- Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies
-
Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using various tool strains of Mtb suggested a novel mechanism of action. The compounds were bactericidal against replicating Mtb and retained potency against clinical isolates of Mtb. Although selected MmpL3 mutant strains of Mtb showed resistance to these compounds, there was no shift in the minimum inhibitory concentration (MIC) against a mmpL3 hypomorph, suggesting mutations in MmpL3 as a possible resistance mechanism for the compounds but not necessarily as the target. RNA transcriptional profiling and the checkerboard board 2D-MIC assay in the presence of varying concentrations of ferrous salt indicated perturbation of the Fe-homeostasis by the compounds. Structure-activity relationship studies identified potent compounds with good physicochemical properties and in vitro microsomal metabolic stability with moderate selectivity over cytotoxicity against mammalian cell lines.
- Soares De Melo, Candice,Singh, Vinayak,Myrick, Alissa,Simelane, Sandile B.,Taylor, Dale,Brunschwig, Christel,Lawrence, Nina,Schnappinger, Dirk,Engelhart, Curtis A.,Kumar, Anuradha,Parish, Tanya,Su, Qin,Myers, Timothy G.,Boshoff, Helena I. M.,Barry, Clifton E.,Sirgel, Frederick A.,Van Helden, Paul D.,Buchanan, Kirsteen I.,Bayliss, Tracy,Green, Simon R.,Ray, Peter C.,Wyatt, Paul G.,Basarab, Gregory S.,Eyermann, Charles J.,Chibale, Kelly,Ghorpade, Sandeep R.
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p. 719 - 740
(2021/02/03)
-
- Design, synthesis, antifungal activity and 3D-QSAR study of novel pyrazole carboxamide and niacinamide derivatives containing benzimidazole moiety
-
A series of novel pyrazole carboxamide and niacinamide derivatives containing a benzimidazole moiety were designed and synthesized as antifungal candidate agents. All target compounds were characterized by FTIR, 1H NMR, 13C NMR, HRMS and elemental analysis techniques. The structure of compound T1 was further confirmed by single crystal X-ray diffraction analysis. The antifungal activities of the target compounds were evaluated in vitro against four phytopathogenic fungi (namely Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum and Alternaria solani) by the mycelium growth inhibition method. The bioassay results indicated that some of the compounds exhibited good antifungal activity against B. cinerea at 100 μg ML?1 compared to other three fungi. In order to better explore the structure-activity relationship (SAR), the EC50 values of target compounds against B. cinerea were measured and assessed. Subsequently, a 3D quantitative structure-activity relationship (3D-QSAR) study was carried out using the comparative molecular field analysis (CoMFA) technique based on the inhibitory activities of tested compounds against B. cinerea. Molecular modelling results revealed fine predictive ability with cross-validated q2 and non-cross-validated r2 values of 0.578 and 0.850, respectively.
- Si, Wei-Jie,Wang, Xiao-Bin,Chen, Min,Wang, Meng-Qi,Lu, Ai-Min,Yang, Chun-Long
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p. 3000 - 3010
(2019/02/17)
-
- Synthesis, nematicidal activity and docking study of novel chromone derivatives containing substituted pyrazole
-
A series of chromone derivatives containing substituted pyrazole were designed and synthesized. Preliminary bioassays showed that most of the synthesized compounds exhibited good nematicidal activity in vivo against Meloidogyne incognita at 10 mg/L. Among the tested compounds, A10 and A11 exhibited 100% inhibition rates. In addition, the molecular docking results indicated that both compound A10 and A11 interacts with amino acid residue Tyr121, Trp279, Tyr70, Trp84 and Phe330 of AChE via hydrogen bond and π–π stacking. This investigation suggested that the chromone containing substituted pyrazole scaffold could be further optimized to explore novel, high-bioactivity nematicidal leads.
