Compound for inhibiting and degrading tyrosine protein kinase ALK

1. A compound represented by the following formula I, or a pharmaceutically acceptable salt thereof:

wherein

— is a single bond;

is a single or a double bond;

A is missing a bond, C(═O)X1, or substituted or unsubstituted C 1-8 hydrocarbyl group, wherein X1 is a bond or (CR 35 R 36 ) k O, wherein R 35 and R 36 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group, and k is an integer between 0 and 3;

W is a bond, O, or NR 17 , wherein R 17 is H or substituted or unsubstituted C 1-8 hydrocarbyl group;

Y is (CR 22 R 23 ) h , wherein h is an integer between 0 and 30, and R 22 and R 23 are each independently selected from the group consisting of H, cyano, hydroxyl, amino, and substituted and unsubstituted C 1-8 hydrocarbyl group;

Z is (CR 24 R 25 ) i , wherein i is an integer between 0 and 30, and R 24 and R 25 are each independently selected from the group consisting of H, cyano, hydroxyl, amino, and substituted or unsubstituted C 1-8 hydrocarbyl group;

B is O;

X is CH 2 ; or C(═O);

R 1 is selected from the group consisting of H, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted C 1-8 cyclic hydrocarbyl group, substituted or unsubstituted C 1-8 heterocyclic hydrocarbyl group, and substituted or unsubstituted C 1-6 acyl group;

R 8 is selected from the group consisting of H, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted C 1-8 cyclic hydrocarbyl group, substituted or unsubstituted C 1-8 heterocyclic hydrocarbyl group, and substituted or unsubstituted C 1-6 acyl group;

R 11 is selected from the group consisting of H, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted C 1-8 cyclic hydrocarbyl group, substituted or unsubstituted C 1-8 heterocyclic hydrocarbyl group and substituted or unsubstituted C 1-6 acyl group;

R 2 is selected from the group consisting of hydrogen, OR 26 , NR 27 R 28 , cyano, halogen, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted C 1-8 cyclic hydrocarbyl group, substituted or unsubstituted C 1-8 heterocyclic hydrocarbyl group, substituted or unsubstituted C 1-6 acyl group, and substituted or unsubstituted C 1-6 amido group, wherein R 26 , R 27 , and R 28 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 5 is selected from the group consisting of hydrogen, OR 26 , NR 27 R 28 , cyano, halogen, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted C 1-8 cyclic hydrocarbyl group, substituted or unsubstituted C 1-8 heterocyclic hydrocarbyl group, substituted or unsubstituted C 1-6 acyl group, and substituted or unsubstituted C 1-6 amido group, wherein R 26 , R 27 , and R 28 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 3 is selected from the group consisting of H, OR 29 , NR 30 R 31 , cyano, halogen, nitro, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted cyclic hydrocarbyl group, and substituted or unsubstituted heterocyclic hydrocarbyl group, wherein R 29 , R 30 , and R 31 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 6 is selected from the group consisting of H, OR 29 , NR 30 R 31 , cyano, halogen, nitro, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted cyclic hydrocarbyl group, and substituted or unsubstituted heterocyclic hydrocarbyl group; wherein R 29 , R 30 , and R 31 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 7 is selected from the group consisting of H, OR 29 , NR 30 R 31 , cyano, halogen, nitro, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted cyclic hydrocarbyl group, and substituted or unsubstituted heterocyclic hydrocarbyl group, wherein R 29 , R 30 , and R 31 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 9 is selected from the group consisting of H, OR 29 , NR 30 R 31 , cyano, halogen, nitro, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted cyclic hydrocarbyl group, and substituted or unsubstituted heterocyclic hydrocarbyl group, wherein R 29 , R 30 , and R 31 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 10 is selected from the group consisting of H, OR 29 , NR 30 R 31 , cyano, halogen, nitro, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted cyclic hydrocarbyl group, and substituted or unsubstituted heterocyclic hydrocarbyl group, wherein R 29 , R 30 , and R 31 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 12 is selected from the group consisting of H, OR 29 , NR 30 R 31 , cyano, halogen, nitro, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted cyclic hydrocarbyl group, substituted or unsubstituted heterocyclic hydrocarbyl group, X6S(═O) j R 32 , and X6C(═O)R 33 , wherein j is an integer between 0 to 2, R 29 , R 30 , R 31 , R 32 , and R 33 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group, and X6 is a bond;

