- 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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- Synthesis of the C5-C30 fragment of cyclodidemniserinol trisulfate via I2-mediated deprotection and ring closure tandem reaction
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The marine natural product cyclodidemniserinol trisulfate displayed moderate HIV-1 integrase inhibitory activity. Its novel structure triggered our interest to synthesize it. In our total synthesis effort, the natural product was dissected into four fragments based on the rational retrosynthetic analysis. All four fragments were successfully prepared with orthogonal protection. And the assembly of fragment A and B furnished the C5-C30 key subunit by employing the I2-mediated deprotection and intramolecular ketal formation tandem reaction in the presence of NaHCO3 in MeCN. Our work provided flexible and practical approaches to synthesize and derive the 3,5,7-trisubstituted 6,8-dioxabicyclo [3.2.1] octane based analogs to search for new structure HIV-1 integrase inhibitors.
- Liu, Jian-Hua,Jin, Yi,Long, Ya-Qiu
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experimental part
p. 1267 - 1273
(2010/04/02)
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- Synthesis of a 11-deoxyprostanoid in the area of Preclavulones: (±)- 8,12-trans-(5Z-14Z)-9-oxo-prosta-5,14-dienoic acid from 2-allyl-2- cyclopenten-1-one
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Following our research on the arachidonic acid metabolites and their derivatives with potential biological activity, we describe the synthesis of the (±-8,12-trans-(5Z, 14Z)-9-oxo-prosta-5,14-dienoic acid, a 11- deoxyprostanoid correlated to the class of Preclavulones, one of the unusual families of marine eicosanoids from the coral Clavularia Viridis with considerable biological interest.
- Di Giacomo,Leggeri,Papeo,Pirillo,Traverso
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p. 379 - 385
(2007/10/02)
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- Diiodosilane. 4. Direct reduction of ketals and acetals in the presence of unprotected carbonyls. A case of inverted chemoselectivity
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Ketals and acetals are selectively reduced by diiodosilane to iodoalkanes in preference to ketones and aldehydes. This inversion of the normal order of reactivity of the 'protected' and 'unprotected' carbonyls allows partial reduction of polycarbonyl compounds with unusual regio- and chemoselectivity. Thus, 8,8-(ethylenedioxy)octan-2-one, 7,7-(ethylenedioxy)octanal, 3,3-(ethylenedioxy)-androstan-17-one and 3,3-(ethylenedioxy)pregnane-11,20-dione are converted to the corresponding iodo compounds.
- Keinan,Sahai,Shvily
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p. 641 - 643
(2007/10/02)
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- Metabolism of phencyclidine. The role of the carbinolamine intermediate in the formation of lactam and amino acid metabolites of nitrogen heterocycles
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The transformation of phencyclidine in a mouse liver microsome preparation to several oxidative metabolites was studied. With use of GLC and HPLC methods with internal standards, phencyclidine and six metabolites were quantitated and the amino acid, resulting from the α-oxidation of the piperidine ring, was produced in 10-50 times greater amounts than the other metabolites. While most piperidines and pyrrolidines produce an amino acid and a corresponding lactam, it was found that phencyclidine was not converted to the lactam.
- Baker,Little
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