- KINASE INHIBITOR
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The present invention aims to provide a novel kinase inhibitor and the like, and a therapeutic agent for a disease, a drug discovery screening method and the like utilizing such inhibitor and the like. The compound represented by the following formula (I) and a salt thereof can inhibit plural kinases including LATS (particularly LATS2) which is the major kinase in the Hippo signal transduction pathway. In addition, diseases or tissue damage associated with failure of cellular proliferation can be treated. Therefore, the present invention is beneficial, for example, in the research field of cell functions and diseases, in which the Hippo signal transduction pathway is involved, and the like. Furthermore, it is beneficial in the medical field for the treatment of such diseases and the like. wherein each symbol is as defined in the DESCRIPTION.
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Paragraph 0200; 0202
(2021/04/16)
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- ADDITIVE COMPOSITION FOR CULTURE MEDIUM, ADDITIVE COMPOUND FOR CULTURE MEDIUM, AND METHOD FOR CULTURE OF CELLS OR TISSUE USING SAME
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The present invention provides a medium additive composition containing a compound represented by the following formula (I), or a salt thereof: {wherein each symbol is as defined in the DESCRIPTION.}
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Paragraph 0185; 0187
(2020/06/15)
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- Protecting-Group-Free Amidation of Amino Acids using Lewis Acid Catalysts
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Amidation of unprotected amino acids has been investigated using a variety of ‘classical“ coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.
- Sabatini, Marco T.,Karaluka, Valerija,Lanigan, Rachel M.,Boulton, Lee T.,Badland, Matthew,Sheppard, Tom D.
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supporting information
p. 7033 - 7043
(2018/05/04)
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- [...] - Orn (ClCH2NH) - AA - benzylamine, its synthesis, activity and application (by machine translation)
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The invention discloses the following formula of 13 for β - Carboline -3 - formyl - Orn (ClCH2 NH) - AA - NHCH2 C6 H5 (In the formula AA is selected from L - Arg, L - Asn, L - Asp, L - Glu, L - Gly, L - Ile, L - Leu, L - Met, L - Phe, L - Pro, L - Thr, L - Trp, L - Val residue), discloses a process for their preparation, discloses their inhibition of tumor cell growth, therefore this invention discloses their use as anti-tumor medicament. (by machine translation)
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Paragraph 0043; 0082; 0083
(2017/08/27)
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- Synthesis and antitumor activities of chiral dipeptide thioureas containing an alpha-aminophosphonate moiety
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Thiourea derivatives demonstrate potent cytotoxic activity against various leukemias and many tumor cell lines. In our previous study, the combination of thiourea and phosphonate has been proven as an effective strategy for developing antitumor agents. Herein, we synthesized and evaluated a series of novel chiral dipeptide thioureas containing an α-aminophosphonate moiety as antitumor agents. Finally, we developed novel dipeptide thioureas 11d and 11f that showed comparable inhibition with that of Cisplatin against BGC-823 and A-549 cells, respectively.
- Liu, Jingzi,Liao, Peng,Hu, Junfeng,Zhu, Hong,Wang, Yonglin,Li, Yongjun,Li, Yan,He, Bin
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- A METHOD OF INHIBITING TAU PHOSPHORYLATION
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A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.
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Page/Page column 181
(2014/02/15)
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- In silico and pharmacological screenings identify novel serine racemase inhibitors
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d-Serine is a coagonist of the N-methyl-d-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.
- Mori, Hisashi,Wada, Ryogo,Li, Jie,Ishimoto, Tetsuya,Mizuguchi, Mineyuki,Obita, Takayuki,Gouda, Hiroaki,Hirono, Shuichi,Toyooka, Naoki
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supporting information
p. 3732 - 3735
(2014/09/03)
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- A novel method for the preparation of 4-arylimidazolones
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A series of 4-arylimidazolones have been accessed via late-stage, palladium-mediated arylation of acetone- and cyclohexanone-derived 4-chloroimidazolones. The 4-chloroimidazolones were prepared via a novel rearrangement of the corresponding imidazolone N-
- Demong, Duane E.,Ng, Irene,Miller, Michael W.,Stamford, Andrew W.
