-
Organic Letters Feb 2015A metal-free one-pot strategy has been developed for the first time to synthesize pharmaceutically important α-amino ketones from readily available benzylic secondary...
A metal-free one-pot strategy has been developed for the first time to synthesize pharmaceutically important α-amino ketones from readily available benzylic secondary alcohols and amines using N-bromosuccinimide. This new reaction proceeds via three consecutive steps involving oxidation of alcohols, α-bromination of ketones, and nucleophilic substitution of α-bromo ketones to give α-amino ketones. Importantly, this novel one-pot greener reaction avoids direct usage of toxic and corrosive bromine. This methodology has been employed efficiently to synthesize pharmaceutically important amfepramone and pyrovalerone in a single step.
Topics: Alcohols; Amines; Bromosuccinimide; Catalysis; Diethylpropion; Halogenation; Ketones; Molecular Structure; Oxidation-Reduction; Pyrrolidines; Stereoisomerism
PubMed: 25633934
DOI: 10.1021/ol503683q -
Journal of Menopausal Medicine Dec 2014Obesity is an important risk factor for metabolic disease and various cancers. Treatments of obesity include lifestyle intervention, pharmacotherapy, and bariatric... (Review)
Review
Obesity is an important risk factor for metabolic disease and various cancers. Treatments of obesity include lifestyle intervention, pharmacotherapy, and bariatric surgery. If weight loss with lifestyle intervention is only modest, pharmacotherapy might be needed. Pharmacotherapy agents can be grouped by treatment period as short term or long term use agent. Several sympathomimetic drugs such as benzphetamine, diethylpropion, phendimetrazine and phentermine, are approved for short term treatment due to their safety issues. For long term treatment, orlistat, lorcaserin, and combination of phentermine/topiramate are approved by U.S. Food and Drug Administration (FDA). Orlistat partially blocks intestinal digestion of fat, therefore producing weight loss. Lorcaserin is a serotonin 2C receptor agonist. The combination of phentermine/topiramate produces a mean weight loss of 8-10 kg. Side effects of each drug are quite different. For obesity patient, side effects are important factor when choosing drugs. The goal of this article is to review currently available anti-obesity drugs.
PubMed: 25580419
DOI: 10.6118/jmm.2014.20.3.90 -
Value in Health : the Journal of the... Nov 2014
PubMed: 27201685
DOI: 10.1016/j.jval.2014.08.1689 -
Journal of Analytical Toxicology Sep 2014Brazil is considered one of the countries with the highest number of amphetamine-type stimulant (ATS) users worldwide, mainly diethylpropion (DIE) and fenproporex (FEN)....
Brazil is considered one of the countries with the highest number of amphetamine-type stimulant (ATS) users worldwide, mainly diethylpropion (DIE) and fenproporex (FEN). The use of ATS is mostly linked to diverted prescription stimulants and this misuse is widely associated with (ab)use by drivers. A validated method was developed for the simultaneous analysis of amphetamine (AMP), DIE and FEN in plasma samples employing direct immersion-solid-phase microextraction, and gas chromatographic/mass spectrometric analysis. Trichloroacetic acid 10% was used for plasma deproteinization. In situ derivatization with propylchloroformate was employed. The linear range of the method covered from 5.0 to 100 ng/mL. The detection limits were 1.0 (AMP), 1.5 (DIE) and 2.0 ng/mL (FEN). The accuracy assessment of the control samples was within 85.58-108.33% of the target plasma concentrations. Recoveries ranged from 46.35 to 84.46% and precision was <15% of the value of relative standard deviation. This method is appropriate for screening and confirmation in plasma forensic toxicology analyses of these basic drugs.
Topics: Adult; Amphetamine; Amphetamines; Brazil; Central Nervous System Stimulants; Diethylpropion; Gas Chromatography-Mass Spectrometry; Humans; Limit of Detection; Male; Reproducibility of Results; Solid Phase Microextraction; Substance Abuse Detection
PubMed: 25038769
DOI: 10.1093/jat/bku063 -
Human & Experimental Toxicology Mar 2015Diethylpropion has been available in the market for treating obesity for over 50 years. Refined studies are lacking to fully elucidate its action spectrum. The aim of...
Diethylpropion has been available in the market for treating obesity for over 50 years. Refined studies are lacking to fully elucidate its action spectrum. The aim of our study was to evaluate possible toxic effects of anorectic diethylpropion in Chinese hamster ovary (CHO) cells. Comet assay (detects breaks in the DNA strand), micronucleus test (detects clastogenic/aneugenic damage), and cell survival test (detects cytotoxic damage) were used to evaluate the toxic effects. In comet assay, we found that the damage scores with diethylpropion treatments at the concentrations of 20 and 40 μg/mL were more significant ( p < 0.05) than that of the negative control. When assessing the possible aneugenic and/or clastogenic damage caused by the drug in CHO cells, we found no difference ( p > 0.05) in the values of micronucleated cells when comparing different diethylpropion treatments and the negative control. Regarding the cell viability, for all the diethylpropion concentrations tested, higher values ( p < 0.05) of apoptosis were found compared with those of the negative control. In relation to the number of necrotic cells, no difference ( p > 0.05) was noted between the means of the three concentrations of diethylpropion evaluated and the negative control. In the experimental conditions, we conclude that diethylpropion has weak genotoxic and cytotoxic activities.
