- Structure-activity relationship and molecular modelling studies of quinazolinedione derivatives MMV665916 as potential antimalarial agent
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A series of new quinazolinedione derivatives have been readily synthesized and evaluated for their in vitro antiplasmodial growth inhibition activity. Most of the compounds inhibited P. falciparum FcB1 strain in the low to medium micromolar concentration. The 2-ethoxy 8ag’, 2-trifluoromethoxy 8ai’ and 4-fluoro-2-methoxy 8ak’ showed the best inhibitory activity with EC50 values around 5 μM and were non-toxic to the primary human fibroblast cell line AB943. However, these compounds were less potent than the original hit MMV665916, which showed remarkable growth inhibition with EC50 value of 0.4 μM and presented the highest selectivity index (SI > 250). In addition, a novel approach for determining the docking poses of these quinazolinedione derivatives with their potential protein target, the P. falciparum farnesyltransferase PfFT, was investigated.
- Albrecht, Sébastien,Florent, Isabelle,Mouray, Elisabeth,Mourot, Laura,Schmitt, Marjorie,Spichty, Martin
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supporting information
(2021/11/22)
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- Synthesis of novel 2,4-disubstituted 3H-pyrido[3,2-e][1,4]diazepin-5-ones and 2,4-disubstituted 3H-pyrido[2,3-e][1,4]diazepin-5-ones derivatives via regioselective thionation and nucleophilic substitutions reactions
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An efficient synthesis leading to novel 2,4-disubstituted 3H-pyrido[3,2-e][1,4]diazepin-5-ones and 2,4-disubstituted 3H-pyrido[2,3-e][1,4] diazepin-5-ones derivatives is presented, using the condensation of ethyl 2-(benzylamino)acetate or ethyl 2-(4-methoxybenzylamino)acetate with 1H-pyrido[3,2-d][1,3]oxazine-2,4-diones and 1H-pyrido[2,3-d][1,3]oxazine-2,4- diones. This synthesis gives 4-substituted 3-hydro-1H-pyrido[3,2-e][1,4] diazepine-2,5-diones and 4-benzyl-3,4-dihydro-1H-pyrido[2,3-e][1,4]diazepine-2, 5-diones in good yields. Finally, after a regioselective thionation and nucleophilic substitutions reactions, various bis-functionalized 1,4-diazepines were easily obtained in excellent yields. These results open an access way to a library of novel bis-functionalized pyrido-1,4-diazepines.
- El Bouakher, Abderrahman,Prié, Gildas,Aadil, Mina,Akssira, Mohamed,Viaud-Massuard, Marie-Claude
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p. 5086 - 5091
(2013/07/05)
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- A convenient synthesis of new pyrido[3,2-e][1,4]diazepine-2,5-diones and pyrido[2,3-e][1,4]diazepine-2,5-diones
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A convenient synthesis of a series of pyrido[3,2-e][1,4]-diazepine-2,5- diones 8 and pyrido[2,3-e][1,4]diazepine-2,5-diones 9, is reported using the condensation of α-amino acid methyl ester derivatives with 1H-pyrido[3,2-d][1,3]oxazine-2,4-dione and 1H-p
- El Bouakher, Abderrahman,Laborie, Hélne,Aadil, Mina,El Hakmaoui, Ahmed,Lazar, Said,Akssira, Mohamed,Viaud-Massuard, Marie-Claude
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scheme or table
p. 5077 - 5080
(2011/10/09)
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- BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS ANTIVARAL AGENTS
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The invention provides compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined in the specification, and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together
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Page/Page column 87-88
(2010/10/03)
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- NOVEL 1,8-NAPHTHYRIDINE COMPOUNDS
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The present invention relates to naphthyridine compounds useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
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Page/Page column 21
(2008/12/08)
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- Anti-infective agents
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Compounds having the formula are hepatitis C (HCV) polymerase inhibitors. Also disclosed are a composition and method for inhibiting hepatitis C (HCV) polymerase, processes for making the compounds, and synthetic intermediates employed in the processes.
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- Anti-infective agents
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The present invention provides an HCV polymerase inhibiting compound having the formula (I) and a composition comprising a therapeutically effective amount of said compound. The present invention also provides a method for inhibiting hepatitis C virus (HC
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Page/Page column 70
(2010/02/08)
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- NOVEL COMPOUNDS
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Compounds of formula (I): are inhibitors of the enzyme Lp-PLA2 and are of use in therapy, in particular for treating atherosclerosis. In Formula (I) R1, R2, R3, R4, R5, R6, X and Y are as d
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Page/Page column 37
(2010/02/07)
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- Synthesis and evaluation of heterocyclic carboxamides as potential antipsychotic agents
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Heterocyclic analogues of 1192U90, 2-amino-N-(4-(4-(1,2-benzisothiazol- 3-yl)-1-piperazinyl)-butyl)benzamide hydrochloride (1), were prepared and evaluated as potential antipsychotic agents. These analogues were evaluated in vitro for their binding to the dopamine D2, serotonin 5-HT2, and serotonin 5-HT(1a) receptors and in vivo for their ability to antagonize the apomorphine-induced climbing response in mice. Nine different types of heterocyclic carboxamides were studied in this investigation (i.e., pyridine- , thiophene-, benzothiophene-, quinoline-, 1,2,3,4-tetrahydroquinoline-, 2,3- dihydroindole-, indole-, benzimidazole-, and indazolecarbox-amides). Two derivatives exhibited potent in vivo activities comparable to 1: 3-amino-N- (4(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-2-pyridinecarboxamide (16) and 3-amino-N-(4(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-2- thiophenecarboxamide (29). Furthermore, these derivatives were found to be much less active in behavioral models predictive of extrapyramidal side effects than in the mouse climbing assay, which predicts antipsychotic activity. Carboxamides 16 and 29 were selected for further evaluation as potential backup compounds to 1.