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supporting information
p. 2830 - 2833
(2013/07/19)
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- Synthesis, physical-chemical characterisation and biological evaluation of novel 2-amido-3-hydroxypyridin-4(1H)-ones: Iron chelators with the potential for treating Alzheimer's disease
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A novel class of 2-amido-3-hydroxypyridin-4-one iron chelators is described. These compounds have been designed to behave as suitable molecular probes which will improve our knowledge of the role of iron in neurodegenerative conditions. Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson disease (PD), can be considered as diverse pathological conditions sharing critical metabolic processes such as protein aggregation and oxidative stress. Interestingly, both these metabolic alterations seem to be associated with the involvement of metal ions, including iron. Iron chelation is therefore a potential therapeutic approach. The physico-chemical (pKa, pFe 3+ and log P) and biological properties (inhibition of iron-containing enzymes) of these chelators have been investigated in order to obtain a suitable profile for the treatment of neurodegenerative conditions. Studies with neuronal cell cultures confirm that the new iron chelators are neuroprotective against β-amyloid-induced toxicity.
- Gaeta, Alessandra,Molina-Holgado, Francisco,Kong, Xiao L.,Salvage, Sarah,Fakih, Sarah,Francis, Paul T.,Williams, Robert J.,Hider, Robert C.
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experimental part
p. 1285 - 1297
(2011/03/23)
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- Copper-free sonogashira cross-coupling for functionalization of alkyne-encoded proteins in aqueous medium and in bacterial cells
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Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddition reaction ("click chemistry"), have provided chemical tools to study biomolecular dynamics and function in living systems. Despite its prominence in organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for biological applications has not been reported. In this work, we report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide range of aromatic groups including fluorophores and fluorinated aromatic compounds can be readily introduced into the HPG-containing ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chemistry.
- Li, Nan,Lim, Reyna K. V.,Edwardraja, Selvakumar,Lin, Qing
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supporting information; experimental part
p. 15316 - 15319
(2011/11/11)
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- Formal olefination and acylaziridination of imidazolones
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(Figure presented) The first formal olefination and acylaziridination of imidazolones were obtained by cycloaddition of cyclic nitrones with alkenes and alkynes, respectively.
- Dai, Xing,Miller, Michael W.,Stamford, Andrew W.
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supporting information; experimental part
p. 2718 - 2721
(2010/08/06)
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- Unprecedented 1,1′-carbonyldiimidazole-mediated amidation of unprotected α-amino acids in water
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The first amidation reaction of unprotected α-amino acids in water under neutral conditions with various aliphatic, aromatic and heteroaromatic amines in the presence of coupling reagent 1,1′-carbonyldiimidazole at ambient temperature is described. Georg Thieme Verlag Stuttgart.
- Sharma, Rohit K.,Jain, Rahul
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p. 603 - 606
(2007/10/03)
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- Design, synthesis and pharmacological evaluation of α-substituted N-benzylamides of γ-hydroxybutyric acid with potential gaba-ergic activity. Part 6. Search for new anticonvulsant compounds
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In the recent study we have extended our investigations to the new anticonvulsant derivatives of α-substituted N-benzylamides of γ-hydroxybutyric acid (GHB). Among the obtained compounds N-benzylamide of α-(1,2,3,4-tetrahydroisoquinoline)-GHB (9) has demo
- Malawska, Barbara,Kulig, Katarzyna,Gajda, Justyna,Szczeblewski, Dominik,Musial, Anna,Wieckowski, Krzysztof,Maciag, Dorota,Stables, James P.