- Li, Wei,Li, Jiuhui,Shen, Hongfeng,Cheng, Jiagao,Li, Zhong,Xu, Xiaoyong
-
supporting information
p. 911 - 914
(2017/11/01)
-
- Design, synthesis and biological evaluation of 1H-pyrazole-5-carboxamide derivatives as potential fungicidal and insecticidal agents
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A series of novel 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety were designed and synthesized by a facile method, and their structures were characterized by 1H NMR, mass spectrometry and elemental analysis. Bioassay results showed that most of the title compounds showed potent fungicidal activities against Erysiphe graminis and insecticidal activity against Aphis fabae. Especially, compound 9b has EC50 values of 3.04 mg/L against Erysiphe graminis, of which the fungicidal activity is better than that of the commercial fungicide Thifluzamide and Azoxystrobinare; compound 9l has LC50 values of 3.81 mg/L against Aphis fabae, which was comparable with the commercial insecticide Tolfenpyrad. It is suggested that 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety could be considered as a precursor structure for further design of pesticides. Graphical Abstract: A series of novel 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety were designed and synthesized by a facile method, and their structures were characterized by 1H NMR, mass spectrometry and elemental analysis. Bioassay results showed that most of the title compounds showed potent fungicidal activities against Erysiphe graminis and insecticidal activity against Aphis fabae. Especially, compound 9b has EC50 values of 3.04 mg/L against Erysiphe graminis, of which the fungicidal activity is better than that of the commercial fungicide Thifluzamide and Azoxystrobinare; compound 9l has LC50 values of 3.81 mg/L against Aphis fabae, which was comparable with the commercial insecticide Tolfenpyrad. It is suggested that 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety could be considered as a precursor structure for further design of pesticides.[Figure not available: see fulltext.]
- Huang, Danling,Huang, Mingzhi,Liu, Weidong,Liu, Aiping,Liu, Xingping,Chen, Xiaoyang,Pei, Hui,Sun, Jiong,Yin, Dulin,Wang, Xiaoguang
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p. 2053 - 2061
(2017/09/30)
-
- Synthesis and insecticidal activities of novel 1H-pyrazole-5-carboxylic acid derivatives
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Fourteen 1H-pyrazole-5-carboxylic acid derivatives containing oxazole and thiazole rings were synthesized and characterized by 1H NMR, mass spectrometry and elemental analysis. Most target compounds were obtained in overall yields in the range of 30-50%. The insecticidal activities of these new compounds against Aphis fabae were evaluated. The bioassays' results indicate that some of these compounds exhibit good activities, especially compound 7h which shows 85.7% mortality against A. fabae at a concentration of 12.5 mg/L. This activity is comparable to that of the commercial insecticide imidacloprid.
- Huang, Danling,Liu, Aiping,Liu, Weidong,Liu, Xingping,Ren, Yeguo,Zheng, Xi,Pei, Hui,Xiang, Jun,Huang, Mingzhi,Wang, Xiaoguang
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p. 455 - 460
(2017/12/18)
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- Design, Synthesis, and Acaricidal Activities of Novel Pyrazole Acrylonitrile Compounds
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Using cyenopyrafen as the lead compound, a series of novel pyrazole acrylonitrile compounds were designed and synthesized via the reaction of butylphenylacetonitrile with the corresponding (substituted pyrazol-5-yl) methanone of pyrethroid alcohols in the presence of potassium tert-butoxide. These compounds showed prominent acaricidal activity against Tetranchus urticae. In particular, IIf, IIh, IIo, and IIp displayed excellent activities, which the median lethal concentrations were all lower 0.4 mg/L. In addition, the structure-activity relationship for the target compounds was discussed.
- Huang, Danling,Huang, Mingzhi,Liu, Aiping,Liu, Xingping,Liu, Weidong,Chen, Xiaoyang,Xue, Hansong,Sun, Jiong,Yin, Dulin,Wang, Xiaoguang
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p. 1121 - 1128
(2017/03/27)
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- Pyrazole amide compound, and preparation method and application thereof
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The invention discloses a pyrazole amide compound represented by the formula (I), and a preparation method and an application thereof, wherein R, R1, R2 and W have the definitions indicated in the specification. The compound represented by the formula (I) has bactericidal, insecticidal or acaricidal biological activities, and specially has quite high activity on pathogenic bacteria such as sphaerotheca fuliginea, botrytis cinerea, melampsora lini and the like.
