Sulfonyl Carboxamide Research Articles

Exploration of carboxamide hybrid indolyl aryl sulfones as antiretroviral agents by HIV-1 reverse transcriptase inhibition and antioxidant effects: Synthesis, biochemical screening and computational analysis

Indolyl aryl sulfones (IASs) have been under investigation as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) since the discovery of Merck's compound l-737,126. This research work reports the synthesis of a novel series of indolyl aryl sulfonyl carboxamides (11 to 21 and 25 to 28) and their biological evaluation. Among the synthesized compounds, 15 (IC50 = 57.4 ± 10.1 µM) and 26 (IC50 = 34.0 ± 1.9 µM) demonstrated potent inhibitory activity in RNA-dependent DNA polymerization (RDDP) reactions. In addition, radical inhibition activity was performed by reacting the synthesized compounds against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and it was observed that compounds 20 (IC50 = 8.2 ± 0.2 µM) and 21 (IC50 = 9.3 ± 0.5 µM) showed promising antioxidant properties. Additionally, Two-Dimensional Quantitative Structure Activity Relationship (2D-QSAR) and molecular docking studies were employed to provide insight into the molecular mechanism of RDDP inhibition.

Enantioselective Synthesis of γ-Lactams by Lewis Base Catalyzed Sulfenoamidation of Alkenes.

A method for the catalytic, enantioselective, intramolecular 1,2-sulfenoamidation of alkenes is described. Lewis base activation of a suitable sulfur electrophile generates an enantioenriched, thiiranium ion intermediate from a β,γ-unsaturated sulfonyl carboxamide. This intermediate is subsequently intercepted by the sulfonamide nitrogen resulting in cyclization to form γ-lactams. Electron-poor alkenes required the use of a new selenophosphoramidate Lewis base catalyst. Subsequent manipulations of the products harness the latent reactivity of both the amide and thioether functionality.

Synthesis of carboxamide and sulfonyl carboxamide linked heterocycles under green conditions

Synthesis of carboxamide and sulfonyl carboxamide linked heterocycles under green conditions

SAR studies in the sulfonyl carboxamide class of HBV capsid assembly modulators.

The HBV core protein has multiple essential functions in the HBV life cycle to enable chronic HBV infection. The core protein oligomerizes to form the viral capsid, and modulation of the HBV capsid assembly process has shown clinical efficacy in early clinical trials. Herein is described the SAR exploration of NVR 3-778, the first clinical compound in the sulfonyl carboxamide class.

New di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands: synthesis and divalent metal ion extraction

New di-ionizable p-tert-butylcalix[4]arene-1,2-crown-4 ligands with elongated side arms in cone, partial-cone, and 1,2-alternate conformations of the calixarene scaffold are prepared and characterized. The acidic groups on the side arms include carboxylic acid and N-(X)sulfonyl carboxamide with X variation of –Me, –Ph, –C6H4–4-NO2, and –CF3. Solvent extractions of alkaline earth metal cations, Hg2+, and Pb2+ from aqueous solutions into chloroform are employed to probe the effects of these structural modifications on the divalent metal ion complexation behavior of the new ligands.

Inclusion Extraction of Alkali Metals by Emulsion Liquid Membranes and Nano-baskets of p-tert-Calix[4]arene Bearing Di-[N-(X)sulfonyl Carboxamide] and Di-(1-propoxy) in ortho-cone Conformation

Nano-assisted inclusion separation of alkali metals from basic solutions was reported by inclusion-facilitated emulsion liquid membrane process. The novelty of this study is application of nano-baskets of calixarene in the selective and efficient separation of alkali metals as both the carrier and the surfactant. For this aim, four derivatives of [4]arene bearing different sulfonamide moieties were synthesized and their inclusion-extraction parameters were optimized including the calixarene scaffold (4 wt %) as the carrier/demulsifier, the commercial kerosene as diluent in membrane, sulphonic acid (0.2 M) and ammonium carbonate (0.4 M) as the strip and the feed phases, the phase and the treat ratios of 0.8 and 0.3, mixing speed (300 rpm), and initial solute concentration (100 mg/L). The selectivity of membrane over more than ten interfering cations was examined and the results reveled that under the optimized operating condition, the degree of inclusion-extraction of alkali metals was as high as 98-99%.

