- Aromatic ring dioxane quinazoline or quinoline compound, composition and application of aromatic ring dioxane quinazoline or quinoline compound
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The invention relates to a novel compound serving as an inhibitor of kinase such as TRK, c-MET, AXL, MER and/or VEGFR2, a composition and application of the novel compound. Specifically, the inventionprovides a compound (as shown in formula (1)) or an isomer, a solvate, a hydrate, a pharmaceutically acceptable salt and a prodrug thereof, and a pharmaceutical composition containing the compound, wherein the compound has the activity of strongly inhibiting kinase such as TRK, c-MET, AXL, MER and/or VEGFR2. The invention further discloses application of the compound or the pharmaceutical composition in preparation of a medicine. The medicine is used for treating autoimmune diseases or cancers.
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Paragraph 0098-0099
(2020/06/09)
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- PHOSPHONATE CONJUGATES AND USES THEREOF
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Phosphonate conjugates, preferably, bisphosphonate conjugates; methods of inhibiting Ron receptor tyrosine kinase and methods of treatment of bone destruction due to cancer or other conditions utilizing the provided phosphonate conjugates.
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Paragraph 00159
(2020/07/31)
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- SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS NADPH OXIDASE INHIBITORS
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The present application relates to substituted fused heteroaryl and heterocyclic compounds, useful as nicotinamide adenine dinucleotide phosphate oxidase inhibitors (NADPH oxidase inhibitors), processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and/or disorders mediated by NADPH oxidase. (Formula I)
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Page/Page column 81
(2018/12/03)
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- Pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety as potential antiviral agents
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A series of pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety were synthesized, characterised, and evaluated for their activity against tobacco mosaic virus (TMV). Biological assays indicated that several of the derivatives exhibited significant activity against TMV. In particularly, compounds 5y and 5aa displayed excellent inactivating activity against TMV, with half maximal effective concentration (EC50) values of 70.3 and 53.65 μg/mL, respectively, which were much better than that of ribavirin (150.45 μg/mL), and 5aa was superior to ningnanmycin (EC50 = 55.35 μg/mL). Interactions of compounds 5y and 5aa with TMV coat protein (TMV-CP) were investigated using microscale thermophoresis and molecular docking. Compounds 5y and 5aa displayed strong binding capability to TMV-CP with dissociation constant (Kd) values of 22.6 and 9.8 μM, respectively. These findings indicate that pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base may be potential antiviral agents.
- Wang, Yan-Yan,Xu, Fang-Zhou,Zhu, Yun-Ying,Song, Baoan,Luo, Dexia,Yu, Gang,Chen, Shunhong,Xue, Wei,Wu, Jian
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p. 2979 - 2984
(2018/07/13)
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- COMPOUNDS USEFUL FOR ALTERING THE LEVELS OF BILE ACIDS FOR THE TREATMENT OF DIABETES AND CARDIOMETABOLIC DISEASE
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Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.
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Page/Page column 40
(2018/03/09)
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- INHIBITORS OF ALPHA-AMINO-BETA-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE
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The present disclosure discloses compounds capable of modulating the activity of α- amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD+ biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.
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Paragraph 0547; 0556
(2018/04/27)
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- CARM1 INHIBITORS AND USES THEREOF
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Provided herein are compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is an optionally substituted 6,5-bicyclic heteroaryl ring system comprising 2 to 5 nitrogen atoms, inclusive, wherein the point of attachment is provided on the 6-membered ring of the 6,5-bicyclic heteroaryl ring system, and wherein the 6-membered ring is further substituted with a group of formula -L1-R3, wherein L1 and R3 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.
