Optimization of 4-aminoquinoline/clotrimazole-based hybrid antimalarials: Further structure-activity relationships, in vivo studies, and preliminary toxicity profiling

Journal of Medicinal Chemistry

Volumn 55, Issue 15, 2012, Pages 6948-6957

  Gemma, Sandra ^a,b   Camodeca, Caterina ^a,b   Sanna Coccone, Salvatore ^a,b   Joshi, Bhupendra P ^a,b   Bernetti, Matteo ^a,b   Moretti, Vittoria ^a,b   Brogi, Simone ^a,b   De Marcos, Maria Cruz Bonache ^a,b   Savini, Luisa ^a,b   Taramelli, Donatella ^a,b,c   Basilico, Nicoletta ^a,b,c   Parapini, Silvia ^a,b,c   Rottmann, Matthias ^d   Brun, Reto ^d   Lamponi, Stefania ^a,b   Caccia, Silvio ^a,e   Guiso, Giovanna ^e   Summers, Robert L ^f   Martin, Rowena E ^f   Saponara, Simona ^a   Gorelli, Beatrice ^a   Novellino, Ettore ^a,g   Campiani, Giuseppe ^a,b   Butini, Stefania ^a,b   more..

^a UNIVERSITY OF SIENA   (Italy)

^b CIRM Centro Interuniversitario di Ricerche sulla Malaria   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

^d SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^e MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^f AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

^g UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOQUINOLINE DERIVATIVE; ANTIMALARIAL AGENT; CHLOROQUINE; CLOTRIMAZOLE; CYTOCHROME P450; HEMATIN; N [(3 CHLOROPHENYL)[3 CHLORO 4 (MORPHOLIN 4 YLMETHYL)PHENYL]METHYL] 6 METHOXY 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[3 CHLORO 4 (MORPHOLIN 4 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[3 CHLORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 6 METHOXY 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[3 CHLORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[3 CHLORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 7 TRIFLUOROMETHYL 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[3 CHLORO 4 [1 (7 CHLOROQUINOLIN 4 YL)PIPERAZIN 4 YLMETHYL]PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[3 FLUORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 6 METHOXY 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[3 FLUORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(3 CHLOROPHENYL)[4 (PIPERAZIN 1 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[(4 PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] N' (7 CHLOROQUINOLIN 4 YL)PIPERAZINE; N [(4 CHLOROPHENYL)[3 CHLORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 6 METHOXY 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[3 CHLORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[3 FLUORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 6 METHOXY 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[3 FLUORO 4 (PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[4 (1 METHYLPIPERAZIN 4 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[4 (4 BENZYLPIPERAZIN 1 YL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[4 (IMIDAZOL 1 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[4 (PIPERAZIN 1 YLMETHYL)PHENYL]METHYL] 6 METHOXY 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[4 (PIPERAZIN 1 YLMETHYL)PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [(4 CHLOROPHENYL)[4 [1 (FERROCEN 1 YLMETHYL)PIPERAZIN 4 YLMETHYL]PHENYL]METHYL] 7 CHLORO 4 AMINOQUINOLINE; N [BIS(4 CHLOROPHENYL)[(4 PYRROLIDIN 1 YLMETHYL)PHENYL]METHYL] N' (7 CHLOROQUINOLIN 4 YL)PIPERAZINE; N,N' BIS[4 [4 CHLORO (7 CHLOROQUINOLIN 4 YLAMINO)BENZYL]PHENYLMETHYL]PIPERAZINE; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMES TEST; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROTOZOAL ACTIVITY; ARTICLE; CARDIOTOXICITY; CARDIOVASCULAR EFFECT; CELL VIABILITY; CHEMICAL MODIFICATION; COMPUTER MODEL; CONTROLLED STUDY; CYTOTOXICITY; DRUG ABSORPTION; DRUG BINDING SITE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG LIVER LEVEL; DRUG METABOLISM; DRUG SYNTHESIS; DRUG TRANSPORT; ENANTIOMER; HEART ELECTROPHYSIOLOGY; HEART LEFT VENTRICLE PRESSURE; HUMAN; HUMAN CELL; HYBRID; IC 50; IN VIVO STUDY; MALE; MOUSE; MUTAGENICITY; NONHUMAN; OOCYTE; PLASMODIUM BERGHEI; PROTON TRANSPORT; RAT; REACTION OPTIMIZATION; STRUCTURE ACTIVITY RELATION; TOXICITY TESTING; XENOPUS LAEVIS;

AMINOQUINOLINES; ANIMALS; ANTIMALARIALS; BIOLOGICAL TRANSPORT; CELL LINE; CHLOROQUINE; CLOTRIMAZOLE; DRUG RESISTANCE; FEMALE; HALF-LIFE; HEMEPROTEINS; HUMANS; MALARIA; MALE; MEMBRANE TRANSPORT PROTEINS; MICE; MODELS, MOLECULAR; MUTATION; OOCYTES; PIPERAZINES; PLASMODIUM BERGHEI; PLASMODIUM FALCIPARUM; PROTOZOAN PROTEINS; RATS; RATS, SPRAGUE-DAWLEY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; VENTRICULAR PRESSURE; XENOPUS LAEVIS;

EID: 84864954364     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300802s     Document Type: Article

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