- An efficient synthesis of enantiomerically pure trans-N1,N 2-dimethylcyclohexane-1,2-diamine
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A new pathway is described to produce a highly optically pure isomer of trans-N1,N2-dimethylcyclohexane-1,2-diamine through four simple steps. Reaction of cyclohexene oxide with aqueous methylamine, followed by cyclisation with Mitsunobu reagent and ring-opening reactions gave rac-trans-N1,N2-dimethylcyclohexane-1,2-diamine, and the enantiomers were obtained via a kinetic resolution using tartaric acid.
- Shen, Yan-Hong,Ye, Qing,Hou, Shao-Gang,Wang, Qun
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Read Online
- M-Type SrFe12O19Ferrite: An Efficient Catalyst for the Synthesis of Amino Alcohols under Solvent-Free Conditions
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Magnetically separable strontium hexaferrite SrFe12O19 was prepared using the chemical coprecipitation method, and the nanostructured material was characterized by X-ray diffraction, scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), and BET analysis. The SEM images showed the homogeneity of the chemical composition of SrFe12O19 and uniform distribution of size and morphology. The pore size of the nanomaterial and its specific area were determined by BET measurements. Strontium hexaferrite SrFe12O19 exhibited a strong magnetic field, which is highly suitable in the heterogeneous catalysis as it can be efficiently separated from the reaction. The magnetic nanocatalyst showed high activity and environmentally benign heterogeneous catalysts for the epoxide ring-opening with amines affording β-amino alcohols under solvent-free conditions. When unsymmetrical epoxides were treated in the presence of aromatics amines, the regioselectivity was influenced by the electronic and steric factors. Total regioselectivity was observed for the reactions performed with aliphatic amines. The magnetically SrFe12O19 nanocatalyst showed excellent recyclability with continuously good catalytic activities after four cycles.
- Laayati, Mouhsine,Hasnaoui, Ali,Abdallah, Nayad,Oubaassine, Saadia,Fkhar, Lahcen,Mounkachi, Omar,El Houssame, Soufiane,Ait Ali, Mustapha,El Firdoussi, Larbi
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- IMMUNOASSAY
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Antibodies, immunoassay methods and kits for the detection and determination of 3,4,-dichloro-N-[2-(dimethylamino)cylohexyl]-N-methylbenzamide and 3,4,-dichloro-N-[2-(methylamino)cylohexyl]-N-methylbenzamide, as well as the precursory immunogens, are desc
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Paragraph 0022
(2018/09/12)
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- Nickel-Catalyzed Intramolecular C?O Bond Formation: Synthesis of Cyclic Enol Ethers
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An efficient and exceptionally mild intramolecular nickel-catalyzed carbon–oxygen bond-forming reaction between vinyl halides and primary, secondary, and tertiary alcohols has been achieved. Zinc powder was found to be an essential additive for obtaining
- Han, Seo-Jung,Doi, Ryohei,Stoltz, Brian M.
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supporting information
p. 7437 - 7440
(2016/07/06)
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- Antihyperlipidemic morpholine derivatives with antioxidant activity: An investigation of the aromatic substitution
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Drugs affecting more than one target could result in a more efficient treatment of multifactorial diseases as well as fewer safety concerns, compared to a one-drug one-target approach. Within our continued efforts towards the design of multifunctional molecules against atherosclerosis, we hereby report the synthesis of 17 new morpholine derivatives which structurally vary in terms of the aromatic substitution on the morpholine ring. These derivatives simultaneously suppress cholesterol biosynthesis through SQS inhibition (IC50 values of the most active compounds are between 0.7 and 5.5 μM) while exhibiting a significant protection of hepatic microsomal membranes against lipid peroxidation (with IC50 values for the most active compounds being between 73 and 200 μM). Further evaluation of these compounds was accomplished in vivo in an animal model of acute experimental hyperlipidemia, where it was observed that compounds reduced the examined lipidemic parameters (TC, TG and LDL) by 15-80%. In order to examine the mode of binding of these molecules in the active catalytic site of SQS, we also performed docking simulation studies. Our results indicate that some of the new compounds can be considered interesting structures in the search for new multifunctional agents of potential application in atherosclerosis.
