FIELD: pharmaceutical industry.
SUBSTANCE: compound of formula (Ia), formula (Ib) or formula (Ic), or a pharmaceutically acceptable salt or enantiomer thereof, having inhibitory activity against IRE1α kinase, pharmaceutical composition based on it, method of treatment associated with IRE1α disease and a method for inhibiting the activity of the IRE1 protein.
EFFECT: development of compounds that effectively inhibit IRE1α kinase. In general formulas (Ia), (Ib) and (Ic), R1 is selected from the group consisting of 
, 
, 
and 
; R2 is selected from the group consisting of H, methyl, ethyl, propyl, CF3, CHF2, 1-methyl-cyclopropyl, isopropyl, t-butyl and C3-C8 cycloalkyl; L is selected from the group consisting of a bond, -CH2- and -C(=O)-; R3 is selected from the group consisting of 
, 
, 
, C3-C8 cycloalkyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,2,3,6-tetrahydropyridinyl, benzyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, triazolyl, tetrazolyl, thiadiazolyl and oxadiazolyl; or -LR3 is 
, where R''' is selected from the group consisting of -OH, C1-C6 alkoxy group, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C1-C6 alkyl) and -NH(oxetanyl); R4 is selected from the group consisting of halogen, -NH2 and -NHR8; in each occurrence, R5 is independently selected from the group consisting of halogenid, C1-C6 alkyl and C1-C6 alkoxy group; R6 is H; in each occurrence R9 is independently selected from the group consisting of H, C1-C8 alkyl, oxetanyl, C1-C6 haloalkyl, C1-C6 carboxamidoalkyl, C1-C6 carboxyalkyl and C1-C6 cyanoalkyl ; R8 is C1-C3 alkyl; Cy is selected from the group consisting of phenyl, naphthyl, pyridyl, pyrimidinyl, thienyl, benzimidazolyl, pyrazolyl, pyrazinyl, pyridazinyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isothiazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, 
, 
and 
; where Cy is substituted with 0 to 'n' X, in each occurrence X is independently selected from the group consisting of H, OH, halogenid, nitrile, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy groups, phenyl and 
in each occurrence, Z, if present, is independently selected from the group consisting of CH and N; m is an integer selected from the group consisting of 0, 1, 2, 3 and 4; n is an integer selected from 0, 1, 2, 3, 4 and 5; q means an integer selected from 0, 1, 2, 3, 4 and 5; p means an integer selected from 0, 1, 2, 3, 4 and 5.
22 cl, 7 tbl, 235 ex
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