SUBSTITUTED DERIVATIVES OF 3-HETEROAROYLAMINOPROPIONIC ACID AND THEIR APPLICATION AS DRUGS Russian patent published in 2017 - IPC C07D213/81 C07D213/82 C07D213/46 C07D413/04 C07D413/06 C07D401/04 C07D403/04 C07D405/04 C07D405/06 C07D409/04 C07D471/04 C07D487/04 C07D217/22 C07D239/28 C07D241/24 A61K31/4439 A61P11/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to a compound of formula I

in any of its stereoisomeric forms or a physiologically acceptable salt thereof, wherein A is selected from the group consisting of C(R¹) and N; D is selected from the group consisting of C(R²) and N; E is selected from the group consisting of C(R³) and N; L is selected from the group consisting of C(R⁴); where at least one and not more than two of A, D, E or L is N; G is selected from the group consisting of R⁷¹-O-C(O)-;R¹ is selected from the group consisting of hydrogen, halogen; R² is selected from the group consisting of hydrogen, halogen, (C₁-C₇)-alkyl, Het² and Ar-C_sH_2s-, where s is 0; R³ is selected from the group consisting of hydrogen, Het², R¹¹-O-; R⁴ and R¹⁰ are selected from the group consisting of hydrogen, halogen; provided that one of the R², R³ is a cyclic substituent; R¹¹ is selected from the group consisting of hydrogen, R¹⁴; R¹² and R¹³ are hydrogen; R¹⁴ is (C₁-C₁₀)-alkyl optionally substituted by one substituent, which is an oxo group; R³⁰ is selected from the group consisting of R³¹, R³²-C_uH_2u-, where u is 0; R³¹ is (C₁-C₁₀)-alkyl; R³² is phenyl, wherein phenyl is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O-, CF₃-; R⁴⁰, R⁵⁰, R⁶⁰ and R⁷¹ are hydrogen; Ar, independently of other Ar groups, is selected from the group consisting of phenyl and aromatic 5-membered or 6-membered monocyclic heterocycle which includes one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and is bonded through the carbon atom of the ring, wherein phenyl and heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C₁-C₆)-alkyl, HO-(C₁-C₆)-alkyl, Het⁴, (C₁-C₆)-alkyl-O-, -CF₃, -CO-(C₁-C₆)-alkyl, -CO-NR¹²R¹³ and NC-; and wherein phenyl can be substituted with -CH=CH-CH=CH-, -O-CH₂-O-, -O-CH₂-CH₂-O-, -O-CF₂-O- or -N((C₁-C₃)-alkyl) -CH=CH-; Het² is a saturated 5-membered - 6-membered monocyclic heterocycle that includes a nitrogen atom in the ring through which Het² is attached and optionally one other ring heteroatom selected from the group consisting of nitrogen and oxygen; Het⁴, regardless of other Het⁴ groups, is a saturated or unsaturated 4-membered to 5-membered monocyclic heterocycle that includes one to three ring heteroatoms selected from the group consisting of nitrogen and oxygen which is optionally substituted by one or more identical or different substituents selected from the group consisting of (C₁-C₄)-alkyl, HO-, (C₁-C₄)-alkyl-O-. Compounds of formula are obtained by the reaction of a compound of formula II with a compound of formula III, where the A, D, E, L, G, R¹⁰, R³⁰, R⁴⁰, R⁵⁰ and R⁶⁰ groups such as defined above for compounds of formula I, and additional functional groups may be present in protected form or in the form of a precursor group, and group J in the compound of formula II is HO-, (C₁-C₄)alkyl-O- or halogen.

EFFECT: substituted derivatives of 3-heteroaroylaminopropionic acid for application as a pharmaceutical agent for catheptase protease A inhibition.

10 cl, 1 tbl, 620 ex