The azulene scaffold from a medicinal chemist's perspective: Physicochemical and in  vitro parameters relevant for drug discovery

Eur J Med Chem. 2022 Apr 12;237:114374. doi: 10.1016/j.ejmech.2022.114374. Online ahead of print.ABSTRACTAzulene is a bicyclic scaffold rarely applied in medicinal chemistry. Here we report physicochemical and in vitro parameters relevant for drug discovery for a series of diversely substituted azulenes. We synthesized and characterized several scaffold hopping series of analogously substituted azulenes, indoles and naphthalenes. This enabled a comparison of azulene with the more common scaffolds indole and naphthalene. Our data indicates that undesirably low photostability of azulenes is restricted to certain substitution patterns. Generally, we conclude that azulene is an underused lipophilic bicycle and should be considered as a valuable complement to the collection of medicinal chemistry scaffolds.PMID:35436668 | DOI:10.1016/j.ejmech.2022.114374

Source: European Journal of Medicinal Chemistry - April 18, 2022 Category: Chemistry Authors: Teppo O Leino Peter Sieger Jari Yli-Kauhaluoma Erik A A Wall én J örg T Kley Source Type: research