PYRAZOLE DERIVATIVE OR ITS PHARMACEUTICALLY ACCEPTABLE SALT Russian patent published in 2019 - IPC C07D231/12 C07D401/04 C07D401/12 C07D401/14 C07D403/12 C07D405/14 C07D409/14 C07D417/12 C07D491/52 A61K31/415 A61K31/4155 A61K31/4178 A61K31/4192 A61K31/4196 A61K31/427 A61K31/436 A61K31/437 A61K31/4375 A61K31/4439 A61K31/444 A61K31/454 A61P13/10 A61P25/00 

FIELD: chemistry.

SUBSTANCE: present invention relates to a novel pyrazole derivative of formula (I) or a pharmaceutically acceptable salt thereof. [Chemical formula 1]

(I). In formula 1 ring A - C_3-6cycloalkyl, C_6-10aryl or 5–6-member heterocycle, having from 1 to 4 heteroatoms selected from a sulfur atom, an oxygen atom and a nitrogen atom; X - CR^4a or a nitrogen atom with the proviso that three X represent CR^4a or one X represents a nitrogen atom and two X represent CR^4a; R¹ and R² - a hydrogen atom, a halogen atom, hydroxy, amino, formyl, hydroxyC_1-6alkyl, C_1-6alkoxy, C_1-6alkyl, halogen C_1-6alkyl, cyano, C_1-6alkylsulphonylamino, imidazolyl, 1,3-dioxolyl or mono (di)C_1-6alkoxyC_1-6alkyl; R³ - a hydrogen atom, a halogen atom, C_1-6alkyl or formyl; R⁴ and R^4a - a hydrogen atom, a halogen atom, hydroxy, C_1-6alkyl, C_1-6alkoxy, C_1-6alkoxyC_1-6alkoxy, halogen C_1-6alkyl, halogen C_1-6alkoxy, hydroxyC_1-6alkyl, hydroxyC_1-6alkoxy, cyano, carbamoyl, C_1-6alkoxycarbonylC_1-6alkoxy, C_7-10aralkyloxy, C_7-10aralkyloxyC_1-6alkoxy or 1,3-dioxolyl; ring B - C_6-10aryl or 5-6-member heterocycle, having from 1 to 4 heteroatoms selected from a sulfur atom, an oxygen atom and a nitrogen atom; R⁵ is a hydrogen atom, C_1-6alkyl, mono (di) hydroxyC_1-6alkyl, C_1-6alkoxy (hydroxy) C_1-6alkyl, carboxyC_1-6alkyl or C_1-6alkoxycarbonylC_1-6alkyl; R^6a is a hydrogen atom, C(=O)R⁹, C(=O) NR¹⁰R¹¹, -CR¹²R¹³R¹⁴ or a group represented by chemical formula 2; R^7a - a hydrogen atom, a fluorine atom, hydroxy, hydroxyC_1-6alkyl, C_1-6alkyl, C_1-6alkoxy, C_1-6alkoxyC_1-6alkyl or aminoC_1-6alkyl; R^7b is a hydrogen atom, a fluorine atom or C_1-6alkyl, or one of R⁵ and R^6a can be bonded together with ring B to form 6-member ring or can be bonded together with R^7a to form 5-member ring; R^6b is a hydrogen atom or C_1-6alkyl; R⁸ - a hydrogen atom, a halogen atom, C_1-6alkyl, C_1-6alkoxy, hydroxy, amino, cyano, C_1-6alkoxycarbonyl, C_1-6alkoxyC_1-6alkoxy, carbamoyl, C_1-6alkoxyC_1-6alkyl, carboxy, azide, halogen C_1-6alkyl or tetrazolyl; R⁹ - hydroxy, C_1-6alkyl or hydroxyl pyrrolidinyl; R¹⁰ and R¹¹ is a hydrogen atom, C_1-6alkyl, hydroxyC_1-6alkyl, mono(di)C_1-6alkylaminoC_1-6alkyl, pyrrolidinyl or piperidinyl; R¹², R¹³ and R¹⁴ is a hydrogen atom, hydroxy, C_1-6alkyl, NR¹⁵R¹⁶, R¹⁵R¹⁶NC_1-6alkyl, C_1-6alkoxy, mono(di)hydroxyC_1-6alkyl, carbamoyl, C_7-10aralkyloxyC_1-6alkyl, C_1-6alkoxyC_1-6alkyl, fluorine atom or fluorine C_1-6alkyl; R¹⁵ is a hydrogen atom, C_1-6alkyl, (C_1-6alkyl) carbonyl or C_7-10aralkyl; R¹⁶ is a hydrogen atom or C_1-6alkyl; n = 0, 1 or 2. There are also presented a number of specific compounds and a pharmaceutical composition.

EFFECT: disclosed compounds have inhibitory effects on TRPM8 and are useful as an agent for treating or preventing diseases or symptoms caused by hyperexcitability or afferent neuron disorder.

13 cl, 139 tbl, 526 ex