ABSTRACT
A series of 7-aminoquinoline derivatives was synthesized and evaluated for their capacity to produce cytotoxicity in KB cells and to inhibit the replication of herpes simplex virus (HSV) type 1. All compounds tested inhibited the replication of HSV-1 with 50% inhibitory concentrations in the range of 2-50 micrograms/mL. The antiviral activity of many compounds, however, was separated from cytotoxicity to replicating uninfected cells by only two- to fivefold higher than those required for antiviral activity. Nonetheless, six compounds (10, 28, 29, 32, 34, and 36) were identified in which the separation was greater than fivefold. All compounds examined were more potent inhibitors of viral DNA synthesis than the cellular DNA synthesis.
Subject(s)
Aminoquinolines/chemical synthesis , Simplexvirus/drug effects , Aminoquinolines/pharmacology , Antiviral Agents/pharmacology , Cell Line , Cell Survival/drug effects , Chemical Phenomena , Chemistry , DNA/biosynthesis , Protein Biosynthesis , Simplexvirus/physiology , Structure-Activity Relationship , Viral Proteins/biosynthesis , Virus Replication/drug effectsABSTRACT
A series of alpha-(2-pyridine)benzyl aryl ketones were prepared as potential hypocholesteremic agents. The synthesis of these compounds was by conversion of 2-benzylpyridine to its anion with n-butyllithium and condensation of the anion with selected aromatic esters. The ketones were tested for their hypocholesteremic activity in rats, and those compounds showing activity were further tested for estrogenicity. Only those aryl ketones with substituents in the ortho position showed a statistically significant reduction in serum cholesterol. Of these compounds the tert-butyl derivative had the most favorable hypocholesteremic to estrogenic ratio.
Subject(s)
Anticholesteremic Agents/chemical synthesis , Pyridines/chemical synthesis , Animals , Estrogens, Non-Steroidal/chemical synthesis , Female , Ketones/chemical synthesis , Ketones/pharmacology , Male , Pyridines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
3-Ethylaminomethyl-2-methyl-4(1H)-quinolone (1a) and its 6-CH3, 6-OCH3, and 7-Cl derivatives were prepared by means of the Mannich reaction. Conversion to the 4-chloro derivatives and condensation with 3-chloroaniline gave the corresponding 4-(3-chloroanilino) derivatives. Cyclization of 4-(3-chloroanilino)-2,6-dimethyl-3-ethyl-aminomethylquinoline (3a) and its 6-OCH3 derivative with paraformaldehyde gave 1-(3-chlorophenyl)-3,9-dimethyl-3-ethyltetrahydropyrimido[5,4-c]quinoline (4a) and the 9-OCH3 derivative 4b. Treatment of 4b with benzaldehyde gave 1-(3-chlorophenyl)-3-ethyl-9-methoxy-5-styryltetrahydropyrimido[5,4-c]quinoline (5). 3-Benzylaminomethyl-6-methoxy-2-methyl-4(1H)-quinolone (1e) and 3,3'-(1,3-benzyliminodimethylene)di[2-methyl-4(1H)-quinolone] (6b) were also synthesized. The compounds were inactive as antimalarials.
Subject(s)
Malaria/drug therapy , Quinolines/therapeutic use , Animals , Antimalarials/chemical synthesis , Chickens , Drug Evaluation, Preclinical , Mice , Plasmodium berghei , Pyrimidines/chemical synthesis , Pyrimidines/therapeutic use , Quinolines/chemical synthesisABSTRACT
The E and Z isomers of 2-[2-(3-chlorophenyl)-1-phenyl-1-propenyl]pyridine (2a,b) and 2-[2-(3-chlorophenyl)-1-(4-hydroxyphenyl)-1-propenyl]pyridine (4a,b) were synthesized and separated as possible metabolites of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1a). Following administration of 1a to rats, a HPLC system was used to examine urine and serum specimens for the less polar metabolites of 1a. Isomers 2a and 2b were not detected but their hydroxylated derivatives 4a and 4b were observed as minor metabolites. Compounds 2a,b and 4a,b exhibited hypocholesteremic activity in rats; compounds 4a and 4b are of special interest because they possessed relatively low estrogenicity.
Subject(s)
Anticholesteremic Agents/chemical synthesis , Pyridines/chemical synthesis , Animals , Anticholesteremic Agents/metabolism , Castration , Chromatography, High Pressure Liquid , Estradiol Congeners/chemical synthesis , Female , Male , Pyridines/metabolism , Pyridines/pharmacology , Rats , StereoisomerismABSTRACT
1-(3-Chlorophenyl)-2-(4-hydroxphenyl)-1-methyl-2(2-pyridine)ethanol (8a) has been synthesized and found to be the major urinary metabolite following intraperitoneal administration of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1) to rats. This metabolite has a hypocholesteremic effect in rats similar to that of the parent drug.
Subject(s)
Anticholesteremic Agents/chemical synthesis , Pyridines/chemical synthesis , Animals , Cholesterol/blood , Male , Pyridines/pharmacology , Pyridines/urine , Rats , Time FactorsABSTRACT
An extension of the Mannich reaction, in which aminomethylation of the five position of uracil, is reported. Thus, primary and secondary alkylamines and primary aromatic amines containing ring-activating groups led to the title compounds 3-10. Compound 11 in which the aromatic ring contains the ring-deactivating nitro group was synthesized in an alternative way. All compounds were characterized by their elemental and spectral properties.
Subject(s)
Uracil/analogs & derivatives , Animals , Chickens , Leukemia L1210/drug therapy , Magnetic Resonance Spectroscopy , Malaria/drug therapy , Malaria, Avian/drug therapy , Mice , Plasmodium berghei , Uracil/chemical synthesis , Uracil/therapeutic useABSTRACT
Polycyclic aromatic isothiocyanates were synthesized in an attempt to produce new fluorescent agents for protein labeling and for use in microanalytical techniques. The relative fluorescence of these reagents, the required intermediates, and the derivatives were established. Of the compounds evaluated, the 9-acridine derivatives were the most promising.