyridazine compounds and methods of use thereof for the treatment of proliferative disorders
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Disclosed are pyrrolopyridazine compounds, methods of preparing such compounds, and their use for the treatment of proliferative, inflammatory, and other disorders.
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