28317-96-6Relevant academic research and scientific papers
Anion Receptor Design: Exploiting Outer-Sphere Coordination Chemistry to Obtain High Selectivity for Chloridometalates over Chloride
Carson, Innis,MacRuary, Kirstian J.,Doidge, Euan D.,Ellis, Ross J.,Grant, Richard A.,Gordon, Ross J.,Love, Jason B.,Morrison, Carole A.,Nichol, Gary S.,Tasker, Peter A.,Wilson, A. Matthew
, p. 8685 - 8692 (2015)
High anion selectivity for PtCl62- over Cl- is shown by a series of amidoamines, R1R2NCOCH2CH2NR3R4 (L1 with R1 = R4 = benzyl and R2 = R3 = phenyl and L3 with R1 = H, R2 = 2-ethylhexyl, R3 = phenyl and R4 = methyl), and amidoethers, R1R2NCOCH2CH2OR3 (L5 with R1 = H, R2 = 2-ethylhexyl and R3 = phenyl), which provide receptor sites which extract PtCl62- preferentially over Cl- in extractions from 6 M HCl solutions. The amidoether receptor L5 was found to be a much weaker extractant for PtCl62- than its amidoamine analogues. Density functional theory calculations indicate that this is due to the difficulty in protonating the amidoether to generate a cationic receptor, LH+, rather than the latter showing weaker binding to PtCl62-. The most stable forms of the receptors, LH+, contain a tautomer in which the added proton forms an intramolecular hydrogen bond to the amide oxygen atom to give a six-membered proton chelate. Dispersion-corrected DFT calculations appear to suggest a switch in ligand conformation for the amidoamine ligands to an open tautomer state in the complex, such that the cationic N-H or O-H groups are also readily available to form hydrogen bonds to the PtCl62- ion, in addition to the array of polarized C-H bonds. The predicted difference in energies between the proton chelate and nonchelated tautomer states for L1 is small, however, and the former is found in the X-ray crystal structure of the assembly [(L1H)2PtCl6]. The DFT calculations and the X-ray structure indicate that all LH+ receptors present an array of polarized C-H groups to the large, charge diffuse PtCl62- anion resulting in high selectivity of extraction of PtCl62- over the large excess of chloride. (Figure Presented).
N-Cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites
Chandrabalan, Arundhasa,McPhillie, Martin J.,Morice, Alyn H.,Boa, Andrew N.,Sadofsky, Laura R.
supporting information, p. 141 - 156 (2019/03/17)
The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel, which detects noxious stimuli leading to pain, itch and cough. However, the mechanism(s) of channel modulation by many of the known, non-reactive modulators has not been fully elucidated. N-Cinnamoylanthranilic acid derivatives (CADs) contain structural elements from the TRPA1 modulators cinnamaldehyde and flufenamic acid, so it was hypothesized that specific modulators could be found amongst them and more could be learnt about modulation of TRPA1 with these compounds. A series of CADs was therefore screened for agonism and antagonism in HEK293 cells stably transfected with WT-human (h)TRPA1, or C621A, F909A or F944A mutant hTRPA1. Derivatives with electron-withdrawing and/or electron-donating substituents were found to possess different activities. CADs with inductive electron-withdrawing groups were agonists with desensitising effects, and CADs with electron-donating groups were either partial agonists or antagonists. Site-directed mutagenesis revealed that the CADs do not undergo conjugate addition reaction with TRPA1, and that F944 is a key residue involved in the non-covalent modulation of TRPA1 by CADs, as well as many other structurally distinct non-reactive TRPA1 ligands already reported.
