- Novel sulfonamide derivatives carrying a biologically active 3,4-dimethoxyphenyl moiety as VEGFR-2 inhibitors
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Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR, 1H-NMR, 13C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug. Among the tested derivatives, compounds 4, 10, 16, and 19 showed good activity as cytotoxic agents. The most active derivatives were evaluated for their ability to inhibit vascular endothelial growth factor receptor (VEGFR)-2. Compounds Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-benzenesulfonamide 10 and Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(1H-indazol-6-yl)-benzenesulfonamide 19 were more active as VEGFR-2 inhibitors than dasatinib. Molecular docking of the most active derivatives on the active site of VEGFR-2 revealed that compound 19 exhibited favorable and promising results.
- Ghorab, Mostafa Mohammed,Alsaid, Mansour Sulaiman,Nissan, Yassin Mohammed,Ashour, Abdelkader Elbadawy,Al-Mishari, Abdullah Abdulalrahman,Kumar, Ashok,Ahmed, Sheikh Fayaz
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Read Online
- Pyridine-ureas as potential anticancer agents: Synthesis and in vitro biological evaluation
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In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a-n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC50 = 0.22 and 1.88 μM after 48 h treatment; 0.11 and 0.80 μM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC50 = 1.93 μM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l-n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12-78%, GI for 8e; 15-91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC50 values 5.0 ± 1.91 and 3.93 ± 0.73 μM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.
- El-Naggar, Mohamed,Almahli, Hadia,Ibrahim, Hany S.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.
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Read Online
- DDQ-mediated oxidative coupling reaction of N,N-dimethyl enaminones with cycloheptatriene
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An efficient 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated oxidative coupling reaction of N,N-dimethyl enaminones with cycloheptatriene is developed. It provides a variety of α-alkenylated 1,3-dicarbonyl compounds in moderate to good yields under mild conditions.
- Cheng, Dongping,Yu, Chenze,Pu, Yueqi,Xu, Xiaoliang
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supporting information
(2022/01/23)
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- Design, synthesis, in silico, and in vitro evaluation of 3-phenylpyrazole acetamide derivatives as antimycobacterial agents
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Mycobacterium tuberculosis (Mtb) is one of the most dangerous pathogens affecting immunocompetent and immunocompromised patients worldwide. Novel molecules, which are efficient and can reduce the duration of therapy against drug-resistant strains, are an
- Gaikwad, Nikhil B.,Nirmale, Krishna,Sahoo, Santosh K.,Ahmad, Mohammad N.,Kaul, Grace,Shukla, Manjulika,Nanduri, Srinivas,Das Gupta, Arunava,Chopra, Sidharth,Yaddanapudi, Madhavi V.
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- Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
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Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
- Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
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supporting information
p. 3672 - 3690
(2021/08/07)
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- Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines
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By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.
- Huo, Xian-Sen,Jian, Xie-Er,Ou-Yang, Jie,Chen, Lin,Yang, Fang,Lv, Dong-Xin,You, Wen-Wei,Rao, Jin-Jun,Zhao, Pei-Liang
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- Harnessing Stereospecific Z-Enamides through Silver-Free Cp?Rh(III) Catalysis by Using Isoxazoles as Masked Electrophiles
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The stereospecific synthesis of Z-enamides is described in this paper. For the first time, isoxazoles have been employed as electrophiles in C-H functionalization to afford thermodynamically less stable Z-enamides utilizing salicylaldehydes in an atom- and step-economic fashion. The stereochemistry of enamides might originate from the relative disposition of atoms present in isoxazole and the intramolecular hydrogen bonding. The reaction showed excellent scope as several structurally and electronically diverse salicylaldehydes and isoxazoles reacted efficiently.
