1d7x: Difference between revisions

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==Overview==

The synthesis and structure-activity relationship (SAR) studies of a, series of proline-based matrix metalloproteinase inhibitors are described., The data reveal a remarkable potency enhancement in those compounds that, contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a, functionalized oxime moiety or an exomethylene at C-4, and the potencies, were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were, then made against compounds with similar functionality where the C-4, carbon was reduced to sp(3) hybridization and the effect was typically an, order of magnitude loss in potency. A comparison of compounds 14 and 34, exemplifies this observation. An X-ray structure was obtained for a, stromelysin-inhibitor complex which provided insights into the SAR and, selectivity trends observed within the series. In vitro intestinal, permeability data for many compounds was also accumulated.

The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.

==Disease==

Line 17:

[[Category: Single protein]]

[[Category: Stromelysin 1]]

[[Category: Almstead, N.G.]]

[[Category: Almstead, N G.]]

[[Category: Cheng, M.Y.]]

[[Category: Cheng, M Y.]]

[[Category: De, B.]]

[[Category: Natchus, M.G.]]

[[Category: Natchus, M G.]]

[[Category: Pikul, S.]]

[[Category: CA]]

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[[Category: zinc protease]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:55 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-The synthesis and structure-activity relationship (SAR) studies of a, series of proline-based matrix metalloproteinase inhibitors are described., The data reveal a remarkable potency enhancement in those compounds that, contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a, functionalized oxime moiety or an exomethylene at C-4, and the potencies, were typically &lt;10 nM for MMP-3 and &lt;100 nM for MMP-1. Comparisons were, then made against compounds with similar functionality where the C-4, carbon was reduced to sp(3) hybridization and the effect was typically an, order of magnitude loss in potency. A comparison of compounds 14 and 34, exemplifies this observation. An X-ray structure was obtained for a, stromelysin-inhibitor complex which provided insights into the SAR and, selectivity trends observed within the series. In vitro intestinal, permeability data for many compounds was also accumulated.
+The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically &lt;10 nM for MMP-3 and &lt;100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.
 ==Disease==
@@ Line 17: / Line 17: @@
 [[Category: Single protein]]
 [[Category: Stromelysin 1]]
-[[Category: Almstead, N.G.]]
+[[Category: Almstead, N G.]]
-[[Category: Cheng, M.Y.]]
+[[Category: Cheng, M Y.]]
 [[Category: De, B.]]
-[[Category: Natchus, M.G.]]
+[[Category: Natchus, M G.]]
 [[Category: Pikul, S.]]
 [[Category: CA]]
@@ Line 29: / Line 29: @@
 [[Category: zinc protease]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:38:57 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:55 2008''