58236-74-1Relevant articles and documents
Alkyne Linchpin Strategy for Drug:Pharmacophore Conjugation: Experimental and Computational Realization of a Meta-Selective Inverse Sonogashira Coupling
Bhowmick, Suman,Guin, Srimanta,Kumar Singh, Vikas,Maiti, Debabrata,Paton, Robert S.,Porey, Sandip,Zhang, Xinglong
supporting information, p. 3762 - 3774 (2020/03/10)
The late-stage functionalization (LSF) of pharmaceutical and agrochemical compounds by the site-selective activation of C-H bonds provides access to diverse structural analogs and expands synthetically-accessible chemical space. We report a C-H functionalization LSF strategy that hinges on the use of an alkyne linchpin to assemble conjugates of sp2-rich marketed pharmaceuticals and agrochemicals with sp3-rich 3D fragments and natural products. This is accomplished through a template-assisted inverse Sonogashira reaction that displays high levels of selectivity for the meta position. This protocol is also amenable to distal structural modifications of α-amino acids. The transformation of alkyne functionality to other functional groups further highlights the applicative potential. Computational and experimental mechanistic studies shed light on the detailed mechanism. Turnover-limiting 1,2-migratory insertion of the bromoalkyne coupling partner occurs after relatively fast C-H activation. While this insertion occurs unselectively, regioconvergence results from one of the adducts undergoing a 1,2-trialkylsilyl migration to form the alkynylated product. A heterobimetallic Pd-Ag transition structure is essential for product formation in the β-bromide elimination step.
Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands
Sadeghzadeh, Masoud,Sheibani, Shahab,Ghandi, Mehdi,Daha, Fariba Johari,Amanlou, Massoud,Arjmand, Mohammad,Hasani Bozcheloie, Abolfazl
, p. 488 - 497 (2013/07/27)
This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and K iσ2 = 91.8 ± 8.1 nM).
Synthesis and PKCθ inhibitory activity of a series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles
Shim, Jaechul,Eid, Clark,Lee, Julie,Liu, Erica,Chaudhary, Divya,Boschelli, Diane H.
scheme or table, p. 6575 - 6577 (2010/06/12)
A series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles were prepared and evaluated as PKCθ inhibitors. Optimization resulted in the identification of compound 15 with an IC50 value 0.44 nM for the inhibition of PKCθ with 150-fold select
