215654-49-2Relevant articles and documents
Synthesis, structural characterization, and catalytic evaluation of phosphinoferrocene ligands bearing extended urea-amide substituents
Solarova, Hana,Cisarova, Ivana,Stepnicka, Petr
supporting information, p. 4131 - 4147 (2014/10/15)
New phosphinoferrocene ligands bearing extended polar amidourea pendants with the general formula Ph2PfcCONHCH2CH 2NHCONR2 (1; R2 = H2 (b), H/Et (c), Me2 (d), H/Ph (e)) and their model bis-amide Ph 2PfcCONHCH2CH2NHCOCH3 (1a) were prepared in good yields by amidation of 1′-(diphenylphosphino)ferrocene-1- carboxylic acid (Hdpf) with the appropriate amines in the presence of peptide coupling reagents. These ferrocene-based phosphinoureas were further employed as ligands in palladium(II) complexes with η3-allyl and NC-chelating supporting ligands: viz., [PdCl(η3-C 3H5)(1-κP)] (5a-e) and [PdCl(LNC)(1- κP)] (6a-e; LNC = [2-(dimethylamino-κN)methyl]phenyl- κC1). Both the free ligands and their Pd(II) complexes were characterized by spectroscopic methods (multinuclear NMR, IR, and MS) and by elemental analysis. The molecular structures of 1b·CH3OH, 1c, 5b,c, 6a, and two additional model complexes, [PdCl(η3-C 3H5)(Hdpf-κP)] (5f) and [PdCl(η3- C3H5)(Ph2PfcCONH2-κP)] (5g), were determined by single-crystal X-ray diffraction analysis. All Pd(II) complexes were evaluated as catalysts in the cross-coupling of boronic acids and acyl halides to give ketones in a toluene/water biphasic mixture. Extensive reaction studies with compound 5e, which not only exerts good catalytic activity but is also readily accessible in a defined crystalline form, demonstrated efficient coupling reactivity for unsaturated substrates such as (substituted) benzeneboronic acids and benzoyl chlorides. The results also revealed that reaction difficulties encountered with less reactive substrates (e.g., insoluble aromatic boronic acids and all saturated aliphatic boronic acids) can be avoided by properly selecting the reaction partners, for example through transposition of substituents between reaction partners. Three representative benzophenones (4-fluoro-, 4-nitro-, and 4,4′-dinitrobenzophenone) were structurally characterized by single-crystal X-ray crystallography.
Sulfur incorporation generally improves Ricin inhibition in pterin-appended glycine-phenylalanine dipeptide mimics
Wiget, Paul A.,Manzano, Lawrence A.,Pruet, Jeff M.,Gao, Grace,Saito, Ryota,Monzingo, Arthur F.,Jasheway, Karl R.,Robertus, Jon D.,Anslyn, Eric V.
supporting information, p. 6799 - 6804 (2014/01/06)
Several 7-aminoamido-pterins were synthesized to evaluate the electronic and biochemical subtleties observed in the 'linker space' when N-{N-(pterin-7-yl)carbonylglycyl}-l-phenylalanine 1 was bound to the active site of RTA. The gylcine-phenylalanine dipeptide analogs included both amides and thioamides. Decarboxy gly-phe analog 2 showed a 6.4-fold decrease in potency (IC50 = 128 μM), yet the analogous thioamide 7 recovered the lost activity and performed similarly to the parent inhibitor (IC50 = 29 μM). Thiourea 12 exhibited an IC50 nearly six times lower than the oxo analog 13. All inhibitors showed the pterin head-group firmly bound in their X-ray structures yet the pendants were not fully resolved suggesting that all pendants are not firmly bound in the RTA linker space. Calculated log P values do not correlate to the increase in bioactivity suggesting other factors dominate.
Design of new beta1-selective adrenoceptor ligands as potential radioligands for in vivo imaging.
Kopka, Klaus,Wagner, Stefan,Riemann, Burkhard,Law, Marilyn P,Puke, Carsten,Luthra, Sajinder K,Pike, Victor W,Wichter, Thomas,Schmitz, Wilhelm,Schober, Otmar,Schaefers, Michael
, p. 3513 - 3527 (2007/10/03)
In general, the failing human heart is characterized by a selective reduction in beta(1)-adrenoceptors (beta(1)-ARs) without change in beta(2)-AR density. Medical imaging techniques, either single photon emission computed tomography (SPECT) or positron emission tomography (PET) with appropriate radioligands, offer the possibility of assessing beta-adrenoceptor density non-invasively in humans. To date, neither a SPECT nor a PET radioligand is available for the selective imaging of cardiac beta(1)-ARs. The aim of this study was to develop potential high affinity beta(1)-selective AR radioligands for the non-invasive in vivo imaging of the beta(1)-AR density in the human heart using SPECT or PET. A variety of racemic N-aryl-N'-[2-[3-aryloxy-2-hydroxy-propylamino]-ethyl]-urea derivatives and chain-elongated analogues, related to the established beta(1)-AR antagonist, ICI 89,406 8i, were synthesized. Competition studies using the non-selective AR ligand, [(125)I]iodocyanopindolol ([(125)I]ICYP), and ventricular membrane preparations of wild-type mice revealed nine ligands with higher beta(1)-AR affinities (up to 76-fold) and beta(1)-AR selectivities (up to 139-fold) than 8i. Mostly, these ligands possess a 2-substituted phenoxy group and a 4-substituted phenyl residue in contrast to the lead compound 8i. The non-radioactive counterparts of the desired SPECT- and PET-radiotracers were synthesized as reference compounds [e.g., 8f, 8g, 8h and 8l as the non-radioactive analogues of the radioiodinated SPECT radioligands, 8e and 8h as the non-radioactive compounds of C-11 labelled PET-tracers (C-11 in the methoxy group)]. The established library of high affinity beta(1)-selective AR antagonists was screened for chemical precursors for the radiosynthesis of the mentioned radioligands. Furthermore, the library consists of some comparison compounds that are unsubstituted, allyl- and alkyl-substituted or chain-elongated (e.g., 8a, 8j, 8o and 8r-t). Future steps will include radiolabelling and pharmacokinetic evaluation of the beta(1)-selective target compounds, which could be applied as sympathetic innervation agents for in vivo investigations and diagnostics in patients suffering from cardiac diseases like heart failure and ventricular arrhythmias.
