- N-(PYRIDIN-2-YLSULFONYL)CYCLOPROPANECARBOXAMIDE DERIVATIVES AND THEIR USE IN THE TREATMENT OF A CFTR MEDIATED DISEASE
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The invention relates to heterocyclic compounds of the formula (I), in which all of the variables are as defined in the specification; capable of modulating the activity of CFTR. The invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including Cystic fibrosis and related disorders.
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Page/Page column 193
(2020/07/14)
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- Base-promoted diastereoselective α-alkylation of borane: N -((S)-1′-phenylethyl)azetidine-2-carboxylic acid ester complexes
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The base-promoted α-alkylation of N-((S)-1-phenylethyl)azetidine-2-carboxylic acid esters 1 was investigated. The use of diastereomerically pure borane complexes 3 as substrates, which are easily prepared from 1, dramatically improved the yields and diastereoselectivities of α-alkylated products 2. For example, the treatment of tert-butyl ester (1S,2S,1′S)-3a with 2.4 equivalents of lithium bis(trimethysilyl)amide (LiHMDS) at 0 °C followed by 2.6 equivalents of benzyl bromide afforded α-benzylated (2S,1′S)-2aa in 90% yield as almost a single diastereomer. Our method enables the production of optically active α-substituted azetidine-2-carboxylic acid esters starting from commercially available (S)-1-phenylethylamine, which is one of the least expensive chiral compounds.
- Tayama, Eiji,Nishio, Ryotaro,Kobayashi, Yoshiaki
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supporting information
p. 5833 - 5845
(2018/08/22)
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- Synthesis of Substituted Cyclopropanecarboxylates via Room Temperature Palladium-Catalyzed α-Arylation of Reformatsky Reagents
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The room temperature palladium-catalyzed cross-coupling of aromatic and heteroaromatic halides with Reformatsky reagents derived from 1-bromocyclopropanecarboxylates provides an exceptionally mild method for enolate α-arylation. The method is tolerant of a wide range of functionalities and dramatically shortens many of the existing routes to access widely used 1,1-disubstituted cyclopropanecarboxylate derivatives.
- Greszler, Stephen N.,Halvorsen, Geoff T.,Voight, Eric A.
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supporting information
p. 2490 - 2493
(2017/05/24)
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- Ring-Strain Effects in Base-Induced Sommelet–Hauser Rearrangement: Application to Successive Stereocontrolled Transformations
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The base-induced Sommelet–Hauser (S–H) rearrangement of azetidine-2-carboxylic acid ester-derived ammonium salts into 2-aryl-substituted derivatives was demonstrated. The ring-strain of four-membered N-heterocycles enables efficient generation of the desired ylide intermediate and enhances the rate of the S–H rearrangement. The asymmetric version of the rearrangement was characterized by excellent levels of successive chirality transmissions. The regio- and stereo-controlled nucleophilic ring opening of the rearrangement products produced quaternary α-aryl amino acid esters with excellent enantiopurities.
- Tayama, Eiji,Watanabe, Kazutoshi,Matano, Yoshihiro
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supporting information
p. 3631 - 3641
(2016/07/29)
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- Peptide deformylase inhibitors
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The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.
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Page/Page column
(2014/12/09)
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- PEPTIDE DEFORMYLASE INHIBITORS
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The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhi-bition of bacterial peptide deformylase (PDF) activity
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Page/Page column
(2014/02/15)
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