The discovery of orally available thrombin inhibitors: studies towards the optimisation of CGH1668

J Ambler; E Baker; L Brown; P Butler; D Farr; K Dunnet; D Le Grand; D Janus; D Jones; K Menear; M Mercer; G Smith; M Talbot; M Tweed

doi:10.1016/s0960-894x(98)00640-4

The discovery of orally available thrombin inhibitors: studies towards the optimisation of CGH1668

Bioorg Med Chem Lett. 1998 Dec 15;8(24):3583-8. doi: 10.1016/s0960-894x(98)00640-4.

Authors

J Ambler¹, E Baker, L Brown, P Butler, D Farr, K Dunnet, D Le Grand, D Janus, D Jones, K Menear, M Mercer, G Smith, M Talbot, M Tweed

Affiliation

¹ Novartis Horsham Research Center, West Sussex.

PMID: 9934475
DOI: 10.1016/s0960-894x(98)00640-4

Abstract

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.

MeSH terms

Administration, Oral
Animals
Antithrombins / chemical synthesis*
Antithrombins / chemistry
Antithrombins / pharmacokinetics
Area Under Curve
Biological Availability
Humans
Partial Thromboplastin Time
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship

Substances

Antithrombins