The invention relates to clotrimazole/quinoline hybrids useful as active ingredients of antimalaria drugs. Compds. of 4-aminoquinoline derivs. with formula I [X and Y = CH; or X and Y together with the carbon atoms to which they are attached, form a bridge selected from C-C, C-CH2-CH2-C and C-CH=CH-C; W and Z = H; or W and Z together with the carbon atoms to which they are attached, form a (un)substituted benzo- fused ring CH=CH-CH=CH; R1 = H, (un)substituted Ph, 3,4-methylenedioxyphenyl or (pyrrolidinylmethyl)phenyl; R2 = halo, trifluoromethyl or alkoxy; R3 = H, halo, OH, CN, sulfonamido or dialkylsulfonamido; R4 = N,N-dialkylamino, pyrrolidinyl, piperazinyl, morpholinyl or imidazolyl; R5 = H, halo, CN, OH or SO2NH2; R6 = H, N,N-dialkylaminomethyl, pyrrolidinylmethyl, piperazinylmethyl, morpholinylmethyl or 1H-imidazolylmethyl], and their isomers, mixt. of isomers or pharmaceutically acceptable salts, are prepd. and disclosed. Thus, e.g., II was prepd. by reacting (3-chlorophenyl)[4-[(pyrrolidin-1-yl)methyl]phenyl]methanone oxime with 4,7-dichloroquinoline. The compds. show a remarkable in vitro biol. activity esp. against the chloroquine-resistant Plasmodium falciparum strains and in vivo activity against P. berghei. For example, II demonstrated IC50 value of 20.7 nM in vitro against D10 (CQ-S strain) of P. falciparum and ED50 value of 6.3 mg/Kg in vivo against P. berghei.

Preparation of 4-aminoquinoline derivatives as antimalaria drugs.

FATTORUSSO, CATERINA;PERSICO, MARCO;
2008

Abstract

The invention relates to clotrimazole/quinoline hybrids useful as active ingredients of antimalaria drugs. Compds. of 4-aminoquinoline derivs. with formula I [X and Y = CH; or X and Y together with the carbon atoms to which they are attached, form a bridge selected from C-C, C-CH2-CH2-C and C-CH=CH-C; W and Z = H; or W and Z together with the carbon atoms to which they are attached, form a (un)substituted benzo- fused ring CH=CH-CH=CH; R1 = H, (un)substituted Ph, 3,4-methylenedioxyphenyl or (pyrrolidinylmethyl)phenyl; R2 = halo, trifluoromethyl or alkoxy; R3 = H, halo, OH, CN, sulfonamido or dialkylsulfonamido; R4 = N,N-dialkylamino, pyrrolidinyl, piperazinyl, morpholinyl or imidazolyl; R5 = H, halo, CN, OH or SO2NH2; R6 = H, N,N-dialkylaminomethyl, pyrrolidinylmethyl, piperazinylmethyl, morpholinylmethyl or 1H-imidazolylmethyl], and their isomers, mixt. of isomers or pharmaceutically acceptable salts, are prepd. and disclosed. Thus, e.g., II was prepd. by reacting (3-chlorophenyl)[4-[(pyrrolidin-1-yl)methyl]phenyl]methanone oxime with 4,7-dichloroquinoline. The compds. show a remarkable in vitro biol. activity esp. against the chloroquine-resistant Plasmodium falciparum strains and in vivo activity against P. berghei. For example, II demonstrated IC50 value of 20.7 nM in vitro against D10 (CQ-S strain) of P. falciparum and ED50 value of 6.3 mg/Kg in vivo against P. berghei.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/361642
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