- SUBSTITUTED PYRIDINE DERIVATIVES AS SARM1 INHIBITORS
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This disclosure is drawn to substituted pyridine compounds and compositions, and associated methods, useful for inhibition of SARM1 activity and/or for treating or preventing a neurological diseases.
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Page/Page column 45
(2022/02/15)
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- SUBSTITUTED PYRAZOLO-PYRIMIDINES AND USES THEREOF
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The present disclosure provides compounds that are inhibitors of PIKfyve kinases useful for the treatment of neurological diseases treatable by inhibition of PIKfyve. Also provided are pharmaceutical compositions containing such compounds, and methods of
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Paragraph 0112; 0113
(2021/07/24)
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- 5- OR 7-AZAINDAZOLES AS BETA-LACTAMASE INHIBITORS
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The present invention relates to β-lactamase inhibitors having the following general formula (I): wherein R1-R4 and X1-X2 are defined in the specification, pharmaceutical composition thereof, and use thereof for the treatment of a bacterial infection, alone or in combination with β-lactam antibiotics and/or other antibiotics and/or other β-lactamase inhibitors.
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Page/Page column 41; 42
(2020/09/19)
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- Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
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To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4–7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 μM = 81.6%), 4w (CMA at 10 μM = 71.2%) and 6b (CMA at 10 μM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 μM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure–activity relationship (SAR) studies were conducted. Para substitution (-Cl, –OCH3, -SO2N(CH3)2) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 μM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.
- Boggu, Pulla Reddy,Venkateswararao, Eeda,Manickam, Manoj,Sharma, Niti,Kang, Jong Seong,Jung, Sang-Hun
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- NOVEL PYRAZOLO-PYRROLO-PYRIMIDINE-DIONE DERIVATIVES AS P2X3 INHIBITORS
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The present invention covers substituted Pyrazolo-pyrrolo-pyrimidine-dione (PPPD) compounds of general formula (I): in which R1, R2 and R3 are as defined herein, methods of preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of neurogenic diseases, as a sole agent or in combination with other active ingredients.
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Page/Page column 102
(2019/05/15)
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- TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to benzyl urea compounds of formula (I) which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence may be useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor Trk-A, Trk-B and/or Trk-C.
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Page/Page column 30-31
(2015/04/15)
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- TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to benzyl urea compounds of formula (I) which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence may be useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor Trk-A, Trk-B and/or Trk-C.
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Page/Page column 31; 32
(2015/04/15)
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- TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF
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The present invention is directed to substituted five membered heteroaryl benzamide compounds compounds of formula (I), which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.
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Page/Page column 46; 47
(2015/12/08)
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- Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and characterization of the potent, selective, and orally efficacious agonist 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H- pyrazol-3-yl] amide (SEN15924, WAY-361789)
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Alpha-7 nicotinic acetylcholine receptors (α7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, α7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around our previously reported chemical series, permitted the discovery of a novel class of α7 nAChR agonists with improved selectivity, in particular against the α3 receptor subtype and better ADME profile. The exploration of this series led to the identification of 5-(4-acetyl[1,4] diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (25, SEN15924, WAY-361789), a novel, full agonist of the α7 nAChR that was evaluated in vitro and in vivo. Compound 25 proved to be potent and selective, and it demonstrated a fair pharmacokinetic profile accompanied by efficacy in rodent behavioral cognition models (novel object recognition and auditory sensory gating).
- Zanaletti, Riccardo,Bettinetti, Laura,Castaldo, Cristiana,Cocconcelli, Giuseppe,Comery, Thomas,Dunlop, John,Gaviraghi, Giovanni,Ghiron, Chiara,Haydar, Simon N.,Jow, Flora,MacCari, Laura,Micco, Iolanda,Nencini, Arianna,Scali, Carla,Turlizzi, Elisa,Valacchi, Michela
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experimental part
p. 4806 - 4823
(2012/07/28)
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- ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS
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The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can a
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Page/Page column 143-144
(2010/04/03)
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- INHIBITORS OF AKT ACTIVITY
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The instant invention provides for substituted fused naphthyridine derivatives that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.
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Page/Page column 262
(2010/10/03)
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- Hit to lead optimization of pyrazolo[1,5-a]pyrimidines as B-Raf kinase inhibitors
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Our continued effort towards optimization of the pyrazolo[1,5-a]pyrimidine scaffold as B-Raf kinase inhibitors is described. Structure guided design was utilized to introduce kinase hinge region interacting groups in the 2-position of the scaffold. This s
- Gopalsamy, Ariamala,Ciszewski, Greg,Shi, Mengxiao,Berger, Dan,Hu, Yongbo,Lee, Frederick,Feldberg, Larry,Frommer, Eileen,Kim, Steven,Collins, Karen,Wojciechowicz, Donald,Mallon, Robert
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scheme or table
p. 6890 - 6892
(2010/05/19)
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- NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS
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The present invention provides compounds of formula (I) and compositions thereof, methods of making them, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.
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Page/Page column 113
(2008/12/07)
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- MODULATORS OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS AND THERAPEUTIC USES THEREOF
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Compounds with α7 nicotinic acetylcholine receptor (α7 nAChR) agonistic activity, processes for their preparation, pharmaceutical compositions containing the same and the use thereof for the treatment of neurological and psychiatric diseases.
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Page/Page column 47-48
(2010/11/28)
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- RAF INHIBITOR COMPOUNDS AND METHODS
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Pyrazolyl compounds of Formulas Ia and Ib are useful for inhibiting Raf kinase and for treating disorders mediated thereby. Methods of using pyrazolyl compounds for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
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Page/Page column 86-87
(2008/06/13)
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- Novel alpha-cyano-beta-oxopropionamides
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α-(Substituted carbamoyl)-β-aryl- and heteroaryl-β-oxo-propionitriles of formula, , A-CO- enol ethers thereof and salts thereof, as well as pharmaceutical preparations containing same and methods of preparing and using these compounds are disclosed. Said compounds represent novel antiinflammatory and antirheumatic agents. Their property to interfere with both the cyclooxygenase and lipoxygenase pathway of the arachidonic fatty acid bioconversion to inflammatory mediators make them valuable therapeutics. These properties render the mentioned substituted carbamoyl-β-oxopropionitriles useful for the treatment of arthritic and rheumatic diseases and other inflammatory conditions in mammals.
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