284044-40-2Relevant articles and documents
Synthesis of prenyl- and geranyl-substituted carbazole alkaloids by DIBAL-H promoted reductive pyran ring opening of dialkylpyrano[3,2-a]carbazoles
Hesse, Ronny,Kataeva, Olga,Schmidt, Arndt W.,Knoelker, Hans-Joachim
, p. 9504 - 9509 (2014/08/18)
The DIBAL-H promoted reductive pyran ring opening of dialkylpyrano[3,2-a] carbazoles provides a direct access to a broad range of prenyl- and geranyl-substituted carbazoles. Formation of a pyran ring followed by reductive ring opening represents a new met
TRIAZOLOPYRIMIDINE DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS
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Page/Page column 55-56, (2008/06/13)
This invention concerns a compound of formula (I), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary arnine and a stereochernic ally isomeric form thereof, wherein ring A represents phenyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl
Acylsulfamide inhibitors of factor VIIa
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Page 27, (2010/02/09)
Compounds having the general formula I are useful for inhibiting serine protease enzymes, such as Tissue Factor VIIa, factor Xa, thrombin and kallikrein and have improved permeability properties. These compounds may be used in methods of preventing and/or
Exploiting subsite S1 of trypsin-like serine proteases for selectivity: Potent and selective inhibitors of urokinase-type plasminogen activator
Mackman,Katz,Breitenbucher,Hui,Verner,Luong,Liu,Sprengeler
, p. 3856 - 3871 (2007/10/03)
A nonselective inhibitor of trypsin-like serine proteases, 2-(2-hydroxybiphenyl-3-yl)-lH-indole-5-carboxamidine (1) (Verner, E.; Katz, B. A.; Spencer, J.; Allen, D.; Hataye, J.; Hruzewicz, W.; Hui, H. C.; Kolesnikov, A.; Li, Y.; Luong, C.; Martelli, A.; Radika. K.; Rai, R.; She, M.; Shrader, W.; Sprengeler, P. A.; Trapp, S.; Wang, J.; Young, W. B.; Mackman, R. L. J. Med. Chem. 2001, 44, 2753-2771) has been optimized through minor structural changes on the S1 binding group to afford remarkably selective and potent inhibitors of urokinase-type plasminogen activator (uPA). The trypsin-like serine proteases1 that comprise drug targets can be broadly categorized into two subfamilies, those with Ser190 and those with Ala190. A single-atom modification, for example, replacement of hydrogen for chlorine at the 6-position of the 5-amidinoindole P1 group on 1, generated up to 6700-fold selectivity toward the Ser190 enzymes and against the Alal90 enzymes. The larger chlorine atom displaces a water molecule (H2O1s1) that binds near residue 190 in all the complexes of 1, and related inhibitors, in uPA, thrombin, and trypsin. The water molecule, H2O1s1, in both the Ser190 or Ala190 enzymes, hydrogen bonds with the amidine N1 nitrogen of the inhibitor. When it is displaced, a reduction in affinity toward the Ala190 enzymes is observed due to the amidine N1 nitrogen of the bound inhibitor being deprived of a key hydrogen-bonding partner. In the Ser190 enzymes the affinity is maintained since the serine hydroxyl oxygen Oγser190 compensates for the displaced water molecule. Highresolution crystallography provided evidence for the displacement of the water molecule and validated the design rationale. In summation, a novel and powerful method for engineering selectivity toward Ser190 proteases and against Ala190 proteases without substantially increasing molecular weight is described.
