• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The present invention is related to new diselenobis benzoic acid amides of primary heterocyclic amines of the general formula I <CHEM> wherein R<1> and R<2>, which are equal or different from another, represent hydrogen, halogen, C1-4-alkyl, C1-4-alkoxy, trifluoromethyl, nitro or, both together, methylenedioxy, n is zero or a numeral from 1 to 4 and R<3> is a saturated or unsaturated heterocyclic residue with one or two heteroatoms in the cyclic nucleus selected from the group of nitrogen, sulphur and oxygen, said residues being unsubstituted or substituted onces or twice, equally or in different manner, by halogen, C1-2-alkyl, C1-2-alkoxy, nitro or hydroxy. processes for producing the same and pharmaceutical compositions comprising the same. The compounds of formula I are useful in the treatment of diseases which are caused by cell damage due to the increased formation of active oxygen metabolites such as liver damages, heart infarctions, infections, psoriasis or damages by radiation.
    公开号:SU1597097A3
    申请号:SU874203234
    申请日:1987-08-06
    公开日:1990-09-30
    发明作者:Велтер Андре；Ремер Аксель；Леик Зигурд；Джон Парнхам Михаэль
    申请人:А.Наттерманн Унд Ко.Гмбх (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to methods for producing new amides of dilelen-bis-benzoic acid, which have valuable pharmacological properties and can be used as active elements in pharmaceutical preparations in the treatment of diseases that are caused by cell damage due to increased formation of metabolites (metabolic products) active oxygen, such as liver damage, heart attacks, infections, psoriasis or 'damage caused by radiation (radiation).
    where R is pyridyl, thienyl, or furfuril, η = 1 or 0, which can be used to treat diseases caused by increased formation of metabolites, active oxygen, such as liver damage, heart attacks, infections, psoriasis, and radiation-related injuries. The goal is to create a new way to obtain new active substances. The synthesis is carried out by reaction of the corresponding benzisoselenazolone with an equimolar amount of mercaptan in an organic solvent at room temperature, followed by treatment with methylamine. The novel compounds can replace glutathione peroxidase, since their activity is at Ebselen 105-61, toxicity LD 5o above 110 mg / kg.
    SLL., 1597997 (L
    The purpose of the invention is the development of a method for the preparation of new derivatives of amides of di-bis-benzoic acid, which could be used in fine-balance reactions in a living organism.
    Example 1. 2.2 — Diseleno — bis (Y-furfurylbenzamide).
    g (0.0071 mol) of 2 — furfuryl —1.2 — benz — iso-selenazole — 3- (2H) -one is dissolved in approximately 50 ml of methanol. The mixture was added to a solution of 0.56 ml of ethyl mercaptan. The mixture was stirred at room temperature. After 30 minutes, precipitate
    I
    1597097 'connection of white color. This precipitate is dissolved in 15 ml of dimethylformamide. 5 ml of a 33% methylamine solution was added to the contents. Stirring ”bastards continue at room pace.” nightlife. The precipitated white compound was additionally separated by adding ether, separated by suction filtration and dried.
    Yield 1.5 g (74.7% of theory), mp 220 ° C.
    Example 2. 2,2-Diseleno "bis" (M "2" pyridylbenzamide) is obtained analogously to example 1, by subjecting to an action of 2 g 2 "(2" pyridyl) "1,2" "benz-iso" selenazole "3" (2H) ”she, 0.53 ml · ethyl mercaptan and 4 ml 33%” but ”methylamine.
    Yield 1 g (50.2% of theory), mp 105 * C.
    Example 3. 2.2 "Diseleno" "bis" (M "2" pyridylmethylbenzamide) is prepared according to example 1 by the interaction of 1 g of 2- (2-pyridylmethyl) -1.2 "bene" from "selenazole" 3 "( 2H) ”she, 0.26 ml of ethyl mercaptan and 3 ml of 33% methylamine.
    Yield 0.6 g (60% of theory.), -G. pl. 192-196 ° C.
    Example 4. 2,2-Diselen-bis- (N-2-thienylbenzamide) is prepared according to example 1, by the interaction of 2 g on zol ”3— (2H) —onan and 5
    Yield 225C.
    When ”(D-3” pyridylbeneamide) receive according to example 1 by reaction of 2 g
    2- (3-pyridyl) -1,2-benz-iso ”selenazole’ —3— (2H) —one, 0.74 ml of ethyl mercaptan and 5 ml of 33%
    Yield 1.19 g, mp 2.48 ° C "
    An example.
    - (N-4-pyridylbenzamide) is prepared according to Example 1 by the reaction of 2 g of 2— (4 — pyridyl) '-1,2 ”benz-iso-selenazole” 3 (2H) -one, 0.74 ml of ethyl mercaptan and 5 ml of 33 % But methyl amine.
    Yield 1.20 g (36.4% of theory),
    city square 210 ° C.
    Determination of glutathione peroxidase-like activity is carried out according to the method of A. Wendel. In this experiment, the conversion of the joint sub—
    2— (2-thienyl) ”!, 2-benz-iso-sele, 0.5 ml ethyl mercap 1 ml 33% methylamine.
    g (50% of theory.), so pl.
    measures 5 "2,2-Diseleno-bis methylamine. (36.1% of theory.),
    45 1
    6. 2,2-Deleleno-bis · stratum nicotinamide adenine dinucleotide ”phosphate. The reducing agent in this reaction is glutathione. It was found that the proposed compounds have a glutathione peroxidase-like asset ”nosg.
    Glutathione peroxidase-like activity.
    The catalysis of the decomposition of peroxidase was studied in vitro. It was found that the proposed compounds are able to replace glutathione peroxidase.
