1055276-55-5Relevant articles and documents
Multivalent design of long-acting β2-adrenoceptor agonists incorporating biarylamines
Jacobsen, John R.,Aggen, James B.,Church, Timothy J.,Klein, Uwe,Pfeiffer, Juergen W.,Pulido-Rios, Teresa M.,Thomas, G. Roger,Yu, Cecile,Moran, Edmund J.
, p. 2625 - 2630 (2014/06/09)
A series of potent β2-adrenoceptor agonists incorporating a biarylamine secondary binding group was identified. The previously reported milveterol (5), identified by a multivalent approach and containing a typical β2-agonist primary binding group linked via a phenethylamine linker to a hydrophilic secondary binding group, served as an initiation point. A more hydrophobic set of secondary binding groups was explored, prepared rapidly from a common intermediate by Buchwald-Hartwig amination. TD-5471 (25), a potent and selective full agonist of the human β2- adrenoceptor, was identified as the most promising agent. It is potent, with slow onset in an in vitro guinea pig trachea model and shows a dose-dependent and long duration of action in an in vivo guinea pig model of bronchoprotection. TD-5471 is structurally differentiated from milveterol and its long duration of action is consistent with a correlation with hydrophobicity observed in other long-acting β2-agonist discovery programs.
Aryl aniline beta2 adrenergic receptor agonists
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Page 40, (2008/06/13)
The invention provides novel β2 adrenergic receptor agonist compounds of formula (I): wherein R1-R13 and w have any of the values described in the specification. The invention also provides combinations of such compounds and other therapeutic agents, pharmaceutical compositions comprising such compounds and combinations, methods of using such compounds to treat diseases associated with β2 adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.
