Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Bioorg Med Chem. 2007 Jun 1;15(11):3768-74. doi: 10.1016/j.bmc.2007.03.037.
Epub  2007 Mar 16.

Synthesis and antifungal activity of novel s-substituted 
6-fluoro-4-alkyl(aryl)thioquinazoline derivatives.

Xu GF(1), Song BA, Bhadury PS, Yang S, Zhang PQ, Jin LH, Xue W, Hu DY, Lu P.

Author information:
(1)Center for Research and Development of Fine Chemicals, Key Laboratory of 
Green Pesticide and Bioengineering, Ministry of Education, Guizhou University, 
Guiyang 550025, PR China.

6-Fluoro-4-quinazolinol is prepared by the cyclization reaction of 
2-amino-5-fluorobenzoic acid and formamide. The resulting thiol obtained by 
treatment of hydroxyl group with phosphorus (V) sulfide is converted under phase 
transfer condition to 4-substituted 4-alkylthio-6-fluoroquinazoline derivatives 
by reaction with halide. The structures of the compounds are confirmed by 
elemental analysis, IR, and (1)H NMR. Title compounds 3a, 3g, and 3h are found 
to possess good antifungal activities. Using the mycelial growth rate method in 
the laboratory, the mechanism of action of 3g against Fusarium oxysporum in 
vitro is studied. The results indicate that 3a, 3g, and 3h have high inhibitory 
effect on the growth of most of the fungi with EC(50) values ranging from 8.3 to 
64.2 microg/mL. After treating F. oxysporum with compound 3g at 100 microg/mL, 
only 6.5% of its spore bourgeoned. The permeability of the cell membrane 
increases along with the malformation of the hypha and condensation of its 
endosome. After treatment with compound 3g at 100 microg/mL within 12h, the 
mycelial reducing sugar, D-GlcNAc, content and chitinase activity decline, but 
the soluble protein content shows no obvious change.

DOI: 10.1016/j.bmc.2007.03.037
PMID: 17412601 [Indexed for MEDLINE]


2. Farmaco. 2000 Nov-Dec;55(11-12):725-9. doi: 10.1016/s0014-827x(00)00100-2.

Quinazoline derivatives with antitubercular activity.

Kunes J(1), Bazant J, Pour M, Waisser K, Slosárek M, Janota J.

Author information:
(1)Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles 
University, Hradec Králové, Czech Republic. kunes@faf.cuni.cz

4-Quinazolinol was prepared by the reaction of anthranilic acid and formamide. 
The hydroxy group was converted into the thiol function by treatment with 
phosphorus(V)sulfide, and the subsequent alkylation of the thiol group was 
carried out with alkylhalides under the conditions of phase-transfer catalysis. 
The structure of the substances was confirmed by 1H, 13C NMR, IR, and MS. Most 
of the synthesized compounds exhibited antimycobacterial activity against the 
strains of Mycobacterium tuberculosis, Mycobacerium avium, Mycobacterium 
fortuitum, Mycobacterium kansasii and Mycobacterium intracellulare. 
4-(S-Butylthio)quinazoline (3c) was even more active than isoniazide against 
atypical strains of mycobacteria.

DOI: 10.1016/s0014-827x(00)00100-2
PMID: 11204949 [Indexed for MEDLINE]


3. J Med Chem. 1983 Sep;26(9):1311-6. doi: 10.1021/jm00363a017.

N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and 
N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines as 
potential antifilarial agents.

Angelo MM, Ortwine D, Worth DF, Werbel LM.

A series of N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and 
N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines 
(XI) was synthesized for antifilarial evaluation. Condensation of the requisite 
beta-keto ester (VI) with N-cyanoguanidine afforded 2-pyrimidinylcyanamides 
(VIIa,b) and (5,6,7,8-tetrahydro-4-hydroxy-2-quinazolinyl)cyanamide (VIIc). 
Reaction of VII with a substituted o-phenylenediamine gave 
2-(1H-benzimidazol-2-ylamino)-4-pyrimidinols and 
2-[(5,6-dichloro-1H-benzimidazol-2-yl)amino]-5,6,7, 8-tetrahydro-4-quinazolinol 
(IX). Chlorination with phosphoryl chloride, followed by condensation with the 
appropriate substituted benzenamine, gave the desired 
N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and 
N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines 
(XI). None of these compounds possessed antifilarial activity against 
Litomosoides carinii or Brugia pahangi infections in jirds.

DOI: 10.1021/jm00363a017
PMID: 6887206 [Indexed for MEDLINE]


4. J Med Chem. 1981 Feb;24(2):127-40. doi: 10.1021/jm00134a002.

Synthesis and antimalarial effects of N2-aryl-N4-[(dialkylamino)alkyl]- and 
N4-aryl-N2-[(dialkylamino)alkyl]-2,4-quinazolinediamines.

Elslager EF, Hess C, Johnson J, Ortwine D, Chu V, Werbel LM.

A series of N2(and N4)-aryl-N4(and 
N2)-[(dialkylamino)alkyl]-2,4-quinazolinediamines has been synthesized for 
antimalarial evaluation. Condensation of the appropriate 2,4-dichloroquinazoline 
(IV) with the requisite N,N-dialkylalkylenediamine afforded a series of 
2-chloro-N-[(dialkylamino)alkyl]-4-quinazolinamines (V) which were condensed 
with the appropriate arylamine to provide the corresponding 
N2-aryl-N4-[(dialkylamino)alkyl]-2,4-quinazolinediamines (VI). Hydrolysis of 
2,4-dichloroquinazoline to 2-chloro-4-quinazolinol was followed by condensation 
with the appropriate N,N-dialkylalkylenediamine to give an array of 
2-[[(dialkylamino)alkyl]amino]-4-quinazolinols (IXa). Chlorination with 
phosphorus oxychloride and condensation with a requisite arylamine provided the 
N2-[(dialkylamino)alkyl]-N4-phenyl-2,4-quinazolinediamines (X). Antimalarial 
activity was general among the 
N2-aryl-N4-[(dialkylamino)alkyl]-2,4-quinazolinediamines (VI), while the reverse 
isomers were of lower activity. Phototoxic liability precluded clinical 
evaluation of a member of the series.

DOI: 10.1021/jm00134a002
PMID: 7009867 [Indexed for MEDLINE]