1mue
From Proteopedia
(New page: 200px<br /> <applet load="1mue" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mue, resolution 2.0Å" /> '''Thrombin-Hirugen-L40...) |
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| - | [[Image:1mue.gif|left|200px]]<br /> | + | [[Image:1mue.gif|left|200px]]<br /><applet load="1mue" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mue" size=" | + | |
caption="1mue, resolution 2.0Å" /> | caption="1mue, resolution 2.0Å" /> | ||
'''Thrombin-Hirugen-L405,426'''<br /> | '''Thrombin-Hirugen-L405,426'''<br /> | ||
==Overview== | ==Overview== | ||
| - | In this manuscript we demonstrate that a modification principally directed | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1MUE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CDD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1MUE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CDD:'>CDD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MUE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Thrombin]] | [[Category: Thrombin]] | ||
[[Category: Bohn, D.]] | [[Category: Bohn, D.]] | ||
| - | [[Category: Burgey, C | + | [[Category: Burgey, C S.]] |
[[Category: Chen, Z.]] | [[Category: Chen, Z.]] | ||
| - | [[Category: Clayton, F | + | [[Category: Clayton, F C.]] |
| - | [[Category: Cook, J | + | [[Category: Cook, J J.]] |
| - | [[Category: Gardell, S | + | [[Category: Gardell, S J.]] |
| - | [[Category: Isaacs, R | + | [[Category: Isaacs, R C.]] |
| - | [[Category: Krueger, J | + | [[Category: Krueger, J A.]] |
[[Category: Kuo, L.]] | [[Category: Kuo, L.]] | ||
| - | [[Category: Lewis, S | + | [[Category: Lewis, S D.]] |
| - | [[Category: Lucas, B | + | [[Category: Lucas, B J.]] |
| - | [[Category: Lyle, E | + | [[Category: Lyle, E A.]] |
| - | [[Category: Lyle, T | + | [[Category: Lyle, T A.]] |
| - | [[Category: Lynch, J | + | [[Category: Lynch, J J.]] |
| - | [[Category: McMasters, D | + | [[Category: McMasters, D R.]] |
[[Category: Miller-Stein, C.]] | [[Category: Miller-Stein, C.]] | ||
| - | [[Category: Nantermet, P | + | [[Category: Nantermet, P G.]] |
[[Category: Pal, S.]] | [[Category: Pal, S.]] | ||
| - | [[Category: Pellicore, J | + | [[Category: Pellicore, J M.]] |
| - | [[Category: Robinson, K | + | [[Category: Robinson, K A.]] |
| - | [[Category: Selnick, H | + | [[Category: Selnick, H G.]] |
| - | [[Category: Shafer, J | + | [[Category: Shafer, J A.]] |
[[Category: Singh, R.]] | [[Category: Singh, R.]] | ||
| - | [[Category: Stranieri, M | + | [[Category: Stranieri, M T.]] |
| - | [[Category: Vacca, J | + | [[Category: Vacca, J P.]] |
| - | [[Category: Wallace, A | + | [[Category: Wallace, A A.]] |
| - | [[Category: Welsh, D | + | [[Category: Welsh, D C.]] |
| - | [[Category: White, R | + | [[Category: White, R B.]] |
[[Category: Wong, B.]] | [[Category: Wong, B.]] | ||
[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
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[[Category: alpha thrombin-hirugen]] | [[Category: alpha thrombin-hirugen]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:59:11 2008'' |
Revision as of 11:59, 21 February 2008
|
Thrombin-Hirugen-L405,426
Contents |
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.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About 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.
Reference
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 Thu Feb 21 13:59:11 2008
Categories: 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