- Norman, Mark H.,Navas III, Frank,Thompson, James B.,Rigdon, Greg C.
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p. 4692 - 4703
(2007/10/03)
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- Indolo[2,1-biquinazoline-6,12-dione antibacterial compounds and methods of use thereof
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Methods, compounds and compositions are provided form inhibiting the growth of pathogenic mycobacteria in vitro and of treatment of pathogenic mycobacterial infections in vivo using indolo[2,1-b]quinazoline-6,12-dione compounds of the formula (I): STR1 wherein A, B, C, D, E, F, G and H are independently selected from carbon and nitrogen, or A and B or C and D can be taken together to be nitrogen or sulfur, and the pharmaceutically acceptable salts thereof. The methods, compounds and compositons are particularly useful for inhibiting the growth of Mycobacterium tuberculosis, and may be used alone, or in combination with other anti-Mycobacterium tuberculosis agents, such as isoniazid, rifampin, pyrazinamide, rifabutin, streptomycin and ciprofloxacin, to provide new agents for the treatment of tuberculosis, including multidrug-resistant tuberculosis (MDRTB).
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- Synthesis of Phosphorus-Containing Heterocycles from 2-Aminonicotinic Acid
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The reaction of 2-aminonicotinic acid with ethyl chloroformate, followed by alkylation with NaH/MeI and decarboxylation with methylamine, led to N-methyl-2-(methylamino)nicotinamide (3).Treatment of 3 with PCl3 in the presence of triethylamine gave the phosphorinanone 4.Substitution of chlorine in 4 by the dimethylamino-, N,N,N'-trimethylethylenediamino-, or bis(2-chloroethyl)amino group furnished 5-7.Hydrolysis of 4 with small amounts of water formed the phosphoryl derivative 8 as the hydrochloride.The spirophosphoranes 9 and 10 were produced by reaction of 5 with hexafluoroacetone and tetrachloro-o-benzoquinone, respectively.In order to evaluate its coordination ability, the N,N,N'-trimethylethylenediamino-substituted diazaphosphorinanone 6 was allowed to react with the tetracarbonyl norbornadiene derivatives of chromium(0) and molybdenum(0).The cis-substituted tetracarbonyl complexes 12 and 13 were formed.In the reaction of 7 with dichloro(1,5-cyclooctadiene)platinum(II) the cis-disubstituted complex 15 was formed.A comparision of benzo- and pyrido-annulated phosphorinanones was made, and their differences were discussed.In the case of the compounds 2, 7, and 9 single-crystal X-ray structure analyses were performed.In 9 the heterocycle C and N atoms are coplanar (the phosphorus lies 60 pm outside the plane); P and N(2) are displaced in 7 to the same side of the plane of the remaining four atoms. - Key Words: Aminonicotinamide/ Diazaphosphorinanones
- Sonnenburg, Ralf,Neda, Ion,Fischer, Axel,Jones, Peter G.,Schmutzler, Reinhard
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p. 627 - 634
(2007/10/02)
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- REACTIONS OF αω-BIS(BROMOMAGNESIO)ALKANES WITH HETEROCYCLIC ANHYDRIDES. A NOVEL SYNTHESIS OF FIVE AND SIX-MEMBERED 1-(o-AMINOPHENYL)CYCLOALKANOLS AND 1-(2'-AMINO-3'-PYRIDINYL)CYCLOALKANOLS
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Isatoic anhydrides and azaisatoic anhydrides are converted by reaction with 1,4-bis(bromomagnesio)butane and 1,5-bis(bromomagnesio)pentane into the corresponding 1-(o-aminophenyl)cycloalkanols and 1-(2'-amino-3'pyridinyl)cycloalcanols.
- Canonne, P.,Boulanger, R.,Chantegrel, B.
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p. 663 - 668
(2007/10/02)
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- Azaisatoic anhydrides
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A method for producing heterocyclic acid anhydrides and pyrimidinediones from the corresponding acids, dicarboxamides, 2,3-and 3,4-pyridinedicarboxamides, and N-monosubstituted 2,3-and 3,4-pyridinedicarboxamides, in which the aforesaid compounds are reacted with lead tetra-acetate in the presence of a suitable anhydrous inert solvent.
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