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  • General Chemistry  (4)
  • adverse effects  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 199-203 
    ISSN: 1432-1041
    Keywords: simvastatin ; fenofibrate ; hypercholesterolaemia ; apolipoproteins ; lipoproteins ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with primary hypercholesterolaemia received double-blind either fenofibrate (n=8; 200 mg bid) or the HMG-CoA reductase inhibitor simvastatin (n=8; 20 mg qid or 40 mg qid if LDL-cholesterol did not fall below 3.6 mmol·l−1 after 4 weeks of treatment). Simvastatin reduced total cholesterol from 9.7 to 7.0 mmol·l−1 after 10 weeks (−28%), and fenofibrate reduced it from 9.2 to 7.7 mmol·l−1 (−15%). The decrease was less during fenofibrate than during simvastatin treatment (time × drug:p=0.02). Serum LDL-cholesterol fell from 8.3 to 5.3 mmol·l−1 (−36%) during simvastatin and from 7.2 to 6.0 mmol·l−1 (−16%) during fenofibrate administration. Again, the effect of simvastatin was more pronounced than that of fenofibrate (time × drug:p=0.03). HDL-cholesterol increased significantly from 1.1 to 1.2 mmol·l−1 (+13%) during fenofibrate administration and it did not change significantly during simvastatin. Serum triglycerides fell from 1.3 to 1.1 mmol·l−1 (−16%) during simvastatin, and even more significantly from 2.2 to 1.1 mmol·l−1 (−51%) during fenofibrate (time × drug:p=0.002). Apolipoprotein B fell on simvastatin from 1.9 to 1.4 g·l−1 (−24%) and from 1.8 to 1.4 g·l−1 (−22%) during fenofibrate. Both drugs were well tolerated and had no significant adverse effects. Simvastatin lowered total and LDL-cholesterol concentrations more than fenofibrate, while the latter had more effect on triglycerides, suggesting specific indications for the two drugs in the treatment of hyperlipoproteinaemias.
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  • 2
    ISSN: 1432-1041
    Keywords: Insulin ; Fosinopril ; insulin sensitivity ; glucose tolerance ; lipoproteins ; ACE inhibition ; normal humans ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of the new ACE-inhibitor, fosinopril, on insulin sensitivity (SI), glucose homoeostasis and lipid profile has been examined in 24 young, healthy, normotensive men. SI, fasting plasma glucose and insulin, serum total triglycerides (Tg) and lipoprotein cholesterol (C) fractions, and ACE activity were assessed after subjects had taken placebo for 1 week and after 3 further weeks either on placebo (12 subjects) or fosinopril 20 mg daily (12 subjects), administered in a doubleblind, randomized order. Measurements were made after 3 days on a standard diet (2500 kcal/d, 45% carbohydrates, 40% fat and 15% proteins) and after an over-night fast. Compared with control values at the end of the runin placebo phase, fosinopril reduced plasma ACE activity (from 106 to 24 nmol·ml−1·min−1), Significantly increased plasma potassium and lowered upright systolic blood pressure. It also improved the k-value of the glucose disappearance rate after glucose load (from −1.70 to −1.88%·min−1) and tended to increase SI slightly although not significantly (from 10.2 to 12.0·10−4·min−1·μU−1·ml−1). Fasting plasma glucose, insulin, serum total, high-, low-, and very-low density lipoprotein cholesterol fractions and total triglycerides were unchanged following fosinopril and placebo. The findings indicate that in healthy lean humans, ACE inhibition with fosinopril is neutral with regard to lipoprotein and carbohydrate metabolism, and that it may slightly enhance cellular glucose disposal. This calls for further evaluation in individuals at high risk of developing insulin resistance and in patients with impaired insulin sensitivity related to hypertension, obesity, decreased glucose tolerance and diabetes mellitus.
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  • 3
    ISSN: 0947-6539
    Keywords: chemoselectivity ; cinchona alkaloids ; clathrates ; osmium tetroxide ; spiro compounds ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Hydrobromination of quinidine (1) with fuming HBr furnished diastereomeric secondary bromides 2a and 2b in 82% yield. After acetylation the resulting bromides 2a-Ac and 2b-Ac could be separated na dconverted stereospecifically into ethylidene rubanes Z)-4 and (E)-4, respectively. cis-Dihydroxylation of (Z)-olefin 4 with OsO4 was shown to be feasible by two catalytic variants, giving the two diastereomeric diols 5a and 5b, separable by chromatography. A simple onepot procedure was developed for converting the sterically hindered 1,2-secondary, tertiary diols stereospecifically into spiroepoxides (5a 6a-Ac; 5b 6b-Ac). Our procedure involves overall inversion of configuration. The procedure complements the Kolb-Sharpless route to epoxides from 1,2-disecondary diols with overall retention of configuration. The other two diastereomeric spiroepoxides 6c and 6d were prepared in one pot under different conditions (chloramine T, then alkali). Two unprecedented tricyclic allylic N,O-acetals (Z)-7 and (E)-7 were also obtained. The structure of spiroepoxide 6c (as a CH2Cl2 monosolvate) and of tricyclic olefinic N,O-acetal (E)-7 was corroborated by X-ray crystallography.
    Additional Material: 1 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Chemistry - A European Journal 2 (1996), S. 680-684 
    ISSN: 0947-6539
    Keywords: amino alcohols ; asymmetric syntheses ; dihydroxylations ; diol cleavage Horner-Wittig reaction ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Spiroepoxide 1 was prepared from quinidine and converted into β-amino alcohol 3 (86% over two steps). Dihydroxylation of enantiopure oxazatricylic olefin (E)-4 provided diastereomeric diols 5a and 5b. Stereospecific conversion of 1,2-secondary, tertiary diol 5b into tetracyclic spiroepoxide 6 was accomplished in high yield by a one-pot tosylation-cyclization procedure. 1,2-Diol cleavage with NaIO4 in 80% acetic acid afforded the new tricyclic dehydrorubanone 7, containing the 4-oxa-7-azatricyclo[4.3.1.03,7]-decan-2-one core structure. Similarly, acetylated rubanone 9 was prepared on a 20 g scale. Reduction with NaBH4 in the presence of CeCl3 provided rubanols 10a and 10b (1:1.1). Horner-Wittig reaction of 9 with diethyl cyanomethylphosphonate was (Z)-selective, furnishing unsaturated nitrile (Z)-13. Conversion into the α,β-unsaturated aldehyde (Z)-14 and reduction afforded enartiopure allylic alcohol (Z)-12, which is a new isomer of the key quinidine metabolite 15.
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  • 5
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0570-0833
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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