- Design, synthesis and biological evaluation of novel 4-(pyrrolo[2,3-d]pyrimidine-4-yloxy)benzamide derivatives as potential antitumor agents
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Cancer is a major cause of death worldwide. Small molecule inhibitors have become a major therapeutic treatment for cancer. In this study, a series of novel 4-(pyrrolo[2,3-d]pyrimidine-4-yloxy)benzamide derivatives were designed, synthesized and evaluated
- Chen, Ting,Fu, Dongxue,He, Jie,Tang, Qidong,Xiong, Hehua,Yang, Feiyi,Zhang, Jianqing,Zheng, Pengwu
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- Synthesis of 2-anilinopyridyl linked benzothiazole hydrazones as apoptosis inducing cytotoxic agents
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A series of 2-anilinopyridyl linked benzothiazole-hydrazone conjugates (5a-aa) were designed, synthesized and evaluated for their in vitro cytotoxic potency against a panel of cancer cell lines like mouse skin melanoma (B16F10), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), triple negative breast cancer (MDA-MB-231) and normal lung epithelial (L132) cell lines. Preliminary screening results revealed that some of these conjugates like 5i and 5l exhibited a significant antiproliferative effect against human breast cancer (MCF-7) with IC50 values of 1.03 and 1.69 μM respectively. Further, detailed biological studies of this promising conjugate (5i) were carried out on MCF-7 cells. The flow cytometric analysis revealed that this conjugate induces cell-cycle arrest in the G2/M phase in a dose dependent manner. Furthermore, in order to determine the effect of the conjugate on cell viability, various cell based assays such as clonogenic assay, ethidium bromide staining, Hoechst staining, detection of ROS generation and annexin V-FITC/PI assays were performed. In these studies, apoptotic features were clearly observed indicating that this conjugate inhibited cell proliferation by apoptosis.
- Sultana, Faria,Saifi, Mohd Aslam,Syed, Riyaz,Mani, Geeta Sai,Shaik, Siddiq Pasha,Osas, Egharevba God'Shelp,Godugu, Chandraiah,Shahjahan, Syeda,Kamal, Ahmed
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p. 7150 - 7161
(2019/05/17)
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- Synthesis and antiproliferative activity of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety
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A series of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety were synthesized, and evaluated for their antiproliferative activity against four cancer cell lines (HT-29, A549, H460, and U87MG) and six tyrosine kinases (c-Met, Flt-3, PDGFR-β VEGFR-2, EGFR, and c-Kit) inhibitory activities in vitro. Most compounds showed moderate to excellent potency, with the most promising analogue 32 showing Flt-3/c-Met IC50 value of 1.16/1.92 nM. Structure-activity relationship studies indicated that the hydrogen atom served as R1 group was benefited to the potency, and mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring (such as R3 = 4-F) showed a higher preference for antiproliferative activity.
- Tang, Qidong,Duan, Yongli,Wang, Linxiao,Wang, Min,Ouyang, Yiqiang,Wang, Caolin,Mei, Han,Tang, Sheng,Xiong, Yinhua,Zheng, Pengwu,Gong, Ping,Zhu, Wufu
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p. 266 - 275
(2017/12/07)
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- Discovery of novel 2-substituted-4-phenoxypyridine derivatives as potential antitumor agents
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A series of 2-substituted-4-phenoxypyridine derivatives were designed, synthesized, and evaluated for their antiproliferative activity against 4 cancer cell lines (A549, HT-29, H460, and U87MG) in vitro. Most compounds showed moderate to excellent potency. Nine tyrosine kinases (c-Met, Flt-3, ALK, VEGFR-2, VEGFR-3, PDGFR-α PDGFR-β c-Kit, and EGFR) were used to evaluate the inhibitory activities with the most promising analogue 39, which showed the Flt-3/c-Met IC50 values of 2.18/2.61 nM. Structure-activity relationship studies indicated that n-Pr served as R1 group showed a higher preference, and stronger mono-EWGs on the phenyl ring (such as R2 = 4-F) was benefited to the potency.
