- Route selection and process development of a multikilogram route to the inhaled A2a agonist UK-432,097
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This article describes the selection, process development, and scale-up of a synthetic route to a complex nucleoside analogue, the A2a agonist UK-432,097 (1), that culminated in the manufacture of over 25 kg of the API. The key steps in the process were (1) a stereoselective glycosidation reaction; (2) a scalable bleach-TEMPO oxidation; and (3) an unusual elevated temperature crystallization process for the final API. The problems that were encountered with the scale-up of the route together with how they were overcome are also presented.
- Ashcroft, Christopher P.,Dessi, Yann,Entwistle, David A.,Hesmondhalgh, Lynsey C.,Longstaff, Adrian,Smith, Julian D.
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p. 470 - 483
(2012/08/08)
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- Novel Ethanediamone Hepcidine Antagonists
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The present invention relates to novel hepcidin antagonists of formula (I), pharmaceutical compositions comprising them and the use thereof as medicaments, in particular for treatment of disorders in iron metabolism, such as, in particular, iron deficiency diseases and anaemias, in particular anaemias in connection with chronic inflammatory diseases (ACD: anaemia of chronic disease and AI: anaemia of inflammation).
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- Discovery of N-{1-[3-(3-Oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl] piperidin-4-yl}-2-phenylacetamide (Lu AE51090): An allosteric muscarinic M 1 receptor agonist with unprecedented selectivity and procognitive potential
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The discovery and Structure-activity relationship (SAR) of a series of allosteric muscarinic M1 receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M1 receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17.
- Sams, Anette G.,Hentzer, Morten,Mikkelsen, Gitte K.,Larsen, Krestian,Bundgaard, Christoffer,Plath, Niels,Christoffersen, Claus T.,Bang-Andersen, Benny
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supporting information; experimental part
p. 6386 - 6397
(2010/11/05)
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- Rifamycin analogs and uses thereof
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The present invention features rifamycin analogs that can be used as therapeutics for treating or preventing a variety of microbial infections. In one form, the analogs are acetylated at the 25-position, as is rifamycin. In another form, the analogs are deacetylated at the 25-position. In yet other forms, benzoxazinorifamycin, benzthiazinorifamycin, and benzdiazinorifamycin analogs are derivatized at various positions of the benzene ring, including 3′-hydroxy analogs, 4′-and/or 6′ halo and/or alkoxy analogs, and various 5′ substituents that incorporate a cyclic amine moiety.
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Page/Page column 35
(2008/06/13)
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- Rifamycin analogs and uses thereof
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The present invention features rifamycin analogs that can be used as therapeutics for treating or preventing a variety of microbial infections. In one form, the analogs are acetylated at the 25-position, as is rifamycin. In another form, the analogs are deacetylated at the 25-position. In yet other forms, benzoxazinorifamycin, benzthiazinorifamycin, and benzdiazinorifamycin analogs are derivatized at various positions of the benzene ring, including 3′-hydroxy analogs, 4′- and/or 6′ halo and/or alkoxy analogs, and various 5′ substituents that incorporate a cyclic amine moiety.
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Page/Page column 39-40
(2008/06/13)
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- 4-Aminopiperidine derivatives as a new class of potent cognition enhancing drugs
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Extrusion of one of the nitrogens of the piperazine ring of potent nootropic drugs previously described gave 4-aminopiperidine analogues that maintained high cognition enhancing activity in the mouse passive avoidance test. One of the new compounds (9, active at 0.01 mg/kg ip) may represent a new lead for the development of cognition enhancers useful to treat the cognitive deficit produced by neurodegenerative pathologies like Alzheimer's disease.
- Manetti, Dina,Martini, Elisabetta,Ghelardini, Carla,Dei, Silvia,Galeotti, Nicoletta,Guandalini, Luca,Romanelli, Maria Novella,Scapecchi, Serena,Teodori, Elisabetta,Bartolini, Alessandro,Gualtieri, Fulvio
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p. 2303 - 2306
(2007/10/03)
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