JP-2025515484-A5 -

Dates

Publication Date

20260511

Application Date

20230427

Description

The tumor volume of vehicle-treated and compound-treated mice as a function of time after the start of treatment, and the results of treatment with selected compounds in SCID Beige mice or nude mice transplanted with HCC15 or OVCAR-3 are shown in Figures 1 and 2. The calculated TGI for treatment with the selected compounds is shown in Table 11. Examples of embodiments of the present invention include the following. [Embodiment 1] Compound of formula (I): [Case 1] or a pharmaceutically acceptable salt thereof X and Z are independently O, N, or CH; Y is NH, N, or CH; V and W are independently N or C; Here, at least one of X and Z is N, or Y is NH; Ring A is, [Case 2] And here, One, two, or three of A1 , A3 , and A4 are independently N, NR A1 , O, or S, and if present, the remaining one or two of A1 , A3 , and A4 are independently CH or CR2 , where RA A1 is H or C1-3 alkyl; A2 is N or C; A5 to A8 are independently CH, CR2 , N, or NRA2 , where at least two of A5 , A6 , A7 , and A8 are CH or CR2 , and if present, the remaining one or two of A5 , A6 , A7 , and A8 are N or NRA2 , where RA2 = O; Here, "*" indicates the connection point to V; B1 and B2 are independently N, CH, or CRB , where RB is a halogen; R1 is C1-6 alkyl, C3-6 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocycloalkyl, -NR a1 C(O)NR a2 R a3 , -NR a4 C(O)OR a5 , -NR a6 R a7 , -N=S(O)R a8 R a9 , -OR a10 , -S(O)R a11 , -S(O)(NR a12 )R a13 , -S(O) 2 NR a14 R a15 , -S(O) 2 R a16 , or -(CR a17 R a18 ) 0-1 C ( O)NR a19 R a20 . Here, the C1 - C6 alkyl of R1 is optionally substituted with one or more substituents independently selected from the group consisting of halogens, -OH, oxo, cyano, C3-10 cycloalkyls, and 3-10 member heterocycloalkyls optionally substituted with one or more halos; here, the C3 -C6 cycloalkyl of R1 is optionally substituted with one or more substituents independently selected from the group consisting of halogens; here, the C3-C10 cycloalkenyl of R1 is optionally substituted with one or more substituents independently selected from the group consisting of halogens; and here, the 3-10 member heterocycloalkyl of R1 is optionally substituted with one or more substituents independently selected from the group consisting of halogens, C1-C6 alkyls, and C1-C6 haloalkyls; R a1 to R a20 are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, C6-14 aryl, or 5-12 membered heteroaryl, and are each optionally substituted with one or more substituents independently selected from the group consisting of halo, cyano, -OH, -O ( C1-6 alkyl), C2-6 alkenyl, C3-10 cycloalkyl, -S ( C1-6 alkyl), =CR 1a1 R 1a2 , and C1-6 alkyl which are optionally substituted with one or more substituents independently selected from the group consisting of halo, -OH, and -O ( C1-6 alkyl), where R 1a1 and R 1a2 are each independently hydrogen or C1-6 alkyl; or, R a14 and R a15 , together with the nitrogen to which they are bound, form a 3- to 10-membered heterocycloalkyl group optionally substituted with one or more halos; Each R2 is independently a halogen, C1-3 alkyl, C3-5 cycloalkyl, cyano, C1-3 alkyloxy, C3-5 cycloalkyloxy, hydroxy, or NR b1 R b2 , where the C1-3 alkyl of R2 is optionally substituted with one or more substituents selected from the group consisting of -OH and oxo, where R b1 and R b2 are independently optionally substituted with C1 - C3 alkyl, or R b1 and R b2 together with the nitrogen to which they are bonded form a 3-6 membered ring; or R1 and R2 of A5 together with the carbon atoms to which they are bonded form a C3 - C6 cycloalkyl or a 3-10 membered heterocycloalkyl; R3 is piperidinyl, pyrrolidinyl, or azepanil, where piperidinyl, pyrrolidinyl, or azepanil is optionally substituted with a C3-10 cycloalkyl or a 3-10 membered heterocycloalkyl, where the C3-10 cycloalkyl or 3-10 membered heterocycloalkyl forms a spirocyclic or fused bicyclic ring system with piperidinyl, pyrrolidinyl, or azepanil, or Here, the piperidinyl, pyrrolidinyl, or azepanyl is optionally substituted with a C1-2 alkylene to form a crosslinked piperidinyl, pyrrolidinyl, or azepanyl ring system, where the spirocyclic, condensed, or crosslinked bicyclic ring system formed by the piperidinyl, pyrrolidinyl, azepanyl, or C3-10 cycloalkyl, 3-10 membered heterocycloalkyl, or C1-2 alkylene with piperidinyl, pyrrolidinyl, or azepanyl is optionally substituted with one or more substituents independently selected from the group consisting of C1 - C3 alkyl, C1 - C3 haloalkyl, and halo; R4 is a C1-6 alkyl group optionally substituted with one or more substituents independently selected from the group consisting of H, halo , cyano , -OH, -NO2 , -C(O)NR c1 R c2 , -NR c3 R c4 , -NR c5 S(O) 2 R c6 , -P(O)R c7 R c8 , -N=S(O)R c9 R c10 , -S(O)(NR c11 )R c12 , -S(O) 2 R c13 , or halo and -OH. Here, if X is N, Y is N, and Z is O, then R4 is not H; R c1 to R c13 are each independently hydro