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p. 127 - 137
(2008/09/17)
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- IRON MODULATORS
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Iron modulator compounds of formula (I) are provided for treating amyloidoses wherein R1 is selected from H, C1-6 alkyl, C1-6 alkenyl, C1-6 hydroxyalkyl, C1-6 hydroxyalkenyl, R2 is selected from H, C1-6 alkyl, C1-6 alkenyl, C1-6 hydroxyalkyl, C1-6 hydroxyalkenyl and C6-10 aralykyl in which the aryl group of the aralkyl group is optionally substituted by hydroxy, halo or C1-4 alkyl R3 is selected from H, C1-6 alkyl, C1-6 alkenyl and C1-12 acyl; R4 is selected from H and C1-3 alkyl R5, R6 and R7 are independently selected from H, C1-6 alkyl, C3-7 aryl, and C1-10 aralkyl; the alkyl, aryl and aralkyl groups being optionally substituted by one or more halo, hydroxy and nitro groups or R5 and R7 together with the nitrogen atom to which they are bonded form a heterocyclic ring optionally substituted by one or more hydroxyl groups or a pharmaceutically acceptable tautomer, ester or addition salt thereof.
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Page/Page column 15; Figure 3
(2010/11/24)
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- NON-ANILINIC DERIVATIVES OF ISOTHIAZOL-3(2H)-ONE 1,1-DIOXIDES AS LIVER X RECEPTOR MODULATORS
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The present invention relates to certain novel compounds of the formula (I) to processes for preparing such compounds, to their the utility in modulation of nuclear hormone receptors Liver X Receptor (LXR) α (NR1H3) and/or β (NR1H2) and in treating and/or preventing clinical conditions including cardiovascular diseases such as atherosclerosis; inflammatory diseases, Alzheimer's disease, lipid disorders (dyslipidemias) whether or not associated with insulin resistance, type 2 diabetes and other manifestations of the metabolic syndrome, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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Page/Page column 197
(2008/06/13)
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- Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors
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Heterocyclic amide derivatives, of formula (I): wherein —X-Y-Z- is selected from —S—CR4═CR5—, —CR4═CR5—S—, —O—CR4═CR5—, —CR4═CR5—O—, —N═CR4—S—, —S—CR4═N—, —NR6—CR4═CR5— and —CR4═CR5—NR6—; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof; (with provisos); possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.
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- Functionalized DL-Amino Acid Derivatives. Potent New Agents for the Treatment of Epilepsy
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Structural analogues of the potent known anticonvulsant agent N-acetyl-DL-alanine N-benzylamide (1a) have been prepared (16 examples).The pharmacological activities of these products were evaluated in the maximal electroshock seizure (MES), the subcutaneous pentylenetetrazole seizure threshold (sc Met), and the rotorod (Tox) tests.The median effective doses (ED50) and the median toxic doses (TD50) for the most active compounds by both intraperitoneal and oral administration are reported.The most active compounds were N-acetyl-DL-phenylglycine N-benzylamide (1d) and N-acetyl-DL-alanine N-m-fluorobenzylamide (1m) along with the parent compound 1a.The ED50 values in the MES test for these three compounds compared well with phenobarbital, while their high TD50 values contributed to their large protective indexes, which approached that of phenytoin.When tested against four convulsant agents, compounds 1a and 1d displayed activity profiles significantly different from those reported for conventionally used antiepileptic drugs.
- Conley, Judith D.,Kohn, Harold
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p. 567 - 574
(2007/10/02)
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- UNE NOUVELLE METHODE DE SYNTHESE PEPTIDIQUE INTRAMOLECULAIRE, APPLICABLE A LA SARCOSINE, A L'AIDE DE DERIVES DE L'ACIDE OXALIQUE
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Two steps are postulated in a new method of intramolecular peptide synthesis using oxalic acid derivates (Fig. 1).Both are verified with model derivatives incorporating one sarcosine residue: cyclisation of 2d into 5 (Fig. 4) and aminolysis of 5 leading t
- Mulliez, Michel,Royer, Jacques
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p. 5143 - 5152
(2007/10/02)
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