accepted Tet paper 150221.pdf (500.04 kB)
Synthesis and biological evaluation of benzodiazepines containing a pentafluorosulfanyl group
journal contribution
posted on 2023-06-09, 23:28 authored by Arathy Jose, Raysa Khan, Martin Mortensen, Remi Legay, Simon J Coles, Graham J Tizzard, Barnaby GreenlandBarnaby Greenland, Trevor G Smart, Mark BagleyMark Bagley, John SpencerJohn SpencerThe widely used pentafluorosulfanyl group (SF5) was deployed as a bioisosteric replacement for a chloro-group in the benzodiazepine diazepam (Valium™). Reaction of 2-amino-5-pentafluorosulfanyl-benzophenone with chloroacetyl chloride followed by hexamethylenetetramine, in the presence of ammonia, led to 7-sulfurpentafluoro-5-phenyl-1H-benzo[1,4]diazepin-2(3H)-one (2c). The latter was able to undergo a Pd-catalysed ortho-arylation, demonstrating that these highly fluorinated benzodiazepines can be further modified to form more complicated scaffolds. The replacement of Cl by the SF5 group, led to a loss of potency for potentiating GABAA receptor activation, most likely because of a lost ligand interaction with His102 in the GABAA receptor a subunit. Dedicated to Professor Jonathan Williams, an inspirational and humble pioneer, a colleague and mentor in chemistry.
History
Publication status
- Published
File Version
- Accepted version
Journal
TetrahedronISSN
0040-4020Publisher
ElsevierExternal DOI
Volume
85Page range
1-6Article number
a132020Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-03-29First Open Access (FOA) Date
2022-02-21First Compliant Deposit (FCD) Date
2021-03-29Usage metrics
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