Document Detail

Membrane permeability related physicochemical properties of a novel gamma-secretase inhibitor.
MedLine Citation:
PMID:  15265546     Owner:  NLM     Status:  MEDLINE    
Pharmaceutical profiling studies were conducted on a novel prototype gamma-secretase inhibitor, to determine the potential of its oral absorption. Such compounds can be of use in the treatment of Alzheimer's disease (AD). The studies included determination of solubility, dissociation constant (pK(a)), octanol/water partition coefficient (log P) and the capacity factor (k'(IAM)) on immobilized artificial membrane (IAM) chromatographic columns. The compound is very slightly solubility in water (120 +/- 50 microg/mL) but the solubility increased considerably in basic medium (270 +/- 60 microg/mL). The compound exhibited pK(a) of (10.36 +/- 0.11); and log P of (3.36 +/- 0.16) determined by shake-flask method and (3.31 +/- 0.01) determined by high performance liquid chromatography (HPLC). The experimentally determined log P values correlated well with the calculated one of 3.44. The observed log k'(IAM) value of (2.79 +/- 0.04) indicates that the compound can reasonably be expected to have high membrane permeability, and therefore, good absorption profile if taken orally. This conclusion is also supported by other parameters determined.
Ahmed M El-Gendy; Adeboye Adejare
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  280     ISSN:  0378-5173     ISO Abbreviation:  Int J Pharm     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-21     Completed Date:  2004-12-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  47-55     Citation Subset:  IM    
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
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MeSH Terms
Adamantane / analogs & derivatives*,  chemistry*,  pharmacokinetics*,  pharmacology
Administration, Oral
Amyloid Precursor Protein Secretases
Cell Membrane Permeability / physiology*
Endopeptidases / metabolism*
Hydrogen-Ion Concentration
Models, Chemical
Protease Inhibitors / chemistry*,  pharmacokinetics*
Sulfonamides / chemistry*,  pharmacokinetics*,  pharmacology
Grant Support
Reg. No./Substance:
0/4-fluoro-N-(adamantan-2-yl)benzenesulfonamide; 0/Protease Inhibitors; 0/Sulfonamides; 281-23-2/Adamantane; EC 3.4.-/Amyloid Precursor Protein Secretases; EC 3.4.-/Endopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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