- -
-
Paragraph 0101-0103
(2017/06/02)
-
- Preparation method of tolfenpyrad impurity
-
The invention discloses a preparation method of N-[4-(4-methylphenoxy)benzyl]-1,3,4-trimethyl-5-pyrazole-carboxamide disclosed as a chemical structural formula I. In methylation reaction for preparing ethyl 1,3-dimethyl-5-pyrazole formate, dimethyl carbonate is adopted as a methylating agent; cesium carbonate is adopted as a catalyst; in the process of preparing ethyl 1,3,4-trimethyl-5-pyrazole formate, the ethyl 1,3-dimethyl-5-pyrazole formate is subjected to chloromethylation and catalytic hydrogenolysis to obtain the ethyl 1,3,4-trimethyl-5-pyrazole formate; and in acyl-chlorination reaction of 1,3,4-trimethyl-5-pyrazole formic acid, triphosgene is used as an acyl-chlorination agent, which is green and environment-friendly.
- -
-
Paragraph 0019; 0020; 0021
(2017/10/13)
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- Design, synthesis and biological activity of novel substituted pyrazole amide derivatives targeting EcR/USP receptor
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In order to discover highly active ecdysone analogs, a series of new substituted pyrazole amide derivatives were obtained using structure-guided optimization method and further screened for their insecticidal activities, in the basis of the core structures of the two active compounds N-(3-methoxyphenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6e) and N-(4-(tert-butyl)phenyl)-3-(tert-butyl)-1-phenyl-1H-pyrazole-5-carboxamide (6i), previously presented by us. The chemical structures of the title compounds were identified by spectral analyses. The preliminary bioassay results indicated that one among the synthesized pyrazole derivatives, compound 34, endowed with good activity against Mythimna Separata at 10 mg/L, which was equal to that displayed by the positive control tebufenozide. In addition, examples of molecular docking and molecular dynamics studies demonstrated that 34 may be the potential inhibitor to EcR and its docking conformation was similar to that of tebufenozide. In addition, increasing the hydrophobic effect and considering the suitable bulk effect on pyrazole ring are beneficial to the inhibiting activity to EcR and activity in vivo.
- Deng, Xi-Le,Xie, Jin,Li, Yong-Qiang,Yuan, De-Kai,Hu, Xue-Ping,Zhang, Li,Wang, Qing-Min,Chi, Ming,Yang, Xin-Ling
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supporting information
p. 566 - 570
(2016/04/26)
-
- Synthesis and biofilm formation reduction of pyrazole-4-carboxamide derivatives in some Staphylococcus aureus strains
-
The ability of several N-phenyl-1H-pyrazole-4-carboxamide derivatives and other pyrazoles opportunely modified at the positions 3, 4 and 5, to reduce the formation of the biofilm in some Staphylococcus aureus strains (ATCC 29213, ATCC 25923 and ATCC 6538) were investigated. All the tested compounds were able, although to a different extent, to reduce the biofilm formation of the three bacterial strains considered. Among these, the 1-(2,5-dichlorophenyl)-5-methyl-N-phenyl-1H-pyrazole-4-carboxamide 14 resulted as the best inhibitor of biofilm formation showing an IC50ranging from 2.3 to 32 μM, against all the three strains of S. aureus. Compound 14 also shows a good protective effect in vivo by improving the survival of wax moth larva (Galleria mellonella) infected with S. aureus ATCC 29213. These findings indicate that 14d is a potential lead compound for the development of new anti-virulence agents against S. aureus infections.
- Cascioferro, Stella,Maggio, Benedetta,Raffa, Demetrio,Raimondi, Maria Valeria,Cusimano, Maria Grazia,Schillaci, Domenico,Manachini, Barbara,Plescia, Fabiana,Daidone, Giuseppe
-
-
- A new class of phenylhydrazinylidene derivatives as inhibitors of Staphylococcus aureus biofilm formation
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In the struggle against the emergence of the antibiotic resistance, new molecules targeting biofilm formation could be useful as adjuvant of conventional antibiotics. This study focused on a new class of 2-phenylhydrazinylidene derivatives as antivirulence agents. The compound 12e showed interesting activities against biofilm formation of all tested Staphylococcus aureus strains with IC50 ranging from 1.7 to 43 μM; compounds 12f and 13a resulted strong inhibitors of S. aureus ATCC 6538 and ATCC 29213 biofilm formation with IC50 of 0.9 and 0.8 μM, respectively. A preliminary study on the mechanism of action was carried on evaluating the inhibition of sortase A transpeptidase. Compound 12e resulted not to be toxic at 1 mg/ml by using an in vivo model (the wax moth larva model, Galleria mellonella).
