Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position.

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Rittle KE, Barrow JC, Cutrona KJ, Glass KL, Krueger JA, Kuo LC, Lewis SD, Lucas BJ, McMasters DR, Morrissette MM, Nantermet PG, Newton CL, Sanders WM, Yan Y, Vacca JP, Selnick HG

Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position.

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3477-82.

PubMed ID

14505652 [ View in PubMed

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Abstract

Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the alpha-thrombin-hirugen complex provides an explanation for these unanticipated results.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
D-phenylalanyl-N-(3-chlorobenzyl)-L-prolinamide	Prothrombin	Ki (nM)	250	N/A	N/A	Details
D-phenylalanyl-N-benzyl-L-prolinamide	Prothrombin	Ki (nM)	4600	N/A	N/A	Details