JP-2025514198-A5 -

Dates

Publication Date

20260511

Application Date

20230425

Description

Various changes and modifications to the disclosed embodiments will be obvious to those skilled in the art and can be made without departing from the spirit and scope thereof. Another aspect of the present invention may be as follows: [1] Compound of formula (I): or a pharmaceutically acceptable salt thereof (In the formula, X1 is selected from O, NRw, S, and bond , R1a , R1b , R2a , and R2b are each independently selected from hydrogen, C1 - C4 alkyl, C1 - C4 alkoxy , C3 - C6 cycloalkyl , halo-C1 - C4 alkyl , amino - C1 - C4 alkyl, hydroxy-C1 - C4 alkyl , C1 - C4 alkoxy - C1 - C4 alkyl, halo, hydroxy, amino, C1 - C4 alkylamino , di-C1 - C4 alkylamino , and cyano; R1a and R1b , or R1a and R2a , or R2a and R2b , together with the carbon atoms to which they are bonded, may optionally form substituted 3- to 6-membered rings. X 4 is CR 4 or N, X 5 is CR 5 or N, X 6 is CR 6 or N, X 7 is CR 7 or N, R3 , R4 , R5 , R6 , and R7 are each independently selected from hydrogen, C1 - C6 alkyl , C2 - C6 alkenyl, C2 - C6 alkynyl, C1 - C6 alkoxy , C1 - C6 alkylthio, C3 - C6 cycloalkyl , halo-C1 - C6 alkyl , halo - C1 - C6 alkoxy, amino-C1 - C6 alkyl , hydroxy-C1 - C6 alkyl , C1 - C6 alkoxy -C1 - C6 alkyl , halo-hydroxy-amino, C1 - C4 alkylamino , di-C1 - C4 alkylamino , cyano, -COORx , -CON(Ry ) 2 , -SO2Rz , oligo or polyethylene glycol chain, and the group -Y- R8 ; R 4 and R5 , R5 and R6 , or R6 and R7 may , together with the carbon atoms to which they are bonded, optionally form a substituted five-membered or six-membered ring. Y is selected from -C(O)-, -C(O)O-, -C(O)NRv- , and -C(O)S-. R8 is a lipid moiety having at least 8 carbon atoms . R v , R w , R x , R y , and R z are each independently selected from hydrogen, C1 - C6 alkyl , C2 - C6 alkenyl, C2 - C6 alkynyl , C3 - C6 cycloalkyl , and halo-C1 - C6 alkyl . L is a linker, Z is a part of equation (a) or equation (b), R10 is hydrogen or a C1 - C6 alkyl group . Q is either CH or N, A is a 5-membered or 6-membered monocyclic heteroaryl having aryl or 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, and P. R20 is selected from hydrogen, halo, C1 - C4 alkyl , C3 - C6 cycloalkyl , C1 - C4 haloalkyl , -OR a1 , -N(Ra2 ) (Ra3 ) , -SO2 Ra4 , -SO2N ( Ra5 ) (Ra6 ) , and -NHSO2 Ra7 , where Ra1 , Ra2 , Ra3 , Ra4 , Ra5 , Ra6 , and Ra7 are each independently selected from hydrogen, C1 - C4 alkyl , and C1 - C4 haloalkyl . R21 is selected from hydrogen and the group -L21 - E. L21 is a bond, C1 - C2 alkylene , -CH=CH-, -C≡C-, -C(O)-, -O-, -NH-, -S-, -C(O)O-, -C(O)NH-, -C(O)S-, arylene, cycloalkylene, heteroarylene, or heterocyclylene, or L21 contains any combination of any two of these groups. E is a bicyclic heterocyclyl or bicyclic heteroaryl, each of which is optionally substituted with one, two, three , four , or five substituents independently selected from -OR b1 , -N ( R b2 ) (R b3 ), -SO₂R b4 , -SO₂N ( R b5 ) (R b6 ) , and -NHSO₂R b7 , where R b1, R b2, R b3, R b4 , R b5 , R b6 , and R b7 are independently selected from hydrogen , C1 - C₄ alkyl , and C1 - C₄ haloalkyl . L b is -(CR c1 R c2 ) m -G b- , R c1 and R c2 are independently selected from hydrogen and C1 - C4 alkyl, m is 0, 1, or 2. G b is a bond, -NHC(O)-, -NH-, -O-, or -S-, B is a bicyclic heteroaryl or bicyclic heterocyclyl, each of which is optionally substituted with one, two , three , four , or five substituents independently selected from -OR d1 , -N ( R d2 ) (R d3 ), -SO₂R d4 , -SO₂N ( R d5 ) ( R d6 ), and -NHSO₂R d7 , where R d1 , R d2 , R d3 , R d4 , R d5 , R d6 , and R d7 are independently selected from hydrogen, C1 - C₄ alkyl, and C1 - C₄ haloalkyl ) . [2] The compound described in [1] above, or a pharmaceutically acceptable salt thereof, wherein X4 is CR4 , X5 is CR5 , X6 is CR6 , and X7 is CR7 . [3] The compound described in [1] or [2] above, or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from hydrogen and halo. [4] A compound according to any one of the above items [1] to [3], wherein R4 is hydrogen, or a pharmaceutically acceptable salt thereof. [5] A compound according to any one of [1] to [4] above, or a pharmaceutically acceptable salt thereof, wherein R5 and R6 are independently selected from C1-C6 alkyl, C2- C6 alkenyl, C2-C6 alkynyl , C1 - C6 alkoxy , C1 - C6 alkylthio , C3 - C6 cycloalkyl , halo - C1 - C6 alkyl , halo - C1 - C6 alkoxy , amino - C1 - C6 alkyl , hydroxy - C1 - C6 alkyl , C1 - C6 alkoxy - C1- C6 alkyl , halo , hydroxy, amino, C1-C4 alkylamino, di-C1-C4 alkylamino , cyano, -COOR x , -CON( Ry ) 2 , and -SO2Rz . [6] A compound according to any one of [1] to [5] above, or a pharmaceutically acceptable salt thereof, wherein R 5 and R 6 are independently selected from C1-C4 alkyl, C2-C4 alkenyl , C2 - C4 alkynyl , C1 - C4 alkoxy , C1 - C6 alkylthio , halo - C1 - C4 alkyl , halo - C1 - C4 alkoxy , hydroxy, halo , and C1-C4 alkylamino. [7] A compound