- Cascioferro, Stella,Maggio, Benedetta,Raffa, Demetrio,Raimondi, Maria Valeria,Cusimano, Maria Grazia,Schillaci, Domenico,Manachini, Barbara,Leonchiks, Ainars,Daidone, Giuseppe
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p. 870 - 878
(2016/04/20)
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- Synthesis, characterization and antibacterial activity of novel Schiff bases
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The present work describes the synthesis of novel Schiff bases (8.1-8.9) in five steps from diethyl oxalate and acetone as starting materials. Condensation of ethyl 1-(2-aminophenyl)-5-methyl-1H-pyrazole-3-carboxylate (6) with aromatic and heteroaromatic aldehydes (7.1-7.9) in presence of sodium sulphate at 50 °C in ethanol gave the corresponding imine derivatives (8.1-8.9) in quantitative yields. The structure of these compounds was determined by 1H NMR, mass and IR spectral data. These Schiff's bases were further evaluated for antibacterial activity against the selected Gram-positive and Gram-negative bacteria pathogens. The antibacterial activity data revealed that Schiff base embedded with heteroaromatic ring was found to exhibit good antibacterial activity than the aromatic ring.
- Sreedhar, Pandiri,Srinivas, Gudipati,Raju, Rallabandi Madhusudan
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p. 1603 - 1606
(2016/05/09)
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- COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
- -
-
Paragraph 0078; 0079
(2015/05/05)
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- COMPOUND OF CAMPTOTHECIN AND PREPARATION AND USE THEREOF
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The present disclosure relates to a compound of formula I, a pharmaceutical composition thereof and the use thereof as an anti-tumor drug.
- -
-
Paragraph 0123; 0124
(2015/06/24)
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- NOVEL PYRROLIDINE DERIVED BETA 3 ADRENERGIC RECEPTOR AGONISTS
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The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.
- -
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Page/Page column 52
(2015/04/22)
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- Pyrazole-oxadiazole conjugates: Synthesis, antiproliferative activity and inhibition of tubulin polymerization
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A number of pyrazole-oxadiazole conjugates were synthesized and evaluated for their ability to function as antiproliferative agents on various human cancer cell lines. These conjugates are comprised of pyrazole and oxadiazole scaffolds closely attached to each other without any spacer as two structural classes. The Type I class has a trimethoxy substituent and the type II class has a 3,4-(methylenedioxy) substituent on their A rings. Among these conjugates, 11a, 11d and 11f manifest potent cytotoxicity with IC50values ranging from 1.5 μM to 11.2 μM and inhibit tubulin polymerization with IC50values of 1.3 μM, 3.9 μM and 2.4 μM respectively. The cell cycle assay showed that treatment with these conjugates results in accumulation of cells in the G2/M phase and disrupts the microtubule network. Elucidation of zebrafish embryos revealed that the conjugates cause developmental defects. Molecular docking simulations determined the binding modes of these potent conjugates at the colchicine site of tubulin.
- Kamal, Ahmed,Shaik, Anver Basha,Polepalli, Sowjanya,Santosh Reddy, Vangala,Bharath Kumar,Gupta, Soma,Rama Krishna,Nagabhushana, Ananthamurthy,Mishra, Rakesh K.,Jain, Nishant
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p. 7993 - 8007
(2015/02/18)
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- Concise synthesis of α-(hydroxymethyl) alkyl and aryl vinyl ketones
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2,4-Diketoesters 2 have first been reported as starting materials for the synthesis of a new class of α-hydroxymethyl-α,β-unsaturated ketones 3. Thus, under heterogeneous liquid-liquid medium in the presence of concentrated aqueous potassium carbonate as a base, both aliphatic and aromatic 2,4-dioxoalkanoates 2 react with aqueous formaldehyde to afford the corresponding ketones 3 in fair to good yields. Copyright Taylor & Francis Group, LLC.
- Kraem, Jihene Ben,Amri, Hassen
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p. 110 - 117
(2012/10/30)
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- AGONISTS OF GPR40
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The present invention relates to compounds that have the ability to modulate the activity of GPR40 and are there-fore useful in the treatment of GPR40 related disorders. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders related to GPR40 activity.