Inclusion desalination of alkali metal cations by emulsion liquid membranes and nano-baskets of p-tert-calix[4]arene bearing di-[N-(X)sulfonyl carboxamide] and di-(1-propoxy) in para-cone conformation

Nano-assisted inclusion separation of alkali metal cations from basic aqueous solutions was reported by inclusion-facilitated emulsion liquid membrane process. The novelty of this study is application of nano-baskets of calixarene in the selective and efficient separation of alkali metal cations as both the carrier and the surfactant. For this aim, four derivatives of p-tert-calix[4]arene bearing different sulfonamide moieties were synthesized and their inclusion–extraction parameters were optimized including the calixarene scaffold 3 (4wt.%) as the carrier/demulsifier, the commercial kerosene as diluent in membrane, sulphonic acid (0.2M) and ammonium carbonate (0.4M) as the strip and the feed phases, the phase and the treat ratios of 0.8 and 0.3, mixing speed (300rpm), and initial solute concentration (100mg/L). The selectivity of membrane over more than ten interfering cations was examined and the results revealed that under the optimized operating condition, the degree of inclusion–extraction of alkali metal cations was as high as 98–99%.

Di-ionizable calix[4]arene-1,3-crown-4 ligands in 1,3-alternate, cone, and partial-cone conformations: synthesis and metal ion extractions

Di-ionizable calix[4]arene-1,3-crown-4 compounds locked in 1,3-alternate, cone, and partial-cone conformations are synthesized for evaluation in metal ion separations. The ionizable functions include carboxylic acid and N-(X)sulfonyl carboxamide groups in which the acidity is tuned by variation of the electron-withdrawing ability of X. Similar synthetic routes were employed for preparation of the cone and 1,3-alternate ligand series. A different preparative route utilizing protection and deprotection was required to obtain the partial-cone analogues. Ligand conformations were confirmed by their proton and/or carbon NMR spectra. X-ray diffraction verified an unusual 1,2-alternate conformation in the solid-state for one synthetic intermediate. Effects of ligand conformation and ionizable group variations on competitive solvent extractions of alkali and alkaline earth metal cations from aqueous solutions into chloroform were assessed. Single species solvent extractions of Hg2+ and Pb2+ were also performed.

PREPARATION AND CHARACTERIZATION OF BONDED-PHASES OF CALIXARENE-SULFONYL-CARBOXAMIDES IN PARTIAL-CONE CONFORMATION FOR DETERMINATION OF SALBUTAMOL IN LIVESTOCK BY NANO-MEDIATED BONDED-PHASES: NANO-BASKETS OF CALIXARENE IN PARTIAL-CONE CONFORMATION

ABSTRACT A new sensitive method for determination of salbutamol, as a nutrient repartitioning agent, in livestock is presented to protect the consumers. Eight nano-baskets of p-tert -calix[4]arene bearing di-[ N -(X)sulfonyl carboxamide] and di-(1-propoxy) in partial-cone conformation were synthesized and were used to prepare bended phases of HPLC–UV. The new synthesized bonded-phases were characterized and optimized, the bonding interactions of solute and stationary phases were examined and the main interactions were reported. The results revealed that for the best bonded-phase, the LOD and LOQ were 0.02 and 0.06 μg/mL, respectively. Keywords : Bonded-Phase; Partial-Cone Conformation; Calixarene; Salbutamol; nanobasket. e-mail: pourabdollah@iaush.ac.ir 1. INTRODUCTION Salbutamol (albuterol) is the international nonproprietary (United States) adopted name for 4-(2-(tert-butylamino)-1-hydroxyethyl)-2-(hydroxymethyl)phenol (Figure 1), which is used for the treatment of asthma in both humans and animals, is a synthetic β