    ROOH P R ° DU KT1 (offered) RQH N D
    RSH
    H 2 O
    RSSR
    Catalytic activity is expressed as the amount of glutathione peroxidase. The product used is the product Ebselen -, '2 — phenyl — 1,2 — benz — iso-selenazole — 3 (2H) one. Ebslen’s activity is taken as 100%, and the activity of the proposed compounds is reduced to Ebslen’s activity.
    Ebselen was studied at a concentration of 30 mmol, and dimethylformamide (DMD) was used as a solubilizing substance. The proposed dyslenides were studied at a concentration of 15 mmol, using DMD as a solubilizing substance, since there are two selenium atoms per 1 mol in dyslenides.
    Catalyticactivility Ebselen 100 2,2-Diseleno-bis- (M-3-pi ”Ridylbenzamide) 105 2,2 — Deleno-bis— (N-3 — pi ”Ridylmethylbenz amide) 68 2,2-Diseleno-bis ”(M-fur)furylbenzamide) 82 2,2 — Diseleno — bis— (N — 2—Thienylbenzamide) 61 Toxicity data LD 5v , mg / kg: 2,2-Diseleno — bis— (M-fur-furylbenzamide) "100 2,2-Diseleno-bis- (M-2-pi-Ridylbenzamide) »1000 2,2-Diseleno-bis ”(H” 2- ·Thienylbenzamide) " 100
    2.2 ”Deleno g 'bis''(N''3 · '•' pyridylbenzamide)” 4670
    Thus, the proposed method makes it possible to obtain new compounds ** that possess valuable properties.
    权利要求:
    Claims (1)
    [1]
    315 white compound "This precipitate is dissolved in 15 ml of dimethylformamide. To the contents is added 5 33% HO solution of methylamine. Stirring is continued at room temperature. Overnight, the precipitated white compound is further separated by adding ether, suction filtered and dried. The yield is 1.5 g (74.7% of theory), t "pl. 220 ° C. Example 2. 2.2-Diskeleno-bis- (H 2 pyridylbenzamide) was prepared as in Example 1, with 2 g of 2 (2-pyridyl) 1, -benz-isoselenazole 3 (2H) on5 5 0.53 ml. ethyl mercaptan and 4 ml of go methylamine. Yield 1 g (50.2% of theor,), t, PLV Example: 3, 2.2 Disteleno bis (S 2 pyridylmethylbenzamide) is prepared in Example 1 by reacting 1 g 2 (2 pyridylmethyl) 1, 2 b o Selenazole-3 (2H) -one, 0.26 ml of methyl mercaptan and 3 ml of go methylamine. Yield: 0.6 g (60% of theory); t, pl. 192-196.C. Example 4 2.2 Diselene BNS (N-2-thiens Ibenzamide) was prepared as in Example 1, by reacting 2 g of 2- (2-phenyl) 1,2 benz-zosel nazol 3 (2H) she, 0.5 ml of ethyl mercaptan and 5 ml 33% methylamine Yield 1 g (50% of Theor "), t PLV 25C, Example 5" 2.2 Diskeleno bis (K-3 Pyridylbenzamide) was prepared as in Example 1 by reacting 2 g of 2- (3 pyridyl) 1.2benz zo-selenazo -3 (2H), 0.74 ml of ethyl mercaptan and 5 ml of 33% methylamine. Yield 1.19 g (36.1% of theoretical), t. pl. 248C. Example: 6c 2,2-Dyselenobis (S 4pyridylbenzamide) was prepared as in example 1 by reacting 2 g of 2- (4 Pyridyl 1,2 benzisomelenazole 3 (2H) it, 0.74 ml of ethyl mercaptan and 5 ml of go methylamine. Yield 1.20 (36.4% of theory,), t. l. 210. Determination of glutathion peroxidazo of similar activity was carried out according to the method of AvVendel. The proposed compounds have been found to have glutathion peroxidase-like activity. Glutathione peroxidases similar to catalysis of peroxidase decomposition was studied in vitro experiments. It was found that the proposed compounds are capable of replacing glutathione peroxidase ROOH (proposed). The catalytic activity is expressed as the amount of glutathione peroxidation. selenazole3 (2H) it was Ebselen’s activity taken over 100% and the activity of the proposed compounds was reduced to Ebselen’s activity “Ebselen was studied at a concentration of 30 mmol The dosing agent was used dimethylformamide (DMD). The proposed diselenides were studied at a concentration of 15 mmol, using DMD as a solubilizing agent, since per 1 mole in the diene compounds there are two atoms of selenium “Catalytic activity 100 Ebselen 2.2 Diseleno bis (Ridylbenzamide) 2, 2 Dislenobis Enz amide) 2, 2 Diskeleno-bis- (Furilbenzamide) 2,2 Dicileno biC (thienylbenzamide) 61 jg, Mr / Kr: Data on toxicity of LD 2.2 Diseleno bis (To furfurylb enz amide) 100 2.2 Disteleno bis (K-2-pyrid, Sh1b enz amide) 2,2 Disteleno bis (Tienylbenzamide) 100 51 2.2Digree bis- (thyridylbenzamide) Thus In this way, the proposed method allows obtaining new compounds that have valuable properties. Claims method for producing amides of disulno bis-benzoic acid of the formula CO-NH - (. CH2) rrR CH2L-R, where Kip has the indicated meanings, is reacted with an equimuolar amount of a mercaptan of the formula R SH, where R is lower alkyl, in an organic solvent at a coarse temperature, followed by treatment of the resulting intermediate of the formula CO-NH- (CH2) HrR Se- SR, where R, R, and n are as defined, methylamine.
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    引用文献:
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    法律状态:
    优先权:
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