- Oxadiazole Amine Derivative Compounds as Histone Deacetylase 6 Inhibitor, and the Pharmaceutical Composition Comprising the same
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The present invention relates to a novel compound having an activity of inhibiting histone deacetylase 6 (HDAC6), an optical isomer thereof or a pharmaceutically acceptable salt thereof, a use thereof for preparation of a drug for treatment, a pharmaceutical composition comprising the same, a treatment method using the composition, and a method for preparing the same. The novel compound, an optical isomer thereof or a pharmaceutically acceptable salt thereof according to the present invention has an activity of inhibiting histone deacetylase 6 (HDAC6), and is effective for preventing or treating HDAC6-related diseases, including infectious diseases; neoplasm; endocrine, nutritional and metabolic diseases; mental and behavior disorders; nerve disorders; eye and adnexa diseases; cardiovascular diseases; respiratory diseases; digestive organ diseases; skin and subcutaneous tissue diseases; musculoskeletal and connective tissue diseases; or congenital malformation, deformation and chromosomal abnormality.COPYRIGHT KIPO 2017
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Paragraph 0255; 0262-0264
(2017/07/18)
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- Syntheses and N-methyl-D-aspartate receptor antagonist pharmacology of fluorinated arylcycloheptylamines
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Selective uncompetitive antagonists of the phencyclidine (PCP) binding site of the N-methyl-D-aspartate receptor (NMDAR) are known to have therapeutic potential as anticonvulsants and neuroprotective agents. Several fluorinated molecules with each containing a cycloheptane ring were designed to probe the PCP pharmacophore and test the influence of fluorine substitution on NMDAR binding and in vivo efficacy. Syntheses and analyses of six novel compounds, 1-(4-fluorophenyl)cycloheptanamine (3), 1-(1-(4-fluorophenyl)cycloheptyl)piperidine (4), 1-(1-(4-fluorophenyl)cycloheptyl) pyrrolidine (5), 1-(3-fluorophenyl)cycloheptanamine (6), 1-(1-(3-fluorophenyl)cycloheptyl)piperidine (7), 1-(1-(3-fluorophenyl)cycloheptyl)pyrrolidine (8) and several related reference arylcyloalkylamines are described. Receptor binding was performed at the PCP site of NMDAR for each compound using [3H]-(+)-MK-801 displacement. Unexpectedly, the 3-fluoro-primary amine 6 had the greatest affinity of the series and these binding results support a different structure activity relationship (SAR) profile for arylcycloheptylamines when compared to arylcyclohexylamines like PCP. Five of the novel compounds have affinity (Ki) in the hundred nM (10-7) range. In addition, compounds 3, 5, 6, 7 and 8 were evaluated and found to exhibit neuroprotective effects from NMDA induced toxicity in vitro and compounds 6, 7 and 8 exhibited anticonvulsant activities in rats. An ED50 of 13.84 mg/kg was found for compound 6 in rat maximal electroshock (MES) test with a protective index (PI) of 3.66 against ataxia. These results support further investigation of the arylcycloheptylamine class.
- Sun, Shengguo,Wallach, Jason,Adejare, Adeboye
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p. 843 - 852
(2015/04/14)
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- 1-Substituted cyclopentylamines from nitriles and tetramethylenebismagnesium dibromide in the presence of Ti(OiPr)4
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Various 1-substituted cyclopentylamines (25 examples, 1089 % yield) have been prepared according to a one-pot procedure by the addition of tetramethylenebismagnesium. di- bromide in the presence of Ti(OiPr)4 to aliphatic, aromatic and heteroaromatic nitriles, respectively.
- Tomashenko, Olesya A.,Rudenko, Andrei E.,Sokolov, Viktor V.,Tomashevskiy, Alexander A.,De Meijere, Armin
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experimental part
p. 1574 - 1578
(2010/06/13)
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- Metabolism of phencyclidine. The role of the carbinolamine intermediate in the formation of lactam and amino acid metabolites of nitrogen heterocycles
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The transformation of phencyclidine in a mouse liver microsome preparation to several oxidative metabolites was studied. With use of GLC and HPLC methods with internal standards, phencyclidine and six metabolites were quantitated and the amino acid, resulting from the α-oxidation of the piperidine ring, was produced in 10-50 times greater amounts than the other metabolites. While most piperidines and pyrrolidines produce an amino acid and a corresponding lactam, it was found that phencyclidine was not converted to the lactam.
- Baker,Little
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