PREPARATION AND CHARACTERIZATION OF BONDED-PHASES OF NANO-BASKETS BEARING SULFONYL-CARBOXAMIDE

A new sensitive method for determination of clenbuterol, as a nutrient repartitioning agent, in livestock is presented to protect the consumers. Four derivatives of p-tert-calix[4]arene bearing di-[N-(X)sulfonyl carboxamide] and di-(1-propoxy) in para-cone conformation were synthesized as nano-baskets and were used to prepare bended phases of HPLC–UV. The new synthesized bonded-phases were characterized and optimized, the bonding interactions of solute and stationary phases were examined and the main interactions were reported. The results revealed that for the best bonded-phase, the LOD and LOQ were 0.01 and 0.05 µg/mL, respectively. Supplemental materials are available for this article. Go to publisher's online edition of Journal of Liquid Chromatography & Related Technologies to view the free supplemental file.

Binding mechanisms of nano-baskets toward alkali metals

Thirty-four nano-basket derivatives of di-ionizable calix[4]arene conformers in nine scaffolds bearing two pendant groups of N-(R)-sulfonyl carboxamides were synthesized and examined using isothermal titration calorimetry. The binding mechanisms of synthesized conformers toward alkali metal cations were evaluated and two main interactions were assessed including cation–π interaction between alkali metal and the aromatic unit of conformer as well as the strong binding ion–dipole interaction between nitrogen atoms in the pendant groups and alkali cation. The ITC data revealed that the bindings of cone and partial-cone conformers toward alkali metal cations exhibited one-step mechanism, while both 1,2 alternate conformer bounds the alkali metal cations in a two-step mechanism.

Solvent extraction of divalent metal ions by lipophilic di-ionizable acyclic polyethers: effect of end group variation

Three series of lipophilic acyclic di-ionizable polyethers are synthesized to probe the effect of structural variation within the acidic end groups on the solvent extraction selectivity and efficiency for divalent metal cations. Common polyether spacers of –O(CH2CH2O)3– connect the two aromatic carboxylic acid or N-(X)sulfonyl carboxamide end groups. For the latter, variation of the X group from methyl to phenyl to 4-nitrophenyl to trifluoromethyl serves to ‘tune’ the acidity of the ionizable group. Results for competitive solvent extractions of alkaline earth metal cations and single species extractions of Hg2+ and of Pb2+ from aqueous solutions into chloroform are reported.

Synthesis of geminal-substituted, sterically congested, proton-ionizable dibenzo-14-crown-4, dibenzo-16-crown-5, dibenzo-19-crown-6 and dibenzo-22-crown-7 lariat ethers

Proton-ionizable dibenzo-14-crown-4, -16-crown-5, -19-crown-6 and -22-crown-7 lariat ethers with different lipophilic geminal alkyl groups and different proton-ionizable groups are synthesized. For each lariat ether platform, butyl, heptyl and decyl groups were incorporated as the geminal lipophilic groups. Carboxylic acid, N-(trifluoromethane)sulfonyl carboxamide and sodium 3-propanesulfonate groups are incorporated on the platforms as proton-ionizable functions.

Mono-ionizable calix[4]arene-benzocrown-6 ligands in 1,3-alternate conformations: synthesis, structure and silver(I) extraction

Two series of novel mono-ionizable calix[4]arene-benzocrown-6 ligands in 1,3-alternate conformations are synthesized. In one series, the proton-ionizable group (PIG) is attached to the para position of one aromatic ring in the calixarene framework, thereby positioning it over the polyether ring cavity. In the other series, the PIG is a substituent on the benzo group in the polyether ring. This orients the PIG away from the crown ether cavity. In addition to carboxylic acid functions, the PIGs include N-(X)sulfonyl carboxamide groups. With X group variation from methyl to phenyl to 4-nitrophenyl to trifluoromethyl, the acidity of the PIG is ‘tuned’. Solvent extraction of Ag + from aqueous solutions into chloroform is used to probe the influence of structural variation within the mono-ionizable calixcrown ligand on metal ion extraction efficiency, including the identity and acidity of the PIG and its orientation with respect to the polyether ring.

