| 主权项 |
1. A method of blocking oocyst formation and transmission of a Plasmodium parasite comprising administering to a mammal in need of such treatment, a therapeutically-effective amount of at least one compound selected from the group consisting of:
a) a compound of Formula I:wherein;
X is C, N or S; and n=1 or 2 (i.e. the A and C rings may be 5-7 membered rings, the B ring may be a 6-8 membered ring, preferably the A and C rings are 6-membered rings and the B ring is a 7-membered ring, each of the A, B, and C rings may be cycloalkyl or aryl, preferably, the A and C rings are aryl and the B ring is cycloalkyl) R1, R2, and R3 are each, independently, H, carbonyl, NR5R6, halide, C1-6 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, or C1-4 alkoxy, aryl, or C1-6 alkyl optionally substituted with NR5R6, hydroxy, mercapto, halide, C1-6 alkyl, C1-6 alkenyl, C1-4 alkoxy, aryl, heteroaryl, or a combination thereof; R4 is H, NR5R6, halide, C1-6 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, aryl, 4-cyclohexylidene-1-methylpiperidine, methylpropan-1-amine, N,N-dimethylpropan-1-amine, N,N,2-trimethylpropan-1-amine, 1-propyl-4-methylpiperazine, or C1-6 alkyl optionally substituted with hydroxy, mercapto, halide, C1-6 alkyl, C1-6 alkenyl, C1-4 alkoxy, cyclo alkyl, heterocyclic, aryl, heteroaryl, or a combination thereof; R5 and R6 are each, independently, H, C1-6 alkyl, C3-8 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, or C1-4 alkoxy, b) a compound that is at least one of ketotifen, dequalinum dichloride, doxipin, protyptiline, carbita pentane, kitotifen, MLS000708402-02, NCGC00163169-03, MLS000556883-02, MLS000556884-02, primaquine, cryphoheptidine, cryphoheptidine, desloratadine, sumotil, desloratadine, quetiapine, quetiapine, amitriptyline, butriptyline, desipramine, doxepin, nortriptyline, rimipramine, amitriptylinoxide, butriptyline, clomipramine, dosulepin, dothiepin, doxepin, imipramine, imipraminoxide, lofepramine, trimipramine, desipramine, norpramin, pertofrane, nortriptyline, protriptyline, demexiptiline, dibenzepin, dimetacrine, iprindole melitracen, metapramine, nitroxazepine, noxiptiline, propizepine, quinupramine, amineptine, opipramol, tianeptine, cianopramine, cyanodothiepin, fluotracen, amoxapine, maprotiline, mianserin, mirtazapine, setiptiline, oxaprotiline, diphenhydramine, doxylamine, loratadine, desloratadine, fexofenadine, pheniramine, cetirizine, promethazine, chlorpheniramine, levocetirizine, quetiapine, meclizine, dimenhydrinate, cimetidine, famotidine, ranitidine, nizatidine, roxatidine, lafutidine, protriptyline, trimipramine, cyproheptadine, trifluoperazine, topotecan, doxorubicin, mitoxantrone, pyrimethamine, iclaprim, amiloride, benzamil, quinidine sulfate, quinine sulfate, quinacrine dihydrochloride , diphenyleneiodonium chloride, dequalinium dichloride, methotrexate, para-fluoro-hexahydrosila-difenidol (p-FHHSiD), emetine dihydrochloride hydrate, pentamidine isethionate, dequalinium analog, paclitaxel, tyrphostin A9, ellipticine, mitoxantrone, cyclosporin A, idarubicin, (S)-(+)-camptothecin, niclosamide, propafenone hydrochloride, calcimycin, (S)-(−)-propafenone hydrochloride, 2′-(4-Aminophenyl)[2,5′-bi-1H-benzimidazol]-5-amine (Ro 90-7501), 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide (BW284c51), WB 64, U-83836 dihydrochloride, aminopterin, methotrexate, halofantrine, pyrimethamine, triamterene, trimethoprim, 1,5-Bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide, mefloquine, artemisinin, and, dihydroergotamine methanesulfonate, and c) at least one of an antihistamine, a tricyclic antidepressant, A serotonin receptor antagonist, a dihydrofolate reductase (DHFR) inhibitor, a Na+ channel blocker, a mast cell stabilizing agent, an endothelial nitric oxide synthase inhibitor, a selective blocker of apamin-sensitive K+ channels, a folic acid antagonist, a muscarinic receptor antagonist, an inducer of apoptosis, a K+ channel blocker, a known antimalarial, a monoamine oxidase inhibitor, an anti-amoebic, an inhibitor of amyloid “42 fibril formation, an inhibitor of microtubule assembly, a selective acetylcholinesterase inhibitor, a modulator of M2 muscarinic acetylcholine receptor activity, a selective PDGF tyrosine kinase receptor inhibitor, a CYP1A1 and DNA topoisomerase II inhibitor, an inhibitor of free radical lipid peroxidation, a DNA synthesis inhibitor, a calcineurin phosphatase inhibitor, an antineoplastic, a DNA topoisomerase I inhibitor, a protonophoric anthelmintic, an adrenoceptor antagonist, a Ca2+ ionophore, a potassium-sparing diuretic, an antibiotic, an acetylcholinesterase inhibitor, a vasoconstrictor, and, an adrenoceptor blocker. |
