AMIDE DERIVATIVES AS TTX-S BLOCKERS Russian patent published in 2017 - IPC C07D213/75 C07D213/82 C07D401/04 C07D401/12 A61K31/44 A61K31/4523 A61K31/455 A61K31/497 A61K31/501 A61K31/506 A61P1/00 A61P25/18 A61P25/28 A61P29/00 

FIELD: chemistry.

SUBSTANCE: invention relates to the amide derivatives of formula

,

where A is selected from the group consisting of phenyl, benzoimidazolyl, dihydroisoquinoline, indole, indazole, pyrazolyl, pyrazinyl, pyridazinyl, pyridyl, chinoline, sochinila and thiazolyl; B is selected from the group consisting of chemical bond, -C₁-₆alkylene-, -O-C_1-6alkylene- and -NR⁷-; W is hydrogen or C_1-6 alkyl; Z represents a nitrogen atom or CH; R¹ represents a fluorinated substituent, independently selected from the group consisting of -CF₃, -CHF₂, -OCF₃, -OCHF₂, -OCH₂CHF₂, -OCH₂CF₃, -OCF₂CHF₂, -OCF₂CF₃, -OCH₂CH₂CF₃, -OCH(CH₃)CF₃, -OCH₂C(CH₃)F₂, -OCH₂CF₂CHF₂, -OCH₂CF₂CF₃, -OCH₂CH₂OCH₂CF₃, -NHCH₂CF₃, -SCF₃, -SCH₂CF₃, -CH₂CF₃, -C (CH₃)₂CF₃, -CH₂CH₂CF₃, -CH₂OCH₂CF₃, -OCH₂CH₂OCF₃, 4,4-difluoropiperidino and (4-fluorobenzyl) oxy; R² is independently selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) -O_n-C_1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R⁷, (7) -O_n-phenyl or -O_n-naphthyl, where specified phenyl or naphthyl is unsubstituted or substituted by one or more of the substituents independently selected from R⁷, and (10) -NR⁸R⁹; where n represents 0 or 1; if n=0, a chemical bond is present instead of-O_n-; p represents 1, 2, 3, or 4; if p is two or more than two, R² may be the same or different; R³ and R⁴ independently represent hydrogen or C_1-6 alkyl; R⁵ is independently selected from the group consisting of: (1) hydrogen, (2) halogen, and (3) -O_n-C_1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R⁷, where n represents 0 or 1; if n=0, a chemical bond is present instead of -O_n-; q represents 1, 2, or 3; if q is equal to two or more than two, R⁵ may be the same or different; R⁶ independently represents hydrogen, C_1-6 alkyl, C_2-6alkenyl, C_3-7 cycloalkyl, phenyl, or heterocyclic group, which is unsubstituted or substituted by one or more of the substituents independently selected from halogen, hydroxyl, C_1-6alkyl and -O-C_1-6 alkyl; R⁷ is selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) -(C=O)_m-O_l-C_1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R¹⁰, (9) -(C=O)_m-O_l-heterocyclic group, where this heterocyclic group is unsubstituted or substituted by one or more of the substituents independently selected from R¹⁰, and (11) -NR⁸R⁹, where l=0 or 1 and m=0 or 1; if l=0 or m=0, a chemical bond is present instead of-O_l- or -(C=O)_m -, and if l=0 and m=0, a chemical bond is present instead of -(C=O)_m-O_l-; R⁸ and R⁹independently represent hydrogen or C_1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from halogen, hydroxyl, C_1-6alkyland -O-C_1-6 alkyl; or R⁸ forms a 4-7-membered ring with R⁹, which may contain a nitrogen atom, an oxygen atom, a sulfur atom, a carbonyl or a double bond, where a 4-7-membered ring is not optionally substituted with 1-6 substituents independently selected from the group consisting of: (1) hydrogen, (2) hydroxyl, (3) halogen, (4) C_1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from R¹⁰, and (6) -O-C_1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from R¹⁰; R¹⁰ is independently selected from the group consisting of: (1) hydrogen, (2) hydroxyl, and (3) halogen, which possess activity relative to blocking the potential-dependent sodium channels, such as TTX-S.

EFFECT: method for producing amido derivatives is improved.

14 cl, 3 tbl