- ROR-GAMMA INHIBITORS
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The present invention relates to compounds of formula I and pharmaceutical compositions comprising compounds of formula I. Compounds of Formula I are useful in treatment of inflammatory, metabolic or autoimmune diseases which are mediated by RORy.
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Page/Page column 237
(2019/04/26)
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- An improved synthesis of 2-oxa-7-azaspiro[3,5]nonane and analogs as novel reagents in medicinal chemistry
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A detailed synthesis of novel spirocyclic oxetane analogs is described for the first time.
- Xu, Ruo,Czarniecki, Michael,Man, Jos De,Pan, Jianping,Qiang, Li,Root, Yuriko,Ying, Shihong,Su, Jing,Sun, Xijun,Zhang, Yuping,Yu, Tao,Zhang, Yang,Hu, Tao,Chen, Shu-Hui
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scheme or table
p. 3266 - 3270
(2011/07/08)
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- Oxetanes in drug discovery: Structural and synthetic insights
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An oxetane can trigger profound changes in aqueous solubility, lipophilicity, metabolic stability, and conformational preference when replacing commonly employed functionalities such as gem-dimethyl or carbonyl groups. The magnitude of these changes depends on the structural context. Thus, by substitution of a gem-dimethyl group with an oxetane, aqueous solubility may increase by a factor of 4 to more than 4000 while reducing the rate of metabolic degradation in most cases. The incorporation of an oxetane into an aliphatic chain can cause conformational changes favoring synclinal rather than antiplanar arrangements of the chain. Additionally spirocyclic oxetanes (e.g., 2-oxa-6-aza-spiro[3.3]heptane) bear remarkable analogies to commonly used fragments in drug discovery, such as morpholine, and are even able to supplant the latter in its solubilizing ability. A rich chemistry of oxetan-3-one and derived Michael acceptors provide venues for the preparation of a broad variety of novel oxetanes not previously documented, thus providing the foundation for their broad use in chemistry and drug discovery.
- Wuitschik, Georg,Carreira, Erick M.,Wagner, Bj?rn,Fischer, Holger,Parrilla, Isabelle,Schuler, Franz,Rogers-Evans, Mark,Müller, Klaus
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supporting information; scheme or table
p. 3227 - 3246
(2010/08/19)
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- Spirocyclic oxetanes: Synthesis and properties
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(Chemical Presented) Wormholes through chemical space: Spirocyclic oxetanes are described as analogues of morpholine and also as topological siblings of their carbonyl counterparts. They are particularly promising in terms of both their physicochemical properties and the ease with which they can be grafted onto molecular structures. The data collected highlight oxetanes as both the hydrophilic sister of a gem-dimethyl unit and the carbonyl group's lipophilic brother.
- Wuitschik, Georg,Rogers-Evans, Mark,Buckl, Andreas,Bernasconi, Maurizio,Maerki, Moritz,Godel, Thierry,Fischer, Holger,Wagner, Bjoern,Parrilla, Isabelle,Schuler, Franz,Schneider, Josef,Alker, Andre,Schweizer, W. Bernd,Mueller, Klaus,Carreira, Erick M.
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supporting information; experimental part
p. 4512 - 4515
(2009/02/08)
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