Contemporary Drug Synthesis by Jie Jack Li, Douglas S. Johnson, Drago R. Sliskovic, Bruce

By Jie Jack Li, Douglas S. Johnson, Drago R. Sliskovic, Bruce D. Roth

Written by means of individuals of Pfizer international study and improvement for chemists getting into the pharmaceutical undefined, this paintings profiles the synthesis of fourteen consultant pharmaceutical items as a way to display the multidisciplinary nature of the recreation. for every drug, they supply a ancient creation and the organic, pharmacological, pharmakinetic, and drug metabolism history sooner than detailing the drug's synthesis.

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Expert Review of Anticancer Therapy 2002, 2, 161-168. 17. Culy, C. R; Faulds, D. Drugs 2002,62,2249-50. 18. Herbst, R. S. Expert Opinion on Investigational Drugs 2002,II, 837-849. 19. Laird, A. ; Chemngton, J. M. Expert Opinion on Investigational Drugs 2003, 12,51-64. 38 Contemporary Drug Synthesiq 20. Gibson, K. H. WO 96/33980 (1996). 21. Barker, A. ; Gibson, K. ; Godfrey, A. ; Barlow, J. ; Healy, M. ; Woodbum, J. ; Ashton, S . ; Curry, B. ; Richards, L. Bioorg. Med. C h m . Left. 2001,11, 1911-1914.

Looking at the structures of 4 versus 41, the only difference is a carboxylic acid versus an alcohol. Therefore, it is reasonable to speculate that the increased polarity of cetirizine (4) may be responsible for lowering the blood-brain barrier penetration. 20x2' CI CI oxidation k O p H 4 41 Fig. 3. Evolution of hydroxyzine (41) to cetirizine (4). In term of pharrnacokinetics, cetirizine (4) is rapidly absorbed, reaching a peak plasma concentration of 257 pg/L within 1 h of administration at a dose of 10 mg in healthy volunteers.

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