- Debbarma, Suvankar,Bera, Sourav Sekhar,Maji, Modhu Sudan
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supporting information
p. 835 - 839
(2019/01/26)
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- The use of enaminones and enamines as effective synthons for MSA-catalyzed regioselective synthesis of 1,3,4-tri- And 1,3,4,5-tetrasubstituted pyrazoles
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In the present work, an efficient regioselective synthesis of 1,3,4-tri- and 1,3,4,5-tetrasubstituted pyrazoles via a methanesulfonic acid (MSA)-catalyzed reaction of hydrazones with enaminones or enamines is reported. Mechanistically, the formation of the title compounds involves the [2+3] cycloaddition of hydrazones with enaminones or enamines followed by aromatization with acid and oxygen. This convenient method under mild conditions with various hydrazones, enaminones, and enamines was well-tolerated to afford products in good to excellent yields. Compared with the literature methods, this strategy has advantages such as materials that are available economically, metal-free catalysis, excellent regioselectivity, and high efficiency.
- Duan, Liancheng,Zhou, Hui,Gu, Yucheng,Gong, Ping,Qin, Mingze
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supporting information
p. 16131 - 16137
(2019/11/03)
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- [3+2] Anionic Cycloaddition of Isocyanides to Acyclic Enamines and Enaminones: A New, Simple, and Convenient Method for the Synthesis of 2,4-Disubstituted Pyrroles
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We herein demonstrate a new approach for the synthesis of 2,4-disubstituted pyrroles by [3+2] cycloaddition reaction of isocyanides to the activated double bond of various enamines and enaminones. This process paved the way for the synthesis a series of 2,4-disubstituted pyrroles, which are known to be intermediates in the synthesis of biologically active compounds, in good to excellent yields from simple and commercially available starting materials. The process is carried out efficiently using a strong base, tBuOK, at low temperatures (0 °C). The described method is simple, proceeds in one step, does not require additional catalysts and hence, has a wide scope.
- Bakulev, Vasiliy A.,Efimov, Ilya V.,Luque, Rafael,Matveeva, Maria D.,Voskressensky, Leonid G.
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supporting information
(2020/02/27)
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- Synthesis and in vitro evaluation of piperazinyl-ureido sulfamates as steroid sulfatase inhibitors
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Two new piperazinyl-ureido single ring aryl sulfamate-based inhibitor series were designed against the emerging oncology drug target steroid sulfatase (STS), for which there are existing potent steroidal and non-steroidal agents in clinical trials. 4-(Pip
- Moi, Davide,Foster, Paul A.,Rimmer, Lucy G.,Jaffri, Alisha,Deplano, Alessandro,Balboni, Gianfranco,Onnis, Valentina,Potter, Barry V.L.
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- Enaminone-Derived Pyrazoles with Antimicrobial Activity
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A series of pyrazoles derived from the substituted enaminones were synthesized and were evaluated for antimicrobial activity. All the compounds were characterized by the spectral data and elemental analysis. The synthesized compounds were initially screen
- Bhat, Mashooq Ahmad,Al-Omar, Mohamed A.,Naglah, Ahmed M.,Khan, Abdul Arif,Bonomo, Maria Grazia
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- Rh(III)-Catalyzed Enaminone-Directed C-H Coupling with α-Diazo-α-phosphonoacetate for Reactivity Discovery: Fluoride-Mediated Dephosphonation for C-C Coupling Reactions
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Rh(III)-catalyzed enaminone-directed C-H coupling with α-diazo-α-phosphonoacetate has been used for the identification of fluoride-mediated dephosphonation C-C coupling reactivity for the synthesis of 4-hydroxy-1-naphthoates. Intermolecular C-C coupling of α-phosphonoacetate and benzaldehyde for (E)-selective α,β-unsaturated ester synthesis has also been achieved.