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Paragraph 00128
(2016/04/09)
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- Discovery of Novel 3-Quinoline Carboxamides as Potent, Selective, and Orally Bioavailable Inhibitors of Ataxia Telangiectasia Mutated (ATM) Kinase
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A novel series of 3-quinoline carboxamides has been discovered and optimized as selective inhibitors of the ataxia telangiectasia mutated (ATM) kinase. From a modestly potent HTS hit (4), we identified molecules such as 6-[6-(methoxymethyl)-3-pyridinyl]-4-{[(1R)-1-(tetrahydro-2H-pyran-4-yl)ethyl]amino}-3-quinolinecarboxamide (72) and 7-fluoro-6-[6-(methoxymethyl)pyridin-3-yl]-4-{[(1S)-1-(1-methyl-1H-pyrazol-3-yl)ethyl]amino}quinoline-3-carboxamide (74) as potent and highly selective ATM inhibitors with overall ADME properties suitable for oral administration. 72 and 74 constitute excellent oral tools to probe ATM inhibition in vivo. Efficacy in combination with the DSB-inducing agent irinotecan was observed in a disease relevant model.
- Degorce, Sébastien L.,Barlaam, Bernard,Cadogan, Elaine,Dishington, Allan,Ducray, Richard,Glossop, Steven C.,Hassall, Lorraine A.,Lach, Franck,Lau, Alan,McGuire, Thomas M.,Nowak, Thorsten,Ouvry, Gilles,Pike, Kurt G.,Thomason, Andrew G.
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supporting information
p. 6281 - 6292
(2016/07/26)
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- The pyrazole derivative or its salt in a pharmaceutical composition containing them
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PROBLEM TO BE SOLVED: To provide a novel compound and a pharmaceutical composition useful for treatment and/or prevention of HIV virus infections.SOLUTION: Provided is a pyrazole derivative represented by the general formula (I) or a salt thereof (in the
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Paragraph 0123; 0126
(2017/01/26)
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- A Michael Equilibration Model to Control Site Selectivity in the Condensation toward Aminopyrazoles
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A Michael equilibration model is presented to provide for site-selective pyrazole condensations between alkoxyacrylonitriles and hydrazines. Both pyrazole isomers were accessed with high selectivity by employment of kinetically or thermodynamically controlled conditions. Substrate scope and identification of Michael intermediates, as well as competitive pathways, support the presented mechanistic proposal. Sandmeyer derivatization provided site-selective access to fully substituted pyrazoles.
- Fandrick, Daniel R.,Sanyal, Sanjit,Kaloko, Joseph,Mulder, Jason A.,Wang, Yuwen,Wu, Ling,Lee, Heewon,Roschangar, Frank,Hoffmann, Matthias,Senanayake, Chris H.
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supporting information
p. 2964 - 2967
(2015/06/30)
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- PRMT1 INHIBITORS AND USES THEREOF
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Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting PRMT1 activity. Methods of using the compounds for treating PRMT1-media
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Paragraph 0207-0208
(2014/09/30)
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- 1 -PHENOXY-3-(ALKYLAMINO)-PROPAN-2-OL DERIVATIVES AS CARM1 INHIBITORS AND USES THEREOF
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Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is an optionally substituted 6,5-bicyclic heteroaryl ring system comprising 2 to 5 nitrogen atoms, inclusive, wherein the point of attachment is provided on the 6-membered ring of the 6,5-bicyclic heteroaryl ring system, and wherein the 6-membered ring is further substituted with a group of formula -L1 -R3, wherein L1 and R3 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.
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Paragraph 00128
(2014/09/29)
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- PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
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Compounds useful in the treatment of mammalian cancers and especially human cancers according to Formula I are disclosed. Formula (I). Pharmaceutical compositions and methods of treatment employing the compounds disclosed herein are also disclosed.
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Paragraph 0101
(2014/09/29)
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- PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
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Compounds useful in the treatment of mammalian cancers and especially human cancers according to Formula I are disclosed. Pharmaceutical compositions and methods of treatment employing the compounds disclosed herein are also disclosed.
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Paragraph 00182
(2013/06/06)
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- METHYLPYRROLOPYRIMIDINECARBOXAMIDES
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The compounds of Formula (I), wherein R1, R2, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, the stereoisomers of the compounds and the salts thereof are effective inhibitors of the type 5 phosphodiesterase.
