|
Title
|
|
|
|
Efforts towards an on‐target version of the Groebke‐Blackburn‐Bienaymé (GBB) reaction for discovery of druglike urokinase (uPA) inhibitors
|
|
|
Author
|
|
|
|
|
|
|
Abstract
|
|
|
|
| Target‐guided synthesis (TGS) has emerged as a promising strategy in drug discovery. While reported examples of TGS generally involve two‐component reactions, there is a strong case for developing target‐guided versions of three‐component reactions (3CRs) because of their potential to deliver highly diversified, druglike molecules. To this end, the Groebke‐Blackburn‐Bienaymé reaction was selected as model 3CR. We recently reported a series of druglike, urokinase inhibitors serving as reference compounds in this study. Due to the limited number of literature reports on target‐guided 3CRs, multiple experimental parameters were optimized here. Most challenging was formation of imine intermediates under near‐physiological conditions. The latter was addressed in this study by exploring chemical imine stabilization strategies. Noteworthy, imines are also crucial intermediates of other 3CRs. Such systematic studies are strongly required for further development of the TGS domain, but absent in literature. Hence this work intends to be a reference for future multicomponent‐based TGS studies. |
|
|
|
Language
|
|
|
|
English
|
|
|
Source (journal)
|
|
|
|
Chemistry: a European journal. - Weinheim
|
|
|
Publication
|
|
|
|
Weinheim
:
2019
|
|
|
ISSN
|
|
|
|
0947-6539
|
|
|
DOI
|
|
|
|
10.1002/CHEM.201901917
|
|
|
Volume/pages
|
|
|
|
25
:53
(2019)
, p. 12380-12393
|
|
|
ISI
|
|
|
|
000484110700001
|
|
|
Pubmed ID
|
|
|
|
31298443
|
|
|
Full text (Publisher's DOI)
|
|
|
|
|
|
|
Full text (open access)
|
|
|
|
|
|
|
Full text (publisher's version - intranet only)
|
|
|
|
|
|