- Duan, Yongli,Xu, Shan,Xiong, Hehua,Wang, Linxiao,Zhao, Bingbing,Wang, Ping,Wang, Caolin,Peng, Yiqing,Cai, Shifan,Luo, Rong,Zheng, Pengwu,Tang, Qidong
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p. 254 - 259
(2018/01/10)
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- Preparation and application of 2-carbamoyl-4-heteroaromatic pyridine compounds
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The invention provides 2-carbamoyl-4-heteroaromatic pyridine derivatives and pharmaceutically acceptable salts, hydrates, solvates and prodrugs thereof. The substituent groups R1, R2 and Y have definitions in the specification. The invention further relates to compounds with a general formula I having strong effects of inhibiting c-Met kinase, and also relates to an application of the compounds and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof in preparation of medicines for treating diseases caused by abnormal high expression of the c-Met kinase, particularly an application in preparation of medicines for treating and/or preventing cancers.
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- Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety
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A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety were designed, synthesized and evaluated for their biological activities. The target compounds exhibited moderate to high antiproliferative activity against three cancer cell lines (A549, HepG2 and MCF-7) and several compounds (25, 27, 33, 37, 41, 43, 49 and 53) were evaluated for the activity against c-Met kinase. The most promising compound 33 (IC50 c-Met = 2.36 nM) showed excellent activity against A549, HepG2 and MCF-7 cell lines with IC50 values of 0.23 μM, 0.42 μM and 0.21 μM, respectively, which was 1.5–2.1 times of the positive control. Furthermore, compound 33 was evaluated for the activity against Flt3, PDGFR-α PDGFR-β c-Kit, Flt4, ALK and EGFR kinase. Structure activity relationship studies indicated that mono-EWGs (such as R2 = F) at 4-position of moiety C was a key factor in improving the antitumor activity. In addition, further research on compound 33 was mainly including concentration dependence, apoptosis (acridine orange staining), apoptosis result analyzing and molecular docking.
- Tang, Qidong,Duan, Yongli,Xiong, Hehua,Chen, Ting,Xiao, Zhen,Wang, Linxiao,Xiao, Yueyue,Huang, Shunmin,Xiong, Yinhua,Zhu, Wufu,Gong, Ping,Zheng, Pengwu
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p. 201 - 213
(2018/09/18)
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- Preparation and application of 6,7-disubstituted-4-aromatic quinoline compound
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The invention relates to a 6,7-disubstituted-4-aromatic quinoline derivative shown as a general formula I as well as pharmaceutically-acceptable salt, a hydrate, a solvate and pro-drug thereof, wherein substituents R1, X and Y have meanings given in the description. The invention further relates to a compound with a strong effect on inhibiting c-Met kinase shown as the general formula I and further relates to application of the compound and pharmaceutically-acceptable salt, a hydrate, a solvate and pro-drug thereof to preparation of a drug for treating a disease caused by the abnormally-high expression of the c-Met kinase, in particular to application to preparation of a drug for treating and/or preventing a cancer.
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Paragraph 0081; 0101; 0102
(2018/08/03)
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- Pyrrolo-pyridine compound containing naphthyridinone structure and application of pyrrolo-pyridine compound
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The invention discloses a pyrrolo-pyridine compound containing a naphthyridinone structure, a geometric isomer and pharmaceutically acceptable salt, hydrate, solvate or prodrug of the pyrrolo-pyridine compound, and a preparation method of the pyrrolo-pyridine compound. The pyrrolo-pyridine compound containing the naphthyridinone structure, the pharmaceutically acceptable salt, the hydrate or the solvate of the pyrrolo-pyridine compound are used as active components and are mixed with a pharmaceutically acceptable carrier or an excipient to prepare a composition and the composition is prepared into a clinically acceptable preparation. The invention provides application of the compound provided by the invention to preparation of a medicine for treating and/or preventing proliferative diseases, application of the compound to preparation of a medicine for treating and/or preventing cancers, and application of the compound to preparation of a medicine for treating and/or preventing lung cancer, liver cancer, stomach cancer, colon cancer and breast cancer. (A formula (I) is shown in the description.).