Di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone conformations: synthesis and divalent metal ion extraction

Two series of di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone conformations are synthesized. The ionizable groups are oxyacetic acid moieties and N-(X)sulfonyl oxyacetamide units with X=methyl, phenyl, 4-nitrophenyl, and trifluoromethyl, which ‘tunes’ their acidity. For competitive solvent extraction of alkaline earth metal cations from aqueous solutions into chloroform, the new ligands with N-(X)sulfonyl carbamoyl groups are efficient extractants with Ba 2+ selectivity. On the other hand, the dicarboxylic acid analogues exhibit little selectivity in extraction of alkaline earth metal cations. For single species extractions of Pb 2+, the ligands with both types of ionizable groups show very good extractions abilities. In single species extractions of Hg 2+, the N-(X)sulfonyl carboxamide ligands are highly efficient, in contrast to the dicarboxylic acid compounds. Influences of the ionizable group identity, the crown ether ring size, and the presence of upper-rim p- tert-butyl groups on divalent metal ion extraction are explored.

Synthesis and lead(II) sorption of silica gel-immobilized, di-ionizable calix[4]arenes

Di-ionizable calix[4]arenes with two lower-rim N-(X)sulfonyl carboxamide groups were covalently linked to silica gel via a single attachment on the upper rim. Both the acidity of the ionizable groups (X group variation) and the length of the spacer that joins the ligands to the silica gel matrix were varied. Preliminary evaluation of these new ion-exchange resins for sorption of lead(II) from aqueous solutions was conducted.

Effect of para-substituents on alkaline earth metal ion extraction by proton di-ionizable calix[4]arene-crown-6 ligands in cone, partial-cone and 1,3-alternate conformations

Two carboxylic acid or N-(X)sulfonyl carboxamide groups were incorporated into calix[4]arene-crown-6 compounds to afford di-ionizable ligands for use in divalent metal ion separations. Acidities of the N-(X)sulfonyl carboxamide groups were tuned by variation of the electron-withdrawing properties of X. Cone, partial-cone and 1,3-alternate conformations were obtained by different synthetic strategies and their structures verified by NMR spectroscopy. Competitive solvent extractions of alkaline earth metal cations from aqueous solutions into chloroform were performed and the results compared with those reported previously for di-ionizable p-tert-butylcalix[4]arene-crown-6 analogues to probe the influence of the para-substituent on the calix[4]arene scaffold on extraction selectivity and efficiency.

Synthesis of Lipophilic Lariat Ethers with Pendant N‐(X)‐Sulfonyl Carboxamide Groups.

Synthetic routes to sixteen lipophilic lariat ether N-(X)sulfonyl carboxamides with X = trifluoromethyl, methyl, phenyl, and p-nitrophenyl are described. For this new family of proton-ionizable lariat ethers in which the acidity can be ‘tuned’ by X group variation, the ring size is systematically varied from 12-crown-4 to 14-crown-4 to 15-crown-5 to 18-crown-6.

Synthesis of lipophilic lariat ethers with pendant N‐(X)sulfonyl carboxamide groups

AbstractSynthetic routes to sixteen lipophilic lariat ether N‐(X)sulfonyl carboxamides with X = trifluoromethyl, methyl, phenyl, and p‐nitrophenyl are described. For this new family of proton‐ionizable lariat ethers in which the acidity can be ‘tuned’ by X group variation, the ring size is systematically varied from 12‐crown‐4 to 14‐crown‐4 to 15‐crown‐5 to 18‐crown‐6.

Calix[4]arenes with a novel proton-ionizable group: synthesis and metal ion separations

New calix[4]arenes with two N-(X)sulfonyl carboxamide groups of ‘tunable’ acidity are synthesized from the corresponding calixarene dicarboxylic acid and exhibit good to excellent extraction selectivity for Pb2+ over most alkali, alkaline earth and transition metal ions.