Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2003 Apr 7;13(7):1353-7.

Pharmacokinetic optimization of 3-amino-6-chloropyrazinone acetamide thrombin inhibitors. Implementation of P3 pyridine N-oxides to deliver an orally bioavailable series containing P1 N-benzylamides.

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. christopher_urgey@merck.com

Abstract

In this manuscript we demonstrate that a modification principally directed toward the improvement of the aqueous solubility (i.e., introduction a P3 pyridine N-oxide) of the previous lead compound afforded a new series of potent orally bioavailable P1 N-benzylamide thrombin inhibitors. An expedited investigation of the P1 SAR with respect to oral bioavailability, plasma half-life, and human liver microsome stability revealed 5 as the best candidate for advanced evaluation.

PMID:
12657281
DOI:
10.1016/s0960-894x(03)00099-4
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center