- PHARMACEUTICAL COMPOSITION CONTAINING, AS ACTIVE INGREDIENT, 7-AZAINDOLIN-2-ONE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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The present invention relates to a 7-azaindolin-2-one derivative or a pharmaceutically acceptable salt thereof, and the 7-azaindolin-2-one derivative or the pharmaceutically acceptable salt thereof can be favorably used as a medicinal material for inhibiting cancer growth and cancer metastasis.
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- 5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: Design, synthesis and cytotoxicity against cancer cells
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Angiogenesis plays important roles in tumor growth and metastasis. Sunitinib (Sutent) is an antitumor agent targeting receptor tyrosine kinases which are involved in angiogenesis as well as cancer cell growth and survival. Using the pyridin-3-ol scaffold, which was previously reported as an excellent antioxidant and antiangiogenic platform, we have synthesized sunitinib mimics 6 by hybridizing bicyclic pyridinol 4 as a key scaffold and pyrrole-2-carbaldehydes 7 as side chains. Cytotoxicity assays showed that compounds 6 have comparable to better anticancer activity than sunitinib against five different cancer cell lines. In addition, compounds 6 showed even lower levels of cytotoxicity against normal cells, resulting in up to 26-fold better safety windows, than sunitinib. Signaling pathway-associated transcription factor reporter assay and western blot analyses revealed that apoptosis induction in MDA-MB-231 human breast cancer cells by 6F is mainly mediated through the p53 increase and down-regulation of phospho-signal transducer and activator of transcription 3 (STAT3) and its target gene products, cyclin D, Bcl-2, and survivin. The data strongly suggest that our hybrid compounds can provide a novel anticancer scaffold with improved and safer cytotoxicity profiles than sunitinib.
- Shah, Sajita,Lee, Chaemin,Choi, Hyukjae,Gautam, Jaya,Jang, Hyeonjin,Kim, Geum Jin,Lee, Yu-Jeong,Chaudhary, Chhabi Lal,Park, Sang Won,Nam, Tae-Gyu,Kim, Jung-Ae,Jeong, Byeong-Seon
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p. 4829 - 4841
(2016/06/13)
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- Pyridoxine-derived bicyclic amido-, ureido-, and carbamato-pyridinols: Synthesis and antiangiogenic activities
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We recently developed an efficient and practical synthesis for a novel series of pyridoxine-derived 6-amido-2,4,5-trimethylpyridin-3-ols and found that this novel scaffold has outstanding activity to inhibit angiogenesis measured by the quantitative chick embryo chorioallantoic membrane (CAM) assay. As an effort to extend the scope of the amidopyridinol scaffold, we here report the synthesis and antiangiogenic activities of a series of bicyclic versions of the amidopyridinol including five- and six-membered cyclic amide-, cyclic urea-, and cyclic carbamate-fused pyridinols. The six membered bicyclic derivatives were prepared by the reported procedures, and the five-membered ring-fused ones were synthesized by new synthetic methods developed in this study. CAM assays showed that both six- and five-membered lactam-fused pyridinols have activities comparable to sunitinib malate, the positive control, in inhibition of vascular endothelial growth factor-induced angiogenesis. On the other hand, the urea and the carbamate derivatives showed modest to moderate antiangiogenic activities. In summary, some bicyclic aminopyridinols can provide a good platform for structural exploitation in future medicinal chemistry work.
- Lee, Hyunji,Kim, Dong-Guk,Banskota, Suhrid,Lee, You Kyoung,Nam, Tae-Gyu,Kim, Jung-Ae,Jeong, Byeong-Seon
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p. 8702 - 8710
(2014/12/11)
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- Novel heteroaryl phosphonates as cardioprotective agents
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The invention teaches compound of general formula: Wherein: R1 is selected from H and CH3, and R2 is selected from H and OH, or R1 and R2 together form an optionally substituted phenyl ring which is fused to the pyridine ring; and R3 is selected from H, CH3, CH2OH and R4 is selected from H, CH3, CH2OH, R5 is selected from H, phenyl, halogen-substituted phenyl and Wherein R6 and R7 are each independently selected from H, Na+, K+, alkyl and optionally substituted aryl, and X and Y are each independently selected from H, OH and F, or at least one of X and Y is an heteroatom and together with R3 forms a bridge with the proviso that R4 is and N-oxides thereof, and biologically acceptable salts thereof, related compounds, related pharmaceutical compositions, and methods for treating various disorders using such compositions.
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