- Identification of a manufacturing route of novel CRF-1 antagonists containing a 2,3-Dihydro-1 H-pyrrolo[2,3-b]pyridine moiety
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A case study on the synthesis of novel CRF-1 antagonists containing the 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine moiety is presented. The development of ever more efficient synthetic routes allowed the progression of three candidates at the same time. A manu
- Ribecai, Arianna,Bacchi, Sergio,Delpogetto, Monica,Guelfi, Simone,Manzo, Angelo Maria,Perboni, Alcide,Stabile, Paolo,Westerduin, Pieter,Hourdin, Marie,Rossi, Sara,Provera, Stefano,Turco, Lucilla
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p. 895 - 901
(2011/03/20)
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- Synthesis and pharmacological characterization of novel druglike corticotropin-releasing factor 1 antagonists
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To identify new CRF1 receptor antagonists, an attempt to modify the bis-hetherocycle moiety present in the top region of the dihydropirrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF1 receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by more hydrophilic non aromatic hetherocycles able to make appropriate H-bond interactions with amino acid residues Thr192 and Tyr195. This exploration, followed by an accurate analysis of the substitution of the pendant aryl ring, enabled to identify in vitro potent compounds showing excellent pharmacokinetics and outstanding in vivo activity in animal models of anxiety, both in rodents and primates.
- Di Fabio, Romano,St-Denis, Yves,Sabbatini, Fabio M.,Andreotti, Daniele,Arban, Roberto,Bernasconi, Giovanni,Braggio, Simone,Blaney, Frank E.,Capelli, Anna M.,Castiglioni, Emiliano,Di Modugno, Enza,Donati, Daniele,Fazzolari, Elettra,Ratti, Emiliangelo,Feriani, Aldo,Contini, Stefania,Gentile, Gabriella,Ghirlanda, Damiano,Provera, Stefano,Marchioro, Carla,Roberts, Karen L.,Mingardi, Anna,Mattioli, Mario,Nalin, Arnaldo,Pavone, Francesca,Spada, Simone,Trist, David G.,Worby, Angela
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experimental part
p. 7370 - 7379
(2010/01/21)
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- PROCESS FOR PREPARING BICYCLIC COMPOUNDS
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The present invention relates to a process for preparing compounds of formula (IA), which are potent and specific antagonists of corticotropin-releasing factor (CRF) receptors, from intermediate compounds of formula (I), by a coupling reaction catalysed b
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Page/Page column 28
(2008/06/13)
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