JPWO2021003157A5 - - Google Patents

Claims (27)

Compounds of Formula III:

or a pharmaceutically acceptable salt thereof,
In the formula:
L ¹ is -(CH ₂ )-, -(CH ₂ ) ₂ -, -(CH ₂ ) ₃ -, -CH((C ₁ -C ₈ )alkyl)(CH ₂ )-, -CH((C ₁ -C ₈ )alkyl)(CH ₂ ) ₂ -, -(CH ₂ ) ₂ -O-, -CH ₂ CH=CH-, -CH ₂ C≡C-, or -CH ₂ (cyclopropyl)- can be;
L ² is -C(R ⁶ )(R ⁶ )-, -C(R ⁶ )(R ⁶ )C(R ⁶ )(R ⁶ )-, -C(R ⁶ )=C(R ⁶ )- , -N(R ⁵ )C(R ⁶ )(R ⁶ )-, -OC(R ⁶ )(R ⁶ )-, -C(=O)-, -C(=O)N(R ⁵ )C (R ⁶ )(R ⁶ )—, or a bond;
Ring C is heteroaryl;
R ¹ is H, OH, halo, CN, (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )haloalkyl, (C ₃ -C ₆ )cycloalkyl, or NR ⁵ R ⁵ ;
R ² is independently H, halo, CN, NO, NO ₂ , C≡H, (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )haloalkyl, CH ₂ SR ⁵ , OR ⁵ , NHR ⁵ , NR ⁵ R ⁵ , [(C ₁ -C ₈ )alkylene]heterocyclyl, [(C ₁ -C ₈ )alkylene]heteroaryl, [(C ₁ -C ₈ )alkylene]NHR ⁵ , [(C ₁ -C ₈ ) Alkylene]NR ⁵ R ⁵ , [(C ₁ -C ₈ )alkyline]NR ⁵ R ⁵ , C(O)R ⁵ , C(O)OR ⁵ , C(O)NHR ⁵ , C(O)NR ^5R5 , ^{SR5 , S(O)R5, SO2R5, SO2NHR5, SO2NR5R5 , NH(CO)R6 ,} _NR5 ^{( CO} ₎ ^{R6 , aryl} _, heteroaryl , cycloalkyl, or heterocyclyl;
R ³ is independently OH, halo, CN, NO ₂ , (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, (C ₁ -C ₆ )alkoxy, C≡H, NHR ⁷ , NR ⁷ R ⁷ , CO ₂ H, CO ₂ R ⁷ , [(C ₁ -C ₃ )alkylene](C ₁ -C ₃ )alkoxy, [(C ₁ -C ₃ )alkylene]CO ₂ H, (C _{3 -C5} ) cycloalkyl, =O. =S, ^SR7 , _SO2R7 , NH(CO) ^R7 , or ^NR7 (CO) ^{R7 ;}
R ⁵ is independently H, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, (C ₃ -C ₅ )cycloalkyl, or heterocyclyl;
R ⁶ is independently H, OH, halo, CN, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )haloalkyl, (C ₁ -C ₃ )alkoxy, NHR ⁷ , NR ⁷ R ⁷ , _CO2H , [( _C1 - _C3 )alkylene] _CO2H , ( _C3 - _C5 )cycloalkyl, ^SR7 , NH(CO) ^R7 , or ^NR7 (CO) ^R7 ;
R ⁷ is independently H, (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )haloalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
^R8 is H, OH, _CO2H , _CO2R7 , _{CF2C (} ^R6 )2OH, C( ^R6 ) _{2OH ,} C( ^CF3 ) _2OH , _SO2H , _SO3H , _CF2SO2C ( ^R6 ) ₃ , _CF2SO2N (H ^{) R5} , _SO2N (H) _R5 , _SO2N (H)C(O) ^R6 , _C (O)N (H) _SO2R5 , C(O)haloalkyl, C(O)N(H) ^OR5 , C(O)N( ^R5 )OH, C(O)N(H) ^{R5 ,} C(O) ) ^NR5C (O)N( ^R5 ) ₂ , P(O)( ^OR5 )OH, P(O)(O)N(H) ^R5 , P(O)(C( ^R6 ) ₃ ) C( ^R6 ) ₃ , B(OH) ₂ , heterocyclyl, or heteroaryl;
R ⁹ is H, (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )haloalkyl, cycloalkyl, or heterocyclyl;
m is 0, 1, or 2;
n is 0, 1, 2, or 3;
p is 0, 1, 2, or 3;
wherein any alkyl, alkylene, cycloalkyl, heterocyclyl, heteroaryl, or aryl is OH, CN, SH, SCH ₃ , SO ₂ CH _3, SO ₂ NH ₂ , SO ₂ NH(C ₁ -C ₄ ) Alkyl, Halogen, NH ₂ , NH(C ₁ -C ₄ )alkyl, N[(C ₁ -C ₄ )alkyl] ₂ , NH(aryl), C(O)NH ₂ , C(O)NH(alkyl) , CH ₂ C(O)NH(alkyl), COOH, COOMe, acetyl, (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )haloalkyl, O(C ₁ -C ₈ )alkyl, O(C _{1 -C8} )haloalkyl, ( _C2 - _C8 )alkenyl, ( _C2 - _C8 )alkynyl, thioalkyl, cyanomethylene, alkylaminyl, alkylene-C(O) _NH2 , alkylene-C(O)-NH (Me), NHC(O)alkyl, CH ₂ —C(O)—(C ₁ -C ₈ )alkyl, C(O)—(C ₁ -C ₈ )alkyl, and alkylcarbonylaminyl optionally substituted with 1, 2, or 3 groups;
A compound or a pharmaceutically acceptable salt thereof. 3. The compound or salt of claim ¹ , wherein L1 is a bond. 3. A compound or salt according to claim 1 or 2 , wherein Ring C is heteroaryl. Ring C is

