55717-46-9Relevant articles and documents
Novel pyridine bioisostere of cabozantinib as a potent c-met kinase inhibitor: Synthesis and anti-tumor activity against hepatocellular carcinoma
Karmacharya, Ujjwala,Guragain, Diwakar,Chaudhary, Prakash,Jee, Jun-Goo,Kim, Jung-Ae,Jeong, Byeong-Seon
, (2021/09/10)
Two novel bioisosteres of cabozantinib, 3 and 4, were designed and synthesized. The ben-zene ring in the center of the cabozantinib structure was replaced by trimethylpyridine (3) and pyridine (4), respectively. Surprisingly, the two compounds showed extremely contrasting mesenchy-mal–epithelial transition factor (c-Met) inhibitory activities at 1 μM concentration (4% inhibition of 3 vs. 94% inhibition of 4). The IC50 value of compound 4 was 4.9 nM, similar to that of cabozantinib (5.4 nM). A ligand-based docking study suggested that 4 includes the preferred conformation for the binding to c-Met in the conformational ensemble, but 3 does not. The anti-proliferative activity of compound 4 against hepatocellular carcinoma (Hep3B and Huh7) and non-small-cell lung cancer (A549 and H1299) cell lines was better than that of cabozantinib, whereas 3 did not show a signifi-cant anti-proliferative activity. Moreover, the tumor selectivity of compound 4 toward hepatocellu-lar carcinoma cell lines was higher than that of cabozantinib. In the xenograft chick tumor model, compound 4 inhibited Hep3B tumor growth to a much greater extent than cabozantinib. The present study suggests that compound 4 may be a good therapeutic candidate against hepatocellular carci-noma.
Synthesis of 2-amino-5-hydroxypyridine via demethoxylation
Cheng,Liu
, p. 1403 - 1404 (2016/04/08)
A convenient and efficient four-step synthesis of 2-amino-5-hydroxypyridine can be achieved by protective reaction of 2-amino-5-bromopyridine in the presence of 2,5-hexanedione to yield 5-bromo-2-(2,5-dimethyl-1H-pyrrol-1yl)pyridine, methoxylation with sodium methylate to give 5-methoxy-2-(2,5-dimethyl-1H-pyrrol-1yl)pyridine, deprotective reaction with hydroxylamine hydrochloride to produce 2-amino-5-methoxypyridine and demethylation with 95 % H2SO4 to afford the title compound in an overall yield of 45 %.
CNS active compounds
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, (2008/06/13)
Compounds of the formula STR1 wherein R may be hydrogen or a straight or branched chain alkyl radical of from 1 to 10 carbon atoms, aryl of from 6 to 10 carbon atoms, or aralkyl of from 7 to 10 carbon atoms; Y may be hydrogen, alkyl of from 1 to 4 carbons, CF3, F, Cl, or Br; and Z may be hydrogen or as defined hereinafter. These compounds are useful as central nervous system stimulants or more specifically in enhancing performance or as mood elevators.