19594-02-6Relevant articles and documents
Air-stable palladium(0) phosphine sulfide catalysts for Ullmann-type C-N and C-O coupling reactions
Majumder, Arpi,Gupta, Ragini,Mandal, Mrinmay,Babu, Madhu,Chakraborty, Debashis
, p. 23 - 34 (2015/03/05)
This paper describes an efficient procedure for palladium(0)-catalyzed N-arylation and O-arylation of aryl halides by Ullmann-type cross coupling reaction under mild reaction conditions in a short reaction time. Two phosphine sulphide ligands and their corresponding Pd(0) complexes namely [Pd(p2S2)(dba)] and [Pd(pp3S4)(dba)], were synthesized, where p2S2 is 1,2-bis(diphenylphosphino)ethane disulfide, pp3S4 is tris[2-(diphenylphosphino)ethyl]phosphine tetrasulfide and dba is dibenzylideneacetone. Optimal reaction conditions were determined for the arylation reactions using iodobenzene and benzimidazole by varying temperature, solvent, base and catalyst loading. The cross coupling reactions were carried out taking iodobenzenes/bromobenzenes and a wide variety of substituted aryl amines/phenols/alcohols with different steric and electronic properties to afford the desired N-aryl amines/diaryl ethers/alkyl aryl ethers in good to excellent yield (70-94%).
Improvement of pharmacological properties of irreversible thyroid receptor coactivator binding inhibitors
Jong, Yeon Hwang,Arnold, Leggy A.,Zhu, Fangyi,Kosinski, Aaron,Mangano, Thomas J.,Setola, Vincent,Roth, Bryan L.,Guy, R. Kiplin
supporting information; experimental part, p. 3892 - 3901 (2010/02/17)
We have previously reported the discovery and preliminary structure activity relationships of a series of β-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity. Finally, utilization of amine moieties having low pKa's resulted in lowered ion channel activity without any loss of pharmacological activity.
Dicyclohexylethyleneglycol,-diethyleneglycol,-triethyleneglycol, and related monosubstituted cyclohexanes. Conformational analysis using low-temperature 13C and 1H NMR spectroscopy
Buchanan, G. W.,Moghimi, A.,Reynolds, V. M.,Bourque, K.
, p. 566 - 572 (2007/10/02)
Two conformations of each of the title molecules have been detected by 100 MHz 13C NMR at 210 K.For the dicyclohexyl systems, the conformations are related via a single ring inversion.In each case the equatorial-axial conformer is 4,7+/-0.4 kJ/mol less stable than the diequatorially substituted form in CD2Cl2 solution.For monosubstituted models, the conformational free energy (-ΔG deg) values of the -O-CH2-CH2-OCH3, -OCH2-CH2-O-CH2-CH3, and -O-CH2-CH2-O-CH-(CH3)2 groups have been determined to be 5.4, 6.1, and 6.1+/-0.2 kJ/mol, respectively.In methanol, the latter equilibria are slightly more biased towards the axially substituted conformers. Key words: substituted ethylene glycols, conformational equilibria.