11. The compound or salt of claim 11 or 2 , which is 3. The compound or salt of claim 11 or 2 , wherein R ¹ is H, (C ₁ -C ₈ )alkyl, or (C ₁ -C ₈ )haloalkyl. 6. The compound or salt of any one of claims 1-5, wherein R ² is halo, CN, (C ₁ -C ₈ )alkyl, (C ₁ -C ₈ )haloalkyl, or OR ⁵ . 6. The compound or salt of any one of claims 1-5 , wherein R ² is halo, CN, or (C ₁ -C ₈ )haloalkyl. 8. The compound or salt of any one of claims 1-7, wherein R ⁵ is H, (C ₁ -C ₃ )alkyl, or (C ₁ -C ₃ )haloalkyl. ^9. A compound or salt according to any one of claims 1 to 8, wherein R8 ^is _CO2H or C(O)N(H) _SO2R5 . ^10. A compound or salt according to any one of claims 1 to 9 , wherein R9 is cycloalkyl, or heterocyclyl. 11. A compound or salt according to any one of claims 1 to 10 , wherein p=0 or 1. formula:

or a pharmaceutically acceptable salt thereof. formula:

A compound having formula:

A pharmaceutically acceptable salt of a compound having formula:

or a pharmaceutically acceptable salt thereof. formula:

A compound having formula:

A pharmaceutically acceptable salt of a compound having formula:

or a pharmaceutically acceptable salt thereof. formula:

A compound having formula:

A pharmaceutically acceptable salt of a compound having 21. A pharmaceutical composition comprising (a) a compound or salt according to any one of claims 1-20; and (b) a pharmaceutically acceptable carrier, diluent or excipient. 22. A pharmaceutical composition according to claim 21 for use in treating cancer. Cancer is colon cancer, stomach cancer, thyroid cancer, lung cancer, leukemia, B cell lymphoma, T cell lymphoma, hairy cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, Burkitt lymphoma, pancreatic cancer, melanoma, brain 23. The pharmaceutical composition of claim 22, which is cancer, CNS cancer, renal cancer, prostate cancer, ovarian cancer, or breast cancer. 24. The pharmaceutical composition according to claim 23, wherein the cancer is metastatic cancer. 24. The pharmaceutical composition of Claim 23, wherein the cancer is breast cancer, prostate cancer, or lung cancer. 26. The pharmaceutical composition according to claim 25, wherein the cancer is breast cancer. 27. The pharmaceutical composition according to claim 26, wherein the breast cancer is hormone receptor positive breast cancer.