- CHEMICAL COMPOUNDS
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The present disclosure describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. Compounds of the disclosure have activity as dual modulators of Janus kinase (JAK), alone, or in combination with one or more of an additional mechanism, including a tyrosine kinase, such as TrkA or Syk, and PDE4, and are useful in the in the treatment or control of inflammation, auto-immune diseases, cancer, and other disorders and indications where modulation of JAK would be desirable. Also described herein are methods of treating inflammation, auto-immune diseases, cancer, and other conditions susceptible to inhibition of JAK and PDE4 by administering a compound herein described.
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Paragraph 0570; 0572
(2021/01/23)
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- Discovery and Structure-Activity Relationships of Quinazolinone-2-carboxamide Derivatives as Novel Orally Efficacious Antimalarials
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A phenotypic high-throughput screen allowed discovery of quinazolinone-2-carboxamide derivatives as a novel antimalarial scaffold. Structure-activity relationship studies led to identification of a potent inhibitor 19f, 95-fold more potent than the origin
- Laleu, Beno?t,Akao, Yuichiro,Ochida, Atsuko,Duffy, Sandra,Lucantoni, Leonardo,Shackleford, David M.,Chen, Gong,Katneni, Kasiram,Chiu, Francis C. K.,White, Karen L.,Chen, Xue,Sturm, Angelika,Dechering, Koen J.,Crespo, Benigno,Sanz, Laura M.,Wang, Binglin,Wittlin, Sergio,Charman, Susan A.,Avery, Vicky M.,Cho, Nobuo,Kamaura, Masahiro
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p. 12582 - 12602
(2021/09/13)
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- NOVEL PIPERIDINE-2,6-DIONE DERIVATIVE AND USE THEREOF
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The present disclosure relates to a novel piperidine-2,6-dione derivative and a use thereof and, more specifically, to a piperidine-2,6-dione derivative compound having a structure of a thalidomide analog. A compound of chemical formula 1 according to the present disclosure specifically binds with CRBN protein, and is involved in functions thereof. Therefore, the compound of the present disclosure can be favorably used in the prevention or treatment of leprosy, chronic graft versus host disease, an inflammatory disease, or cancer, which are caused by actions of CRBN protein.
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Paragraph 0204-0206
(2020/03/09)
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- EGFR PROTEOLYSIS TARGETING CHIMERIC MOLECULES AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of receptor tyrosine kinase (RTK) proteins. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an E3 ubiquitin ligase and on the other end a moiety which binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effectuate ubiquitination, and therefore, degradation (and inhibition) of the target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 001004; 001005
(2018/07/29)
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- Methods and compositions using PDE4 inhibitors for the treatment and management of autoimmune and inflammatory diseases
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Methods of treating, preventing, or managing autoimmune inflammatory diseases and disorders including but not limited to spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, osteoarthritis, ankylosing spondylitis, and rheumatoid arthritis by the administration of phosphodiesterase 4 (PDE4) inhibitors in combination with other therapeutics are disclosed. Pharmaceutical compositions, dosage forms, and kits suitable for use in methods of the invention are also disclosed.
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Page/Page column 28-29
(2016/05/02)
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- CONTROLLED RELEASE ORAL DOSAGE FORMS OF POORLY SOLUBLE DRUGS AND USES THEREOF
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Provided herein are controlled release oral dosage forms of poorly soluble drugs, methods of making the dosage forms, and methods of their use for the treatment of various diseases and/or disorders.
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Paragraph 0220
(2016/06/06)
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- USE OF PDE4 INHIBITORS AND COMBINATIONS THEREOF FOR THE TREATMENT OF CYSTIC FIBROSIS
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Methods of treating cystic fibrosis by administering a PDE4 inhibitor in combination with one or more cystic fibrosis transmembrane conductance regulator (CFTR) potentiators, including ivacaftor, and/or one or more CFTR correctors, including lumacaftor. Pharmaceutical compositions, dosage forms, and kits suitable for use in methods of the invention are also disclosed.
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Paragraph 0117
(2016/02/16)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASES WITH PDE4 MODULATORS
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Provided herein are methods of treating, preventing or managing atherosclerosis by administering a PDE4 modulator. Pharmaceutical compositions, dosage forms, and kits suitable for use in methods are also provided.
