182633-13-2Relevant academic research and scientific papers
Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing
Lewis, Timothy A.,De Waal, Luc,Wu, Xiaoyun,Youngsaye, Willmen,Wengner, Antje,Kopitz, Charlotte,Lange, Martin,Gradl, Stefan,Ellermann, Manuel,Lienau, Philip,Schreiber, Stuart L.,Greulich, Heidi,Meyerson, Matthew
, p. 1537 - 1542 (2019)
6-(4-(Diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, potently and selectively inhibits phosphodiesterases 3A and 3B (PDE3A and PDE3B) and kills cancer cells by inducing PDE3A/B interactions with SFLN12. The structure-activity relationship (SAR) of DNMDP analogs was evaluated using a phenotypic viability assay, resulting in several compounds with suitable pharmacokinetic properties for in vivo analysis. One of these compounds, BRD9500, was active in an SK-MEL-3 xenograft model of cancer.
Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents
Sijm, Maarten,Siciliano de Araújo, Julianna,Ramos Llorca, Alba,Orrling, Kristina,Stiny, Lydia,Matheeussen, An,Maes, Louis,de Esch, Iwan J. P.,de Nazaré Correia Soeiro, Maria,Sterk, Geert Jan,Leurs, Rob
supporting information, p. 1662 - 1668 (2019/08/30)
Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.
COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
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, (2014/10/18)
Disclosed are compounds, such as pyridazinones, that can be, inter alia, used for treating cancer.
Synthesis and structure-activity relationships of miticidal 4,5- dihydropyrazole-5-thiones
Tada,Motoki,Takahashi,Miyata,Takechi,Uchida,Takagi
, p. 165 - 173 (2007/10/03)
A series of novel 4,5-dihydropyrazole-5-thiones (DHPs) was synthesised by treating the corresponding dihydropyrazolones with Lawesson's reagent and evaluated for miticidal activity against two-spotted spider mites (Tetranychus urticae Koch). Of these, 3-(
