| 4-[4-[(2-Hydroxybenzoyl)amino]phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone. | |
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MedLine Citation:
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PMID: 8691455 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 39 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1996 Jun |
Date Detail:
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Created Date: 1996-08-23 Completed Date: 1996-08-23 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2571-8 Citation Subset: IM |
Affiliation:
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Emisphere Technologies, Inc., Hawthorne, New York 10532, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Drug Carriers / chemical synthesis*, chemistry, pharmacokinetics* Drug Design Growth Hormone / administration & dosage*, pharmacokinetics Haplorhini Humans Hydrogen Bonding Intestinal Absorption Macaca fascicularis Magnetic Resonance Spectroscopy Male Molecular Structure Phenylbutyrates / chemical synthesis*, chemistry, pharmacokinetics* Rats Recombinant Proteins / administration & dosage, pharmacokinetics Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/4-(4-((2-hydroxybenzoyl)amino)phenyl)butyric acid; 0/Drug Carriers; 0/Phenylbutyrates; 0/Recombinant Proteins; 9002-72-6/Growth Hormone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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