- Identification of Imidazo[1,2- b]pyridazine Derivatives as Potent, Selective, and Orally Active Tyk2 JH2 Inhibitors
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In sharp contrast to a previously reported series of 6-anilino imidazopyridazine based Tyk2 JH2 ligands, 6-((2-oxo-N1-substituted-1,2-dihydropyridin-3-yl)amino)imidazo[1,2-b]pyridazine analogs were found to display dramatically improved metabolic stabilit
- Liu, Chunjian,Lin, James,Moslin, Ryan,Tokarski, John S.,Muckelbauer, Jodi,Chang, ChiehYing,Tredup, Jeffrey,Xie, Dianlin,Park, Hyunsoo,Li, Peng,Wu, Dauh-Rurng,Strnad, Joann,Zupa-Fernandez, Adriana,Cheng, Lihong,Chaudhry, Charu,Chen, Jing,Chen, Cliff,Sun, Huadong,Elzinga, Paul,D'Arienzo, Celia,Gillooly, Kathleen,Taylor, Tracy L.,McIntyre, Kim W.,Salter-Cid, Luisa,Lombardo, Louis J.,Carter, Percy H.,Aranibar, Nelly,Burke, James R.,Weinstein, David S.
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- SYSTEMIC FORMULATION OF A PYRIDINONE DERIVATE FOR COELIAC DISEASE
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The present invention relates to a systemic formulation, in particular an oral formulation, for the prophylaxis and/or treatment of coeliac disease, i.e. for use in the prophylaxis and/or treatment of coeliac disease.
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Paragraph 0713; 0724-0726
(2021/11/04)
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- SYSTEMIC FORMULATION OF A PYRIDINONE DERIVATE FOR TG2-RELATED DISEASES
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The present invention relates to a formulation in particular an oral formulation for the prophylaxis and treatment of TG2-related disorders like fibrosis in particular diabetic nephropathy and/or diabetic associated non-alcoholic steatohepatitis (NASH) an
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Paragraph 0666-0668
(2021/11/04)
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- Optimization of peptide-based inhibitors targeting the HtrA serine protease in Chlamydia: Design, synthesis and biological evaluation of pyridone-based and N-Capping group-modified analogues
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The obligate intracellular bacterium Chlamydia trachomatis (C. trachomatis) is responsible for the most common bacterial sexually transmitted infection and is the leading cause of preventable blindness, representing a major global health burden. While C.
- Hwang, Jimin,Strange, Natalie,Phillips, Matthew J.A.,Krause, Alexandra L.,Heywood, Astra,Gamble, Allan B.,Huston, Wilhelmina M.,Tyndall, Joel D.A.
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- ARYL, HETEROARY, AND HETEROCYCLIC PHARMACEUTICAL COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, and Formula V, or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.
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Page/Page column 708
(2018/09/21)
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- ARYLPYRIDINONE ITK INHIBITORS FOR TREATING INFLAMMATION AND CANCER
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Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein Ar, R2, R4, R5, n and X are as defined in
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Paragraph 0176; 0215; 0216
(2015/08/04)
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- Arylpyridinone ITK inhibitors for treating inflammation and cancer
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Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein Ar, R2, R4, R5, n and X are as defined in
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Page/Page column 46
(2015/11/27)
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- IMIDAZOPYRIDAZINE COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSES
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Compounds having the following formula (I), or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.
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Page/Page column 83; 84
(2015/06/25)
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- Development of Novel Peptidomimetics Containing a Vinyl Sulfone Moiety as Proteasome Inhibitors
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Proteasome inhibition is a topic of great interest in anticancer research. The proteolytic activity of this multicatalytic complex relies on three subunits, β1, β2 and β5, containing a caspase-like, a trypsin-like and a chymotrypsin-like active site, respectively. Several studies have demonstrated that, of the three activities, the chymotrypsin-like activity was the most necessary for cell viability and protein processing. Thus, most efforts towards the development of proteasome inhibitors have focused on the selective inhibition of the β5 subunit active site. Herein, we report the design and synthesis of a series of conformationally constrained tripeptidyl vinyl sulfones were determined to be good inhibitors of the chymotrypsin-like activity of proteasome, with KI values in the sub-micromolar to micromolar range. These compounds were also tested against bovine pancreatic α-chymotrypsin and human cathepsinB and L, revealing a good selectivity for the target enzyme over these related enzymes. Molecular straitjackets! Conformationally constrained tripeptidyl vinyl sulfones were identified as good inhibitors of proteasome chymotrypsin-like activity, with KI values in the sub-micromolar to micromolar range. Derivatives were also tested against bovine pancreatic α-chymotrypsin and human cathepsins B andL, revealing a good selectivity for the target enzyme.
- Ettari, Roberta,Bonaccorso, Cinzia,Micale, Nicola,Heindl, Cornelia,Schirmeister, Tanja,Calabro, Maria Luisa,Grasso, Silvana,Zappala, Maria
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experimental part
p. 1228 - 1237
(2012/04/18)
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- 3, 5-DISUBSTITUTED PYRID-2-ONES USEFUL AS INHIBITORS OF TEC FAMILY OF NON-RECEPTOR TYROSINE KINASES
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The present invention relates to pyrid-2-one compounds of formula (I) useful as inhibitors of protein kinase of Tec family (e.g., Tec, Btk, Itk/Emt/Tsk, Bmx,Txk/Rlk) protein kinases. These compounds and pharmaceutically acceptable compositions thereof are
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Page/Page column 39-40
(2010/11/26)
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- Cgrp Receptor Antagonists
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Compounds of Formula I: and Formula II: (where variables R1, R2, R3, R4, A, B, D, G, J, Q, T, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or pr
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Page/Page column 33
(2008/06/13)
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- Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
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Compounds of the formula: where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the picornaviral 3C protease. Also disclosed are compounds of the formula: where the formula variables are as defined herein that advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as rhinovirus 3C proteases. Intermediates and synthetic methods for preparing such compounds are also described.
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- HETEROCYCLIC AMIDE COMPOUNDS AND PHARMACEUTICAL USE OF THE SAME
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Heterocyclic amide compounds of the formula (I) STR1 wherein each symbol is as defined in the specification, pharmacologically acceptable salts thereof, pharmaceutical compositions thereof and pharmaceutical use thereof. The heterocyclic amide compounds and pharmacologically acceptable salts thereof of the present invention have superior inhibitory activity against chymase groups in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be effective for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.
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- Non-peptidic inhibitors of human leukocyte elastase. 1. The design and synthesis of pyridone-containing inhibitors
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Human leukocyte elastase (HLE) is a serine protease produced by neutrophils that has been implicated in diseases such as amphysema and cystic fibrosis. An HLE inhibitor may have therapeutic value in these diseases. An active site model of HLE bound to a t
- Warner,Green,Gomes,Strimpler
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p. 3090 - 3099
(2007/10/02)
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