- Song, Chao,Yang, Chen,Zeng, Hua,Zhang, Wenjing,Guo, Shan,Zhu, Jin
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supporting information
p. 3819 - 3823
(2018/07/22)
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- 1-phenyl-3-benzenemethylamido-2-propylene-1-ketone compounds and preparation method and use thereof
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The invention provides 1-phenyl-3-benzenemethylamido-2-propylene-1-ketone compounds and a preparation method and use thereof. The compounds are a series of compounds with brand-new structures, have a very good inhibitory effect on aggregation of A beta protein, meanwhile, can also be used for inhibiting the aggregation of Tau proteins and can be used for developing drugs for treating neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
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Paragraph 0068; 0069; 0070
(2017/08/30)
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- Amberlyst-15 in PEG-400: Green synthesis of 3-benzoyl-5-hydroxy benzofuran and naphtho[1,2-b]furan derivatives at room temperature
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Background: Oxygen heterocycles exhibit diverse biological and pharmacological activities. In particular, benzofurans are available in a wide number of natural products and have drawn considerable attention over the last few years due to their profound physiological and biological properties. The aim of this paper describes a green methodology to synthesize this potent molecule with high selectivity by using ionic resin in PEG at room temperature. Methods: The methodology is very simple and easily accessible at room temperature. It uses low catalyst loadings and is recycled subsequently. In addition, detailed experimental procedure for the selected compounds including the spectral data are provided. Results: Among the various ionic resins attempted, Amberlyst-15 in PEG-400 was the choice of selection for the synthesis of 3-benzoyl-5-hydroxy benzofuran and naphtho[1,2-b]furan derivatives at room temperature in an environmentally friendly method. This catalyst system resulted in excellent yields in short reaction times and high selectivity. Conclusion: We have developed a green highly efficient and environmentally friendly protocol for the facile synthesis of 3-benzoyl-5-hydroxy benzofuran and naphtho[1,2-b]furan derivatives at room temperature in high yields (>90-95%) using nontoxic and inexpensive ion exchange resin Amberlyst-15. The notable advantages of the catalyst approach enables the reactions with high selectivity, short reactions time and excellent yields without generating any waste and was reused.
- Bathula, Surendra Bose,Khagga, Mukkanti,Venkatasubramanian, Hariharakrishnan
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p. 353 - 360
(2017/07/26)
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- Dimethoxyphenyl derivatives, preparation method and composition for anti-inflammatory and skin whitening comprising the same
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The present invention relates to a dimethoxyphenyl derivatives, to a preparation method thereof, and to an anti-inflammatory and skin whitening composition comprising the same, wherein a compound represented by the chemical formula 1 according to the present invention has excellent solubility, is excellent in an effect of inhibiting the activity of NF-andkappa;B transcription factor, and thus may be useful for prevention, improvement or treatment of inflammatory diseases, and has an excellent inhibitory effect on melanin formation due to alpha-melanocyte stimulating hormone (andalpha;-MSH) inhibitory activity, thereby being useful as a cosmetic composition for preventing, improving or treating melanin pigment over-deposition disease and for whitening the skin.COPYRIGHT KIPO 2018
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Paragraph 0233-0234; 0241-0242
(2018/05/03)
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- Co(III)-Catalyzed Enaminone-Directed C-H Amidation for Quinolone Synthesis
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We report herein the development of a Co(III)-catalyzed enaminone-directed C-H amidation method for synthetic access to quinolones, an important heterocyclic scaffold for diverse pharmaceutically active structures. The C-H coupling with dioxazolones and subsequent deacylation of an installed amide group allow consecutive C-N coupling generation of quinolones with wide-ranging compatible substituent patterns.
- Shi, Pengfei,Wang, Lili,Chen, Kehao,Wang, Jie,Zhu, Jin
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supporting information
p. 2418 - 2421
(2017/05/12)
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- Enaminones as Synthons for a Directed C?H Functionalization: RhIII-Catalyzed Synthesis of Naphthalenes
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The use of enaminones as effective synthons for a directed C?H functionalization is reported. Proof-of-concept protocols have been developed for the RhIII-catalyzed synthesis of naphthalenes, based on the coupling of enaminones with either alkynes or α-diazo-β-ketoesters. Two inherently reactive functionalities (hydroxy and aldehyde groups) are integrated into the newly formed cyclic framework and a broad range of substituents are tolerated, rendering target products readily available for further elaboration.
- Zhou, Shuguang,Wang, Jinhu,Wang, Lili,Song, Chao,Chen, Kehao,Zhu, Jin
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supporting information
p. 9384 - 9388
(2016/08/05)
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- Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase
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In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50 = 19.4 ± 2.5 μM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury.
- Deng, Chang-Bo,Li, Juan,Li, Lu-Yi,Sun, Feng-Jie
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supporting information
p. 3195 - 3201
(2016/06/13)
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- Design, synthesis and antitubercular activity of certain nicotinic acid hydrazides
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Three series of 6-Aryl-2-methylnicotinohydrazides 4a-i, N'-Arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M.Tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 μg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.
