27475-14-5Relevant articles and documents
Conformational control enabled by the fluorine gauche effect in a model of the β2-AR agonist salbutamol (Ventolin)
Teschers, Charlotte S.,Daniliuc, Constantin G.,Kehr, Gerald,Gilmour, Ryan
supporting information, p. 1 - 5 (2018/03/13)
The bronchodilator salbutamol adopts a characteristic gauche conformation about the ?O-C-C-N torsion angle. This topology is predicated on stabilizing stereoelectronic interactions of the type σ → σC-X*. X-ray crystallographic analysis of salbutamol also indicates that an intramolecular hydrogen bond reinforces this intuitive conformation (?O-C-C-N ≈ 60°). In this study, we demonstrate that single site OH → F substitution in model salbutamol systems preserves the gauche conformational preference by virtue of reinforcing hyperconjugative interactions of the type σC-H → σC-F* and σC-C → σC-N*. Since the amine remains fully protected throughout this conformational analysis, intramolecular hydrogen bonding can be discounted. Conformational mimesis is confirmed by NMR spectroscopy in solution, and also in the solid state.
A multivalent approach to the discovery of long-acting β2- adrenoceptor agonists for the treatment of asthma and COPD
Jacobsen, John R.,Choi, Seok Ki,Combs, Jesse,Fournier, Eric J.L.,Klein, Uwe,Pfeiffer, Juergen W.,Thomas, G. Roger,Yu, Cecile,Moran, Edmund J.
scheme or table, p. 1213 - 1218 (2012/03/11)
A multivalent approach was applied to the design of long-acting inhaled β2-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting β2-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C2-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection.
Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity
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Page/Page column 42, (2008/06/13)
The invention is directed to compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7a, R7b, W, G1, G2, a, b, c, d and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.