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Best practice and advices for designing and generating fluorinated libraries and for their efficient 19F-NMR Screening

Vulpetti, Anna and Dalvit, Claudio (2013) Best practice and advices for designing and generating fluorinated libraries and for their efficient 19F-NMR Screening. ChemMedChem, 8. pp. 2057-2069.


Fragment screening performed with 19F NMR spectroscopy is
becoming increasingly popular in drug discovery projects.
With this approach, libraries of fluorinated fragments are first
screened using the direct-mode format of the assay. The
choice of fluorinated motifs present in the library is fundamental
in order to ensure a large coverage of chemical space and
local environment of fluorine (LEF). Mono- and poly-fluorinated
fragments to be included in the libraries for screening are selected
from both in-house and commercial collections, and
those that are ad hoc designed and synthesized. Additional fluorinated
motifs to be included in the libraries derive from the
fragmentation of compounds in development and launched
on the market, and compounds contained in other databases
(such as Integrity, PDB and ChEMBL). Complex mixtures of
highly diverse fluorine motifs can be rapidly screened and deconvoluted
in the same NMR tube with a novel on the fly combined
procedure for the identification of the active molecule(s).
Issues and problems encountered in the design, generation
and screening of diverse fragment libraries of fluorinated compounds
with 19F NMR spectroscopy are analyzed and technical
solutions are provided to overcome them. The versatile screening
methodology described here can be efficiently applied in
laboratories with limited NMR setup and could potentially lead
to the increasing role of 19F NMR in the hit identification and
lead optimization phases of drug discovery projects.

Item Type: Article
Additional Information: The only structure shown (Figure 4) is commercial: and already disclosed in OAK ID=1376
Keywords: Fragment Screening, Fluorine NMR spectroscopy, fluorinated fragment libraries, Local Environment of Fluorine (LEF)
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13


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