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.
Method for synthesizing Meriolin
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, (2019/07/01)
The invention belongs to the field of medicinal chemistry, and concretely relates to a method for synthesizing Meriolin. The method comprises the following steps: 7-azaindole used as a raw material undergoes an oxidation reaction to generate an intermediate 2; the intermediate 2 undergoes a halogenations reaction to generate an intermediate 3; the intermediate 3 is subjected to a Friedel-Crafts acylation to generate an intermediate 4; and the amino group of the intermediate 4 is protected to obtain an intermediate 5, the intermediate 5 undergoes an alkylation reaction to generate an intermediate 6, and the intermediate 6 is cyclized to obtain the target products Merilin 10 and Meriolin 7. The method adopting the inexpensive 7-azaindole as the raw material has the advantages of simple operation steps, mild reaction conditions, avoiding the use of CO, high temperature, high pressure and expensive Pd catalytic reagent and hazardous chemicals, obtaining of the Meriolin 10 and Meriolin 7 ata high yield, and provision of a new idea for the synthesis of Meriolins series new derivatives.