- Ladopoulou, Eleni M.,Matralis, Alexios N.,Nikitakis, Anastasios,Kourounakis, Angeliki P.
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p. 7015 - 7023
(2015/11/11)
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- 4 - [CYCLOALKYLOXY (HETERO) ARYLAMINO] THIENO [2, 3 - D] PYRIMIDINES HAVING MNKL/ MNK2 INHIBITING ACTIVITY FOR PHARMACEUTICAL COMPOSITIONS
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The present invention relates to novel thienopyrimidine compounds of general formula (I), pharmaceutical compositions comprising these compounds and their therapeutic use for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.
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Page/Page column 64
(2011/09/30)
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- Design of more potent squalene synthase inhibitors with multiple activities
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With the increasing realization that modulating a multiplicity of targets can be an asset in the treatment of multifactorial disorders, we hereby report the synthesis and evaluation of the first compounds in which antioxidant, anti-inflammatory as well as squalene synthase (SQS) inhibitory activities are combined by design, in a series of simple molecules, extending their potential range of activities against the multifactorial disease of atherosclerosis. The activity of the initially synthesized antihyperlipidemic morpholine derivatives (1-6), in which we combined several pharmacophore moieties, was evaluated in vitro (antioxidant, inhibition of SQS and lipoxygenase) and in vivo (anti-dyslipidemic and anti-inflammatory effect). We further compared the in vitro SQS inhibitory action of these derivatives with theoretically derived molecular interactions by performing an in silico docking study using the X-ray crystal structure of human SQS. Based on low energy preferred binding modes, we designed potentially more potent SQS ligands. We proceeded with synthesizing and evaluating these new structures (7-12) in vitro and in vivo, to show that the new derivatives were significantly more active than formerly developed congeners, both as SQS inhibitors (20-70-fold increase in activity) and antioxidants (4-30-fold increase in activity). A significant correlation between experimental activity [Log(1/IC50)] and the corresponding binding free energy (ΔGb) of the docked compounds was shown. These results, taken together, show a promising alternative and novel approach for the design and development of multifunctional antiatherosclerosis agents.
- Kourounakis, Angeliki P.,Matralis, Alexios N.,Nikitakis, Anastasios
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experimental part
p. 7402 - 7412
(2010/12/25)
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- Lipid-lowering (hetero)aromatic tetrahydro-1,4-oxazine derivatives with antioxidant and squalene synthase inhibitory activity
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A number of newly synthesized 2-[4-(hetero)aromatic]phenyl-2-hydroxy- tetrahydro-1,4-oxazine derivatives were found to inhibit lipid peroxidation (IC50 of the most potent was 20 μM) as well as rat squalene synthase (IC50 for most between 1-10 μM). Antidyslipidemic action was demonstrated in vivo: the most active compound decreased triglycerides, total cholesterol, and LDL-cholesterol of hyperlipidemic rats by 64, 67, and 82%, respectively, at 56 μmol/kg (ip). Most of the novel compounds are more active than the structurally related and reference biphenyl-morpholine, pointing to useful structural approaches for the design of antiatherosclerotic agents.
- Kourounakis, Angeliki P.,Charitos, Christos,Rekka, Eleni A.,Kourounakis, Panos N.
