- A convenient synthesis of 4-aryl-1,8-naphthyridin-2(1H)-ones by the Suzuki coupling
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4-Halo-1,8-naphthyridin-2(1H)-ones readily available from 2-chloronicotinic acid were subjected to the Suzuki coupling reaction with arylboronic acids to give a diversity of 4-aryl-1,8-naphthyridin-2(1H)-ones.
- Ban, Hitoshi,Muraoka, Masami,Ohashi, Naohito
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- 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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supporting information
(2020/12/25)
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- Design, synthesis and biological evaluation of anthranilamide derivatives as potent SMO inhibitors
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A series of anthranilamide derivatives were designed and synthesized as novel smoothened (SMO) inhibitors based on the SMO inhibitor taladegib (LY2940680), which can also inhibit the SMO-D473H mutant, via a ring-opening strategy. The phthalazine core in LY2940680 was replaced with anthranilamide, which retained the inhibitory activity towards the hedgehog (Hh) signaling pathway as evidenced by a dual luciferase reporter gene assay. Compound 12a displayed the best inhibitory activity against the Hh signaling pathway with IC50 value of 34.09 nM, and exhibited better proliferation inhibitory activity towards the Daoy cell line (IC50 = 0.48 μM) than LY2940680 (IC50 = 0.79 μM).
- Ji, Dezhong,Xu, Yungen,Zhang, Jing-Jing,Zhang, Wanwan
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- Nicotinic acid ester compound and preparation method and application thereof
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The invention discloses a nicotinic acid ester compound shown as a general formula (I) (please see the specifications for the general formula). All substituent groups are seen in a specification. Theinvention further discloses a preparation method and app
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Paragraph 0076-0081
(2020/01/08)
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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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Paragraph 0088; 0089
(2018/04/02)
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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; 0099; 0100
(2018/08/03)
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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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- 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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- 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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Paragraph 0097; 0098
(2017/07/21)
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- Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia
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Homeobox transcription factor A9 (HoxA9) is overexpressed in 70% of patients diagnosed with acute myeloid leukemia (AML), whereas only a small subset of AML patients respond to current differentiation therapies. A cell line overexpressing HoxA9 was derive
- Lewis, Timothy A.,Sykes, David B.,Law, Jason M.,Mu?oz, Benito,Rustiguel, Joane K.,Nonato, Maria Cristina,Scadden, David T.,Schreiber, Stuart L.
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supporting information
p. 1112 - 1117
(2016/12/16)
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- TRPA1 MODULATORS
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Compounds of formula la or lb, wherein R1 and R2 are as defined in the claims, exhibit TRPA1 activity and are thus useful as TRPA1 modulators.
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Page/Page column 25
(2015/12/08)
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- Synthesis and anticancer potential of benzothiazole linked phenylpyridopyrimidinones and their diones as mitochondrial apoptotic inducers
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A series of benzothiazole linked phenylpyridopyrimidinones (8a-g) and their diones (9a-g) have been designed, synthesized and evaluated for their anticancer activity. Among the series one of the conjugate 8b showed significant cytotoxicity against human cervical cancer cell line ME-180 with IC 50 value of 4.01 μM. This compound was tested on the cell cycle perturbations and DNA damage. Flow cytometry analysis revealed that the compound 8b showed drastic cell cycle perturbations due to concentration dependent increase in the sub-G0 phase in ME-180 cell line. DNA fragmentation and Hoechst staining reveals that this compound induced cell death by apoptosis. Further caspase-3 and loss of mitochondrial membrane potential suggested that the compound induces cell death by apoptosis.
- Kamal, ?hmed,Ashraf, Md.,Vishnu Vardhan,Faazil, Shaikh,Nayak, V. Lakshma
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supporting information
p. 147 - 151
(2014/01/17)
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- 2-ANILINO NICOTINYL LINKED 2-AMINO BENZOTHIAZOLE CONJUGATES AND PROCESS FOR THE PREPARATION THEREOF
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The present invention provides compounds of general formula A useful as potential anticancer agents against human cancer cell lines and apoptosis inducers. The present invention further provides a process for the preparation of 2-anilino nicotinyl linked 2-amino benzothiazole conjugates of general formula (A), wherein R1═H or CI; R2═H, OCH3 or F; R3═H, OCH3, F or CI; R4═H, OCH3 or F and X═OCH3, F or N02.
