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ACS Omega May 2019A transition-metal-free synthesis of quinazolin-4-ones by CsCO-promoted SAr reaction of -fluorobenzamides with amides followed by cyclization in dimethyl sulfoxide has...
A transition-metal-free synthesis of quinazolin-4-ones by CsCO-promoted SAr reaction of -fluorobenzamides with amides followed by cyclization in dimethyl sulfoxide has been developed. The present procedure can provide efficient synthetic methods for the formation of both 2-substituted and 2,3-disubstituted quinazolin-4-one rings depending on the use of easily available starting materials and an efficient, one-pot protocol for the synthesis of the marketed drug product of methaqualone.
PubMed: 31459909
DOI: 10.1021/acsomega.9b00699 -
Journal of Lipid Research Jul 1996Apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins, is assembled into a lipoprotein particle via a complex, multistep process. Recent...
Apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins, is assembled into a lipoprotein particle via a complex, multistep process. Recent studies indicate that triglyceride-rich lipoprotein assembly requires the activity of the heterodimeric protein, microsomal triglyceride transfer protein (MTP). We identified a novel inhibitor of apolipoprotein B secretion using the human hepatoma cell line, HepG2. CP-10447, a derivative of the hypnotic drug methaqualone (Quaalude), inhibited apoB secretion from HepG2 cells with an IC50 of approximately 5 microM. CP-10447 also inhibited apoB secretion from Caco-2 cells, a model of intestinal lipoprotein production. In experiments using [3H]glycerol as a precursor for triglyceride synthesis, CP-10447 (20 microM) inhibited radiolabeled triglyceride secretion by approximately 83% (P < 0.0001) in HepG2 cells and 76% (P < 0.05) in Caco-2 cells with no effect on radiolabel incorporation into cellular triglyceride, indicating that CP-10447 inhibited triglyceride secretion without affecting triglyceride synthesis. RNA solution hybridization assay indicated that CP-10447 did not affect apoB or apoA-I mRNA levels. Pulse-chase experiments in HepG2 cells confirmed that CP-10447 inhibited the secretion of apoB (not its synthesis) without affecting secretion of total proteins or albumin and suggested that CP-10447 stimulates the early intracellular degradation of apoB in the endoplasmic reticulum (ER). Further studies demonstrated that CP-10447 is a potent inhibitor of human liver microsomal triglyceride transfer activity (IC50 approximately 1.7 microM) in an in vitro assay containing artificial liposomes and partially purified human MTP. These data suggest that CP-10447 may inhibit apoB and triglyceride secretion by inhibiting MTP activity and stimulating the early ER degradation of apoB. CP-10447 should provide a useful tool for further study of the mechanisms of apoB secretion and triglyceride-rich lipoprotein assembly.
Topics: Apolipoproteins B; Caco-2 Cells; Carcinoma, Hepatocellular; Carrier Proteins; Cholesterol Ester Transfer Proteins; Glycerol; Glycoproteins; Humans; Liposomes; Methaqualone; Oleic Acid; RNA, Messenger; Triglycerides; Tritium; Tumor Cells, Cultured
PubMed: 8827519
DOI: No ID Found -
British Journal of Clinical Pharmacology Apr 1977
Clinical Trial Randomized Controlled Trial
Topics: Adult; Behavior; Cognition; Diphenhydramine; Double-Blind Method; Drug Combinations; Drug Interactions; Ethanol; Female; Humans; Male; Methaqualone; Time Factors; Visual Acuity
PubMed: 861141
DOI: 10.1111/j.1365-2125.1977.tb00705.x -
British Journal of Clinical Pharmacology Apr 19741 The plasma profiles of methaqualone obtained from different commercially available preparations have been compared. Tablets were absorbed more efficiently than...
1 The plasma profiles of methaqualone obtained from different commercially available preparations have been compared. Tablets were absorbed more efficiently than capsules. Mandrax preparations achieved much higher plasma levels than Melsedin tablets or the Melsed or Sedaquin capsules. These differences appear to be due to formulation factors. 2 The efficacy of the different drugs as hypnotics corresponded well with the blood levels achieved. 3 There was a significant correlation between the in vitro l/t(50%) and the in vivo peak plasma levels. Thus in vitro dissolution studies can be used to predict the efficiency of absorption of different formulations in man.
PubMed: 22454895
DOI: 10.1111/j.1365-2125.1974.tb00217.x -
Canadian Medical Association Journal Dec 1967
Clinical Trial
Topics: Aged; Arteriosclerosis; Bronchitis; Chronic Disease; Diabetes Complications; Diphenhydramine; Female; Humans; Hypertension; Male; Mental Disorders; Methaqualone; Middle Aged; Parkinson Disease; Placebos; Sleep Wake Disorders; Vaginitis
PubMed: 6060843
DOI: No ID Found -
American Journal of Public Health May 1990This study employs a prospective design to examine possible personality, drug use, stressful life event, and social support-related variables associated with the onset...
