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Biomedical subjects

F I Carroll

Publications and source records attributed to F I Carroll.

At least 181 records · Page 10Linked to original sources
PubMed1979

Synthesis of some 4-substituted 8-amino-6-methoxyquinolines as potential antimalarials.

The 4-vinyl, 4-ethyl, and three 4-[beta-(arylthio)ethyl] derivatives of primaquine and other 8-aminoquinoline antimalarial agents were prepared for antimalarial evaluation. 8-[(4'-Amino-1'-methylbutyl)amino]-4-ethyl-6-methoxyquinoline (4-ethylprimaquine), which showed activity approximately equal to that of primaquine against Plasmodia cynomolgi in Rhesus monkey, was the most active of the compounds tested. 4-Ethylprimaquine was also less toxic than primaquine, as measured in the Rane mouse screen.

Aminoquinolines↗
PubMed1979

Synthesis of 4-alkyl and 4-(beta-alkylvinyl) derivatives of primaquine as potential antimalarials.

4(beta-Alkylvinyl)-6-methoxy-8-nitroquinolines (6) were prepared from 6-methoxy-8-nitroquinoline-4-carboxaldehyde (5) via a Wittig reaction. Stannous chloride reduction of 6 gave 4-(beta-alkylvinyl)-8-amino-6-methoxyquinolines (8), whereas catalytic reduction of 6 using Raney nickel catalyst gave 4-alkyl-8-amino-6-methoxyquinolines (7). Alkylation of 7 and 8 with 4-iodo-1-phthalimidopentane, followed by removal of the phthaloyl-protecting group with hydrazine, gave 4-alkyl and 4-(beta-alkylvinyl) derivatives of primiquine, respectively. These compounds were evaluated for antimalarial activity against P. berghei and P. berghei yoelii in mice and against P. cynomolgi in rhesus monkeys. Several of the compounds were active in the P. bergheii yoelii screen. None of the compounds showed significant activity in the other two screens.

Animals↗
PubMed1978

Synthesis and biological evaluation of 10-oxa-11-deoxyprostaglandin E1 and 10-nor-9,11-secoprostaglandin F1 and their derivatives.

Three 10-oxa-11-deoxyprostaglandin E1 and two 10-nor-9,11-secoprostaglandin F1 analogues were prepared. The compounds were evaluated for pregnancy interruptions, oxytocin-like activity (uterine strip), and antiprostaglandin activity. One of the 10-nor-9,11-secoprostaglandin F1 analogues displayed activity as a PGE2 antagonist in the gerbil colon smooth muscle preparation.

Abortifacient Agents, Nonsteroidal↗
PubMed1978

Resolution of antimalarial agents via complex formation with alpha-(2,4,5,7-tetranitro-9-fluorenylideneaminooxy) propionic acid.

The resolution of several antimalarial agents via pi-complex formation with alpha-(2,4,5,7-tetranitro-9-fluorenylideneaminooxy) propionic acid (TAPA) is reported. Since this represents the first use of this agent for the resolution of amines, some details of the separations are presented. The method proved successful for resolving weakly alkaline amines that did not form stable salts with common resolving acids, highly insoluble amines that did not form soluble salts with usual resolving acids, and amines that did not form crystalline salts with commonly available resolving acids. The optical isomers of several antimalarial agents were evaluated against Plasmodium berghei in the mouse. None of the optically active forms showed any significant differences. The curative activity of (+)- and (-)-primaquine against Plasmodium cynomolgi in the rhesus monkey was essentially identical; however, significant differences in toxicity were noted.

Animals↗
PubMed1978

Carbon-13 nuclear magnetic resonance study of the alpha- and beta- isomers of methadol and acetylmethadol hydrochlorides.

The 13C-NMR spectra reported in these studies give direct evidence for the presence of two contributing conformers for alpha-methadol hydrochloride, alpha-acetylmethadol hydrochloride and beta-acetylmethadol hydrochloride. Indirect evidence is also available for the presence of more than one conformer for beta-methadol hydrochloride. However, in order to be more descriptive about the structures of the conformers, it is necessary to obtain 13C-NMR spectra that have a higher degree of resolution than is available from our present NMR system. Such systems are available, and plans are currently in progress to obtain 13C-NMR spectra or these compounds at high enough magnetic fields and low enough temperatures to give us the necessary data.

Isomerism↗
PubMed1978

The identification and measurement of two new metabolites of naltrexone in human urine.

