3137-63-1Relevant academic research and scientific papers
Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum
Gellis, Armand,Primas, Nicolas,Hutter, Sébastien,Lanzada, Gilles,Remusat, Vincent,Verhaeghe, Pierre,Vanelle, Patrice,Azas, Nadine
, p. 34 - 44 (2016/05/24)
A DMAP catalyzed synthesis of new 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines was studied, in a view to react 4-chloroquinazolines with poorly nucleophilic alcohols such as benzylic alcohols, via a simple and cheap SNAr reaction ap
A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring
Gellis, Armand,Kieffer, Charline,Primas, Nicolas,Lanzada, Gilles,Giorgi, Michel,Verhaeghe, Pierre,Vanelle, Patrice
, p. 8257 - 8266 (2015/03/03)
We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald-Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the SNAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest.
Synthesis of triazole-linked 2-trichloromethylquinazolines and exploration of their efficacy against P. falciparum
Hamann, Anton R.,De Kock, Carmen,Smith, Peter J.,Van Otterlo, Willem A.L.,Blackie, Margaret A.L.
, p. 231 - 236 (2013/09/23)
Using 2-trichloromethylquinazoline as scaffold, seven novel triazole-linked compounds have been synthesized using CuAAC chemistry. The in vitro biological activity of four of the compounds on the Plasmodium falciparum chloroquine-sensitive strain NF54 was then determined. The compounds which were tested showed moderate activity with 1.45 μM as the lowest inhibitory concentration.
Targeting the human malaria parasite Plasmodium falciparum: In vitro identification of a new antiplasmodial hit in 4-phenoxy-2- trichloromethylquinazoline series
Castera-Ducros, Caroline,Azas, Nadine,Verhaeghe, Pierre,Hutter, Sebastien,Garrigue, Philippe,Dumtre, Aurelien,Mbatchi, Litaty,Laget, Michle,Remusat, Vincent,Sifredi, France,Rault, Sylvain,Rathelot, Pascal,Vanelle, Patrice
experimental part, p. 4184 - 4191 (2011/11/29)
From the promising results we previously obtained in quinazoline series and to complete the evaluation of the in vitro antiplasmodial activity of original 2-trichloromethylquinazolines, we synthesized new quinazolines possessing a variously substituted phenoxy group at position 4 through a simple and efficient two-step-synthesis approach. The studies of their activity toward the multi-resistant W2 Plasmodium falciparum strain and of their cytotoxicity on the human hepatocyte HepG2 cell line highlighted a hit compound (molecule 7) displaying a W2 IC50 value of 1.1 μM and a HepG2 CC50 value of 50 μM, comparable to chloroquine and doxycycline. Structure-activity- and toxicity relationships indicate that the trichloromethyl group plays a key role in the antiplasmodial activity of such chemical scaffold and also that the phenoxy group substitution as a direct influence on the molecules selectivity. Moreover, molecule 7 displays significant specific activity against the Plasmodium genus in comparison with Toxoplasma and does not show any mutagenic property at the Ames test.
Access to original vinylic chlorides in the quinazoline series via a monoelectronic transfer reaction approach
Maillard-Boyer, Martine,Castera-Ducros, Caroline,Verhaeghe, Pierre,Sifredi, France,Rathelot, Pascal,Vanelle, Patrice
scheme or table, p. 2719 - 2729 (2010/07/03)
A series of new quinazoline derivatives bearing a vinylic chloride group on the 2-position was prepared by using a consecutive SRN1 / ERC1 radical strategy. Copyright
QUINAZOLINE DERIVATIVES FOR THE TREATMENT AND PREVENTION OF DIABETES AND OBESITY
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Page/Page column 17, (2008/12/08)
The present invention relates to novel quinazoline derivatives effective in lowering blood glucose level and body weight, and a medicine for treatment and/or prevention of diabetes and/or obesity, which comprises the compound as an active ingredient.
Synthesis and antiplasmodial activity of new 4-aryl-2-trichloromethylquinazolines
Verhaeghe, Pierre,Azas, Nadine,Gasquet, Monique,Hutter, Sebastien,Ducros, Christophe,Laget, Michele,Rault, Sylvain,Rathelot, Pascal,Vanelle, Patrice
, p. 396 - 401 (2008/12/21)
A series of original 4-aryl-substituted 2-trichloromethylquinazoline derivatives was synthesized using a microwave-assisted Suzuki-Miyaura cross-coupling approach. Antiplasmodial activity was evaluated on both chloroquino-resistant and -sensitive Plasmodi
Highly efficient microwave assisted α-trichlorination reaction of α-methylated nitrogen containing heterocycles
Verhaeghe, Pierre,Rathelot, Pascal,Gellis, Armand,Rault, Sylvain,Vanelle, Patrice
, p. 8173 - 8176 (2007/10/03)
A new methodology permitting the chlorination of different α-methylated nitrogen containing heterocycles into N-α-trichloromethylated derivatives is described here. The combination of microwave technology with a PCl5/POCl3 protocol has allowed to reach trichloromethyl derivatives with high yields in a few minutes.
Organic phenyl arsonic acid compounds with potent antileukemic activity
Liu, Xing-Ping,Narla, Rama Krishna,Uckun, Fatih M.
, p. 581 - 583 (2007/10/03)
A series of 12 organic arsonic acid compounds has been synthesized and evaluated against human B-lineage (NALM-6) and T-lineage (MOLT-3) acute lymphoblastic leukemia (ALL) cell lines. The lead compounds 2-trichloromethyl-4-[4′-(4″-phenylazo)phenylarsonic acid]aminoquinazoline (compound 19, PHI-P518; IC50=1.1±0.5 μM against NALM-6 and 2.0±0.8 μM against MOLT-3) and 2-methylthio-4-(2′-phenylarsonic acid)aminopyrimidine (compound 15, PHI-P381; IC50=1.5±0.3 μM against NALM-6 and 2.3±0.5 μM against MOLT-3) exhibited potent antileukemic activity at low micromolar concentrations.
Quinazolines as cyclin dependent kinase inhibitors
Sielecki, Thais M.,Johnson, Tricia L.,Liu, Jie,Muckelbauer, Jodi K.,Grafstrom, Robert H.,Cox, Sarah,Boylan, John,Burton, Catherine R.,Chen, Haiying,Smallwood, Angela,Chang, Chong-Hwan,Boisclair, Michael,Benfield, Pamela A.,Trainor, George L.,Seitz, Steven P.
, p. 1157 - 1160 (2007/10/03)
Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.