- Eldehna, Wagdy M.,Fares, Mohamed,Abdel-Aziz, Marwa M,Abdel-Aziz, Hatem A
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p. 8800 - 8815
(2016/09/04)
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- First examples of 2,6-diarylnicotinaldehydes prepared under conventional and microwave conditions
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Enaminoketones undergo unexpected self condensation in acetic acid to produce a wide range of 2,3,6-trisubstituted pyridine derivatives in excellent yields in the presence of NH4OAc. This is the first Letter on the synthesis of 2,6-diarylnicoti
- Shankaraiah,Chandrasekhar,Siva Nagi Reddy,Sabitha, Gowravaram
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p. 842 - 846
(2015/03/04)
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- OXAZOLIDINONE COMPOUNDS AND THEIR USES IN PREPARATION OF ANTIBIOTICS
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The invention belongs to the field of medicaments, and particularly relates to oxazolidinone compounds and their uses in the preparation of antibiotics. A technical problem to be solved by the invention is to provide new oxazolidinone compounds having the structure represented by Formula I. The oxazolidinone compounds of the invention, which are new compounds obtained through numerous screening, have significant antibacterial activity against bacteria such as drug-resistant staphylococcus aureus, fecal coliform bacteria, and streptococcus pneumoniae, while exhibiting low toxicity. The invention provides new options for the development and application of antibiotics.
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Paragraph 0086; 0087; 0088; 0089
(2014/06/24)
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- Facile synthesis of 6-aryl-3-cyanopyridine-2-(1H)-thiones from aryl ketones
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An improved synthesis of 6-aryl-3-cyanopyridine-2-(1H)-thiones utilizing enaminones as starting materials catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) was described. Moreover, a convenient one-pot conversion of aryl ketones to 6-aryl-3-cyanopyridine-2-(1H)-thiones was also developed in moderate to good yields (up to 80%). Copyright Taylor & Francis Group, LLC.
- Zheng, Ren-Lin,Zeng, Xiu-Xiu,He, Hai-Yun,He, Jun,Yang, Sheng-Yong,Yu, Luo-Ting,Yang, Li
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experimental part
p. 1521 - 1531
(2012/04/17)
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- Identification of benzofuran-4,5-diones as novel and selective non-hydroxamic acid, non-peptidomimetic based inhibitors of human peptide deformylase
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Selective inhibitors of human peptide deformylase (HsPDF) are predicted to constitute a new class of antitumor agents. We report the identification of benzofuran-4,5-diones as the first known selective HsPDF inhibitors and we describe their selectivity pr
- Antczak, Christophe,Shum, David,Bassit, Bhramdeo,Frattini, Mark G.,Li, Yueming,Stanchina, Elisa De,Scheinberg, David A.,Djaballah, Hakim
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supporting information; experimental part
p. 4528 - 4532
(2011/09/12)
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- The application of (Z)-3-aryl-3-haloenoic acids to the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)-ones
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Studies directed at the synthesis of (Z)-5-benzylidene-4-arylpyrrol-2(5H)- ones from (Z)-3-aryl-3-haloenoic acids are described. The successful strategy relies on the preparation of (Z)-3-aryl-3-haloenoic acids from acetophenones through the corresponding
- Gupton, John T.,Telang, Nakul,Banner, Edith J.,Kluball, Emily J.,Hall, Kayleigh E.,Finzel, Kara L.,Jia, Xin,Bates, Spencer R.,Welden, R. Scott,Giglio, Benjamin C.,Eaton, James E.,Barelli, Peter J.,Firich, Lauren T.,Stafford, John A.,Coppock, Matthew B.,Worrall, Eric F.,Kanters, Rene P.F.,Keertikar, Kerry,Osterman, Rebecca
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experimental part
p. 9113 - 9122
(2011/01/12)
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- Discovery of a long-acting, peripherally selective inhibitor of catechol- O -methyltransferase
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Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4, 6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to l-Dopa therapy of Parkinson's disease.
- Kiss, László E.,Ferreira, Humberto S.,Torr?o, Leonel,Bonifácio, Maria Jo?o,Palma, P. Nuno,Soares-Da-Silva, Patrício,Learmonth, David A.