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Paragraph 0192
(2016/04/26)
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- PHTHALAZINONE AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for e
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Paragraph 0391; 0392
(2013/07/31)
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- MACROCYCLIC KINASE INHIBITORS
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Compounds of Formula (I): wherein variables are defined herein, and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancers for which FAK inhibition is beneficial.
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Page/Page column 64
(2012/06/16)
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- OXYGEN SCAVENGING MOLECULES, ARTICLES CONTAINING SAME, AND METHODS OF THEIR USE
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The invention relates to compounds of the structure of formula I and II: where X is selected from the group consisting of O, S and NH; Y, A and B are independently selected from the group consisting of N and CH; D, E and F are independently selected from the group consisting of CH, N, O and S; the symbol represents a single or a double bond; and R1, R2 and R3 are independently selected from the group consisting of H, electron withdrawing groups and electron releasing groups. In other embodiments, the compounds are used as oxygen scavengers and in barrier compositions and articles.
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Page/Page column 15
(2011/10/19)
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- Processes for the Preparation of 2-(1-Phenylethyl)isoindolin-1-one Compounds
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Methods for preparation of isoindolin-1-one compounds are described.
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Page/Page column 10-11
(2011/04/25)
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- ISOINDOLINONE AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for e
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Page/Page column 126
(2010/08/04)
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- PHTHALAZINONE AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for e
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Page/Page column 103-104
(2010/08/04)
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- 5-SUBSTITUTED QUINAZOLINONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
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Provided are 5-substituted quinazolinone compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
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Page/Page column 59
(2010/11/30)
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- A microwave-assisted alternative synthesis of 8-amino-2-methyl-3,4- dihydroisoquinolin-1-one
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A shorter, alternative synthesis of 8-amino-2-methyl-3,4- dihydroisoquinolin-1-one is described in 32% overall yield, over three steps starting from commercially available 2-methyl-6-nitrobenzonitrile. The synthesis includes two 'one-pot' procedures in wh
- Glossop, Steve C.
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p. 981 - 983
(2008/02/02)
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- Substituted quinolinone derivatives and methods of use
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Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and
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Page/Page column 26
(2010/02/11)
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- Substituted 2,3-dihydro-1h-isoindol-1-one derivatives and methods of use
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Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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Page/Page column 27
(2010/02/11)
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- Cyclooxygenase inhibitors derived from thalidomide
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Several N-3,5-dimethylphenylphthalimide analogs possessing more potent cyclooxygenase-inhibiting activity than that of aspirin were prepared during structural development studies based on thalidomide. Substituent effects on the activity were investigated.
- Suizu, Mamiko,Muroya, Yohei,Kakuta, Hiroki,Kagechika, Hiroyuki,Tanatani, Aya,Nagasawa, Kazuo,Hashimoto, Yuichi
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p. 1098 - 1102
(2007/10/03)
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- Amino-substituted thalidomide analogs: Potent inhibitors of TNF-α production
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Thalidomide, (1), is a known inhibitor of TNF-α release in LPS stimulated human PBMC. Herein we describe the TNF-α inhibitory activity of amino substituted analogs of thalidomide (1) and its isoindolin-1-one analog, EM-12 (2). The 4-amino substituted analogs were found to be potent inhibitors of TNF-α release in LPS stimulated human PBMC.
- Muller, George W.,Chen, Roger,Huang, Shaei-Yun,Corral, Laura G.,Wong, Lu Min,Patterson, Rebecca T.,Chen, Yuxi,Kaplan, Gilla,Stirling, David I.
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p. 1625 - 1630
(2007/10/03)
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- 6-Alkoxymethyl-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-ones and 7-alkoxymethyl-6-[H]-1,2,3,4-tetrahydropyrimido[2,1-b]quinazolin-2-ones
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Optionally substituted 6-alkoxymethyl-1,2,3,5-tetrahydroimidazo[2,1-b]-quinazolin-2-ones and 7-alkoxymethyl-6-[H]-1,2,3,4-tetrahydropyrimido[2,1-b]-quinazolin-2-ones or the pharmaceutically acceptable salts thereof are compounds useful as blood platelet a
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