- Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors
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A series of novel compounds carrying 1,2,4-triazole scaffold were prepared and evaluated for their antiproliferative activities against NCI 60 cell line. Compounds 10 (a, c), 11 (a-d), and 14 (a-e) were selected for evaluation at single concentration of 10 μM towards panel of sixty cancer cell lines. Some of nitric oxide (NO) donating triazole/oxime hybrids 11a-d showed antiproliferative activity better than their corresponding ketones. On the other hand, the thiazolo [3,2-b][1,2,4]-triazoles 14a-e showed remarkable antiproliferative activities against the same cell lines. Compound 14d was selected for five dose testing against the full panel of 60 human tumor cell lines. Compound 14d showed high selectivity against renal subpanel with selectivity ratio of 6.99 at GI50 level. Compounds 11a-d, 10a-d and 14a-e were tested against four cell lines using MTT assay then compounds of the least IC50 were evaluated against three known anticancer targets including EGFR, BRAF and Tubulin. The results revealed that compound 14d showed promising EGFR inhibitory activity of cancer cell proliferation and were also observed to be moderate BRAF and tubulin inhibitors. Moreover, cell cycle analysis and apoptosis assay were finished for compounds 14d and 14f. Finally molecular modeling studies were performed to explore the binding mode of the most active compounds to the target enzymes.
- El-Sherief, Hany A.M.,Youssif, Bahaa G.M.,Abbas Bukhari, Syed Nasir,Abdelazeem, Ahmed H.,Abdel-Aziz, Mohamed,Abdel-Rahman, Hamdy M.
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p. 774 - 789
(2018/07/29)
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- Substituted (1H-pyrazolo[3,4-b]pyridine)urea compounds and antineoplastic application thereof
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The invention provides substituted (1H-pyrazolo[3,4-b]pyridine)urea compounds and antineoplastic application thereof. Specifically, the invention provides the compounds as shown in a formula I which is described in the specification. Each group in the formula is as defined in the specification. The compounds as shown in the formula I can inhibit receptor tyrosine kinases (including c-Kit, PDGFRalpha and VEGFR2) related to the occurrence and development of tumors and are used for treatment of tumors.
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Paragraph 0208; 0209; 0210; 0211
(2018/06/26)
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- THIAZOLE CARBOXAMIDE DERIVATIVE AND METHOD FOR USE THEREOF
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PROBLEM TO BE SOLVED: To provide a plant disease control agent having excellent performance as compared to the conventional art, particularly a compound useful as a blast control agent by box treatment and seed treatment. SOLUTION: The present invention provides a thiazole carboxamide derivative represented by formula (I) (where R is a hydrogen atom or a formyl group) or a salt thereof, and a plant disease control agent comprising the derivative as an active ingredient. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPO&INPIT
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Paragraph 0072-0074
(2017/10/31)
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- Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)
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Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFRα) kinases play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFRα dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRα. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PDGFRα-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 μM concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T670I tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.
- Lu, Yanli,Mao, Fei,Li, Xiaokang,Zheng, Xinyu,Wang, Manjiong,Xu, Qing,Zhu, Jin,Li, Jian
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supporting information
p. 5099 - 5119
(2017/06/28)
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- INHIBITORS OF AKT ACTIVITY
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The instant invention provides for substituted fused naphthyridine derivatives that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.
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Page/Page column 136
(2010/10/03)
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- 5-SULFANYLMETHYL-PYRAZOLO [1,5-A] PYRIMIDIN-7-OL DERIVATIVES AS CXCR2 ANTAGONISTS
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The present invention relates to compounds of formula (I) and the use of these compounds as pharmaceuticals, e.g. in preventing or treating a CXCR2 receptor mediated condition or disease.
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Page/Page column 31
(2008/12/05)
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- HETEROBICYCLIC METALLOPROTEASE INHIBITORS
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The present invention relates generally to heterobicyclic containing pharmaceutical agents, and in particular, to heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic metalloprotease inhibiting compounds that exhibit an increased potency in relation to currently known metalloprotease inhibitors.
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Page/Page column 133-134
(2008/12/05)
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- PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
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Compounds of formula (I): and their use in the inhibition of Trk activity are described.
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Page/Page column 97
(2008/06/13)
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