Synthesis and Caco-2 cell permeability of N-substituted anthranilamide esters as ADP inhibitor in platelets
Kim, Sohee,Shin, Beom Soo,Ma, Eunsook
, p. 1147 - 1156 (2015/02/19)
Twelve N-substituted anthranilamide esters (1-5, 8, 9, 12, 13, and 15-17) were synthesized and evaluated for their ability to inhibit the in vitro aggregation by washed human platelets induced by adenosine 5′-diphosphate (10 μM). The antiplatelet activity of DL-n-butyl 5-hydroxy-N-(2-phenoxypropionyl)anthranilate (9, IC50 = 10.5 μM) was most active among the tested compounds and ethyl ester 8 (IC50 = 11.2 μM) showed the second most activity. DL-Ethyl and DL-n-butyl 5-(p-toluenesulfonyloxy)-N-(2-phenoxypropionyl)anthranilate (12, IC50 = 13.1 μM and 13, IC50 = 14.0 μM), DL-methyl N-(2-phenoxybutyryl)anthranilate (2, IC50 = 12.7 μM), DL-N-(2-phenoxypropionyl)anthranilic acid (5, IC50 = 13.7 μM) displayed lower antiplatelet activity than 8 and 9. Compound 5 was more active than methyl ester prodrug 1. n-Butyl 5-hydroxy-N-(4′-acetoxybenzoyl)anthranilate (15, IC50 = 28.3 μM) showed moderate activity. Compounds 1 (IC50 = 42.8 μM), 4 (IC50 = 56.7 μM), 16 (IC50 = 51.0 μM), and 17 (IC50 = 49.8 μM) exhibited low antiplatelet activity. Methyl N-phenoxyacetylanthranilate (3, IC50 = 78.0 μM) showed the lowest antiplatelet activity. The compounds with branched alkyl chain (2 and 5) were more active than compounds with straight chain (3 and 4). The apparent permeability coefficient (Papp, cm/s) values of compounds 2 and 9 were determined as 45.34 ± 4.67 and 33.17 ± 5.15 × 10-6 cm/s by Caco-2 cell permeability assay.
Intramolecular Friedel-Crafts Acylation Reaction Promoted by 1,1,1,3,3,3-Hexafluoro-2-propanol
Motiwala, Hashim F.,Vekariya, Rakesh H.,Aubé, Jeffrey
supporting information, p. 5484 - 5487 (2015/11/18)
Simple dissolution of an arylalkyl acid chloride in 1,1,1,3,3,3-hexafluoro-2-propanol promotes an intramolecular Friedel-Crafts acylation without additional catalysts or reagents. This reaction is operationally trivial in both execution and product isolation (only requiring concentration followed by purification) and accommodates a broad range of substrates. Preliminary studies that bear upon potential reaction mechanisms are reported.
The development of the first catalyzed reaction of ketenes and imines: Catalytic, asymmetric synthesis of β-lactams
Taggi, Andrew E.,Hafez, Ahmed M.,Wack, Harald,Young, Brandon,Ferraris, Dana,Lectka, Thomas
, p. 6626 - 6635 (2007/10/03)
We report practical methodology for the catalytic, asymmetric synthesis of β-lactams resulting from the development of a catalyzed reaction of ketenes (or their derived zwitterionic enolates) and imines. The products of these asymmetric reactions can serve as precursors to a number of enzyme inhibitors and drug candidates as well as valuable synthetic intermediates. We present a detailed study of the mechanism of the β-lactam forming reaction with proton sponge as the stoichiometric base, including kinetics and isotopic labeling studies. Stereochemical models based on molecular mechanics (MM) calculations are also presented to account for the observed stereoregular sense of induction in our reactions and to provide a guidepost for the design of other catalyst systems.
Presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs. 2. 2-Phenoxy-, 2-(phenylthio)-, and 2-(phenylamino)alkanoic acid esters
Gualtieri,Bottalico,Calandrella,Dei,Giovannoni,Mealli,Romanelli,Scapecchi,Teodori,Galeotti,Ghelardini,Giotti,Bartolini
, p. 1712 - 1719 (2007/10/02)
Further modifications of the leads ((R)-(+)-hyoscyamine and (p- chlorophenyl)propionic acid α-tropanyl ester), which show analgesic and nootropic activities as a consequence of increased central presynaptic ACh release, are reported. 2-Phenoxy- and 2-(phenylthio)alkanoic acid esters showed the best results. Several members of these classes possess analgesic properties which are comparable to that of morphine and at the same time are able to reverse dicyclomine-induced amnesia. Confirmation was found that the mechanism of action is due to an increase in ACh release at central muscarinic synapses and that both auto- and heteroreceptors controlling ACh release are very likely involved. According to the results obtained with (R)- (+)-hyoscyamine, analgesic activity is stereochemistry dependent, since the R-(+)-enantiomers are always more efficacious than the corresponding S-(-)- ones. On the basis of their potency and acute toxicity, compounds (±)-28 (SM21) and (±)-42 (SM32) were selected for further study.