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- PYRIDOPYRIMIDINONE INHIBITORS OF KINASES
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The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein R1, R2, R3, R4, and B are defined in the description. The present invention relates also to compositions cont
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Paragraph 0540
(2013/09/12)
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- 2-ANILINO NICOTINYL LINKED 2-AMINO BENZOTHIAZOLE CONJUGATES AND PROCESS FOR THE PREPARATION THEREOF
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The present invention provides compounds of general formula A useful as potential anticancer agents against human cancer cell lines and apoptosis inducers. The present invention further provides a process for the preparation of 2-anilino nicotinyl linked 2-amino benzothiazole conjugates of general formula (A), wherein R1 = H or CI; R2 = H, OCH3 or F; R3 = H, OCH3, F or CI; R4=H, OCH3 or F and X= OCH3, F or N02.
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- Synthesis of 2-(arylamino)nicotinic acids in high-temperature water
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In hydrothermal reactions at 150-180 °C, 2-(arylamino)nicotinic acids were synthesized by amination of 2-chloronicotinic acid with aromatic amine derivatives, with potassium carbonate as base. The procedure is efficient, environmentally friendly, and practical, with moderate to excellent yields (up to 98%). Springer Science+Business Media B.V. 2012.
- Li, Zhenghua,Xiao, Shangyou,Liang, Ronghui,Xia, Zhining
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p. 1691 - 1697
(2012/10/29)
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- 2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers
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A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a-n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a-j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h-k, 4n, and
- Kamal, Ahmed,Srikanth,Naseer Ahmed Khan,Ashraf, Md.,Kashi Reddy,Sultana, Farheen,Kaur, Tandeep,Chashoo, Gousia,Suri, Nitasha,Sehar, Irum,Wani, Zahoor A.,Saxena, Arpita,Sharma, Parduman R.,Bhushan, Shashi,Mondhe, Dilip M.,Saxena, Ajit K.
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experimental part
p. 7136 - 7150
(2012/01/02)
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- Catalyst-free amination of 2-chloronicotinic acid in water under microwave irradiation
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A simple, efficient and environmental friendly method for the synthesis of 2-arylaminonicotinic acids derivatives by reacting 2-chloronicotinic acid with anilines with potassium carbonate as the base and water as the media under microwave irradiation is described. The synthesis of 2-arylaminonicotinic acids is important because they are nonsteroidal anti-inflammatory drugs.
- Li, Zheng-Hua,Xia, Zhi-Ning,Chen, Gang
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experimental part
p. 709 - 711
(2012/03/09)
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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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Page/Page column 71
(2011/12/12)
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- Improvement of the Ullmann's condensation method for the synthesis of 2-anilinonicotinic acids
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Several 2-anilinonicotinic acid derivatives were prepared under the Ullmann's reaction conditions by condensation of 2-chloronicotinic acid and various substituted anilines. Improvement of the procedure based on the effect of the catalyst and that of the
- Misbahi, Houria,Brouant, Pierre,Barbe, Jacques
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p. 335 - 336
(2007/10/03)
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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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- Ring Transformation Reactions of 1-Substituted 2(1H)-Pyrimidinones and Related Compounds with Active Methylene Compounds
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1-Substituted 2(1H)-pyrimidinones (I) underwent ring transformation with malononitrile and ethyl acetoacetate in the presence of sodium ethoxide to give 2-amino-3-pyridinecarbonitriles (II-VII) and N-(substituted)amino-3-pyridinecarboxylic acids (XIV and XV), respectively.Further, I reacted with ethyl cyanoacetate, dialkyl malonate, or ethyl benzoylacetate to give pyridine derivatives (VIII-XIII) bearing various functional groups at the C-3 position.The reaction of 1-substituted 2(1H)-pyrimidinethiones and 4,6-dimethyl-1-phenyl-2-phenylimino-1,2-dihydropyrimidine with active methylene compounds is also discussed.Keywords - ring transformation; 1-substituted 2(1H)-pyrimidinone; 1-substituted 2(1H)-pyrimidinethione; active methylene compound; sodium alkoxide; pyridine derivative.
- Katoh, Akira,Omote, Yoshimori,Kashima, Choji
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p. 2942 - 2946
(2007/10/02)
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