Ethyl 3-nitro-4-(n-propyl­amino)benzoate

In the mol­ecule of the title compound, C12H16N2O4, an intra­molecular N—H⋯O hydrogen bond results in the formation of a six-membered ring having an envelope conformation. In the crystal structure, a bifurcated intra/intermolecular N—H⋯(O,O) hydrogen bond generates inversion dimers

Syntheses and analytical characterizations of N-alkyl-arylcyclohexylamines.

The rise in new psychoactive substances that are available as 'research chemicals' (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continue to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act predominantly via antagonism of the N-methyl-D-aspartate (NMDA) receptor. To aid in the identification of newly emerging substances of abuse, the current studies were performed. The syntheses of fifteen N-alkyl-arylcyclohexylamines are described. Analytical characterizations were performed via gas chromatography and high performance liquid chromatography coupled to multiple forms of mass spectrometry as well as nuclear magnetic resonance spectroscopy, ultraviolet diode array detection and infrared spectroscopy. The series consisted of the N-alkyl derivatives (N-methyl, N-ethyl, N-propyl) of phenyl-substituted and isomeric 2-, 3- and 4-methoxy phenylcyclohexylamines, as well as the N-alkyl derivatives obtained from 3-methylphenyl and 2-thienyl moieties. In addition to the presentation of a range of previously unreported data, it was also found that positional isomers of aryl methoxyl-substituted arylcyclohexylamines were readily distinguishable under a variety of analytical conditions. Copyright © 2015 John Wiley & Sons, Ltd

NMDA Receptor Antagonists for Treatment of Depression

Depression is a psychiatric disorder that affects millions of people worldwide. Individuals battling this disorder commonly experience high rates of relapse, persistent residual symptoms, functional impairment, and diminished well-being. Medications have important utility in stabilizing moods and daily functions of many individuals. However, only one third of patients had considerable improvement with a standard antidepressant after 2 months and all patients had to deal with numerous side effects. The N-methyl-d-aspartate (NMDA) receptor family has received special attention because of its critical role in psychiatric disorders. Direct targeting of the NMDA receptor could result in more rapid antidepressant effects. Antidepressant-like effects of NMDA receptor antagonists have been demonstrated in different animal models. MK-801 (a use-dependent channel blocker), and CGP 37849 (an NMDA receptor antagonist) have shown antidepressant properties in preclinical studies, either alone or combined with traditional antidepressants. A recent development is use of ketamine clinically for refractory depression. The purpose of this review is to examine and analyze current literature on the role of NMDA receptor antagonists for treatment of depression and whether this is a feasible route in drug discovery

Genotoxicity studies of tetrahydro-naphthalene-benzimidazole/thiazolidinedione as retinoid derivatives

Objective: Mutagenicity is an undesirable side effect of clinically prescribed drugs, thus raises the question of their potential carcinogenicity. Taking into account that nitro compounds are known for their genotoxicity, it will be considerable interest to assess the genotoxic activities of the benzimidazole/thiazolidinedione retinoid derivatives. For this reason, the present study reports the genotoxicity of previously synthesized benzimidazole/thiazolidinedione-retinoid derivatives (Ates-Alagoz and Buyukbingol, 2001; Ates-Alagoz et. al., 2009) by the umu-microplate test system

Genotoxicity studies on benzimidazole retinoids

Retinoids consist of a family of naturally occuring compounds including all-trans retinoic acid (ATRA), retinal, retinol (vitamin A), 9-cis retinoic acid, 13-cis retinoic acid as well as a large number of synthetic derivatives. Retinoids are known to elicit diverse pharmacological profiles such as controlling cell differentiation/proliferation and modulating specific premalignant lesions and reducing second primary tumors in patients. Clinical use of retinoids is limited due to their toxicity. Three benzimidazole retinoid derivatives (BITN, BITNm, BITNe) were synthesized and were examined in terms of genotoxicity towards human lymphocyte cultures by sister chromatid exchange (SCE) analysis. It has been found that BITN decreased the number of SCEs 20% at 10(-6) M, but had no effect at 10(-5) M. No significant effect on SCEs was observed for BITNm and BITNe at both concentrations. ATRA increased the SCEs (35%) at 10(-5) M but had no effect at 10(-6) M. The results have shown that benzimidazole retinoids did not induce SCE significantly. Besides this, BITN reduced the SCEs and had a protective effect at low concentration. Since the induction of glutathione S-transferase (GST) is associated with anticancer drug resistance, the effects of BITN, BITNm, BITNe and ATRA on human lymphocyte GSTs were also investigated using CDNB as substrate. BITN and BITNm induced GST activities 54% and 49% respectively at 10(-5) M, but had no effect at 10(-6) M. BITNe induced GST activity 62% at 10(-5) M and 35% at 10(-6) M. ATRA had no effect on GST activity at 10(-5) M

Value set-based numerical analysis of robust stability for fractional-order retarded quasi-polynomials with uncertain parameters and uncertain fractional orders

This example-oriented contribution deals with the value set-based numerical analysis of robust stability for the family of fractional-order retarded quasi-polynomials with both uncertain parameters and uncertain fractional orders. The specific investigated feedback control system consists of the fractional-order PID controller and the controlled plant, represented by a heat transfer process described by the linear time-invariant fractional-order time-delay model with parametric uncertainty (with three uncertain parameters, namely, gain, fractional time constant, and fractional time-delay term, and furthermore two fractional orders). The graphical robust stability analysis is based on the numerical calculation of the value sets and the application of the zero exclusion principle. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG