JPWO2021154664A5 - - Google Patents

Claims (13)

Formula (I) below:
[In the formula,
W is H, halo, C ₁ -C ₃ alkyl, CN, (C ₁ -C ₄ alkanediyl)OH,
And;
each X is independently N or ^CR2 ;
R ¹ is (C ₁ -C ₈ alkanediyl) _0-1 (C ₃ cycloalkyl),
(C ₁ -C ₈ alkanediyl) _0-1 (C ₅ -C ₆ cycloalkyl),
(C ₁ -C ₄ alkanediyl) _0-1 (5-6 membered heteroaryl),
(C ₁ -C ₄ alkanediyl) _0-1 phenyl, or (C ₁ -C ₄ alkanediyl) CF ₃ ;
Each R ² is independently H, O (C ₁ -C ₃ alkyl), S (C ₁ -C ₃ alkyl),
SO ₂ (C ₁ -C ₃ alkyl), C ₁ -C ₃ alkyl, O (C ₃ -C ₄ cycloalkyl),
S (C ₃ -C ₄ cycloalkyl), SO ₂ (C ₃ -C ₄ cycloalkyl),
C ₃ -C ₄ cycloalkyl, Cl, F, CN; or [C(=O)] _0-1 NR ^x R ^y ;
^R3 is H, halo, OH, CN,
_NH2 ,
NH[C(=O)] _0-1 (C ₁ -C ₅ alkyl),
N(C ₁ -C ₅ alkyl) ₂ ,
NH[C(=O)] _0-1 (C ₁ -C ₄ alkanediyl) _0-1 (C ₃ -C ₈ cycloalkyl),
N(C ₃ -C ₆ cycloalkyl) ₂ ,
N[C ₁ -C ₃ alkyl]C(=O) (C ₁ -C ₆ alkyl),
NH(SO ₂ )(C ₁ -C ₅ alkyl),
NH(SO ₂ )(C ₁ -C ₄ alkanediyl) _0-1 (C ₃ -C ₈ cycloalkyl),
a 6-membered aromatic or heteroaromatic moiety;
A 5-membered heteroaromatic moiety, or the following structure:
is a part having;
R ⁵ is H, C ₁ -C ₅ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₆ cycloalkyl,
Halo, O(C ₁ -C ₅ alkyl), (C ₁ -C ₄ alkanediyl)OH,
(C ₁ -C ₄ alkanediyl)O(C ₁ -C ₃ alkyl), phenyl,
NH (C ₁ -C ₅ alkyl), 5- or 6-membered heteroaryl,
And;
R ⁶ is NH ₂ ,
(NH) _0-1 (C ₁ -C ₅ alkyl),
N(C ₁ -C ₅ alkyl) ₂ ,
(NH) _0-1 (C ₁ -C ₄ alkanediyl) _0-1 (C ₃ -C ₈ cycloalkyl),
N(C ₃ -C ₆ cycloalkyl) ₂ ,
Or the structure below:
is a part having;
R ^{X and R y} are independently H or C ₁ -C ₃ alkyl, or R ;
n is 1, 2, or 3;
p is 0, 1, 2, or 3;
Here, in R ¹ , R ² , R ³ , and R ⁵ ,
Alkyl moiety, alkanediyl moiety, cycloalkyl moiety, or the formula:
The part indicated by
OH, halo, CN, (C ₁ -C ₃ alkyl), O (C ₁ -C ₃ alkyl),
C (=O) (C ₁ -C ₃ alkyl), SO ₂ (C ₁ -C ₃ alkyl), NR ^x R ^y ,
(C ₁ -C ₄ alkanediyl)OH, (C ₁ -C ₄ alkanediyl)O(C ₁ -C ₃ alkyl)
May be optionally substituted with one or more substituents selected from;
Alkyl, alkanediyl, cycloalkyl, or the formula:
The part indicated by
O, _SO2 , _CF2 , C(=O), NH,
N[C(=O)] _0-1 (C ₁ -C ₃ alkyl),
N[C(=O)] _0-1 (C ₁ -C ₄ alkanediyl)CF ₃ ,
N[C(=O)] _0-1 (C ₁ -C ₄ alkanediyl)OH,
or N[C(=O)] _0-1 (C ₁ -C ₄ alkanediyl) _0-1 (C ₃ -C ₅ cycloalkyl)
may have a CH ₂ group substituted with]
A compound having the structure shown in R ¹ is
2. A compound according to claim 1, selected from the group consisting of. ^2. A compound according to claim 1, wherein R2 is OMe. R ³ is
2. A compound according to claim 1, selected from the group consisting of. 2. A compound according to claim 1, wherein ^R5 is H. Formula (Ia) below:
2. The compound according to claim 1, having a structure represented by: R ¹ is
7. A compound according to claim 6, selected from the group consisting of. R ³ is
7. A compound according to claim 6, selected from the group consisting of. Formula (Ia) below:
[In the formula,
^R1 is
And;
^R3 is OH,
]
A compound having the structure shown in A pharmaceutical composition for treating cancer, comprising an anti -cancer immunotherapeutic agent and a compound according to any one of claims 1 to 9 . The pharmaceutical composition according to claim 10, wherein the anti-cancer immunotherapeutic agent is an antagonist anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibody. The pharmaceutical composition according to claim 10 , wherein the anti-cancer immunotherapeutic agent is ipilimumab, nivolumab, or pembrolizumab. The cancer is lung cancer (including non-small cell lung cancer), pancreatic cancer, kidney cancer, head and neck cancer, lymphoma (including Hodgkin lymphoma), skin cancer (including melanoma and Merkel skin cancer), urothelial cancer The pharmaceutical composition according to any one of claims 10 to 12 , which is cancer of the stomach (including bladder cancer), gastric cancer, hepatocellular carcinoma, or colorectal cancer.