- Structure-Activity Relationship of Phenylpyrazolones against Trypanosoma cruzi
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Chagas disease is a neglected parasitic disease caused by the parasitic protozoan Trypanosoma cruzi and currently affects around 8 million people. Previously, 2-isopropyl-5-(4-methoxy-3-(pyridin-3-yl)phenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0227) was discovered to be a sub-micromolar inhibitor (pIC50=6.4) of T. cruzi. So far, SAR investigations of this scaffold have focused on the alkoxy substituent, the pyrazolone nitrogen substituent and the aromatic substituent of the core phenylpyrazolone. In this study, modifications of the phenyldihydropyrazolone scaffold are described. Variations were introduced by installing different substituents on the phenyl core, modifying the geminal dimethyl and installing various bio-isosteres of the dihydropyrazolone group. The anti T. cruzi activity of NPD-0227 could not be surpassed as the most potent compounds show pIC50 values of around 6.3. However, valuable additional SAR data for this interesting scaffold was obtained, and the data suggest that a scaffold hop is feasible as the pyrazolone moiety can be replaced by a oxazole or oxadiazole with minimal loss of activity.
- Sijm, Maarten,Sterk, Geert Jan,Caljon, Guy,Maes, Louis,de Esch, Iwan J. P.,Leurs, Rob
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supporting information
p. 1310 - 1321
(2020/05/08)
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- Selective NK-3 receptor antagonist, preparation and application thereof
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The invention provides a selective NK-3 receptor antagonist, preparation and application thereof, particularly a compound represented by the following formula (I). The compound of the invention has unexpected activity to modulate cytokines and/or interferon, and is useful in the treatment of CNS and peripheral diseases or disorders.
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Paragraph 0223-0224; 0241-0242
(2020/11/09)
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- COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF ABL1, ABL2 AND BCR-ABL1
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The present invention relates to compounds of formula I: in which Y, Y1, Y 4, Y5, Y 6, R1, R2, R3 and R4 are defined in the Summary of the Invention; capable of inhibiting the activity of BCR-ABL1 and mutants thereof. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.
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Paragraph 00283-00284
(2013/12/03)
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- CGRP ANTAGONISTS
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The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2 and R3 are defined as stated hereinafter, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, their use and processes for preparing them.
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Page/Page column 88
(2011/04/18)
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- INSECTICIDAL ARYLPYRROLINES
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The invention relates to novel arylpyrroline compounds of formula (I) which have excellent insecticidal activity and which can thus be used as insecticides.
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Page/Page column 55
(2009/10/09)
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- NOVEL BENZOFURAN DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, AND USES OF THESE
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[From equivalent EP1710233A1] The present invention provides compounds represented by general formula (I): or pharmaceutical acceptable salts thereof, wherein R1 is hydrogen or lower alkyl; R2 is lower alkyl, halo-lower alkyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, arylalkenyl, aryloxy-lower alkyl, heteroaryl, heteroaryl-lower alkyl, etc; R3, R4, R5 and R6 are each hydrogen, halogen, cyano, lower alkyl, halo-lower alkyl, lower alkoxy, hydroxy, aryl, etc; provided that at least one of R3, R4, R5 and R6 is other than hydrogen. Compound (I) of the present invention shows a potent adenosine A2A receptor antagonistic activity, and are useful for treating or preventing a disease mediated by adenosine A2A receptors such as motor function disorders, depression, anxiety disorders, cognitive function disorders, cerebral ischemia disorders, restless legs syndrome and the like.
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Page/Page column 27
(2008/06/13)
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- Substituted bromofluorobenzene derivatives and process for its manufacture
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Substituted bromofluorobenzene, wherein the fluorine is in para-position and the bromine in meta-position to another substituent, is prepared by direct bromination of the corresponding fluorobenzene derivative. Bromination is advantageously carried out in the presence of a catalyst, preferably a metal or metal salt. The elementary bromine is used in an amount of 0.9 to 1.3 mols per mol of fluorobenzene derivative and the reaction temperature is between 20° and 200° C. The bromofluorobenzene derivatives are suitable for the synthesis of medicaments and plant protective agents.
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