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Page/Page column 97-98
(2012/02/05)
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- New analogues of (E)-β-farnesene with insecticidal activity and binding affinity to aphid odorant-binding proteins
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(E)-β-Farnesene is a strong and efficient alarm pheromone in most aphid species. However, applications in agriculture are prevented by its relatively high volatility, its susceptibility to oxidation and its complex and expensive synthesis. To develop novel compounds for aphid control, we have designed and synthesized analogues of (E)-β-farnesene, containing a pyrazole moiety present in several insecticides. Their structures have been confirmed by 1H NMR, elemental analysis, high-resolution mass spectroscopy and IR. Binding activities to three odorant-binding proteins (OBPs) of the pea aphid Acythosiphon pisum have been evaluated and correlated with their structures with reference to (E)-β-farnesene. Several derivatives were shown both to bind to A. pisum OBPs with a specificity similar to that of (E)-β-farnesene and to have aphicidal activity comparable to that of thiacloprid, a commercial insecticide. The compounds synthesized in this work represent new potential agents for aphid population control and provide guidelines to design analogues of (E)-β-farnesene endowed with both insecticidal and repellent activity for aphids.
- Sun, Yufeng,Qiao, Huili,Ling, Yun,Yang, Shaoxiang,Rui, Changhui,Pelosi, Paolo,Yang, Xinling
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experimental part
p. 2456 - 2461
(2011/10/12)
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- Microwave-assisted synthesis of tetrazolyl pyrazole amides
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A rapid and efficient microwave-assisted synthesis N-(1H-tetrazol-5-yl) derivatives of 3-methyl-1-phenyl-1H-pyrazole- 5-carboxamide is described. These tetrazole pyrazole amides have interesting bacteriocidal, pesticidal, herbicidal and antimicrobial activities. They were identified by IR and 1H NMR elemental analyses. The target compounds were obtained in a shorter reaction time compared to conventional heating methods.
- Hu, Jun,Wang, Jikui,Zhou, Taoyu,Xu, Yanhua
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scheme or table
p. 525 - 527
(2011/11/30)
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- Phosphate ester derivatives of homocamptothecin: Synthesis, solution stabilities and antitumor activities
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Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0.
- Miao, Zhenyuan,Zhang, Jing,You, Liang,Wang, Juan,Sheng, Chunquan,Yao, Jiangzhong,Zhang, Wannian,Feng, Hao,Guo, Wei,Zhou, Lei,Liu, Wenfeng,Zhu, Linjian,Cheng, Pengfei,Che, Xiaoying,Wang, Wenya,Luo, Chuan,Xu, Yulan,Dong, Guoqiang
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scheme or table
p. 3140 - 3146
(2010/07/06)
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- Approach to the library of fused pyridine-4-carboxylic acids by combes-type reaction of acyl pyruvates and electron-rich amino heterocycles
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A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.
- Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Plaskon, Andrey S.,Dmytriv, Yuri V.,Grygorenko, Oleksandr O.,Mykhailiuk, Pavel K.,Krotko, Dmitriy G.,Pushechnikov, Alexei,Tolmachev, Andrey A.
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scheme or table
p. 510 - 517
(2010/09/05)
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- Regioselective synthesis of 4-acyl-1-hydroxy-2,3-benzodioates by chelation-controlled [3+3] annulation of 3-acyl-4-ethoxy-2-oxo-3-enoates with 1,3-bis(trimethylsilyloxy)-1,3-butadienes
-
4-Acyl-1-hydroxy-2,3-benzodioates were regioselectively prepared by chelation-controlled [3+3] cyclization of 1,3-bis(trimethylsilyloxy)-1,3- butadienes with 3-acyl-4-ethoxy-2-oxo-3-enoates.
- Riahi, Abdolmajid,Shkoor, Mohanad,Fatunsin, Olumide,Khera, Rasheed Ahmad,Fischer, Christine,Langer, Peter
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supporting information; experimental part
p. 4248 - 4251
(2009/12/06)
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- Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a
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A series of 5-alkyl pyrazole-3-carboxylic acids were prepared and found to act as potent and selective agonists of the human GPCR, GPR109a, the high affinity nicotinic acid receptor. No activity was observed at the highly homologous low affinity niacin receptor, GPR109b. A further series of 4-fluoro-5-alkyl pyrazole-3-carboxylic acids were shown to display similar potency. One example from the series was shown to have improved properties in vivo compared to niacin.