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Page/Page column 101
(2012/06/18)
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- METHYLPYRROLOPYRIMIDINECARBOXAMIDES
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The compounds of formula (I) wherein R1, R2, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, and the stereoisomers of the compounds and the salts thereof are effective inhibitors of the type 5 phosphodiestera
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Page/Page column 160-161
(2011/04/14)
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- PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITES
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Compounds useful in the treatment of mammalian cancers and especially human cancers according to Formula I are disclosed. Pharmaceutical compositions and methods of treatment employing the compounds disclosed herein are also disclosed.
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Page/Page column 59
(2011/11/30)
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- Keggin heteropolyacid catalyzed synthesis of isoxazolo- [5,4-d]pyrimidine-4,6(5H,7H)-diones at room temperature
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Isoxazolo[5,4-d]pyrimidine-4,6(5H,7H)diones 2a-2f have been synthesized from the reaction of ethyl 5-amino-3-methyl-4-isoxazole carboxylate (1) with aryl isocyanates in the presence of Keggin heteropolyacid H3[PW12O40] as
- Bamoharram, Fatemeh F.,Roshani, Minaa,Heravi, Majid M.,Mahdavi, Masoumeh,Javid, Alia,Emampour, Jalal Sh.
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experimental part
p. 974 - 976
(2010/10/18)
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- NOVEL 5,6-DIHYDROPYRAZOLO[3,4-E] [L,4]DIAZEPIN-4 (IH) -ONE DERIVATIVES FOR THE TREATMENT OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE.
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The present invention provides a compound of a formula (I): wherein the variables are defined herein; to a process for preparing such a compound; and to the use of such a compound in the treatment of a PDE 4 mediated disease state.
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Page/Page column 50
(2008/06/13)
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- Microwave-assisted synthesis of substituted pyrazoles and pyrazolo [3,4-d]thiopyrimidines
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Ethyl(ethoxymethylene)cyanoacetate and ethoxymethylene malononitrile were synthesized from the reaction of malononitrile or ethylcyanoacetate with triethyl orthoformate or orthoacetate in N, N-dimethylacetamide under microwave irradiation. In a similar manner, substituted pyrazoles were synthesized from the reaction of ethyl (ethoxymethylene)cyanoacetate and ethoxymethylene malononitrile with phenylhydrazine. These pyrazoles were converted to pyrazolo[3,4-d]thiopyrimidines upon treatment with arylisothiocyanate and thiourea under microwave irradiation. Copyright Taylor & Francis Group, LLC.
- Heravi, Majid M.,Nami, Navabeh,Seifi, Nasim,Oskooie, Hossein A.,Hekmatshoar, Rahim
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p. 591 - 599
(2007/10/03)
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- Synthesis and evaluation of polycyclic pyrazolo[3,4-d]pyrimidines as PDE1 and PDE5 cGMP phosphodiesterase inhibitors
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Polycyclic pyrazolo[3,4-d]pyrimidines (represented by 3 and 4) were synthesized as analogues of the recently reported polycyclic guanine phosphodiesterase (PDE) inhibitors. From the structure-activity relationship (SAR) development of a series of compounds, it was discovered that C-3 benzyl and N-2 methyl disubstitution on the pyrazole ring gave the best combination of potency and selectivity for PDE1 and PDE5 cGMP PDEs as represented by compound 4c: PDE1, IC50 = 60 nM; PDE3, IC50 = 55 000 nM; PDE5, IC50 = 75 nM. These compounds were also evaluated in vivo and found to be good orally active antihypertensives in laboratory animal models. Finally, comparisons were made of the in vitro and in vivo profiles of the pyrazolo- [3,4-d]pyrimidine compound 4c with those of two representative guanine compounds.
- Xia, Yan,Chackalamannil, Samuel,Czarniecki, Michael,Tsai, Hsingan,Vaccaro, Henry,Cleven, Renee,Cook, John,Fawzi, Ahmad,Watkins, Robert,Zhang, Hongtao
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p. 4372 - 4377
(2007/10/03)
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