41470-19-3Relevant academic research and scientific papers
Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis
Meta, Elda,Brullo, Chiara,Sidibe, Adama,Imhof, Beat A.,Bruno, Olga
, p. 24 - 35 (2017/04/06)
Taking into account the structure activity relationship information given by our previous studies, we designed and synthesized a small library of pyrazolylureas and imidazopyrazolecarboxamides fluorinated on urea moiety and differently decorated on pyrazo
Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists
Hasui, Tomoaki,Ohyabu, Norio,Ohra, Taiichi,Fuji, Koji,Sugimoto, Takahiro,Fujimoto, Jun,Asano, Kouhei,Oosawa, Masato,Shiotani, Sachiko,Nishigaki, Nobuhiro,Kusumoto, Keiji,Matsui, Hideki,Mizukami, Atsushi,Habuka, Noriyuki,Sogabe, Satoshi,Endo, Satoshi,Ono, Midori,Siedem, Christopher S.,Tang, Tony P.,Gauthier, Cassandra,De Meese, Lisa A.,Boyd, Steven A.,Fukumoto, Shoji
, p. 5428 - 5445 (2014/12/10)
In the course of our study on selective nonsteroidal mineralocorticoid receptor (MR) antagonists, a series of novel benzoxazine derivatives possessing an azole ring as the core scaffold was designed for the purpose of attenuating the partial agonistic activity of the previously reported dihydropyrrol-2-one derivatives. Screening of alternative azole rings identified 1,3-dimethyl pyrazole 6a as a lead compound with reduced partial agonistic activity. Subsequent replacement of the 1-methyl group of the pyrazole ring with larger lipophilic side chains or polar side chains targeting Arg817 and Gln776 increased MR binding activity while maintaining the agonistic response at the lower level. Among these compounds, 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (37a) showed highly potent in vitro activity, high selectivity versus other steroid hormone receptors, and good pharmacokinetic profiles. Oral administration of 37a in deoxycorticosterone acetate-salt hypertensive rats showed a significant blood pressure-lowering effect with no signs of antiandrogenic effects.
PYRAZOLE COMPOUNDS
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Page/Page column 25, (2010/04/30)
The present invention relates to wherein each symbol is as defined in the specification. The compound has a superior mineralocorticoid receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of a disease or condition mediated by the mineralocorticoid receptor activation.
1-Methyl and 1-(2-hydroxyalkyl)-5-(3-alkyl/cycloalkyl/phenyl/naphthylureido)-1H-pyrazole-4-carboxylic acid ethyl esters as potent human neutrophil chemotaxis inhibitors
Bruno, Olga,Brullo, Chiara,Bondavalli, Francesco,Schenone, Silvia,Spisani, Susanna,Falzarano, Maria Sofia,Varani, Katia,Barocelli, Elisabetta,Ballabeni, Vigilio,Giorgio, Carmine,Tognolini, Massimiliano
scheme or table, p. 3379 - 3387 (2009/09/27)
In this paper we report the synthesis and the chemotaxis inhibitory activity of a number of 1H-pyrazole-4-carboxylic acid ethyl esters 2 functionalized in N1 with a methyl group or different hydroxyalkyl chains and in position 5 with a series of 3-substituted urea groups. These compounds were designed as development of previous pyrazole-urea derivatives that resulted potent IL8-induced neutrophil chemotaxis inhibitors in vitro. Most of the new compounds revealed a potent inhibition of both IL8- and fMLP-OMe-stimulated neutrophil chemotaxis. The most active compounds in the fMLP-OMe induced chemotaxis test showed IC50 in the range 0.19 nM-2 μM; but we observed a very strong inhibition in the IL8-induced chemotaxis test, having the most active compounds IC50 at pM concentrations. In vivo compounds 2e and 2f, although to a lesser extent, at 50 mg/kg os decreased granulocyte infiltration in zymosan-induced peritonitis in mice.
