SUBSTITUTED DERIVATIVES OF N-PHENYL-2-HYDROXY-2-METHYL-3,3,3-TRIFLUOROPROPANEAMIDE ENHANCING ACTIVITY OF PYRUVATE DEHYDROGENASE Russian patent published in 2005 - IPC

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to substituted derivatives of N-phenyl-2-hydroxy-2-methyl-3,3,3-trifluoropropaneamide of the formula (I): wherein n = 1 or 2; R¹ represents chlorine, fluorine, bromine atom, methyl or methoxy-group; R² is taken among of one the following groups: (i) halogen atom, nitro-, hydroxy- amino- or cyano-group; (ii) -X¹-R⁵ wherein X¹ represents -O-, -S-, -SO-, -SO₂-, NR⁶-, -CO-, -CONR⁶-, -NR⁶CO- wherein R⁶ represents hydrogen atom and R⁵ is taken among (C₁-C₆)-alkyl optionally substituted with one or some A, and so on; (iii) 4-8-membered heterocyclic group joined by nitrogen atom that represents saturated monocyclic ring comprising 4-8 carbon atoms among that at least one is nitrogen atom and so on; R³ represents (C₁-C₆)-alkyl optionally substituted with one or some A and so on; A is taken among hydroxy-, amino-group, halogen atom, carboxy-, N-(C₁-C₄-alkyl)-amino-, N,N-di-(C₁-C₄-alkyl)-amino-group, carbamoyl and (C₁-C₆)-alkoxy-group; D is taken among: (i) -X^a-R^c wherein X^a represents -SO₂, -CO-, -NR^dCO-, -NR^d- or -CONR^d-; (iv) cyano-group or halogen atom; (v) -X^cR^f wherein X^c represents -C(O)- and R^f represents 4-8-membered heterocyclic group joined by nitrogen atom that represents saturated monocyclic ring comprising 4-8 carbon atoms among that at least one is nitrogen atom with optionally additional heteroatom taken independently among oxygen atom (O), optionally substituted at ring carbon atom by the hydroxy-group, halogen atom, (C₁-C₄)-alkoxy-group, (C₁-C₄)-alkyl or cyano-group; G represents (C₁-C₆)-alkanoyl; R⁴ represents hydrogen or fluorine atom; or to its pharmaceutically acceptable salt or its ester hydrolyzed in vivo. Also, invention proposes a method for preparing compound of the formula (I). Also, invention proposes pharmaceutical composition enhancing activity of pyruvate dehydrogenase comprising substituted derivatives of N-phenyl-2-hydroxy-2-methyl-3,3,3-trifluoropropaneamide of the formula (I) or its pharmaceutically acceptable salt or ester hydrolyzed in vivo in combination with pharmaceutically acceptable vehicle or carrier. Invention provides preparing derivatives of N-phenyl-2-hydroxy-2-methyl-3,3,3-trifluoropropaneamide enhancing activity of pyruvate dehydrogenase.

EFFECT: valuable medicinal and biochemical properties of compounds.

14 cl, 1 tbl, 85 ex