Document Detail

4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone.
MedLine Citation:
PMID:  8691455     Owner:  NLM     Status:  MEDLINE    
A series of N-acetylated, non-alpha, aromatic amino acids was prepared and shown to promote the absorption of recombinant human growth hormone (rhGH) from the gastrointestinal tract. Seventy compounds in this family were tested in vivo in rats. Of the compounds tested, 4-[4-[(2-hydroxybenzoyl)amino]phenyl]butyric acid was identified as a preclinical candidate and was used to demonstrate the oral delivery of rhGH in primates. A significant positive correlation was found between the relative log k' of the delivery agents, as determined by HPLC on an immobilized artificial membrane (IAM) column, and serum rhGH concentrations following oral or colonic dosing in rats. Structure-activity relationships have also been developed on the basis of electronic effects and hydrogen-bonding characteristics of the aromatic amide substituents.
A Leone-Bay; K K Ho; R Agarwal; R A Baughman; K Chaudhary; F DeMorin; L Genoble; C McInnes; C Lercara; S Milstein; D O'Toole; D Sarubbi; B Variano; D R Paton
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  39     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-08-23     Completed Date:  1996-08-23     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2571-8     Citation Subset:  IM    
Emisphere Technologies, Inc., Hawthorne, New York 10532, USA.
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MeSH Terms
Administration, Oral
Drug Carriers / chemical synthesis*,  chemistry,  pharmacokinetics*
Drug Design
Growth Hormone / administration & dosage*,  pharmacokinetics
Hydrogen Bonding
Intestinal Absorption
Macaca fascicularis
Magnetic Resonance Spectroscopy
Molecular Structure
Phenylbutyrates / chemical synthesis*,  chemistry,  pharmacokinetics*
Recombinant Proteins / administration & dosage,  pharmacokinetics
Structure-Activity Relationship
Reg. No./Substance:
0/4-(4-((2-hydroxybenzoyl)amino)phenyl)butyric acid; 0/Drug Carriers; 0/Phenylbutyrates; 0/Recombinant Proteins; 9002-72-6/Growth Hormone

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