Topics: Animals; Appetite Depressants; CHO Cells; Cell Survival; Comet Assay; Cricetinae; Cricetulus; Cytotoxins; DNA Damage; Diethylpropion; Micronucleus Tests; Mutagens
PubMed: 25005806
DOI: 10.1177/0960327114542884 -
Progress in Neuro-psychopharmacology &... Oct 2014Mephedrone, an erstwhile "legal high", and some non-abused cathinones (ethcathinone, diethylpropion and bupropion) were tested for stimulant effects in vitro, through... (Comparative Study)
Comparative Study
Mephedrone, an erstwhile "legal high", and some non-abused cathinones (ethcathinone, diethylpropion and bupropion) were tested for stimulant effects in vitro, through assessing their abilities to increase basal and electrically evoked dopamine efflux in rat accumbens brain slices, and compared with cocaine and amphetamine. We also tested mephedrone against cocaine in a dopamine transporter binding study. Dopamine efflux was electrically evoked and recorded using voltammetry in the rat accumbens core. We constructed concentration response curves for these cathinones for effects on basal dopamine levels; peak efflux after local electrical stimulation and the time-constant of the dopamine decay phase, an index of dopamine reuptake. We also examined competition between mephedrone or cocaine and [(125)I]RTI121 at the dopamine transporter. Mephedrone was less potent than cocaine at displacing [(125)I]RTI121. Mephedrone and amphetamine increased basal levels of dopamine in the absence of electrical stimulation. Cocaine, bupropion, diethylpropion and ethcathinone all increased the peak dopamine efflux after electrical stimulation and slowed dopamine reuptake. Cocaine was more potent than bupropion and ethcathinone, while diethylpropion was least potent. Notably, cocaine had the fastest onset of action. These data suggest that, with respect to dopamine efflux, mephedrone is more similar to amphetamine than cocaine. These findings also show that cocaine was more potent than bupropion and ethcathinone while diethylpropion was least potent. Mephedrone's binding to the dopamine transporter is consistent with stimulant effects but its potency was lower than that of cocaine. These findings confirm and further characterize stimulant properties of mephedrone and other cathinones in adolescent rat brain.
Topics: Amphetamine; Amphetamines; Animals; Bupropion; Central Nervous System Stimulants; Cocaine; Diethylpropion; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Electric Stimulation; Iodine Radioisotopes; Male; Methamphetamine; Microelectrodes; Nucleus Accumbens; Propiophenones; Radioligand Assay; Rats, Wistar; Tissue Culture Techniques
PubMed: 24795175
DOI: 10.1016/j.pnpbp.2014.04.009 -
International Journal of Obesity (2005) Aug 2014No long-term studies have compared centrally acting drugs for treating obesity. (Comparative Study)
Comparative Study Randomized Controlled Trial
CONTEXT
No long-term studies have compared centrally acting drugs for treating obesity.
OBJECTIVE
To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss.
DESIGN AND SETTING
A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution.
PATIENTS
A total of 174 obese premenopausal women.
INTERVENTION
Participants randomly received DEP 75 mg (n=28), FEN 25 mg (n=29), MZD 2 mg (n=29), SIB 15 mg (n=30), FXT 20 mg (n=29) or PCB (n=29) daily over 52 weeks. Diet and physical activity were encouraged.
MAIN OUTCOME MEASURES
The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters.
RESULTS
Weight loss was greater than PCB (-3.1±4.3 kg) with DEP (-10.0±6.4 kg; P<0.001), SIB (-9.5±5.9 kg; P<0.001), FEN (-7.8±6.9 kg; P<0.01) and MZD (-7.4±4.9 kg; P<0.01) but not with FXT (-2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P<0.001) with DEP, 20 (69%; P<0.02) with FEN, 21 (72.4%; P<0.01) with MZD, 22 (73.3%; P<0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB (P<0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD (P<0.01); anxiety was more prevalent with DEP (P=0.01); and irritability occurred more frequently with DEP and FEN (P=0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss.
CONCLUSION
The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit-risk profile.
Topics: Adult; Amphetamines; Anti-Obesity Agents; Body Mass Index; Brazil; Cyclobutanes; Diet, Reducing; Diethylpropion; Female; Fluoxetine; Follow-Up Studies; Humans; Mazindol; Obesity; Prospective Studies; Surveys and Questionnaires; Treatment Outcome; Weight Loss
PubMed: 24287940
DOI: 10.1038/ijo.2013.225