1mu6
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Recent efforts in the field of thrombin inhibitor research have focused on | + | Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2-phenethylamino)-6-methylpyrazinone acetamide template (e.g., 1) which resulted in the modification of each of the three principal components (i.e., P1, P2, P3) comprising this series. As a result of these studies, several potent thrombin inhibitors (e.g., 20, 24, 25) were identified which exhibit high levels of oral bioavailability and long plasma half-lives. |
==Disease== | ==Disease== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Barrow, J | + | [[Category: Barrow, J C.]] |
[[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: Coburn, C | + | [[Category: Coburn, C A.]] |
| - | [[Category: Cook, J | + | [[Category: Cook, J J.]] |
| - | [[Category: Dorsey, B | + | [[Category: Dorsey, B D.]] |
| - | [[Category: Gardell, S | + | [[Category: Gardell, S J.]] |
| - | [[Category: Holahan, M | + | [[Category: Holahan, M A.]] |
| - | [[Category: Jr., J | + | [[Category: Jr., J J.Lynch.]] |
| - | [[Category: Jr., T | + | [[Category: Jr., T J.Detwiler.]] |
| - | [[Category: Krueger, J | + | [[Category: Krueger, J A.]] |
[[Category: Kuo, L.]] | [[Category: Kuo, L.]] | ||
| - | [[Category: Leonard, Y | + | [[Category: Leonard, Y M.]] |
| - | [[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: McDonough, C | + | [[Category: McDonough, C M.]] |
| - | [[Category: McMasters, D | + | [[Category: McMasters, D R.]] |
[[Category: Miller-Stein, C.]] | [[Category: Miller-Stein, C.]] | ||
| - | [[Category: Robinson, K | + | [[Category: Robinson, K A.]] |
| - | [[Category: Sanders, W | + | [[Category: Sanders, W M.]] |
| - | [[Category: Sanderson, P | + | [[Category: Sanderson, P E.]] |
| - | [[Category: Shafer, J | + | [[Category: Shafer, J A.]] |
[[Category: Singh, R.]] | [[Category: Singh, R.]] | ||
| - | [[Category: Sitko, G | + | [[Category: Sitko, G R.]] |
| - | [[Category: Stranieri, M | + | [[Category: Stranieri, M T.]] |
| - | [[Category: Vacca, J | + | [[Category: Vacca, J P.J.]] |
| - | [[Category: Wallace, A | + | [[Category: Wallace, A A.]] |
| - | [[Category: White, R | + | [[Category: White, R B.]] |
| - | [[Category: Williams, P | + | [[Category: Williams, P D.]] |
[[Category: Wong, B.]] | [[Category: Wong, B.]] | ||
[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:59:07 2008'' |
Revision as of 11:59, 21 February 2008
|
Crystal Structure of Thrombin in Complex with L-378,622
Contents |
Overview
Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2-phenethylamino)-6-methylpyrazinone acetamide template (e.g., 1) which resulted in the modification of each of the three principal components (i.e., P1, P2, P3) comprising this series. As a result of these studies, several potent thrombin inhibitors (e.g., 20, 24, 25) were identified which exhibit high levels of oral bioavailability and long plasma half-lives.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1MU6 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
Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines., Burgey CS, Robinson KA, Lyle TA, Sanderson PE, Lewis SD, Lucas BJ, Krueger JA, Singh R, Miller-Stein C, White RB, Wong B, Lyle EA, Williams PD, Coburn CA, Dorsey BD, Barrow JC, Stranieri MT, Holahan MA, Sitko GR, Cook JJ, McMasters DR, McDonough CM, Sanders WM, Wallace AA, Clayton FC, Bohn D, Leonard YM, Detwiler TJ Jr, Lynch JJ Jr, Yan Y, Chen Z, Kuo L, Gardell SJ, Shafer JA, Vacca JP, J Med Chem. 2003 Feb 13;46(4):461-73. PMID:12570369
Page seeded by OCA on Thu Feb 21 13:59:07 2008
Categories: Homo sapiens | Protein complex | Thrombin | Barrow, J C. | Bohn, D. | Burgey, C S. | Chen, Z. | Clayton, F C. | Coburn, C A. | Cook, J J. | Dorsey, B D. | Gardell, S J. | Holahan, M A. | Jr., J J.Lynch. | Jr., T J.Detwiler. | Krueger, J A. | Kuo, L. | Leonard, Y M. | Lewis, S D. | Lucas, B J. | Lyle, E A. | Lyle, T A. | McDonough, C M. | McMasters, D R. | Miller-Stein, C. | Robinson, K A. | Sanders, W M. | Sanderson, P E. | Shafer, J A. | Singh, R. | Sitko, G R. | Stranieri, M T. | Vacca, J P.J. | Wallace, A A. | White, R B. | Williams, P D. | Wong, B. | Yan, Y. | CDA | Blood clotting | Hydrolase
