FIELD: medicine.
SUBSTANCE: invention relates to a compound of the formula [I-a] or the formula [II] or its pharmaceutically acceptable salt, where a dotted line bond is a single bond or a double bond, X1 is a carbon atom, a nitrogen atom, or an oxygen atom, X2 is a carbon atom or a nitrogen atom, R1a is C1-4 alkyl or C1-4 alkyl carbonyl, R2 is halogen, cyano group, or C1-4 alkyl, m is 0 or 1, n is 0, 1, or 2, if n is 2, all R2 are the same or different, A1, A2, A3, A4, A5, A6, and A7 are all independently selected from a group including a carbon atom, a nitrogen atom, and an oxygen atom, A8 is selected from a group including a carbon atom and a nitrogen atom, and the total number of nitrogen atoms and oxygen atoms contained in the structural formula of a fragment (a) is 0, 1, 2, or 3, t is 0 or 1, r is 0, 1, or 2, and the sum of t and r is 1 or 2, w is 0 or 1, R3 and R4, all independently, are hydrogen or C1-4 alkyl; Cy1 is (1) (i) C4-6 cycloalkyl or (ii) 4-6-element saturated or partially saturated heterocyclyl containing one nitrogen atom, C4-6 cycloalkyl and saturated or partially saturated heterocyclyl is optionally substituted with one substitute independently selected from a group including C1-4 alkyl and an oxo group, or (2) (i) phenyl or (ii) 5- or 6-element heteroaryl containing 1, 2, or 3 heteroatoms independently selected from a group including a nitrogen atom and an oxygen atom, phenyl and heteroaryl are optionally substituted with 1 or 2 substitutes independently selected from a group including halogen, cyano group, carboxy group, C1-4 alkyl, halogen-C1-4 alkyl, and C3-6 cycloalkyl; Cy2 is (1) (i) C3-6 cycloalkyl or (ii) 4-6-element saturated heterocyclyl containing 1 or 2 heteroatoms independently selected from a group including a nitrogen atom and an oxygen atom, and C3-6 cycloalkyl and saturated heterocyclyl are optionally substituted with 1 or 2 substitutes independently selected from a group including halogen, hydroxy group, and C1-4 alkyl, or (2) (i) phenyl or (ii) 5- or 6-element heteroaryl containing 1, 2, 3, or 4 nitrogen atoms, and phenyl and heteroaryl are optionally substituted with 1 or 2 substitutes independently selected from a group including halogen, cyano group, C1-4 alkyl, C1-4 alkoxy group, and C1-4 alkyl sulfonyl, and v is 0 or 1. The invention also relates to a pharmaceutical composition having an inhibitory effect on the activity of PDHK1 and 2, containing effective amount of a compound, according to the invention, or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. Compounds, according to the invention, are intended for use in the treatment of diseases associated with an inhibitory effect on the activity of PDHK1 and 2.
EFFECT: nitrogen-containing heterocyclic amide, which has an inhibitory effect on pyruvate dehydrogenase kinase (PDHK 1 and 2).
, ,
46 cl, 26 tbl, 140 ex
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Authors
Dates
2023-02-07—Published
2019-01-30—Filed