- JNK inhibitor as well as pharmaceutical composition and application thereof
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The invention provides a compound represented by a formula (I), racemates, stereoisomers, tautomers, isotope markers, solvates, polymorphic substances, nitrogen oxides, or pharmaceutically acceptablesalts thereof, and application as a JNK inhibitor. The invention also provides a preparation method of the compound shown in the formula (I), a pharmaceutical composition containing the compound shownin the formula (I), and application of the compound shown in the formula (I) to preparation of a medicine, and the medicine is used for treating diseases which can be treated by inhibiting the activity of JNK.
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Paragraph 0556-0559
(2021/03/31)
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- Gold(I)-Catalyzed Reactions between 2-(1-Alkynyl)-2-alken-1-ones and Vinyldiazo Ketones for Divergent Synthesis of Nonsymmetric Heteroaryl-Substituted Triarylmethanes: N-versus C-Attack Paths
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Gold-catalyzed synthesis of nonsymmetrical heteroaryl-substituted triarylmethanes using 2-(1-alkynyl)-2-alken-1-ones and vinyldiazo ketones is described. In this catalytic sequence, vinyldiazo ketones attack gold-containing 3-furylbenzyl cations to form the observed C(1)-addition products. We also note that vinyldiazo ketones can be thermally cyclized to yield pyrazole derivatives, which can react with 3-furylbenzyl cations to afford pyrazole-containing triarylmethanes, corresponding to a N(5)-addition path.
- Kardile, Rahul Dadabhau,Liu, Rai-Shung
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supporting information
p. 8229 - 8233
(2020/11/03)
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- Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand–based drug design
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Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development. This novel chemical tool, endowed with favourable pharmacological characteristics, was successfully developed, and a preliminary Structure–Activity Relationship investigation was carried out.
- Magalh?es, Joana,Franko, Nina,Annunziato, Giannamaria,Welch, Martin,Dolan, Stephen K.,Bruno, Agostino,Mozzarelli, Andrea,Armao, Stefano,Jirgensons, Aigars,Pieroni, Marco,Costantino, Gabriele,Campanini, Barbara
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p. 1444 - 1452
(2018/09/25)
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- 6,7-DIHYDROPYRAZOLO[1,5-A]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). The invention is also directed to pharmaceutical compositi
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Page/Page column 33
(2016/03/19)
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- 6,7-DIHYDROPYRAZOLO[1,5-A]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved.
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Page/Page column 58
(2016/03/19)
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- 6,7-DIHYDROPYRAZOLO[1,5-α]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved.
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Page/Page column 49; 50
(2016/04/04)
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- RADIOLABELLED MGLUR2 PET LIGANDS
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The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a mammal, in vitro or in vivo and to precursors of said compounds.
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Page/Page column 30
(2016/06/28)
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- 6,7-DIHYDROPYRAZOLO[1,5-a]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives of Formula (I) as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved, especially CNS disorders.
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Page/Page column 77
(2015/01/06)
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- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1, 2-A]PYRIDINE-3- CARBOXAMIDE COMPOUNDS AS CFMS INHIBITORS
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Compounds of Formula (I): and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4 and R5 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases and pain.
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Page/Page column 114
(2011/07/09)
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- Regioselective synthesis of ethyl pyrazolecarboxylates from ethyl 3-[(dimethylamino)methylidene]pyruvate and diethyl 3-[(dimethylamino)methylidene]-2-oxosuccinate. Isolation of ethyl 4,5-dihydro-1-heteroaryl-5-hydroxy-1H-pyrazole-5-carboxylates as stable intermediates in the pyrazole ring formation
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Reactions of ethyl 3-[(E)-(dimethylamino)methylidene]pyruvate (3) and 3-[(dimethylamino)methylidene]-2-oxosuccinate (4) with hydrazine monohydrochloride (5a) and (hetero)arylhydrazines (5b-i) afforded, regioselectively, 1-substituted ethyl 1H-pyrazole-5-carboxylates 9a-f and diethyl 1H-pyrazole-3,4-dicarboxylates, 11a-i, respectively. Upon treatment of 3 with pyridazinylhydrazines 5d-f, the stable intermediates, 1-substituted ethyl 4,5-dihydro-5-hydroxy-1H-pyrazole-5-carboxylates 8d-f, were isolated. Treatment of compounds 8d-f in acetic acid under reflux furnished the pyrazoles 9d-f. On the other hand, reaction of 3 with N,N′-dimethylhydrazine (5I) gave ethyl 1-methyl-1H-pyrazole-3-carboxylate (14). The structures of compounds 3, 4, 14 were determined by nmr (noesy and hmbc techniques), while the structures of compounds 8f, 9f, and 11e,f were determined by X-ray diffraction.
- Hanzlowsky, Andrej,Jelencic, Blanka,Recnik, Simon,Svete, Jurij,Golobic, Amalija,Stanovnik, Branko
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p. 487 - 498
(2007/10/03)
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- One-pot synthesis of 3(5)-ethoxycarbonylpyrazoles
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A one-pot synthesis of ethoxycarbonylpyrazoles 2a-e, by the cyclocondensation of β-alkoxyvinyl trichloromethyl ketones 1a-e with hydrazine hydrochloride under mild conditions, is reported. A study using compounds 1a-e with different substituents proved that these are versatile building blocks for the synthesis of pyrazole derivatives, having a 3(5)-ethoxycarbonyl substituent, in good yields (70-91%).
- Martins,Freitag,Flores,Zanatta
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p. 1491 - 1492
(2007/10/02)
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