Two metabolites of naltrexone were identified in human and rat urine following drug administration. The metabolites, 2-hydroxy-3-0-methylnatrexone and 2-hydroxy-3-0-methyl-6 beta-naltrexol, were identified by comparison of their respective gas chromatographic retention times and methane chemical ionization spectral patterns with authentic standards. The standards were obtained by chemical synthesis from naltrexone. Urinary excretion of the two metabolites was measured by single ion recording of the pseudomolecular ions of the metabolites and an internal standard. Excretion data was collected from 5 human subjects over a period of 5 days following a single dose of naltrexone. The metabolites, 2-hydroxy-3-0-methylnatrexone and 2-hydroxy-3-0-methyl-6 beta-natrexol were found to account for an average (+/- standard error) of 0.45 +/- 0.08% and 4.6 +/- 2.1% of the administered dose, respectively. An unusually long half-life of elimination of the latter metabolite (mean of 20.2 +/- 1.8 hr) was observed. Acid-hydrolysis of the samples failed to produce a significant increase of either metabolite indicating that the major protion of these metabolites is excreted in the free form.

Animals↗
PubMed1976

Circular dichroism and carbon-13 nuclear magnetic resonance spectra of (S)-5-alkyl-5-(2'-pentyl)-2-thiobarbituric acids.

The circular dichroism (CD) and carbon-13 nuclear magnetic resonance (13C NMR) spectra of (S)-5-(2'-pentyl)-2-thiobarbituric acid and several (S)-5-alkyl-5-(2'-pentyl)-2-thiobarbituric acids were obtained. The results were compared to CD and 13C NMR spectral data obtained from (S)-5-(2'-pentyl)bartituric acid and (S)-5-alkyl-5-(2'-pentyl)barbituric acids.

Carbon Isotopes↗
PubMed1976

Reduced 8-aminoquinoline analogues as potential antimalarial agents.

The synthesis of 1-alkyl-8-(aminoalkylamino)-6-methyl1-1,2,3,4-tetrahydroquinolines, 8-(4'-amino-1'-methylbutylamino)-6-methoxy-1-methyl1-1,2-dihydroquinoline, 5-substituted 8-(4'-amino-1'-methylbutylamino)-1-methyl-1,2-dihydroquinolines, 8-alkylamino-1-(2-N,N-diethylaminoethyl)-6-methoxy-1,2,3,4-tetrahydroquinolines, 1-)2-N,N-diethylaminoethyl)-6-methoxy-1,2,3,4-tetrahydroquinoline, 1-(2-N,N-diethylaminoethyl)-8-(2-N,N-diethylaminoethylamino)-6-methoxy-1,2,3,4-tetrahydroquinoline, and 2-substituted 8-methoxy-5,6,-dihydro-4-imidazo [i,j]quinolines is described. These compounds as well as most of the intermediates used in their preparation were tested against Plasmodium berghei in mice, and a few compounds were tested for prophylactic activity against Plasmodium cynomolgi in rhesus monkeys.

Aminoquinolines↗
PubMed1975

Synthesis and absolute stereochemistry of 5-alkyl-5-(3'-hydroxy-1'-methylbutyl)barbituric acid and 5-alkyl-5-(3'-hydroxy-1'-methylbutyl)-2-thiobarbituric acids.

5-Alkyl-5-(3-hydroxy-1-methylbutyl) barbituric acid (2) and 5-alkyl-5-(3-hydroxy-1-methylbutyl)-2-thiobarbituric acids (3) are matabolites of 5-alkyl-5-(2-pentyl) barbituric acid and 5-alkyl-5-(2-pantyl)-2-thiobarbituric acid, respectively. We have synthesized the four possible optical isomers of 2 and 3 by a procedure which established the absolute stereochemistry of each isomer. The two racemic pairs in each case were also prepared. The properties of these synthetic samples of 2 and 3 of known stereochemistry are compared to the properties of 2 and 3 which have been isolated from metabolism studies.

Barbiturates↗
PubMed1975

Etonitazene. An improved synthesis.

1-(BETA-Kiethylaminoethyl)-2-(p-ethoxybenzyl)-5-nitrobenzimidazole (u, etonitazene) is a potent analgesic that has value in drug addiction studies. We have developed a simple high-yield synthesis of 1 that is adaptable to alrge scale preparations. The synthesis involves the condensation of 2-(beta-diethylaminoethylamino)-5-mitroaniline and p-ethoxyphenylacetic acid in Thf in the presence of EEDQ.

Analgesics, Opioid↗