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- Synthesis of 2-anilinopyridine-arylpropenone conjugates as tubulin inhibitors and apoptotic inducers
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A series of new (Z)-3-(arylamino)-1-(2-(arylamino)pyridin-3-yl)prop-2-en-1-one conjugates 9a-p were synthesized and evaluated for their cytotoxic activity against some human cancer cell lines. Some of the treated compounds like 9a, 9g and 9j showed significant activity with IC50 values ranging from 0.51 to 1.29 μM. Flow cytometry results revealed that for A549 cells these compounds caused accumulation of cells in the G2/M phase. Interestingly, compound 9a demonstrated a considerable inhibitory effect on tubulin polymerization and showed significant inhibition of tubulin polymerization with an IC50 value of 1.34 μM, whereas nocodazole showed antitubulin activity with an IC50 value 2.64 μM. Further, Hoechst staining and activation of caspase-3 suggested that these conjugates induced cell death by apoptosis. Fluorescence based competitive colchicine binding assay and docking studies suggest that these conjugates 9a and 9g bind to the tubulin perfectly at the colchicine binding site.
- Kamal, Ahmed,Reddy, Vangala Santhosh,Vishnuvardhan,Kumar, G. Bharath,Shaik, Anver Basha,Chourasiya, Sumit S.,Reddy, M. Kashi,Sayeed, Ibrahim Bin,Adiyala, Praveen Reddy,Jain, Nishant
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p. 97367 - 97380
(2015/12/01)
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- RING-FUSED 2-PYRIDONE DERIVATIVES AND HERBICIDES
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Provided are 2-pyridone derivatives which have excellent herbicidal activity and exhibit high safety to useful crops and so on; salts thereof; and herbicides containing same. In more detail, 2-pyridone derivatives represented by general formula [I] or agrochemically acceptable salts thereof, and herbicides containing these compounds are provided. In general formula [I], X1 is an oxygen atom or a sulfur atom; X2, X3, and X4 are to each CH or N(O)m; m is an integer of 0 or 1; R1 is a hydrogen atom, a C1-12 alkyl group, or the like; R2 is a halogen atom, a cyano group, or the like; n is an integer of 0 to 4; R3 is a hydroxyl group, a halogen atom, or the like; A1 is C(R11R12); A2 is C(R13R14) or C═O; A3 is C(R15R16); and R11, R12, R13, R14, R15, and R16 are each independently a hydrogen atom or a C1-6 alkyl group.
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- N-cyanoamidine derivatives as anti-influenza agents
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Antiinfluenza A activity was found in compounds of the formula: STR1 wherein: X is 2-phenylethyl, 2-furanylmethyl, or STR2 where one of R1 and R2 is H and the other is phenylamino; Z is --SCH3 when X is STR3 when X is 2-ph
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- Substituted 1,3-Dihydro-2H-pyrrolopyridin-2-ones as Potential Antiinflammatory Agents
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A series of analogues based on the 1,3-dihydro-2H-pyrrolopyridin-2-one ring system have been synthesized and shown to possess oral antiinflammatory activity in both the reverse passive Arthus reaction (RPAR) pleural cavity assay in rats and in the adjuvant-induced arthritic rat model (AAR).Several members of this series additionally exhibit an inhibitory effect on the in vivo production of prostaglandin- and leukotriene-derived products or arachidonic acid metabolism although these compounds exhibit no significant inhibitory activity against the cyclooxygenase and 5-lipoxygenase enzymes in vitro.Structure-activity relationships in this series are discussed.
- Ting, Pauline C.,Kaminski, James J.,Sherlock, Margaret H.,Tom, Wing C.,Lee, Joe F.,et al.
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p. 2697 - 2706
(2007/10/02)
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