This study employs a prospective design to examine possible personality, drug use, stressful life event, and social support-related variables associated with the onset of a depressive episode in a cohort of psychoactive drug using young adults. Two waves of data, collected one year apart, were available on 942 individuals. Cases (n = 62) were free of depressive symptoms at time 1 but reported significant symptomatology at time 2 as measured by the depression subscale of the Brief Symptom Inventory. Controls (n = 490) were those free of depressive symptoms at both time points. In multivariate analyses, users of the central nervous system depressant methaqualone had a nearly four-fold elevated risk for depressed mood as compared to nonusers. Additional risk factors significant after multivariate adjustment included lower self-esteem at time 1 and negative life events. These results highlight the multifactorial nature of depressive symptomatology.
Topics: Adult; Alcohol Drinking; Analysis of Variance; Case-Control Studies; Depression; Female; Humans; Life Change Events; Logistic Models; Male; Maryland; Multivariate Analysis; Prospective Studies; Risk Factors; Self Concept; Smoking; Social Support; Substance-Related Disorders
PubMed: 2327536
DOI: 10.2105/ajph.80.5.580 -
Canadian Medical Association Journal Feb 1973The microcapsule artificial kidney was used in the treatment of three patients with acute drug intoxication. The apparatus contains 300 g. of microencapsulated activated...
The microcapsule artificial kidney was used in the treatment of three patients with acute drug intoxication. The apparatus contains 300 g. of microencapsulated activated charcoal with a total membrane area available for diffusion of more than 2m.(2) The membrane thickness is only 500 A. These properties make possible a compact artificial kidney whose efficiency for the removal of uremic metabolites and drugs is much higher than standard hemodialysis apparatus. The microcapsules are made blood-compatible by coating with human albumin. A roller pump was used to propel the blood through the microcapsule artificial kidney at a flow rate of 300 ml./min. for two to three hours. The clearance values for glutethimide, methyprylon and methaqualone were much higher than those achieved by standard hemodialysis. Hemoperfusion quickly lowered the drug level in the blood with resulting clinical improvement.
Topics: Adult; Charcoal; Female; Glutethimide; Humans; Kidneys, Artificial; Male; Methaqualone; Middle Aged; Piperidones
PubMed: 4405716
DOI: No ID Found -
British Medical Journal Feb 1973A significant rise in plasma gamma-glutamyl transpeptidase activity (GGT) was observed on 13 out of 14 occasions on which patients on long-term treatment with the oral...
A significant rise in plasma gamma-glutamyl transpeptidase activity (GGT) was observed on 13 out of 14 occasions on which patients on long-term treatment with the oral anticoagulant warfarin were given amylobarbitone, quinalbarbitone, or phenazone (antipyrine) for 30 days. In 13 of these 14 studies there was evidence that drug administration had stimulated the rate of warfarin metabolism. One patient showed no increase in plasma GGT activity, yet a significantly increased rate of warfarin metabolism, and another patient showed an increase in plasma GGT activity without a change in warfarin metabolism. When alterations in both plasma GGT activity and plasma warfarin concentration occurred together in response to drug administration the changes followed a similar time course, occurring after about one week of drug administration with maximal changes at about 10 or 15 days. Administration of chlordiazepoxide, diazepam, nitrazepam, and methaqualone did not stimulate the rate of warfarin metabolism in four patients studied, but plasma GGT activity increased significantly in two of these four instances. The implications of these observations in the interpretation of plasma GGT activities are discussed.
Topics: Acyltransferases; Adult; Aged; Amobarbital; Antipyrine; Chlordiazepoxide; Diazepam; Enzyme Induction; Female; Humans; Male; Methaqualone; Middle Aged; Nitrazepam; Secobarbital; Time Factors; Warfarin; gamma-Glutamyltransferase
PubMed: 4405530
DOI: 10.1136/bmj.1.5849.316 -
Journal of Clinical Pathology Oct 1972A rapid gas-chromatographic method has been developed for the determination of butobarbitone, amylobarbitone, hexabarbitone, pentobarbitone, quinalbarbitone,...
A rapid gas-chromatographic method has been developed for the determination of butobarbitone, amylobarbitone, hexabarbitone, pentobarbitone, quinalbarbitone, phenobarbitone glutethimide, and methaqualone in ;finger-prick' samples of plasma. This has been applied to the analysis of some of these drugs in plasma taken from patients after therapeutic dosage and over-dosage.
Topics: Amobarbital; Animals; Barbiturates; Blood Specimen Collection; Cattle; Chromatography, Gas; Evaluation Studies as Topic; Glutethimide; Hexobarbital; Humans; Methaqualone; Methods; Microchemistry; Pentobarbital; Phenobarbital; Secobarbital; Time Factors
PubMed: 4646303
DOI: 10.1136/jcp.25.10.899 -
Anaesthesia Sep 1974
Topics: Adult; Cholinesterase Inhibitors; Dextromoramide; Diphenhydramine; Drug Combinations; Galantamine; Humans; Intensive Care Units; Male; Methaqualone; Respiratory Insufficiency
PubMed: 4433018
DOI: 10.1111/j.1365-2044.1974.tb00722.x