91135-89-6Relevant academic research and scientific papers
Synthesis, Identification, and Structure-Activity Relationship Analysis of GATA4 and NKX2-5 Protein-Protein Interaction Modulators
Jumppanen, Mikael,Kinnunen, Sini M.,V?lim?ki, Mika J.,Talman, Virpi,Auno, Samuli,Bruun, Tanja,Boije Af Genn?s, Gustav,Xhaard, Henri,Aumüller, Ingo B.,Ruskoaho, Heikki,Yli-Kauhaluoma, Jari
supporting information, p. 8284 - 8310 (2019/10/11)
Transcription factors GATA4 and NKX2-5 directly interact and synergistically activate several cardiac genes and stretch-induced cardiomyocyte hypertrophy. Previously, we identified phenylisoxazole carboxamide 1 as a hit compound, which inhibited the GATA4-NKX2-5 transcriptional synergy. Here, the chemical space around the molecular structure of 1 was explored by synthesizing and characterizing 220 derivatives and structurally related compounds. In addition to the synergistic transcriptional activation, selected compounds were evaluated for their effects on transcriptional activities of GATA4 and NKX2-5 individually as well as potential cytotoxicity. The structure-activity relationship (SAR) analysis revealed that the aromatic isoxazole substituent in the southern part regulates the inhibition of GATA4-NKX2-5 transcriptional synergy. Moreover, inhibition of GATA4 transcriptional activity correlated with the reduced cell viability. In summary, comprehensive SAR analysis accompanied by data analysis successfully identified potent and selective inhibitors of GATA4-NKX2-5 transcriptional synergy and revealed structural features important for it.
Synthesis and biological activity of ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylate
Wang, Wei,Wang, Lie-Ping,Mao, Min-Zhen,Zhang, Xiao-Guang,Zheng, Xiao-Rui,Huang, Xiao-Ying,Xue, Chao,Ning, Bin-Ke
, p. 164 - 167 (2017/11/20)
A series of novel ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylates I-1-6 were synthesized. The structures of all target compounds were characterized by 1H NMR, 13C NMR, IR,MS and elemental analyses. Their fungicidal and herbicidal activities were evaluated. The results of preliminary bioassays show that the title compounds I-4 possess 20-50% inhibition against most of the tested plants at the dosage of 150 g ai/ha, while the title compounds I-1-5 possess 32-58% inhibition against FusaHum graminearum, Thanatephorus cucumeris, Botrytis cinereapers and Fusarium oxysporum in vitro at the concentration of 100 mg/L.
Synthesis and structure-activity relationships of isoxazole carboxamides as growth hormone secretagogue receptor antagonists
Xin, Zhili,Zhao, Hongyu,Serby, Michael D.,Liu, Bo,Schaefer, Verlyn G.,Falls, Douglas H.,Kaszubska, Wiweka,Colins, Christine A.,Sham, Hing L.,Liu, Gang
, p. 1201 - 1204 (2007/10/03)
A series of isoxazole carboxamide derivatives has been developed as potent ghrelin receptor antagonists. The synthesis and structure-activity relationship (SAR) are described.
