55052-28-3Relevant articles and documents
4-Amino-pyrrolopyridine-5-carboxamide: A novel scaffold for JAK1-selective inhibitors
Shin, Heerim,Kim, Mi Kyoung,Chong, Youhoon
, p. 217 - 220 (2014)
Despite a high level of interest in selective Janus kinase 1 (JAK1) inhibitors and their potential for the treatment of inflammatory diseases such as rheumatoid arthritis (RA), only a few such inhibitors have been reported to date. In this study, a novel 4-amino-1H-pyrrolo[2,3-b]pyridine-5-carboxamide scaffold was designed through structural modification of the potent JAK1-selective inhibitor, C2-methyl imidazopyrrolopyridine. Among the series studied, the 4-(2-aminoethyl)amino-pyrrolopyridine derivative, 2j, exhibited a significant 24.7-fold JAK1/JAK2 selectivity along with reasonable inhibitory activity against JAK1 (IC50=2.2 μM). The noticeable JAK1-selectivity of 2j was then tackled through a molecular docking study, which showed that the aminoethyl functionality of 2j is well positioned to discriminate the subtle but significant difference in the size of the ligand binding sites between JAK1 and JAK2.
Design and synthesis of 7-azaindole derivatives and their antitumor and analgesic activities
Liu, Xue-Kun,Wang, Yan-Qiu,Zhao, Tong-Jian,Lu, Yuan-Hua,Zhao, Jia-Nan,Geng, Xiao-Yu,Ma, Jie
, p. 460 - 467 (2021/01/20)
To develop effective anti-tumor and analgesic drugs, a series of novel 7-azaindole derivatives were designed and synthesized through a four-step reaction. 18 target compounds were obtained and characterized through Nuclear Magnetic Resonance and High Resolution Mass Spectrometry. Their anti-proliferative activities and analgesic effect were evaluated. When the 1-position was a methylsulfonyl group and the 5-position was a nitro group, compound 4f demonstrated the best activity. Furthermore, there was a dramatic difference between the IC50 values of compound 4f in tumor and in healthy cell line. The IC50 values of compound 4f in MCF7 breast cancer cell line was 5.781 μmol/L and 8.077 μmol/L in HepG2 hepatoma carcinoma cell line, but more than 100 μmol/L in HL7702 liver cell line. Preliminary results showed that compounds 3a, 3g and 4i had significant analgesic effects in mice, which were stronger than aspirin. These compounds have good prospects for new drug development.
Synthesis and structure?activity?relationship of 3,4?Diaryl?1H?pyrrolo[2,3?b]pyridines as irreversible Inhibitors of mutant EGFR?L858R/T790M
Günther, Marcel,Laux, Julian,Laufer, Stefan
, p. 91 - 96 (2018/12/04)
The epidermal growth factor receptor (EGFR) is a well?validated drug target for the treatment of non?small cell lung cancer. Here we present an optimization approach and preliminary structure?activity relationship for 1H?pyrrolo[2,3?b]pyridines as covalent irreversible mutant EGFR inhibitors. We synthesized a focused library to investigate the effect of different aromatic substituents in the 4?position of this scaffold, interacting with the gatekeeper. We determined the activity of the synthesized compounds mutant EGFR enzyme assays and determined the selectivity over the wild type.