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supporting information; experimental part
p. 5861 - 5865
(2009/09/25)
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- Synthesis of 6-amino-3,5-deoxyinositol 1-phosphates via (1R,2R,4R,6S)- 1,6-epoxy-2,4-bis-benzyloxycyclohexane aminolysis in aqueous ytterbium triflate solution
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(1R,2R,4R,6S)-1,6-Epoxy-2,4-bis-benzyloxycyclohexane was prepared from (-)-quinic acid and this, and cyclohexene oxide, were treated with various N- nucleophiles under a variety of conditions. In aqueous solution containing catalytic amounts of ytterbium (III) triflate, ammonia and alkylamines reacted smoothly to give the required trans-1,2-amino alcohols in quantitative recovery. Conversion of the 6-amino-2,4-bis-benzyloxycyclohexan- 1-ols to 6-amino-1,2,4-trihydroxycyclohexane 1-phosphates, probes for the mechanism of inositol monophosphatase, was achieved in good overall yield.
- Beaton, Martin,Gani, David
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p. 8549 - 8552
(2007/10/03)
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- 2(1H)-Quinolinone derivatives as novel anti-arteriostenotic agents showing anti-thrombotic and anti-hyperplastic activities
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In order to search for anti-arteriostenotic agents, a series of 2(1H)- quinolinone derivatives was synthesized and evaluated for anti-thrombotic activity and for anti-hyperplastic activity. From this series, (-)-6-[3-[3- cyclopropyl-3-[(1R,2R)-2-hydroxycycyclohexyl]ureido]propoxy]-2(1H)- quinolinone (1p, OPC-33509) was selected as the best candidate by balancing the efficacy on anti-thrombosis and anti-hyperplasia.
- Koga, Yasuo,Kihara, Yoshito,Okada, Minoru,Inoue, Yoshihiro,Tochizawa, Shirou,Toga, Kazuyuki,Tachibana, Kazue,Kimura, Yukio,Nishi, Takao,Hidaka, Hiroyoshi
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p. 1471 - 1476
(2007/10/03)
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- O.N-Bis(diphenylphosphino) Derivatives of Chiral trans- and cis-2-Aminocyclohexanols: Synthesis and Enantioselective Behaviour as Ligands in Rh-based Homogeneous Hydrogenation Catalysts
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trans- and cis-2-Methylamino cyclohexanols (MAC) were prepared in enantiomerically pure forms and transformed into O.N-bis(diphenylphosphino) derivatives ("PONP").An analogous trans-1R;2R-aminocyclohexanol PONP could only be isolated in an impure form, whereas the attempted synthesis of PONP's of diastereomeric trans-2-(N-α-phenylethylamino)-cyclohexanols failed.Cationic Rh(I)-chelates of the new PONP's catalyzed the enantioselective hydrogenation of dehydro-α-acylamino acids with /= 97percent ee.A comparison of the enantiodiscriminating properties of the MAC-PONP's with structurally related chiral ligands leads to surprising conclusions.
- Pracejus, H.,Pracejus, G.,Costisella, B.
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p. 235 - 245
(2007/10/02)
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- RING OPENING OF CYCLOHEXENE EPOXIDE WITH TRIMETHYLSILYL CYANIDE
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Contrary to its reaction with epoxides in the presence of aluminum catalysts, trimethylsilyl cyanide reacts with cyclohexene epoxide to give 2-hydroxycyclohexyl isonitrile in the presence of ZnCl2.
- Spessard, Gary O.,Ritter, Allen R.,Johnson, Dawn M.,Montgomery, Anne M.
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p. 655 - 656
(2007/10/02)
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- A new class of nitrosoureas. VIII. Synthesis and antitumor activity of 3-substituted 1-(2-chloroethyl)-3-(trans-2-hydroxy-cyclohexyl)-1-nitrosoureas
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A series of six 3-substituted 1-(2-chloroethyl)-3-(trans-2-hydroxycyclohexyl)-1-nitrosoureas (IVa-f) was prepared and tested for antitumor activities. Heating of cyclohexene oxide with various alkylamines followed by reaction with 2-chloroethyl isocyanate
- Morikawa,Tsujihara,Takeda,Arai
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p. 1646 - 1651
(2007/10/02)
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