Dynamic adsorption characteristics of thin layered activated charcoal materials used in chemical protective overgarments

The efficiency of a thin layered activated charcoal material used in chemical protective overgarments has been evaluated. The study has been conducted with the aim to obtain protective materials with best characteristics considering resistance to benzene effect under dynamic conditions and to create a new filtration protection device. In order to evaluate dynamic adsorption characteristics of thin layered sorption materials, sophisticated dynamic gas chromatography method is used. The curves of benzene penetration are determined for sandwich materials, and sorption layers used in filtrating protective clothing shows that thin layered carbon sorption materials (type M00) have good protective properties as compared to other similar materials. The findings will help to create conditions for developing a functional model for producing a new protective overgarment in the near future

High performance MMICs with submillimeter wave InP-based HEMTs

This paper presents some recently developed MMICs based on a 0.1-/spl mu/m gate-length InAlAs/InGaAs/InP HEMT process with an f/sub max/ above 600 GHz. InP-based HEMTs provide more power gain and lower noise at higher frequencies than any other transistor, including GaAs-based pHEMTs. A number of state-of-the-art InP HEMT MMICs will be presented. This includes a 150-205 GHz amplifier with 15 dB of gain, a broadband 60-140 GHz amplifier with 25 mW output power at 140 GHz, a high gain Ka-band LNA and static frequency-divider circuits operating at clock rates above 45 GHz. The high frequency performance of a next-generation 0.08-/spl mu/m-gate InAlAsSb/InAlAs/InGaAs/InP HEMT technology will also be presented

Importance of inter-residue interactions in ligand-receptor binding

In the present study, the role of inter-residue interactions in ligand binding and the ligand-receptor interactions were examined. Computational chemistry methods of ligand docking and molecular dynamics simulations were used to study the binding of beta-funaltrexamine (beta-FNA) and N-methyl-beta-funaltrexamine (N-methyl-beta-FNA) to mu- and kappa-opioid receptors and to the mu-receptor with Lys303(6.58) Glu mutation. It was found that inter-residue interactions Lys233(5.39)-Glu303(6.58) in the mutant receptor and Lys227(5.39) Asp223(5.35) in the.-receptor are more likely to prevent covalent bond formation between beta-FNA and the receptor than the ligand-receptor interactions. This emphasizes the importance of inter-residue interactions in ligand binding as well as the effects of point-mutations. (C) 2016 Institute of Chemistry, Slovak Academy of Science

An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate

An efficient synthesis of methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate (7) has been developed, starting from 1-benzylpiperidin-4-one (1). The compound is a key intermediate in the synthesis of new generation, highly active narcotic analgesics, such as remifintanil, as well as the novel classes of fentanyl analogues. An optimized Strecker-type condensation of piperidone 1 with aniline and HCN yielded the anilino-nitrile 2(»90 %) which, upon selective hydrolysis with conc.H2SO4, gave the anilino-amide 3.After vigorous basic hydrolysis of 3, followed by acidification and successive treatment with SOCl2and MeOH, the anilino-ester 5 was obtained (4045 %, in 3 steps). N-Acylation of 5 with propionyl chloride yielded the anilido-ester6(7080 %). In the final step, the catalytic N-debenzylation of6was examined under various conditions and optimized to yield 7 in near quantitative yields

Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor

Fentanyl is a highly potent and clinically widely used narcotic analgesic. The synthesis of its analogs remains a challenge in the attempt to develop highly selective p-opioid receptor agonists with specific pharmacological properties. In this paper, the use of flexible molecular docking in a Study of the formation of complexes between a series of active fentanyl analogs and the mu-opioid receptor is described. The optimal position and orientation Of fourteen fentanyl analogs in the binding pocket of the mu-receptor were determined. The major receptor amino acids and the ligand functional groups participating in the complex formation were identified. Stereochemical effects on the potency and binding are explained. The proposed model of ligand-receptor binding is in agreement with point mutation experiments explaining the role of the amino acids: Asp147, Tyr148, Asn230, His297, Trp318, His319, Cys321, and Tyr326 in the complex formation. In addition, the following amino acids were identified as being important for ligand binding or receptor activation: Ile322, Gly325, Val300, Met203, Leu200, Val143, and Ile144. (c) 2005 Elsevier Ltd. All rights reserved

