Late-Stage Functionalization of Drug-Like Molecules Using Diversinates.

Autor: Kuttruff CA; Department for Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397, Biberach an der Riss, Germany., Haile M; Department for Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397, Biberach an der Riss, Germany., Kraml J; Department for Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397, Biberach an der Riss, Germany., Tautermann CS; Department for Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397, Biberach an der Riss, Germany.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2018 May 23; Vol. 13 (10), pp. 983-987. Date of Electronic Publication: 2018 Apr 23.
DOI: 10.1002/cmdc.201800151
Abstrakt: Late-stage functionalization (LSF) is a powerful method to quickly generate new analogues of a lead structure without resorting to de novo synthesis. We have leveraged Baran Diversinates to carry out late-stage functionalizations on lead structures from internal drug discovery projects and accurately predicted regioselectivities using computational methods. Our functionalization successfully afforded specific regioisomers which were in line with our predictions. To enhance reactivity, decrease reaction time, and increase reaction yields, we have developed new functionalization conditions involving iron(III) catalysis. Finally, we demonstrate how our LSF reactions using Baran Diversinates can lead to new analogues with improved in vitro DMPK parameters.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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