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supporting information; experimental part
p. 3396 - 3411
(2010/09/05)
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- BENZOFURAN-4,5-DIONES AS SELECTIVE PEPTIDE DEFORMYLASE INHIBITORS
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The instant invention provides novel benzofuran-4,5-diones and pharmaceutical compositions thereof useful for inhibiting PDF and for treating proliferative and infectious diseases. Compounds may be selective for eukaryotic (e.g., human) PDF or prokaryotic PDF
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Page/Page column 116; 127
(2010/11/18)
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- Novel thienopyridine derivatives as specific anti-hepatocellular carcinoma (HCC) agents: Synthesis, preliminary structure-activity relationships, and in vitro biological evaluation
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Novel thienopyridine derivatives 1b-1r were synthesized, based on a hit compound 1a that was found in a previous cell-based screening of anticancer drugs. Compounds 1a-1r have the following features: (1) their anticancer activity in vitro was first reported by our group. (2) The most potent analog 1g possesses hepatocellular carcinoma (HCC)-specific anticancer activity. It can specifically inhibit the proliferation of the human hepatoma HepG2 cells with an IC50 value of 0.016 μM (compared with doxorubicin as a positive control, whose IC50 was 0.37 μM). It is inactive toward a panel of five different types of human cancer cell lines. (3) Compound 1g remarkably induces G0/G1 arrest and apoptosis in HepG2 cells in vitro at low micromolar concentrations. These results, especially the HCC-specific anticancer activity of 1g, suggest their potential in targeted chemotherapy for HCC.
- Zeng, Xiu-Xiu,Zheng, Ren-Lin,Zhou, Tian,He, Hai-Yun,Liu, Ji-Yan,Zheng, Yu,Tong, Ai-Ping,Xiang, Ming-Li,Song, Xiang-Rong,Yang, Sheng-Yong,Yu, Luo-Ting,Wei, Yu-Quan,Zhao, Ying-Lan,Yang, Li
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supporting information; experimental part
p. 6282 - 6285
(2010/12/18)
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- Toward safer processes for C-C biaryl bond construction: Catalytic direct C-H arylation and tin-free radical coupling in the synthesis of pyrazolophenanthridines
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(Chemical Equation Presented) A series of pyrazolo[1,5-f]phenanthridine derivatives has been efficiently synthesized by a short, straightforward sequence. A tandem amine-exchange/heterocyclization of enaminones was successfully applied to the regioselective preparation of 1,5-diarylpyrazole intermediates with structure resemblance to relevant nonsteroidal anti-inflammatory drugs such as celecoxib or tepoxalin. The final key step, cyclization by intramolecular biaryl bond formation, was accomplished by two alternative methodologies: radical coupling and catalytic direct arylation via C-H activation. The scope and limitations of the two methodologies have been explored and their complementariness has been established. In addition, polymer-supported heterogeneous catalysts have been compared with homogeneous analogues. In the radical process, toxic tin derivatives have been avoided in order to employ environmentally safer protocols.
- Hernandez, Susana,Moreno, Isabel,SanMartin, Raul,Gomez, German,Herrero, Maria Teresa,Dominguez, Esther
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supporting information; experimental part
p. 434 - 441
(2010/03/30)
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- 6-Aryl-pyrazolo[3,4-b]pyridines: Potent inhibitors of glycogen synthase kinase-3 (GSK-3)
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A novel series of 6-aryl-pyrazolo[3,4-b]pyridines has been identified that are potent inhibitors of glycogen synthase kinase-3 (GSK-3).
- Witherington, Jason,Bordas, Vincent,Gaiba, Alessandra,Garton, Neil S.,Naylor, Antoinette,Rawlings, Anthony D.,Slingsby, Brian P.,Smith, David G.,Takle, Andrew K.,Ward, Robert W.
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p. 3055 - 3057
(2007/10/03)
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- Pyrazolo[1,5-a]pyrimidines and imidazo-[1,5-a]pyrimidines
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This disclosure describes substituted pyrazolo[1,5-a]pyrimidines and imidazo[1,5-a]pyrimidines which possess anxiolytic activity.
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