The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues

A general, five step method for the synthesis of 3-alkylfentanyl analogues (i.e., cis and trans 3-alkyl-4-anilidopiperidines 6.16.6) has been developed. The starting N-phenethyl-4-piperidone 1 was first converted into the cyclohexylimine derivative 2, a-deprotonated with butyllithium and the resulting imine anion efficiently monoalkylated with primary and secondary alkyl halides. After mild acid hydrolysis, the obtained 3-alkyl-4-piperidones 3.13.6 were isolated in good yields (7985 %), then condensed with aniline to form imines 4.14.6. Subsequent reduction of the imines (LiAlH4/THF) yielded cis/trans mixtures of 3-alkyl-4-anilinopiperidines 5.15.6. Quantitative separation of the diastereoisomers by column chromatography of Al2O3 gave pure cis 5.15.6 (2951 % yield) and trans 5.15.6 (1927 % yield), with the cis/trans ratio in the range 7/36/4. The synthesis was concluded by N-acylation of the purified 5.15.6, with propionyl chloride, to afford cis and trans 3-alkyl-4-anilidopiperidines 6.16.6 (~95 % yield, as monooxalate salts). No enatioseparation was attempted at any stage. The relative cis/trans stereochemistry was provisionally assigned from the 1H-NMR spectra. Of the twelve synthesized 3-alkylfentanyls, ten compounds (two known and eight novel derivatives, all as the monooxalate salts) were preliminarily tested as analgesics in rats, comparing the potency to fentanyl. Except for the known (±)-cis-3-Me fentanyl 6.1cis, (8 × fentanyl), and the novel (±)-cis-3-Et fentanyl 6.2cis, (1.5 × fentanyl), all of the others were less active than fentanyl or inactive. Some tentative conclusions on the structure-activity relationship (SAR) in this series of derivatives have been made

The synthesis and pharmacological evaluation of (±)-2,3-seco-fentanyl analogues

An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.15.5 (all new compounds) were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting b-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methylphenethylamine, (93 % yield), was successively reacted with NaH and BuLi, to form the highly reactive a,g-dienolate anion 1.1a. Regio and chemoselective g-alkylation of the dienolate with various primary and secondary alkyl halides furnished the b-keto-amides 1.21.5 (7691 %). Reductive amination of the keto-amides 1.11.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.12.5, afforded the b-anilino amides 3.13.5 (7485 %). After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.14.5 were obtained (8797 %). The synthesis of (±)-2,3-seco-fentanyls 5.15.5 was completed by N-acylation of the diamines 4.14.5 with propionyl chloride, followed by precipitation of the monooxalate salts (8695 %). The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 56 times more active than morphine in rats, while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance, the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers

Impacts of Exogenously Derived Nitrogen Oxide and Sulfur Compounds on the Structure and Function of the Vascular Endothelium Link Pregnancy Hypertension with Later Life Hypertension

The relationship between pregnancy hypertension and later life hypertension is explained by long-term impacts of environmental oxidants on the vascular endothelium. These impacts may precede the onset of the disease as a primary defect and may participate in the pathogenesis of hypertension itself. Continuous exposure to strong exogenous oxidants such as NOx (NO and NO2) reversibly oxidizes oxyhemoglobin (Fe2+) to methemoglobin (Fe3+), and irreversible methemoglobinemia can arise because of disruption of the oxidant/antioxidant balance supported by SO2 metabolites, as inhibitors of antioxidants, and by synergistic degradation of antioxidant thiols. Methemoglobin by itself and from heme, redox-active ferric iron as product of methemoglobin catabolism, have prooxidant properties and cause important structural and functional changes in the vascular endothelium such as growth arrest, senescence, morphological alterations and cell apoptosis. In 1975, an epidemiological study among 204 pregnant women in Labin (Croatia) identified 30 (14.7%) cases of preeclampsia and 25 (12.3%) cases of hypertension in pregnancy. Ten years later, we found a significant number of hypertension cases (N=5; P=0.0027), and among them, we found a significant number of pregnancy-induced hypertension cases (N=3; P=0.0003) and a significant number of psychoneurotic disturbances (P=0.0190), but these conditions were not found in the normotensive women ten years after giving birth (P = 0.1161). Our original findings confirm that hypertension in pregnancy is not a transient impairment but instead is an extension of the effects of exogenously induced oxidative stress on the structure and function of the vascular endothelial, and indicate delayed effects plausibly manifesting as hypertension in later life