title: Effect of lipophilicity modulation on inhibition of human rhinovirus capsid binders.
abstract: To try and generate broad spectrum human rhinovirus VP1 inhibitors with more attractive physicochemical, DMPK and safety profiles, we explored the current SAR of known VP1 compounds. This lead to the identification of specific structural regions where reduction in polarity can be achieved, so guiding chemistry to analogues with significantly superior profiles to previously reported inhibitors.
authors: Department of Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. andy.morley@astrazeneca.com
authors: Andrew
authors: A
authors: Morley
authors: Nicholas
authors: N
authors: Tomkinson
authors: Andrew
authors: A
authors: Cook
authors: Catherine
authors: C
authors: MacDonald
authors: Richard
authors: R
authors: Weaver
authors: Sarah
authors: S
authors: King
authors: Lesley
authors: L
authors: Jenkinson
authors: John
authors: J
authors: Unitt
authors: Christopher
authors: C
authors: McCrae
authors: Tim
authors: T
authors: Phillips
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002213:Capsid / Q000187:drug effects*; D036022:Capsid Proteins / Q000378:metabolism*; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D010850:Picornaviridae Infections / Q000188:drug therapy*; D011485:Protein Binding; D011724:Pyridazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012229:Rhinovirus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D011724:Pyridazines