- Semicarbazone derivatives and use thereof
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The invention belongs to the technical field of medicine, and relates to semicarbazone derivatives disclosed as general formula I, and geometrical isomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein the substituent groups M, R1, R2, R and n are defined in the specification. The invention also relates to a method for preparing compounds disclosed as Formula I, a pharmaceutical composition containing the compounds and application of the compounds and pharmaceutical composition in preparing drugs for treating and/or preventing cancers and other hyperplastic diseases.
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Paragraph 0541; 0542; 0543; 0544
(2017/08/14)
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- Palladium-Catalyzed Fluoroalkylative Cyclization of Olefins
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A palladium-catalyzed fluoroalkylative cyclization of olefins with readily available Rf-I reagents to afford the corresponding fluoroalkylated 2,3-dihydrobenzofuran and indolin derivatives with moderate to excellent yields is reported. This novel procedure provides an efficient method for the construction of Csp3-CF2 and C-O/N bonds in one step. A wide range of functional groups are tolerated. It is proposed that a radical/SET (single electron transfer) pathway proceeding via the fluoroalkyl radical may be involved in the catalytic cycle.
- Liao, Jianhua,Fan, Lianfeng,Guo, Wei,Zhang, Zhenming,Li, Jiawei,Zhu, Chuanle,Ren, Yanwei,Wu, Wanqing,Jiang, Huanfeng
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supporting information
p. 1008 - 1011
(2017/03/15)
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- Design, synthesis and biological evaluation of novel 4-phenoxy-6,7-disubstituted quinolines possessing (thio)semicarbazones as c-Met kinase inhibitors
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In continuing our efforts to identify small molecules able to inhibit c-Met kinase, three series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives (23a-w, 26a-d and 30a-d) bearing (thio)semicarbazone scaffold were designed, synthesized and evaluated for their cytotoxicity. The biological data revealed that most compounds exhibited moderate-to-excellent activity against HT-29, MKN-45, A549 cancer cell lines and relative poor potency toward MDA-MB-231 cell as well as hardly any cytotoxicity in normal PBL cell. Eleven compounds were further examined for their inhibitory activity against c-Met kinase and three compounds (23h, 23n and 26a) demonstrated good inhibitory activity. This work resulted in the discovery of a potent c-Met inhibitor 23n, bearing 2-hydroxy-3-allylphenyl group at R2 moiety, as a valuable lead molecule, which possessed remarkable cytotoxicity and high selectivity against A549 and HT-29 cell lines with IC50 values of 11 nM and 27 nM. Besides, it displayed excellent c-Met kinase inhibition on a single-digital nanomolar level (IC50 = 1.54 nM). Meanwhile, the results from preliminarily in vivo study reflected that compound 23n showed promising overall PK profiles, consistent with the efficacy in both MKN-45 and HT-29 tumor xenograft mice model. These results clearly indicated that compound 23n is a potent and highly selective c-Met inhibitor and its favorable in vitro and in vivo profiles warrant further investigation.
- Zhai, Xin,Bao, Guanglong,Wang, Limei,Cheng, Mingke,Zhao, Meng,Zhao, Sijia,Zhou, Hongyang,Gong, Ping
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p. 1331 - 1345
(2016/03/01)
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- Removal of metabolic liabilities enables development of derivatives of procaspase-activating compound 1 (PAC-1) with improved pharmacokinetics
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Procaspase-activating compound 1 (PAC-1) is an o-hydroxy-N-acylhydrazone that induces apoptosis in cancer cells by chelation of labile inhibitory zinc from procaspase-3. PAC-1 has been assessed in a wide variety of cell culture experiments and in vivo models of cancer, with promising results, and a phase 1 clinical trial in cancer patients has been initiated (NCT02355535). For certain applications, however, the in vivo half-life of PAC-1 could be limiting. Thus, with the goal of developing a compound with enhanced metabolic stability, a series of PAC-1 analogues were designed containing modifications that systematically block sites of metabolic vulnerability. Evaluation of the library of compounds identified four potentially superior candidates with comparable anticancer activity in cell culture, enhanced metabolic stability in liver microsomes, and improved tolerability in mice. In head-to-head experiments with PAC-1, pharmacokinetic evaluation in mice demonstrated extended elimination half-lives and greater area under the curve values for each of the four compounds, suggesting them as promising candidates for further development.
- Roth, Howard S.,Botham, Rachel C.,Schmid, Steven C.,Fan, Timothy M.,Dirikolu, Levent,Hergenrother, Paul J.
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p. 4046 - 4065
(2015/05/27)
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- Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate: A facile approach for the synthesis of substituted 2H-chromene-3-carboxylates
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A highly efficient and simple protocol has been developed for the preparation of ethyl 2-oxo-2H-chromene-3-carboxylates 3a-v by the condensation of salicylaldehydes 1a-v with ethyl 4,4,4-trichloro-3-oxobutanoate 2 for the first time. The reaction is proceeding via Knoevenagel pathway followed by a selective addition of the phenolic hydroxyl group to the carbonyl group adjacent to the CCl3 group rather than ester carbonyl due to a strong electron withdrawing effect and produced coumarin derivative 3a with the elimination of CHCl3.
