36754-60-6Relevant articles and documents
SNAr catalysis enhanced by an aromatic donor-acceptor interaction; Facile access to chlorinated polyfluoroarenes
Senaweera, Sameera,Weaver, Jimmie D.
supporting information, p. 7545 - 7548 (2017/07/12)
Selective catalytic SNAr reaction of polyfluoroaryl C-F bonds with chloride is shown. Stoichiometric TMSCl makes the reaction exergonic and allows catalysis, which involves ground state elevation of chloride, aromatic donor-acceptor interactions, and stabilization of the Meisenheimer complex. Traditional cross-coupling of the products is now possible and demonstrates the utility.
A systematic exploration of the effects of flexibility and basicity on sigma (σ) receptor binding in a series of substituted diamines
Conroy, Trent,Manohar, Madhura,Gong, Yu,Wilkinson, Shane M.,Webster, Michael,Lieberman, Brian P.,Banister, Samuel D.,Reekie, Tristan A.,Mach, Robert H.,Rendina, Louis M.,Kassiou, Michael
supporting information, p. 9388 - 9405 (2016/10/13)
The sigma-1 receptor (S1R) has attracted a great deal of attention as a prospective drug target due to its involvement in numerous neurological disorders and, more recently, for its therapeutic potential in neuropathic pain. As there was no crystal structure of this membrane-bound protein reported until 2016, ligand generation was driven by pharmacophore refinements to the general model suggested by Glennon and co-workers. The generalised S1R pharmacophore comprises a central region where a basic amino group is preferred, flanked by two hydrophobic groups. Guided by this pharmacophore, S1R ligands containing piperazines, piperazinones, and ethylenediamines have been developed. In the current work, we systematically deconstructed the piperazine core of a prototypic piperazine S1R ligand (vide infra) developed in our laboratories. Although we did not improve the affinity at the S1R compared to the lead, we identified several features important for affinity and selectivity. These included at least one basic nitrogen atom, conformational flexibility and, for S1R, a secondary or tertiary amine group proximal to the anisole. Furthermore, S2R selectivity can be tailored with functional group modifications of the N-atom proximal to the anisole.
Synthesis and binding assays of novel 3,3-dimethylpiperidine derivatives with various lipophilicities as σ1 receptor ligands
Ferorelli, Savina,Abate, Carmen,Pedone, Maria P.,Colabufo, Nicola A.,Contino, Marialessandra,Perrone, Roberto,Berardi, Francesco
experimental part, p. 7612 - 7622 (2012/01/04)
Starting from two carbocyclic analogs, a series of 3,3-dimethylpiperidine derivatives was prepared and tested in radioligand binding assays at σ1 and σ2 receptors, and at Δ8-Δ7 sterol isomerase (SI) site. The novel compounds mostly bear heterocyclic rings or bicyclic nucleus of differing lipophilicities. Compounds 18a and 19a,b demonstrated the highest σ1 affinity (Ki = 0.14-0.38 nM) with a good selectivity versus σ2 binding. Among them, 18a had the lowest C log D value (3.01) and only 19b was selective versus SI too. Generally, it was observed that more planar and hydrophilic heteronuclei conferred a decrease in affinity for both σ receptor subtypes.
