- PYRAZINE DERIVATIVES
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The invention concerns pyrazine derivatives of the Formula (I) or pharmaceutically-acceptable salts thereof; wherein each of n, m and R has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of bone-related disorders or conditions
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Page/Page column 66
(2011/08/08)
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- Design of peptide hydroxamate-based photoreactive activity-based probes of zinc-dependent metalloproteases
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Metalloproteases (ADAMs, MMPs) are multidomain proteins that play key roles in extracellular matrix remodelling and degradation, in cell-cell and cell-matrix interactions and in the proteolytic liberation of membrane-anchored proforms of cytokines and gro
- Geurink, Paul P.,Klein, Theo,Prely, Laurette,Paal, Krisztina,Leeuwenburgh, Michiel A.,Van Der Marel, Gijs A.,Kauffman, Henk F.,Overkleeft, Herman S.,Bischoff, Rainer
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experimental part
p. 2100 - 2112
(2010/08/19)
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- Design and preparation of potent, nonpeptidic, bioavailable renin inhibitors
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Starting from known piperidine renin inhibitors, a new series of 3,9-diazabicyclo[3.3.1]nonene derivatives was rationally designed and prepared. Optimization of the positions 3, 6, and 7 of the diazabicyclonene template led to potent renin inhibitors. The substituents attached at the positions 6 and 7 were essential for the binding affinity of these compounds for renin. The introduction of a substituent attached at the position 3 did not modify the binding affinity but allowed the modulation of the ADME properties. Our efforts led to the discovery of compound (+)-26g that inhibits renin with an IC 50 of 0.20 nM in buffer and 19 nM in plasma. The pharmacokinetics properties of this and other similar compounds are discussed. Compound (+)-26g is well absorbed in rats and efficacious at 10 mg/kg in vivo.
- Bezen?on, Olivier,Bur, Daniel,Weller, Thomas,Richard-Bildstein, Sylvia,Remeň, Lubo?,Sifferlen, Thierry,Corminboeuf, Olivier,Grisostomi, Corinna,Boss, Christoph,Prade, Lars,Delahaye, Stéphane,Treiber, Alexander,Strickner, Panja,Binkert, Christoph,Hess, Patrick,Steiner, Beat,Fischli, Walter
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supporting information; experimental part
p. 3689 - 3702
(2010/04/02)
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- Novel Piperidine Carboxylic Acid Amide Derivatives
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The invention relates to novel piperidine carboxylic acid amide derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of these
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Page/Page column 9
(2008/12/08)
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- RENIN INHIBITORS
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The present invention relates to novel renin inhibitors of the general Formula (I), and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds. These novel renin inhibitors are used in treating cardiovascular events and renal insufficiency.
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- NOVEL DIAZABICYCLONONENE DERIVATIVE
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The invention relates to a novel 3,9-diazabicyclo[3.3.1]nonene derivative and the enantiomers thereof and the use thereof as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including proces
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Page/Page column 15-16
(2010/11/08)
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- Design and synthesis of a potent biotinylated Smac mimetic
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A biotinylated Smac mimetic (2) was designed based upon our previously reported potent, conformationally constrained Smac mimetic (1). Smac mimetic (2) was synthesized and determined to bind to XIAP protein with a high-affinity (Ki value of 13
- Sun, Haiying,Nikolovska-Coleska, Zaneta,Yang, Chao-Yie,Wang, Shaomeng
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p. 7015 - 7018
(2007/10/03)
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- 19-nor steroids substituted in position 11β, preparation method and intermediates, application as medicines and pharmaceutical compositions containing them
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A compound selected from the group consisting of the compounds of the formula wherein the substituents are defined as in the specification and their addition salts with non-toxic, pharmaceutically acceptable acids and bases having estrogenic activity at t
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- Fused pyridine derivatives
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The present provides a condensed pyridine compound (I) represented by the following formula: (wherein, R2represents ring A represents benzene ring, pyridine ring, thiophene ring or furan ring; and B represents its pharmaceutically acceptable salt or hydrates thereof, which is a clinically useful medicament having a serotonin antagonism, in particular, that for treating, ameliorating or preventing spastic paralysis or central muscle relaxants for ameliorating myotonia.
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- Synthesis of a photoaffinity-labeling analog of alternariolide (AM-toxin I), a host-specific phytotoxin
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A photoaffinity-labeling analog of alternariolide (AM-toxin I) which contains L-2-amino-5-[4-(1-azi-2,2,2-trifluoro)ethyl-phenyl]pentanoic acid (10) was synthesized.
- Hashimoto, Kimiko,Yoshioka, Takuya,Morita, Chikanori,Sakai, Mitsuru,Okuno, Toshikatsu,Shirahama, Haruhisa
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p. 203 - 204
(2007/10/03)
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- Asymmetric synthesis of benzilic acid analogues using 8-phenylmenthol as a chiral auxiliary
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Our program on the synthesis of 18F-labeled muscarinic receptor ligands required the preparation of chiral fluoroalkyl benzilic acids. An enantioselective synthesis of substituted benzilic acids was achieved using 8-phenylmenthol as the chiral auxiliary. Grignard addition to the si face of 8-phenylmenthyl benzoylformate 7 proceeded with high selectivity. The results of the chiral induction support assignments of the chirality of benzilic acids previously resolved by crystallization. The method was used to synthesize (R)-quinuclidinyl-(R)-4-iodo)benzilate, which proved identical to an authentic sample. In addition, the method allows the preparation of (R)- and (S)-fluoroethyl benzilic acids in a stereoselective manner.
- Kiesewetter
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p. 2183 - 2198
(2007/10/02)
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