- Discovery of a novel class of inhaled dual pharmacology muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD)
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The targeting of both the muscarinic and β-adrenergic pathways is a well validated therapeutic approach for the treatment of chronic obstructive pulmonary disease (COPD). In this communication we report our effort to incorporate two pharmacologies into a single chemical entity, whose characteristic must be suitable for a once daily inhaled administration. Contextually, we aimed at a locally acting therapy with limited systemic absorption to minimize side effects. Our lung-tailored design of bifunctional compounds that combine the muscarinic and β-adrenergic pharmacologies by the elaboration of the muscarinic inhibitor 7, successfully led to the potent, pharmacologically balanced muscarinic antagonist and β2 agonist (MABA) 13.
- Rancati, Fabio,Linney, Ian D.,Rizzi, Andrea,Delcanale, Maurizio,Knight, Chris K.,Schmidt, Wolfgang,Pastore, Fiorella,Riccardi, Benedetta,Mileo, Valentina,Carnini, Chiara,Cesari, Nicola,Blackaby, Wesley P.,Patacchini, Riccardo,Carzaniga, Laura
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supporting information
(2021/04/12)
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- Preparation and properties of a novel solution of hydrogen bromide (HBr) in 1,4-dioxane: An alternative reagent to HBr gas without protic solvents
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A solution of hydrogen bromide (HBr) in 1,4-dioxane was prepared and investigated for its ability to brominate alcohols, and hydrobrominate alkenes. This study revealed that the brominating ability of this HBr/1,4-dioxane solution is equal or superior to that of hydrobromic acid or HBr in acetic acid. The solution of HBr in 1,4-dioxane is robust, exhibiting no decomposition of the solvent, and retaining 97% of its original concentration, when kept at ?25 °C for 30 days. This solution is a liquid alternative to HBr gas without protic solvents.
- Nishio, Yuya,Mifune, Ryota,Sato, Taisuke,Ishikawa, Shin-ich,Matsubara, Hiroshi
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p. 1190 - 1193
(2017/03/02)
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- METHOD FOR PRODUCING BROMINE-CONTAINING CYCLIC ACETAL COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for producing a bromine-containing cyclic acetal compound with high efficiency and high yields and, additionally, provide a highly safe and inexpensive production method. SOLUTION: A bromine-containing cyclic acetal compound is obtained with high yields by the reaction of an α,β-unsaturated carbonyl compound, hydrogen bromide and ethylene glycol in coexistence of ether. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0039
(2017/06/24)
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- Concise catalytic asymmetric total synthesis of biologically active tropane alkaloids
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A general strategy for the total asymmetric synthesis of valuable tropane alkaloids by catalytic stereoselective transformations is disclosed. The power of this approach is exemplified by the concise catalytic enantioselective total syntheses of (+)-methylecgonine, (-)-cocaine and (+)-cocaine as well as the first catalytic asymmetric total syntheses of a cocaine C-1 derivative and (+)-ferruginine starting from 5-oxo-protected-α,β-unsaturated enals using only two and three column chromatographic purification steps, respectively. Copyright
- Cordova, Armando,Lin, Shuangzheng,Tseggai, Abrehet
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supporting information; experimental part
p. 1363 - 1372
(2012/06/18)
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- AN IMPROVED SYNTHESIS OF 2-(β-BROMOETHYL)-2-METHYL-1,3-DIOXOLANE, A USEFUL METHYL VINYL KETONE EQUIVALENT
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A general method for the formation of β-bromo-ketals, and its application to an improved synthesis of 2-(β-bromoethyl)-2-methyl-1,3-dioxolane, a useful methyl vinyl ketone equivalent, in 82percent yield, are described.
- Hsung, Richard P.
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p. 1175 - 1179
(2007/10/02)
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- INTRAMOLECULAR DIELS-ALDER REACTION OF THIOALDEHYDES
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Intramolecular Diels-Alder reaction of thioaldehydes which were generated from bis(trimethylsilyl)sulfide and dienals gave the corresponding bicyclic adducts.
- Segi, Masahito,Takahashi, Mamoru,Nakajima, Tadashi,Suga, Sohei,Sonoda, Noboru
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p. 2431 - 2440
(2007/10/02)
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- TRIMETHYLSILYL-HALIDE-MEDIATED CONJUGATED ADDITION TO ALLYLIC ACETALS
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Trimethylsilyl chloride can effect the conjugated addition of NaX (X=Br, I, SCN) to α,β-unsaturated acetals and ketals without deprotection of the carbonyl group.
- Feringa, Ben L.
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