- Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum
-
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
- Gellis, Armand,Primas, Nicolas,Hutter, Sébastien,Lanzada, Gilles,Remusat, Vincent,Verhaeghe, Pierre,Vanelle, Patrice,Azas, Nadine
-
-
- A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring
-
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.
- Gellis, Armand,Kieffer, Charline,Primas, Nicolas,Lanzada, Gilles,Giorgi, Michel,Verhaeghe, Pierre,Vanelle, Patrice
-
p. 8257 - 8266
(2015/03/03)
-
- Synthesis of triazole-linked 2-trichloromethylquinazolines and exploration of their efficacy against P. falciparum
-
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.
- Hamann, Anton R.,De Kock, Carmen,Smith, Peter J.,Van Otterlo, Willem A.L.,Blackie, Margaret A.L.
-
p. 231 - 236
(2013/09/23)
-
- Targeting the human malaria parasite Plasmodium falciparum: In vitro identification of a new antiplasmodial hit in 4-phenoxy-2- trichloromethylquinazoline series
-
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.
- 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)
-
- Access to original vinylic chlorides in the quinazoline series via a monoelectronic transfer reaction approach
-
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
- Maillard-Boyer, Martine,Castera-Ducros, Caroline,Verhaeghe, Pierre,Sifredi, France,Rathelot, Pascal,Vanelle, Patrice
-
scheme or table
p. 2719 - 2729
(2010/07/03)
-
- Synthesis and antiplasmodial activity of new 4-aryl-2-trichloromethylquinazolines
-
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
- Verhaeghe, Pierre,Azas, Nadine,Gasquet, Monique,Hutter, Sebastien,Ducros, Christophe,Laget, Michele,Rault, Sylvain,Rathelot, Pascal,Vanelle, Patrice
-
p. 396 - 401
(2008/12/21)
-
- QUINAZOLINE DERIVATIVES FOR THE TREATMENT AND PREVENTION OF DIABETES AND OBESITY
-
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.
- -
-
-
- Highly efficient microwave assisted α-trichlorination reaction of α-methylated nitrogen containing heterocycles
-
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.
- Verhaeghe, Pierre,Rathelot, Pascal,Gellis, Armand,Rault, Sylvain,Vanelle, Patrice
-
p. 8173 - 8176
(2007/10/03)
-
- Organic phenyl arsonic acid compounds with potent antileukemic activity
-
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.
- Liu, Xing-Ping,Narla, Rama Krishna,Uckun, Fatih M.
-
p. 581 - 583
(2007/10/03)
-
- Quinazolines as cyclin dependent kinase inhibitors
-
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.
- 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)
-