N-(AZAARYL)CYCLOLACTAM-1-CARBOXAMIDE DERIVATIVE, ITS PREPARATION METHOD AND ITS APPLICATION Russian patent published in 2022 - IPC C07D401/14 C07D407/14 C07D413/14 C07D417/14 A61K31/4439 A61K31/497 A61P35/00 

FIELD: organic chemistry; pharmaceutics.

SUBSTANCE: group of inventions relates to the field of organic chemistry and pharmaceutics; it is intended for use in the treatment of a disorder associated with the activity of colony stimulating factor 1 receptor (hereinafter – CSF-1R). A new N-(azaaryl)cyclolactam-1-carboxamide derivative is presented, having a structure described by the formula (IIa), where X₁ is selected from -O- or -CH₂-; X₂ is selected from a bond, -O- or -CH₂-; R₁ and R₂, each independently, are selected from a group consisting of hydrogen, hydroxy, methyl, ethyl, propyl, phenylmethoxy, and methoxyethyl, or R₁ and R₂, together with a carbon atom directly attached to them, form C_3-6 cycloalkyl; R₃ is selected from a group consisting of hydrogen, methyl and ethyl; R₄ is selected from 5-8-element heteroaryl or -NR₁₄R₁₅, where the specified 5-8-element heteroaryl is selected from structures proposed in cl.1; where each R₁₆ is independently selected from a group consisting of hydrogen, C_1-4 alkyl, C_3-8 cycloalkyl and 3-8-element heterocyclyl; the above-mentioned groups, in turn, are optionally substituted with one or several additional substituents selected from a group consisting of deuterium, C_1-4 alkyl, 3-8-element heterocyclyl and C_0-4 alkyl-OR₁₂; each R₁₇ is independently selected from C_1-4 alkyl, each R₁₂ is independently selected from a group consisting of hydrogen and C_1-8 alkyl; R₁₄ and R₁₅, each independently, are selected from a group consisting of hydrogen and C_1-8 alkyl; Z₅ is CH or N; unless otherwise specified, “heterocyclyl” contains 1-2 heteroatoms selected from nitrogen or oxygen. In addition, a method for producing a compound of the formula (IIa), a pharmaceutical composition for inhibiting the kinase activity of the colony stimulating factor 1 receptor (CSF-1R), including a compound of the formula (IIa), and the use of a compound of the formula (IIa) to obtain a drug for the treatment associated with CSF-1R activity are described. A method for the treatment of cancer, tumor, autoimmune disease, metabolic disease or metastatic disease associated with the activity of the colony stimulating factor 1 receptor (CSF-1R) is also described, where the specified method includes the injection of a compound of the formula (IIa) to a patient.

EFFECT: increase in the inhibitory effect on the CSF-1R target and the selectivity of related kinase receptors.

13 cl, 1 tbl, 42 ex