38577-53-6

Upstream product

• 14384-45-3 N,N'-dihydroxy-2,3-dimethylbutane-2,3-diamine 
• 100-10-7 4-dimethylamino-benzaldehyde 
• 14538-51-3 2,3-bis(hydroxyamino)-2,3-dimethylbutane monosulfate 
• 3964-18-9 2,3-dimethyl-2,3-dinitrobutane 

Downstream Products

• 899419-49-9 C₁₅H₂₃N₃O 
• 259093-33-9 2-(4-dimethylaminophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole 1-oxyl 
• 38582-76-2 2-[4-(N,N-dimethylamino)phenyl]-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl 

Relevant academic research and scientific papers

NMR and semiempirical conformational analysis of the 2-aryl-1,3-dihydroxy-4,4,5,5-tetramethylimidazolidines

2-Aryl-1,3-dihydroxy-4,4,5,5-tetramethylimidazolidines (1) were synthesized and their 1H and 13C NMR spectra recorded. Quantum mechanical semiempirical calculations were also performed for a better understanding of the signals recorded in the NMR spectra of imidazolidines. The conformation of the imidazolidine ring was initially studied for the 2-methyl-1,3-dihydroxy-4,4,5,5-tetramethylimidazolidine (2), used as a model molecule. The results of the calculations obtained for structure 2 showed that the methyl groups are located in axial and equatorial positions. At these positions, the methyl groups are affected by the magnetic anisotropic effects of carbon-nitrogen and carbon-carbon bonds of the imidazolinyl ring with different intensities. Semiempirical calculations for structure 2, suggested that the effect of the γ-oxygen on the carbon atoms of methyl groups (γ-effect) might lead to an alteration of the electronic charge density and consequently to a change in the diamagnetic shielding on these groups. These data were used for the analysis of the NMR spectra of compound 1. The diamagnetic shielding effects, estimated from the calculated electronic charge densities on the carbon atoms of methyl groups, are in agreement with the signals observed in the NMR spectra of compound 1. By combining the contribution of the anisotropic and γ-effects, it appears that the axial methyl groups are located relatively closer to the γ-oxygens in compound 1.

A new class of analgesic agents toward prostacyclin receptor inhibition: Synthesis, biological studies and QSAR analysis of 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines

By studying the structural similarity of analgesic imidazolines and 2-phenylnitronyl nitroxides, 20 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines (2a-t) were newly synthesized as selective antagonists of prostacyclin receptor (IP receptor). In the in vivo tail-flick assay, 2a-t (dose, 0.13 mmol/kg) receiving mice showed increased pain thresholds ranging from 20.52 ± 7.25% to 90.94 ± 11.97%, which were significantly higher than that ranged from 12.27 ± 9.56% to 17.71 ± 7.00% shown by normal saline (NS) receiving mice. In the in vivo tail bleeding assay, 2a-t (dose, 1.30 mmol/kg) receiving mice gave a bleeding time ranging from 116.3 ± 8.0 s to 119.6 ± 7.1 s, and NS receiving mice gave a bleeding time ranging from 116.7 ± 7.5 s to 119.1 ± 8.7 s, which were at a substantially equal level. These observations imply that no bleeding risk occurred even when 10-fold dose of analgesic assay was used. In the in vitro vasorelaxation assay, it was found that when the aortic strip contracted by noradrenaline (NE, final concentration, 10-7 M) was treated with the solution of 2a-t in NS (final concentration, 5 × 10-3 M) only lower percentage inhibitions ranged from 6.63 ± 2.72% to 46.28 ± 2.63% were recorded. Relatively higher concentration of 2a-t (5 × 10-3 M) and relatively lower percentage inhibitions (13 of 20 less than 23.27 ± 3.47%) suggest that 2a-t exhibit few vasodilation activity. To shed some light on the potential analgesic mechanisms of 2a-t, moreover, a QSAR analysis was carried out by using the multiple linear regression method. Taken altogether, the current study confirms that as selective antagonist of IP receptor 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazoline may be a promising lead compound of analgesic agent without cardiovascular and bleeding side effects.

Transformation of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole derivatives into isoxazoles

The reactions of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole derivatives with electrophilic reagents, such as protic acids, benzoyl chloride, BF 3, and bromine, produce isoxazole, 2,2,3,3-tetramethylaziridine, and 2,3,3-trimethylpropen-2-ylamine

Novel 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines: Synthesis, selectively analgesic action, and QSAR analysis

