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The article summarized results of long term studies on active site structures of monoamine oxi dase (MAO) performed in the Institute of Biomedical Chemistry (Russia) by computer modeling approaches. In mammals MAO exists in two highly homologous forms, MAO A and MAO B, distinguished by substrate specificity, inhibitor selectivity, and other characteristics. The development of approaches for active site mod eling of these enzymes (with unknown three dimensional structures) was originally based on analysis of inhibitory activity of selective inhibitors. It started from the analysis of relationships between the geometrical sizes of conformationally rigid molecules and their inhibitory activity. These studies resulted in molding of the active site structures of MAO A and MAO B. These molds reflect the sizes and shapes of active sites of these enzymes. These mold models have been used for virtual screening of molecular databases for new selec tive and non selective MAO inhibitors. The generated models have been compared with three dimensional structures of MAO A and MAO B, which appeared later.

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“…Four benzofuroxan derivatives, which stimulate guanylate cyclase activity due to release of nitric oxide [45,46], have been examined.…”

Section: Use Of the Mao A Active Site Mold For Search Of New Inhibitorsmentioning

confidence: 99%

Computer modelling of monoamine oxidases

Veselovsky

Ivanov

Медведев

2015

Biochem. Moscow Suppl. Ser. B

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“…[2][3][4] The high activity could be expected from BTDO annulated with electron withdrawing heterocycles. Re cently, 1 we have synthesized BTDO annulated with the furoxan ring at the C(5)-C(6) bond.…”

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confidence: 99%

Annulated benzotetrazine 1,3-dioxides 2.* [1,2,5]Oxadiazolo[3,4-f ][1,2,3,4]benzotetrazine 1,3,7-trioxide

et al. 2006

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“…In both cases, the initial materials were difficultly accessible compounds. Taking into account recent data, such compounds attract interest as nitrogen oxide donors [4], as well as components of gas-generating compositions.…”

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confidence: 99%

New Synthetic Approaches to Functionally Substituted 4,5-Dihydro-1,2,3-oxadiazole 2-Oxides

et al. 2005

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A practical procedure has been proposed for the synthesis of functionally substituted 4,5-dihydro-1,2,3-oxadiazole 2-oxides on the basis of sulfamic acid derivatives.Functionally substituted 4,5-dihydro-1,2,3-oxadiazole 2-oxides were synthesized for the first time by alkaline hydrolysis of the corresponding N-nitrosulfamides [1,2] or functionalized N-nitro-2-cyanoethylalkylamines [3]. In both cases, the initial materials were difficultly accessible compounds. Taking into account recent data, such compounds attract interest as nitrogen oxide donors [4], as well as components of gas-generating compositions.The goal of the present work was to develop a practical procedure for the preparation of both previously known and new functionally substituted 4,5-dihydro-1,2,3-oxadiazole 2-oxides. We previously studied in detail reactions of sulfamic acid salts with epoxy derivatives [5,6] and found that this transformation can be used to obtain a wide series of the corresponding N-(2-hydroxyalkyl)sulfamates (compounds IaIc and Ie) in high yields. Some compounds I can be subjected to further modification. For example, by nucleophilic substitution of the chlorine atom in Ic we obtained compounds Id and If (Scheme 1). The latter were brought into further syntheses without additional purification, for it was difficult to separate them from inorganic salts.The next stage of our study was aimed at selecting optimal conditions for nitration of compounds I. The nitration was performed using a mixture of nitric and sulfuric acids. Only in the reaction with N-(3-azido-2-hydroxypropyl)sulfamate Id we used a mixture of nitric acid and acetic anhydride to avoid replacement of the azido group by nitrate moiety. The yields of the corresponding N-nitro amines II varied from 70 to 90%. Nitroamines II were then converted into ammonium salts III by saturation of their solutions in diethyl ether with gaseous ammonia. It should be emphasized that this stage was simultaneously the final stage of purification of compounds II from nitrolysis products. Salts III were subjected to cyclization in methanol in the presence of an equimolar amount of alkali or in the absence of it. As a result, we isolated a series of 4,5-dihydro-1,2,3-oxadiazole 2-oxides IV having functional substituents in the 5-position; the overall yield was about 50% (Scheme 2). +1 &+ &+&+ &O 62 0 2+ ,F 1D1 &+ 1+62 0 2+ +1 &+ &+&+ 1 62 0 2+ ,G +1 &+ &+&+ 1&+ 62 0 2+ 62 0 ,I '0) +1 &+ &+5 62 0 2+ ,D B ,I 12 +1 &+ &+5 12 212 ,,D B ,,I 1+ 1 1 2 5 2+ 0H2+ 2 ,9D B ,9I 1+ 1 1&+ &+5 2 2 212,,,D B ,,,I M = Na, K; R = R' = H (a), CH 2 OCH 3 (b), CH 2 Cl (c), CH 2 N 3 (d); R = CH 2 OH, R' = CH 2 ONO 2 (e); R = CH 2 N(SO 3 M)CH 3 , R' = CH 2 N(NO 2 )CH 3 (f). M = Na, K. Scheme 1. Scheme 2.

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Cited by 20 publications

References 17 publications

Computer modelling of monoamine oxidases

Computer modelling of monoamine oxidases

Annulated benzotetrazine 1,3-dioxides 2.* [1,2,5]Oxadiazolo[3,4-f ][1,2,3,4]benzotetrazine 1,3,7-trioxide

New Synthetic Approaches to Functionally Substituted 4,5-Dihydro-1,2,3-oxadiazole 2-Oxides

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