- Skinner, Philip J.,Cherrier, Martin C.,Webb, Peter J.,Shin, Young-Jun,Gharbaoui, Tawfik,Lindstrom, Andrew,Hong, Vu,Tamura, Susan Y.,Dang, Huong T.,Pride, Cameron C.,Chen, Ruoping,Richman, Jeremy G.,Connolly, Daniel T.,Semple, Graeme
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p. 5620 - 5623
(2008/04/02)
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- Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors
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Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.
- Ghosh, Arun K.,Xi, Kai,Ratia, Kiira,Santarsiero, Bernard D.,Fu, Wentao,Harcourt, Brian H.,Rota, Paul A.,Baker, Susan C.,Johnson, Michael E.,Mesecar, Andrew D.
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p. 6767 - 6771
(2007/10/03)
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- Discovery of α,γ-Diketo Acids as Potent Selective and Reversible Inhibitors of Hepatitis C Virus NS5b RNA-Dependent RNA Polymerase
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α,γ-Diketo acids (DKA) were discovered from screening as selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. The diketo acid moiety proved essential for activity, while substitution on the γ position was necessary for selectivity and potency. Optimization led to the identification of a DKA inhibitor of NS5b polymerase with IC50 = 45 nM, one of the most potent HCV NS5b polymerase inhibitors reported.
- Summa, Vincenzo,Petrocchi, Alessia,Pace, Paola,Matassa, Victor G.,De Francesco, Raffaele,Altamura, Sergio,Tomei, Licia,Koch, Uwe,Neuner, Philippe
-
-
- Synthesis of Highly Functionalized Cyclobutene Derivatives
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Protonation of the reactive 1:1 intermediates produced in the reaction between triphenyl-phosphine and dialkyl acetylenedicarboxylates with CH-acids, such as ethyl 2,4-dioxo-hexanoate and ethyl 2,4-dioxo-5-methylhexanoate, lead to vinyltriphenylphosphonium salts, which undergo an intra-molecular Wittig reaction to produce cyclobutene derivatives in fairly high yields.
- Yavari, Issa,Bayat, Mohammad
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p. 1221 - 1227
(2007/10/03)
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- Process for the preparation of tetrahydroindolizines
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Described is a process for the preparation of Compound (7) in accordance with the following reaction scheme by reacting Compound (5) with ethylene glycol in a solvent in the presence of a Lewis acid, thereby obtaining Compound (6), and then reacting the resulting compound with a carbonate diester in a solvent in the presence of a metal alkoxide (R1, R6each represents a C1-6alkyl group or the like and R5represents H or C1-5alkyl group). Compound (7) so obtained is useful as an intermediate for camptothecins useful as antitumor agents.
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-
-
- Process for the preparation of tetrahydro-indolizines
-
Described is a process for the preparation of Compound (7) in accordance with the following reaction scheme by reacting Compound (5) with ethylene glycol in a solvent in the presence of a Lewis acid, thereby obtaining Compound (6), and then reacting the resulting compound with a carbonate diester in a solvent in the presence of a metal alkoxide (R1, R6 each represents a C1-6 alkyl group or the like and R5 represents H or C1-5 alkyl group). Compound (7) so obtained is useful as an intermediate for camptothecins useful as antitumor agents.
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-
- Camptothecin analogs as potent inhibitors of topoisomerase I
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A method for synthesizing camptothecin and camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase.I and show antileukemic and anti-tumor activity.
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-
- Camptothecin analogs as potent inhibitors of topoisomerase I
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A method for synthesizing camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase.
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-
-
- Camptothecin analogs as potent inhibitors of topoisomerase I
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A method for synthesizing camptothecin and camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase I and show anti-leukemic and anti-tumor activity.
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-
- Synthesis of camptothecin and analogs thereof
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A method for synthesizing camptothecin and camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase I and show anti-leukemic and anti-tumor activity.
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-
- A CONVENIENT SYNTHESIS OF γ-OXO-ACRYLATES
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Ethyl 2,4-dioxoalkanoates react chemoselectively with pyrrolidine acetate at the more electrophilic C-2 carbonyl, producing enaminone esters which on reduction with NaCNBH3 followed by pyrrolidine elimination, were transformed into γ-oxo-acrylates.
- Manfredini, S.,Simoni, D.,Zanirato, V.,Casolari, A.
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p. 3997 - 4000
(2007/10/02)
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