- Sairam, Mudulkar,Saidachary, Gannerla,Raju, Bhimapaka China
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supporting information
p. 1338 - 1343
(2015/03/04)
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- Synthesis and biological evaluation of benzothiazole derivatives bearing the ortho-hydroxy-N-acylhydrazone moiety as potent antitumor agents
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A novel series of benzothiazole derivatives bearing the ortho-hydroxy-N-acylhydrazone moiety were designed, synthesized, and evaluated for their procaspase-3 kinase activation activities and antiproliferative activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN-45, and MDA-MB-231). Most target compounds showed moderate to excellent cytotoxic activity against all five tested cancer lines. The most promising compound 18e (procaspase-3 EC50- 0.31μM) with IC50 values ranging from 0.24 to 0.92 μM against all tested cell lines was 4.24-12.2 times more active than PAC-1 (procaspase-3 EC50 - 0.41 μM). Structure-activity relationship studies indicated that the phenyl group on the 2-hydroxyphenyl ring (moiety A) was critical for pharmacological activity in vitro. In addition, introduction of a benzyloxyl group on moiety A and a mono-electron-withdrawing group at the 4-position of the benzyloxyl group were more favorable for antitumor activity. Moreover, reduction of the electron density in the phenyl ring of the benzyloxy group led to a dramatic decrease in the procaspase-3 kinase activation activity. -
- Ma, Junjie,Zhang, Guangyan,Han, Xiaoqi,Bao, Guanglong,Wang, Lihui,Zhai, Xin,Gong, Ping
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p. 936 - 949
(2015/02/19)
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- The development of catalytic oxovanadium(IV)-containing microspheres for the oxidation of various organosulfur compounds
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The development of poly[allylSB-co-EGDMA] beads containing a tetradentate ligand was achieved via suspension polymerization. The catalyst poly[allylSB-co-EGDMA]-VO was synthesized by reacting VIVOSO 4 with poly[allylSB-co-EGDMA]. XPS
- Ogunlaja, Adeniyi S.,Khene, Samson,Antunes, Edith,Nyokong, Tebello,Torto, Nelson,Tshentu, Zenixole R.
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p. 157 - 167
(2013/07/26)
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- Synthesis of 1-indanonyl oxepanes
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A variety of 1-indanonyl oxepanes with the novel structure of indanonyl oxepanes was prepared from reaction of hydroxybenzaldehydes via a series of reasonable transformations, including the regioselective PhBClmediated allylation (or Claisen rearrangement), one-pot reaction of ring-closing metathesis and the Wittig olefination, hydrogenation, and the Friedel-Crafts intramolecular cyclization. Georg Thieme Verlag Stuttgart . New York.
- Chang, Meng-Yang,Lee, Nien-Chia
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scheme or table
p. 867 - 872
(2012/06/01)
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- SUBSTITUTED HYDRAZIDE COMPOUNDS AND APPLICATION THEREOF
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The invention relates to substituted hydrazide compounds as shown by general formula I, including geometrical isomers, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and use of the same, wherein the substitutents Ar and R having the same meanings as given in the Description. T The invention further relates to the use of compounds of general formula I in the preparation of medicament for the treatment and/or prevention of cancer and other proliferative diseases.
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- SUBSTITUTED HYDRAZIDE COMPOUNDS AND USE THEREOF
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The invention relates to substituted hydrazide compounds as shown by general formula I, including geometrical isomers, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and use of the same, wherein the substitutents Ar and R have the same meanings as given in the Description. The invention further relates to the use of compounds of general formula I in the preparation of medicament for the treatment and/or prevention of cancer and other proliferative diseases.
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- Enantioselective intramolecular formal [2 + 4] annulation of acrylates and α,β-unsaturated imines catalyzed by amino acid derived phosphines
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The first chiral phosphine-catalyzed activation of acrylates for intramolecular formal [2 + 4] reactions with unsaturated imines is described. The catalytic reactions afford N-heterocycles with exceptionally high diastereo- and enantioselectivities. The [2 + 4] products are amenable for further transformations to useful molecules such as chiral piperidines and multicyclic structures.
- Jin, Zhichao,Yang, Ruojie,Du, Yu,Tiwari, Bhoopendra,Ganguly, Rakesh,Chi, Yonggui Robin
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supporting information; experimental part
p. 3226 - 3229
(2012/08/08)
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- DESIGN, SYNTHESIS AND EVALUATION OF PROCASPASE ACTIVATING COMPOUNDS AS PERSONALIZED ANTI-CANCER DRUGS
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Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.
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Page/Page column 31
(2010/08/18)
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- Microwave-assisted zeolite catalyzed claisen rearrangement of allyl aryl ethers under solvent-free conditions
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Claisen rearrangement of allyl aryl ethers has been studied extensively over various zeolites under microwave activation and solvent free conditions at 80°C. Hβ-zeolite is found to be an efficient catalyst for the rearrangement. The reaction gives ω-rearranged product selectively instead of expected further cyclized dihydrobenzofuran derivative.
