1mue: Difference between revisions
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|PDB= 1mue |SIZE=350|CAPTION= <scene name='initialview01'>1mue</scene>, resolution 2.0Å | |PDB= 1mue |SIZE=350|CAPTION= <scene name='initialview01'>1mue</scene>, resolution 2.0Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=CDD:2-(6-CHLORO-3-{[2,2-DIFLUORO-2-(1-OXIDO-2-PYRIDINYL)ETHYL]AMINO}-2-OXO-1(2H)-PYRAZINYL)-N-[(2-FLUOROPHENYL)METHYL]ACETAMIDE'>CDD</scene> | |LIGAND= <scene name='pdbligand=CDD:2-(6-CHLORO-3-{[2,2-DIFLUORO-2-(1-OXIDO-2-PYRIDINYL)ETHYL]AMINO}-2-OXO-1(2H)-PYRAZINYL)-N-[(2-FLUOROPHENYL)METHYL]ACETAMIDE'>CDD</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1mu6|1mu6]], [[1mu8|1mu8]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mue OCA], [http://www.ebi.ac.uk/pdbsum/1mue PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mue RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wong, B.]] | [[Category: Wong, B.]] | ||
[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
[[Category: alpha thrombin-hirugen]] | [[Category: alpha thrombin-hirugen]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:21:15 2008'' | ||
Revision as of 22:21, 30 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Related: | 1mu6, 1mu8
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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.
About this StructureAbout this Structure
1MUE is a Protein complex structure of sequences from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 22:21:15 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
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.
- Alpha thrombin-hirugen