In:
Chemical Biology & Drug Design, Wiley, Vol. 69, No. 6 ( 2007-06), p. 444-450
Abstract:
A novel series of pyrrolidine‐1,2‐dicarboxamides was discovered as factor Xa inhibitors using structure‐based drug design. This series consisted of a neutral 4‐chlorophenylurea P1, a biphenylsulfonamide P4 and a d ‐proline scaffold ( 1 , IC 50 = 18 n m ). Optimization of the initial hit resulted in an orally bioavailable, subnanomolar inhibitor of factor Xa ( 13 , IC 50 = 0.38 n m ), which was shown to be efficacious in a canine electrolytic model of thrombosis with minimal bleeding.
Type of Medium:
Online Resource
ISSN:
1747-0277
,
1747-0285
DOI:
10.1111/jpp.2007.69.issue-6
DOI:
10.1111/j.1747-0285.2007.00520.x
Language:
English
Publisher:
Wiley
Publication Date:
2007
detail.hit.zdb_id:
2216600-2
SSG:
12
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