JPWO2019213318A5 - - Google Patents

Claims (17)

Compound of structural formula I, or salt thereof or tautomer:

(In the formula, a is 0 or 1;
b is 0 or 1;
R _1a is from a 5-6 membered heteroaryl group containing halo, phenyl, and a group consisting of 1 to 4 heteroatoms or independently selected from the group consisting of N, C (O), O, and S. The phenyl or heteroaryl of the R _1a is halo, hydroxy, amino, C _1-4 alkylamino, C _1-4 dialkylamino, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 hydroxyalkyl, C _1-4 dihydroxyalkyl, hydroxy C _1-4 alkoxy, dihydroxy C _1-4 alkoxy, C _1-4 haloalkyl, C _1-4 aminoalkyl, C _3-8 cycloalkyl, C _{3 -8} Cycloalkenyl, NR ₁₅ C (O) R ₁₃ , NR ₁₅ C (O) OR ₁₃ , NR ₁₃ C (O) NR ₁₅ R ₁₆ , NR ₁₅ S (O) R ₁₃ , NR ₁₅ S (O) ₂ R ₁₃ , C (O) NR ₁₅ R ₁₆ , S (O) NR ₁₅ R ₁₆ , S (O) ₂ NR ₁₅ R ₁₆ , C (O) R ₁₃ , C (O) OR ₁₃ , OR ₁₃ , SR ₁₃ , S (O) R ₁₃ , and S (O) ₂ R ₁₃ optionally substituted with 1-5 R ₁₂ groups independently selected from the group;
_R1b is selected from the group consisting of halogens and C _1-6 alkyls ;
R ₂ , R ₃ , R ₁₀ and R ₁₁ are each independently selected from the group consisting of hydrogen, C _1-4 alkyl, and C _3-8 cycloalkyl;
R ₄ , R ₅ , R ₈ and R ₉ are hydrogen, cyano, C _1-4 alkyl, C _1-4 alkoxy, amino, hydroxy, C _3-8 cycloalkyl, halo, and C _1-4 alkyl amino. Selected independently of the group consisting of;
R ₆ and R ₇ are independently selected from the group consisting of 1 to 3 heteroatoms or N, C (O), O, and S (O) _m , together with the carbon atoms to which they are both bonded. A 3- to 7-membered saturated or unsaturated group that can contain the groups to be used and are optionally substituted with one _R17 group and optionally with one or more _R18 groups. Form a ring;
m is 0, 1, or 2;
Any two groups of R ₂ , R ₃ , R ₄ , R ₅ , R ₈ , R ₉ , R ₁₀ and R ₁₁ optionally contain an N, O or S heteroatom, a 5- to 6-membered ring. Can form;
Any two groups of R ₂ , R ₄ , R ₈ and R ₁₀ can be directly bonded or form a carbon bridge of one or two atoms;
R ₁₃ , R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, C _1-4 alkyl, C _3-8 cycloalkyl, and 3- to 6-membered heterocyclyls, wherein said alkyl,. Cycloalkyl and 3- to 6-membered heterocyclyls are optionally substituted with one or more substituents selected from the group consisting of hydroxy, cyano and halo;
Each of R ₁₇ and R ₁₈ is independently selected from the group consisting of amino, halo, hydroxy, cyano, trifluoromethyl, trifluoromethoxy, C _1-4 alkyl, and C _1-4 alkoxy ) . The 5- to 6 -membered heteroaryl in which the R _1a comprises a phenyl, or 1 to 4 heteroatoms, or a group independently selected from the group consisting of N, C (O), O, and S. Is the basis;
The phenyl or heteroaryl of R _1a is halo, hydroxy, amino, C _1-4 alkylamino, C _1-4 dialkylamino, cyano, C _1-4 alkyl, C _1-4 alkoxy, C _1-4 hydroxyalkyl. , C _1-4 haloalkyl, C _1-4 aminoalkyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, NR ₁₅ C (O) R ₁₃ , NR ₁₅ C (O) OR ₁₃ , NR ₁₃ C ( O) NR ₁₅ R ₁₆ , NR ₁₅ S (O) R ₁₃ , NR ₁₅ S (O) ₂ R ₁₃ , C (O) NR ₁₅ R ₁₆ , S (O) NR ₁₅ R ₁₆ , S (O) ₂ NR 1 to 5 independently selected from the group consisting of ₁₅ R ₁₆ , C (O) R ₁₃ , C (O) OR ₁₃ , SR ₁₃ , S (O) R ₁₃ , and S (O) ₂ R ₁₃ . Arbitrarily substituted by the _R12 group of; and _R13 , _R15 , and _R16 are independently selected from the group consisting of hydrogen, C _1-4 alkyl, and C _3-8 cycloalkyl, wherein said. The compound according to claim 1, wherein the alkyl or cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy, cyano and halo. The compound according to claim 1 , wherein R ₂ , R ₃ , R ₄ , R ₅ , R ₈ , R ₉ , R ₁₀ and R ₁₁ are each hydrogen. The R ₆ and R ₇ are independent of the group consisting of 1 to 3 heteroatoms or N, C (O), O, and S (O) _m , together with the carbon atoms to which they are both bonded. A 3- to 7-membered saturated or unsaturated ring containing selected groups and optionally substituted with one _R17 group and optionally with one or more _R18 groups. The compound according to any one of claims 1 to 3 to be formed. R ₆ and R ₇ are optionally substituted with one R ₁₇ group and optionally with one or more R ₁₈ groups, together with a carbon atom to which both of them are bonded, 3-to. The compound according to any one of claims 1 to 3 , which forms a 6-membered heterocycloalkyl ring. The compound according to any one of claims 1 to 3 , wherein each of the R _17s is amino; and each R ₁₈ is methyl. The R _1a is:

Selected from the group consisting of, and each R ₁₂ consists of halo, hydroxy, amino, C _1-4 alkylamino, C _1-4 dialkylamino, cyano, C _1-4 alkyl, and C _1-4 alkoxy. The compound according to claim 1, which is independently selected from the above. The compound according to claim 7 , wherein each of the R _12s is independently selected from the group consisting of halo, amino, methylamino, and ethylamino. The compound according to claim 1, wherein R _1a is phenyl or pyridyl, each of which is substituted with 0 to 2 R ₁₂ . The compound according to claim 1 , wherein R _1b is a halogen. The compound according to claim 10 , wherein R _1b is chloro. The compound according to claim 1, wherein R _1b is C _1-6 alkyl . The compound according to claim 12 , wherein R _1b is methyl. The compound according to claim 1, or a salt or tautomer thereof, having a structure selected from the group consisting of the following:

A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1 for treating a subject PTPN11-mediated disease , wherein the composition is administered to a patient in need thereof. Composition . The pharmaceutical composition according to claim 15 , wherein the disease is cancer. 16. The pharmaceutical composition of claim 16 , wherein the cancer is selected from the group consisting of breast cancer, colon cancer, leukemia, and melanoma.