1mue
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Thrombin-Hirugen-L405,426
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1MUE is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
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., Burgey CS, Robinson KA, Lyle TA, Nantermet PG, Selnick HG, Isaacs RC, Lewis SD, Lucas BJ, Krueger JA, Singh R, Miller-Stein C, White RB, Wong B, Lyle EA, Stranieri MT, Cook JJ, McMasters DR, Pellicore JM, Pal S, Wallace AA, Clayton FC, Bohn D, Welsh DC, Lynch JJ Jr, Yan Y, Chen Z, Kuo L, Gardell SJ, Shafer JA, Vacca JP, Bioorg Med Chem Lett. 2003 Apr 7;13(7):1353-7. PMID:12657281
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OCA- Pages with broken file links
- Homo sapiens
- Protein complex
- Thrombin
- Bohn, D.
- Burgey, C S.
- Chen, Z.
- Clayton, F C.
- Cook, J J.
- Gardell, S J.
- Isaacs, R C.
- Krueger, J A.
- Kuo, L.
- Lewis, S D.
- Lucas, B J.
- Lyle, E A.
- Lyle, T A.
- Lynch, J J.
- McMasters, D R.
- Miller-Stein, C.
- Nantermet, P G.
- Pal, S.
- Pellicore, J M.
- Robinson, K A.
- Selnick, H G.
- Shafer, J A.
- Singh, R.
- Stranieri, M T.
- Vacca, J P.
- Wallace, A A.
- Welsh, D C.
- White, R B.
- Wong, B.
- Yan, Y.
- CDD
- Alpha thrombin-hirugen