- 4-ALKYNYL IMIDAZOLE DERIVATIVE AND MEDICINE COMPRISING SAME AS ACTIVE INGREDIENT
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There are provided 4-alkynylimidazole derivatives represented by the following general formula (I) or phamaceutically acceptable salts thereof; the derivatives have a superior EP4 receptor antagonistic action and are useful as pharmaceuticals for the trea
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- 4-ALKYNYL IMIDAZOLE DERIVATIVE AND MEDICINE COMPRISING SAME AS ACTIVE INGREDIENT
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There are provided 4-alkynylimidazole derivatives represented by the following general formula (I) or phamaceutically acceptable salts thereof; the derivatives have a superior EP4 receptor antagonistic action and are useful as pharmaceuticals for the trea
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- Design, synthesis, and structure-activity relationship studies of a potent PACE4 inhibitor
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PACE4 plays an important role in the progression of prostate cancer and is an attractive target for the development of novel inhibitor-based tumor therapies. We previously reported the design and synthesis of a novel, potent, and relatively selective PACE4 inhibitor known as a Multi-Leu (ML) peptide. In the present work, we examined the ML peptide through detailed structure-activity relationship studies. A variety of ML-peptide analogues modified at the P8-P5 positions with leucine isomers (Nle, DLeu, and DNle) or substituted at the P1 position with arginine mimetics were tested for their inhibitory activity, specificity, stability, and antiproliferative effect. By incorporating d isomers at the P8 position or a decarboxylated arginine mimetic, we obtained analogues with an improved stability profile and excellent antiproliferative properties. The DLeu or DNle residue also has improved specificity toward PACE4, whereas specificity was reduced for a peptide modified with the arginine mimetic, such as 4-amidinobenzylamide.
- Kwiatkowska, Anna,Couture, Frédéric,Levesque, Christine,Ly, Kévin,Desjardins, Roxane,Beauchemin, Sophie,Prahl, Adam,Lammek, Bernard,Neugebauer, Witold,Dory, Yves L.,Day, Robert
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- COMPOUNDS AND METHODS
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Disclosed are compounds having the formula (I) and salts thereof wherein A, B, m, and n are as defined herein, and methods of making and using the same
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Page/Page column 31
(2013/05/22)
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- INHIBITORS OF FURIN AND OTHER PRO-PROTEIN CONVERTASES
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Disclosed herein are Furin/PC inhibitors for inhibiting Furin and other Propprotein Convertases. Method of making the Furin/PC inhibitors, chemical and biological characterization of the Furin/PC inhibitors, and the use of the Furin/PC inhibitors to treat
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- Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1α
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By design: Novel small-molecule inhibitors of the interaction between the von Hippel-Lindau ligase (VHL) and its molecular target HIF1α, a transcription factor involved in oxygen sensing, have been developed and studied. The most potent inhibitor binds with an IC50 value of 0.9-μM and is thus the first sub-micromolar inhibitor of the VHL-HIF1α interaction. Copyright
- Buckley, Dennis L.,Gustafson, Jeffrey L.,Van-Molle, Inge,Roth, Anke G.,Tae, Hyun Seop,Gareiss, Peter C.,Jorgensen, William L.,Ciulli, Alessio,Crews, Craig M.
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supporting information
p. 11463 - 11467
(2013/01/15)
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- TRIAZOLE OXADIAZOLES DERIVATIVES
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The invention relates to compounds of formula (I), wherein R1, R2, Ra, Rb, X have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.
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Page/Page column 113
(2009/07/25)
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- OXADIAZOLE DERIVATIVES WITH ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE PROPERTIES
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Disclosed are polycyclic compounds of the following formula (I) and their use as anti-inflammatory and immunosuppressive agents.
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Page/Page column 12-13
(2008/06/13)
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- Base-substituted benzylamine analogs for use as coagulation factor xa inhibitors, the production and use thereof
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The invention relates to the novel base-substituted benzylamine analogs of general formula (I), wherein A represents P2-P1 with P1=(A) and P2=(B), for use as coagulation factor Xa inhibitors. The invention also relates to the production and use of said analogs in the therapy and prophylaxis of cardiovascular diseases and thromboembolic events.
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Page/Page column 8
(2008/06/13)
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- 4-Amidinobenzylamine-Based Inhibitors of Urokinase
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A series of 4-amidinobenzylamine-based peptidomimetic inhibitors of urokinase was synthesized. The most potent one, benzylsulfonyl-D-Ser-Ala-4-amidinobenzylamide 16, inhibits uPA with a Ki of 7.7 nM but is less selective than 10 with a Gly as P2 residue. Hydroxyamidine and carbonate prodrugs were prepared, which are rapidly converted into the active inhibitors in rats after subcutaneous application.
- Kuenzel, Sebastian,Schweinitz, andrea,Reissmann, Siegmund,Stuerzebecher, Joerg,Steinmetzer, Torsten
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p. 644 - 648
(2007/10/03)
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