Synthesis and biological evaluation of benzodiazepines containing a pentafluorosulfanyl group

Chemistry of Pentafluorosulfanyl Derivatives and Related Analogs: From Synthesis to Applications

“…In 2015, Duda and Lentz reported the synthesis of F 5 SÀ C�CÀ CF 3 (136) in two steps from 3,3,3-trifluoropropyne and used it in Diels-Alder reactions with various dienes such as diphenylbenzoisofuran, furan, cyclohepta-1,3,5-triene, 2H-pyran-2-one, and a cyclopentadienone derivative to name a few. The respective addition products 137a-d were obtained in fair to excellent yields (Scheme 42).…”

“…However, such modification induced a loss of potency and GABA A selectivity compared to diazepam. [136] Besides the abovementioned applications in medicinal chemistry, the SF 5 group has been recently deployed to protein design, through the incorporation of unnatural SF 5 -containing amino acids. The first reported amino acid sequence bearing an SF 5 has been reported by the group of Welch.…”

Recent Advances in the Synthesis and Medicinal Chemistry of SF5 and SF4Cl Compounds

“…Alkylation of the starting phenylpiperazine derivatives with 5-bromovaleronitrile, followed by reduction with Raney Ni led to the corresponding amines in good yields. Eventually, the primary amines were The synthesis of a benzodiazepine diazepam analogue bearing an SF 5 group as a bioisosteric replacement of the chlorine atom was reported by Spencer et al 56 Acylation of commercially available 2-amino-5-SF 5 -benzophenone with chloroacetyl chloride followed by amination with hexamethylenetetramine, led to 7-SF 5 -5-phenyl-1H-benzo [1,4]diazepin-2(3H)-one, which was then converted into the desired compound by N-methylation (Scheme 63). Biological tests demonstrated that the substitution of Cl with the SF 5 group led to a loss of potency (60-fold lower) in terms of potentiating GABA A receptor activation, probably due to a loss of ligand interaction with His102 in the GABA A receptor α subunit.…”

Expanding the Repertoire of Low‐Molecular‐Weight Pentafluorosulfanyl‐Substituted Scaffolds

“…Recent years have seen a rise in SF 5 ‐substituted compounds as direct access to aryl‐ and alkyl‐SF 5 building blocks has been achieved [9,10] . We have recently incorporated the SF 5 group in benzodiazepine and oxindole analogues (Figure 1) [11,12] . In the former example, significant activity was lost, likely due to the steric size of the SF 5 group compared to a Cl substituent.…”

“…[ 9 , 10 ] We have recently incorporated the SF 5 group in benzodiazepine and oxindole analogues (Figure 1). [ 11 , 12 ] In the former example, significant activity was lost, likely due to the steric size of the SF 5 group compared to a Cl substituent.…”