- Deodhar, Deepak K.,Tipnis, Amol S.,Samant, Shriniwas D
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experimental part
p. 1552 - 1555
(2011/02/23)
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- Diels-Alder cycloaddition and ring-closing metathesis: A versatile, stereoselective, and general route to embellished bridged bicyclic systems, carbocyclic framework of secoatisanes, and homologues
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(Chemical Equation Presented) A general and stereoselective methodology for the synthesis of bridged bicyclic octenones having various types of alkenyl chains and a tricyclic framework of secoatisanes and higher analogues is reported. In situ generation and cycloaddition of 2-allyl-6,6- spiroepoxycyclohexadienones with ethyl acrylate gave bicyclo[2.2.2]octanes having an allyl group at the bridgehead and other chemically distinguishable functionality in a regio- and stereoselective fashion. Selective manipulation of adducts led to the introduction of other olefinic chain of variable lengths at the carbon adjacent to the bridge head. Ring-closing metathesis in bicyclooctanes having olefin tethers provided an efficient route to tricyclic systems having bicyclo[2.2.2]octane framework having spiro-fused six-, seven-, and eight-membered rings.
- Singh, Vishwakarma,Sahu, Pramod K.,Sahu, Bharat C.,Mobin, Shaikh M.
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scheme or table
p. 6092 - 6104
(2009/12/26)
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- Structure-activity relationship studies on ortho-substituted cinnamic acids, a new class of selective EP3 antagonists
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A series of novel ortho-substituted cinnamic acids have been synthesized, and their binding activity and selectivity on the four prostaglandin E 2 receptors evaluated. Many of them are very potent and selective EP3 antagonists (Ki 3-10 nM), while compound 9 is a very good and selective EP2 agonist (Ki 8 nM). The biological profile of the EP2 agonist 9 in vivo and the metabolic profile of selected EP3 antagonists are also reported.
- Belley, Michel,Gallant, Michel,Roy, Bruno,Houde, Karine,Lachance, Nicolas,Labelle, Marc,Trimble, Laird A.,Chauret, Nathalie,Li, Chun,Sawyer, Nicole,Tremblay, Nathalie,Lamontagne, Sonia,Carriere, Marie-Claude,Denis, Danielle,Greig, Gillian M.,Slipetz, Deborah,Metters, Kathleen M.,Gordon, Robert,Chan, Chi Chung,Zamboni, Robert J.
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p. 527 - 530
(2007/10/03)
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- An isomerization-ring-closing metathesis strategy for the synthesis of substituted benzofurans
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Twelve substituted benzofurans were synthesized from their corresponding substituted 1-allyl-2-allyloxybenzenes using ruthenium-mediated C- and O-allyl isomerization followed by ring-closing metathesis.
- Van Otterlo, Willem A.L.,Morgans, Garreth L.,Madeley, Lee G.,Kuzvidza, Samuel,Moleele, Simon S.,Thornton, Natalie,De Koning, Charles B.
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p. 7746 - 7755
(2007/10/03)
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- Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes
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Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.
- Van Otterlo, Willem A.L.,Ngidi, E. Lindani,Kuzvidza, Samuel,Morgans, Garreth L.,Moleele, Simon S.,De Koning, Charles B.
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p. 9996 - 10006
(2007/10/03)
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- Soft drugs. 12. Design, synthesis, and evaluation of soft bufuralol analogues
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In the search for more potent but still short-acting β-blockers (BB), the methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, 2-(1-adamantyl)ethyl, and methylthiomethyl esters of the acidic inactive metabolite of bufuralol were synthesized based on the 'ina
- Hwang, Sung-Kwan,Juhasz, Attila,Yoon, Sung-Hwa,Bodor, Nicholas
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p. 1525 - 1532
(2007/10/03)
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- Synthesis and in vitro cytotoxicity of a series of 3-aminoflavones
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To further understand the molecular requirements for the antiproliferative activity of flavonoids, a series of 3-aminoflavones and some of their derivatives were prepared and evaluated using L1210 murine leukemia. Our novel five-step synthetic approach required easily available substituted aromatic aldehydes as starting materials and proved more convenient and more general than previously reported methods. Our results in the 3-aminoflavones series indicated that the 4'-methoxy group is important for cytotoxic activity. Moreover, for the flavone-8-acetic analogs, a marked increase in potency was observed with the addition of a 3-amino or a 3-nitro group. Methoxy groups on the 6 and 7 positions of flavonoids (as in cirsiliol) also appear to be important for antiproliferative activity. These results are essential for the further understanding of the critical molecular requirements that lead to antiproliferative properties in the flavonoid series.
- Dauzonne,Folleas,Martinez,Chabot
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- Synthesis of the 3-aminoflavone-8-acetic acid
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The synthesis of the so far unknown 3-amino-4-oxo-2-phenyl-4H-1-benzopyran-8-acetic acid (3-aminoflavone-8-acetic acid) starting from 2-hydroxy-3-(prop-2-ene)benzaldehyde and (Z)-(2-chloro-2-nitorethenyl)benzene is described.
- Dauzonne, Daniel,Martinez, Laetitia
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p. 1845 - 1848
(2007/10/02)
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