R 13 is selected from the group consisting of H, OR 29 , NR 30 R 31 , cyano, halogen, nitro, substituted or unsubstituted C 1-8 hydrocarbyl group, substituted or unsubstituted cyclic hydrocarbyl group, and substituted or unsubstituted heterocyclic hydrocarbyl group, wherein R 29 , R 30 , and R 31 are each independently selected from the group consisting of H and substituted or unsubstituted C 1-8 hydrocarbyl group;

R 4 is selected from the group consisting of H, cyano, carboxyl, substituted or unsubstituted C 1-8 hydrocarbyl group, and substituted or unsubstituted C 1-8 hydrocarbyloxycarbonyl group;

a is an integer between 0 and 5;

b is an integer between 0 and 3;

c is an integer between 1 and 30;

d is an integer between 0 and 9;

e is an integer between 0 and 3;

f is an integer between 0 and 4; and

wherein any of the substituents is selected from the group consisting of halogen, unsubstituted or halogenated C1-C6 alkyl, unsubstituted or halogenated C1-C6 alkoxy, unsubstituted or halogenated C2-C6 alkoxyalkyl, unsubstituted or halogenated C3-C8 cycloalkyl, unsubstituted or halogenated C2-C6 alkylcarbonyl, unsubstituted or halogenated C1-C6 alkylene-hydroxyl, and unsubstituted or C1-C6 alkyl substituted amine.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

in formula I, A is a bond; W is a bond or O; Y is (CR 22 R 23 ) h , wherein R 22 and R 23 are each independently selected from the group consisting of H, hydroxyl, and substituted or unsubstituted C 1-4 hydrocarbyl group, and h is an integer between 0 and 3; Z is (CR 24 R 25 ) i , wherein R 24 and R 25 are each independently selected from the group consisting of H, hydroxyl, and substituted or unsubstituted C 1-4 hydrocarbyl group and i is an integer between 0 and 3; and c is an integer between 1 and 6; or

in formula I, A is a bond; W is NR 17 , wherein R 17 is H or substituted or unsubstituted C 1-4 hydrocarbyl group; Y is (CR 22 R 23 ) h , wherein R 22 and R 23 are each independently selected from the group consisting of H, hydroxyl, and substituted or unsubstituted C 1-4 hydrocarbyl group, and h is an integer between 0 and 3; Z is (CR 24 R 25 ) i , wherein R 24 and R 25 are each independently selected from the group consisting of H, hydroxyl, and substituted or unsubstituted and C 1-4 hydrocarbyl group, and i is an integer between 0 and 4; and c is an integer between 1 and 6; or

in formula I, A is a bond; W is a bond; Y is (CR 22 R 23 ) h , wherein R 22 and R 23 are each independently selected from the group consisting of H, hydroxyl, and substituted and unsubstituted C 1-4 hydrocarbyl group, and h is an integer between 0 and 3; Z is (CR 24 R 25 ) i , wherein R 24 , and R 25 are each independently selected from the group consisting of H, hydroxyl, and substituted or unsubstituted C 1-4 hydrocarbyl group, and i is an integer between 0 and 3; and c is an integer between 1 and 10.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein in formula I, X is C(═O).

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 12 is selected from the group consisting of hydrogen, halogen, cyano, nitro, and X6S(═O) j R 32 , wherein j is 2, and R 32 is selected from the group consisting of H and substituted or unsubstituted C 1-6 alkyl.

5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from the group consisting of H, cyano, and substituted or unsubstituted C 1-6 alkyl.

6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

Com-

pound

No.

Structure of compound

7

10

14

15

7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is represented by formula I′:

8. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is represented by formula I″:

9. A pharmaceutical composition, wherein the composition comprises the compound according to claim h or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.