Bioorg Med Chem Lett. 2009 Oct 1;19(19):5712-5. doi: 10.1016/j.bmcl.2009.08.008. Epub 2009 Aug 7.

Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA).

West CW, Adler M, Arnaiz D, Chen D, Chu K, Gualtieri G, Ho E, Huwe C, Light D, Phillips G, Pulk R, Sukovich D, Whitlow M, Yuan S, Bryant J.

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Department of Medicinal Chemistry, Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, United States. cwest@icagen.com

Abstract

In this Letter we report the synthesis and evaluation of a series of non-amidine inhibitors of Urokinase Plasminogen Activator (uPA). Starting from compound 1, a significant change provided compounds in which the amidine, binding in the S1 pocket, was replaced with a primary amine. Further modifications led to the identification of potent, selective, and orally bioavailable uPA inhibitors.

PMID:: 19703768; [PubMed - indexed for MEDLINE]

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Structures reported by this article

Low Molecular Weigth Human Urokinase Type Plasminogen Activator 2-[6- (3'-Aminomethyl-Biphenyl-3-Yloxy)-4-(3-Dimethylamino-Pyrrolidin-1- Yl)-3,5-Difluoro-Pyridin-2-Yloxy]-4-Dimethylamino-Benzoic Acid Complex

PDB: 3IG6

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 1.83 Å

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Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasm...
Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA).
Bioorg Med Chem Lett. 2009 Oct 1 ;19(19):5712-5. doi: 10.1016/j.bmcl.2009.08.008. Epub 2009 Aug 7 .

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Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA).

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