The Discovery of orally available thrombin inhibitors : Studies towards the optimisation of CGH1668

The chemical optimisation of CGH1668 1 is described employing an in vivo model of absorption to determine the influence on bioavailability of single point modifications to five key molecular templates. The discovery of an orally bioavailable and selective thrombin inhibitor, 24, highlights the utili...

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 8; no. 24; pp. 3583 - 3588
Main Authors Ambler, John, Baker, Emma, Brown, Lyndon, Butler, Paul, Farr, Dave, Dunnet, Karen, Grand, Darren Le, Janus, Diana, Jones, Darryl, Menear, Keith, Mercer, Mark, Smith, Garrick, Talbot, Mark, Tweed, Morris
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 15.12.1998
Elsevier
Subjects
Administration, Oral
Animals
Antithrombins - chemical synthesis
Antithrombins - chemistry
Antithrombins - pharmacokinetics
Area Under Curve
Biological and medical sciences
Biological Availability
Blood. Blood coagulation. Reticuloendothelial system
Humans
Medical sciences
Partial Thromboplastin Time
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Intravenous administration
Rat
Non peptide compound
Thrombin
Selectivity
Structure activity relation
Piperidine derivatives
Chemical synthesis
Human
Sulfonamide
Serine endopeptidases
Enzyme
Aminoamide
Rodentia
Benzene derivatives
Oral administration
Enzyme inhibitor
Bioavailability
In vitro
Primary alcohol
Peptidases
In vivo
α-Aminoacid
Vertebrata
Mammalia
Animal
Tertiary amine
Hydrolases
Carboxamide
Fluorine Organic compounds
Pharmacokinetics
Online AccessGet full text

Cover

More Information
Summary:The chemical optimisation of CGH1668 1 is described employing an in vivo model of absorption to determine the influence on bioavailability of single point modifications to five key molecular templates. The discovery of an orally bioavailable and selective thrombin inhibitor, 24, highlights the utility of this approach. The chemical optimisation of CGH1668 1 is described employing an in vivo model of absorption to determine the influence on bioavailability of single point modifications to five key molecular templates. The discovery of an orally bioavailable and selective thrombin inhibitor highlights the utility of this approach.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(98)00640-4