SUBSTITUTED DERIVATIVES OF 1-OXA-2,8-DIAZASPIRO[4,5]DEC-2-ENE, METHOD FOR PRODUCTION THEREOF AND DRUG HAVING ANALGESIC ACTION Russian patent published in 2007 - IPC C07D498/10 A61K31/438 A61P29/02 

FIELD: organic chemistry.

SUBSTANCE: invention relates to substituted derivatives of 1-oxa-2,8-diazaspiro[4,5]dec-2-ene of general formula I in form of racemates, pure stereoisomers, particularly enantiomers or diastereomers in any ratio in mixture, in form of acids, or bases, or salts thereof, preferably physiologically acceptable salts, more preferably in form of hydrochlorides or solvates, in particular hydrates, wherein R¹ and R² are independently H, C₃-C₁₀-cycloalkyl, optionally substituted with O-alkylaryl, (C₁-C₁₂-alkyl)aryl, with the proviso, that at least one R¹ and R² is not H; R³ is H, SOR¹² or COR¹³; R¹² and R¹³ are independently C₁-C₁₀-alkyl, monocyclic 5-membered heterocyclic group having at least one heteroatom selected from sulfur atoms, optionally substituted with halogen; OR²⁰, wherein R²⁰ represents H, C₁-C₁₀-alkyl. Invention also relates to method for production of 1-oxa-2,8-diazaspiro[4,5]dec-2-ene of general formula I including a) compound of formula II interaction with methylenation agent, preferably with Ph₃PCH₃Br in presence of potassium tert-butylate in tetrahydrofuran (THF) to produce compound of formula III; d) compound of formula III interaction with ethylchloroximidoacetate of formula IV in presence of base, preferably of sodium hydrocarbonate or lithium hydroxide, preferably in organic solvent such as methanol, dichloromethane or TGF to produce 1-oxa-2,8-diazaspiro[4,5]dec-2-ene derivative of general formula V; c) compound of formula V interaction, directly or after previous saponification of functional group presenting in formula V (namely carboxylic acid ethyl ester) and optionally after activation of formed functional group (namely carboxylic acid) with amine of formula HNR¹R² wherein R¹ and R² are as defined above, to produce 1-oxa-2,8-diazaspiro[4,5]dec-2-ene derivative of general formula VI; d) protective group removing from compound of formula VI to produce compound of formula I, wherein R³ is H; and optionally e) converting of compound of formula I, wherein R³ is H, by treatment with acid chloride of formula R¹²SO₂Cl to compound of formula I, wherein R³ is SO₂R¹² or converting by treatment with carboxylic acid chloride of formula R¹³COCl to compound of formula I, wherein R³ is COR¹³. Moreover disclosed is drug having analgesic action and containing at least one substituted 1-oxa-2,8-diazaspiro[4,5]dec-2-ene derivative of general formula I.

EFFECT: new drug with analgesic action.

11 cl, 6 tbl