Based on the knowledge that imidazoline can result in analgesic action due to its selective binding with the prostacyclin receptor, 20 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazolines (3a-t) were prepared in moderate yields. At 0.13 mmol/kg dose, their in vivo analgesic activities were evaluated after the mice were administered at 30, 60, 90, and 150 min. Compared with the pain threshold (12.27 ± 9.56-17.71 ± 7.00%) of normal saline (NS) receiving mice, the pain threshold (23.42 ± 8.14% to 102.58 ± 10.66%) of 3a-t receiving mice increases significantly. Considering a prostacyclin receptor targeting analgesic agent usually had bleeding action and to appraise the bleeding risk, the in vivo tail bleeding time of 1.30 mmol/kg 3a-t receiving mice was found to be ranged from 116.3 ± 8.2 s to 120.3 ± 9.2 s, which was substantially equal to that (117.8 ± 8.4 s to 119.0 ± 8.6 s) of NS receiving mice. Based on the possibility of imidazoline acting as vasodilator, the in vitro vasorelaxations of 3a-t were tested using the rat aortic strip model. When the aortic strip contracted by noradrenaline (NE, final concentration 10-7 mol/l) was treated with 3a-t (final concentration 5 × 10-4 mol/l), only lower percentage inhibitions (6.55 ± 5.70-37.40 ± 4.07%) were recorded, implying that the vasorelaxation of 3a-t was neglectable. By selecting appropriate molecular descriptors generated from e-dragon server, the QSAR model of the analgesic activities of 3a-t was constructed using the multiple linear regression method. The established QSAR model showed reasonable accuracy and thus it is promising to be used for screening new 1-oxyl-2-substitutedphenyl-4,4,5,5-tetramethylimidazoline derivatives as analgesic agents.

Novel 2-substituted nitronyl nitroxides as free radical scavengers: Synthesis, biological evaluation and structure-activity relationship

To develop more potent small molecules with enhanced free radical scavenger properties, we designed and synthesized a series of nitronyl nitroxide derivatives 4a-h. A lead compound 4f was discovered based on Ach-induced vascorelaxation assay. Further chemical modification based on this scaffold provided a new series of 2-substituted phenylnitronyl nitroxide derivatives 6a-s. The newly synthesized compounds 6a-s possess improved radical scavenger's activity based on PC12 cell survival assay. Compounds 6g,n,o, and s are some of the most potent compounds in terms of NO, H2O2, and OH scavenging ability. 2-Substitued phenylnitronyl nitroxides had a higher radical scavenging activity with the electron-donating group (EDG). In contrast, the introduction of electron-withdrawing group (EWG) to the aromatic ring led to a dramatic decrease in its radical scavenging activity. These results suggest that the electron-donating group (EDG) of the aromatic ring may be an important factor influencing the radical scavenging behavior of these compounds, and the potency of free radical scavenging activity largely depended on the position and electronic properties of the phenyl ring substituents. The enhanced radical scavenging capacities of the novel 2-substituted nitronyl nitroxides may be potential drug leads against the deleterious action of ROS (reactive oxygen species)/RNS (reactive nitrogen species).

Preparation and Characterization of New Chiral Nitronyl Nitroxides Bearing a Stereogenic Center in the Imidazolyl Framework

A synthetic procedure for optically active and racemic α-nitronyl nitroxides (α-NNs) having a stereogenic center at the 4-position of the imidazolyl ring is described. This procedure consists of (1) the synthesis of a dissymmetric vic-dinitro compound by Kornblum reaction, (2) the enantiomeric resolution of the racemate by a diastereomer method for obtaining the optically active sample, (3) the quick reduction of the optically active or racemic vic-dinitro compound to the bis(hydroxyamino) derivative with Al/Hg, (4) the solvent-free condensation of the bis(hydroxyamino) compound with an aldehyde to give the 1,3-dihydroxyimidazolidine, and (5) the final oxidation of the α-NN precursor with aqueous NaIO4. The absolute configuration of the optically active α-NNs was assigned by correlating with the X-ray crystal structure of the (-)- (1S,4R)-camphanic acid ester derivative of the optically active vic-dinitro compound. The molecular conformation of the optically active α-NNs was found to be folded both in solution and in the solid state by CD spectroscopy and energy minimization with the Monte Carlo method. The magnetic properties of both optically active and racemic α-NNs in solution and in the solid state were characterized by EPR spectroscopy and magnetic susceptibility measurement, respectively.

Design, preparation, and electronic structure of high-spin cation diradicals derived from amine-based spin-polarized donors

Amine-based donor radicals, such as dimethylamino-, diethylamino-and morpholinonitronyl nitroxides, were synthesized, and their donor abilities were examined by cyclic voltammetry. ESR spectra of the singly oxidized donor radicals showed ground state triplet signals derived from the cation radicals of these donor radicals. The result was interpreted by the presence of the ferromagnetic coupling between the generated π-spin and the localized unpaired electron on the radical unit. According to the molecular orbital calculations, the ferromagnetic coupling between these two spins is originated from the space-sharing nature between SOMO which is localized on the radical unit and SOMO' which is derived from HOMO of the donor radical upon one-electron oxidation. Therefore, the cation-radicals of these donor radicals can be regarded as a heteroanalogue of trimethylenemethane. p-and m-dimethylaminophenyl nitronyl nitroxides were synthesized in order to expand the π-electronic structure of the donor unit, and the singly oxidized species were also found to afford triplet ESR signals. The origin of the ferromagnetic coupling of these aminophenyl nitronyl nitroxides was discussed on the same basis. Charge transfer complexes of some of the donor radicals with chloranil or 2,3-dichloro5,6-dicyano-1,4-benzoquinone were prepared, and the conducting and magnetic properties were examined.