IP Library Granted Patent US 11,464,780
Granted Patent B2
US 11,464,780 · App. 16/975,824 · Granted Oct 11, 2022

Pyrazolopyrimidine derivative and use thereof

Inventors: Jianfei Wang (Shanghai, CN); Jikui Sun (Shanghai, CN); Wenyuan Zhu (Shanghai, CN); Yang Zhang (Shanghai, CN); Jie Li (Shanghai, CN); Jian Li (Shanghai, CN); Shuhui Chen (Shanghai, CN)
Assignee: Simcere Pharmaceutical Co. Ltd.
A61K31/529A61P35/00C07D498/22
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Quick Facts
Patent No.
US 11,464,780
App. No.
16/975,824
Granted
Oct 11, 2022
Kind
B2
Abstract

A compound of formula (II), a tautomer thereof or a pharmaceutically acceptable salt thereof, and use thereof in the preparation of medicaments for treating solid tumor-related diseases.

Claims (41)

1. A compound represented by formula (II), an isomer thereof or a pharmaceutically acceptable salt thereof,

wherein,

T 1 , T 2 , T 3 , T 4 , T 5 , and T 6 are each independently selected from the group consisting of CR 3 and N;

W is selected from the group consisting of CR 4 and N;

X 1 and X 2 are each independently CR 5 R 6 ;

R 1 is selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted by 1, 2 or 3 R a ;

R 2 is selected from the group consisting of H and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted by 1, 2 or 3 R b ;

R 3 and R 4 are each independently selected from the group consisting of H, F, Cl, Br, I, OH and NH 2 ;

R 5 and R 6 are each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 and C 1-6 alkyl;

L 1 is selected from the group consisting of —C 1-3 alkyl—, —C 3-6 cycloalkyl— and -4-to 6-membered heterocycloalkyl—, wherein the —C 1-3 alkyl—, —C 3-6 cycloalkyl— and -4- to 6-membered heterocycloalkyl— are optionally substituted by 1, 2 or 3 R c ;

L 2 is selected from the group consisting of —C 1-3 alkyl—, —C 1-3 alkyl—O—, —N(Rd)—, —C 1-3 alkyl—N(Rd)— and —O—;

R a is independently selected from the group consisting of H, F, Cl, Br, I, OH and NH 2 ;

R b is selected from the group consisting of H, F, Cl, Br, I, OH and NH 2 ;

R c is selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, C 1-3 alkyl and C 1-3 alkyl—C═O—, wherein the C 1-3 alkyl and C 1-3 alkyl—C═O— are optionally substituted by 1, 2 or 3 R;

R d is selected from the group consisting of H and C 1-3 alkyl;

R is independently selected from the group consisting of F, Cl, Br, I, OH and NH 2 ;

the carbon atom marked with “*” is a chiral carbon atom present in a single enantiomer form of (R) or (S) or in a form enriched in one enantiomer;

the 4- to 6-membered heterocycloalkyl independently comprises 1, 2, 3 or 4 heteroatoms or heteroatomic groups independently selected from the group consisting of —NH—, —O—, —S—and N.

2. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein R 1 is independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN and CH 3 .

3. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein R 2 is selected from the group consisting of H and CH 3 .

4. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein R 5 and R 6 are each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 and CH 3 .

5. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein R c is selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, CH 3 , CH 3 CH 2 and CH 3 C(=O), wherein the CH 3 , CH 3 CH 2 and CH 3 C(=O) are optionally substituted by 1, 2 or 3 R.

6. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 5 , wherein R c is selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, CH 3 , CH 2 F, CHF 2 , CF 3 , CH 3 CH 2 and CH 3 C(=O).

7. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein L 1 is selected from the group consisting of —CH 2 —, —CH 2 CH 2 —, —cyclopropyl—, —cyclobutyl—, —cyclopentyl—, —oxetanyl—, —tetrahydrofuranyl—, —tetrahydropyranyl—, —pyrrolidinyl— and —piperidinyl—, wherein the —CH 2 —,—CH 2 CH 2 —, —cyclopropyl—, —cyclobutyl—, —cyclopentyl—, —oxetanyl—, — tetrahydrofuranyl—, —tetrahydropyranyl—, —pyrrolidinyl— and —piperidinyl— are optionally substituted by 1, 2 or 3 R c .

8. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 7 , wherein L 1 is selected from the group consisting of —CH 2 —, —CH(CH 3 )—, —C(CH 3 ) 2 —, —CH 2 CH 2 —,

9. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 8 , wherein L 1 is selected from the group consisting of —CH 2 —, —CH 2 CH 2 —, —CH(CH 3 )—, —C(CH 3 ) 2 —,

10. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein L 2 is selected from the group consisting of —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 O—, —CH(CH 3 )O—, —O—, —NH—, —CH 2 NH— and —CH 2 O—.

11. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the moiety

is selected from the group consisting of

12. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the moiety

13. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the moiety

14. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the compound is selected from:

wherein,

W, R 1 , R 2 , L 1 and L 2 are as defined in claim 1 .

15. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 14 , wherein the compound is selected from:

wherein,

n is selected from the group consisting of 0 and 1.

16. A compound, an isomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

17. The compound, isomer thereof or pharmaceutically acceptable salt thereof as defined in claim 16 , wherein the compound is selected from

18. A pharmaceutical composition comprising a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof as defined in claim 1 as active ingredient and a pharmaceutically acceptable carrier.

19. A method for treating a disease related to Trk, ALK and Ros1 kinase in a subject in need thereof, comprising: administering an effective amount of the compound or pharmaceutically acceptable salt thereof as defined in claim 1 to the subject, the disease related to Trk, ALK and Ros1 kinase is a colon cancer or a lung cancer.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 15, 2023
From: SIMCERE PHARMACEUTICAL CO. LTD.
To: NANJING ZAIMING PHARMACEUTICAL CO., LTD.
Reel/Frame 064587/0851 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2021
From: MEDSHINE DISCOVERY INC.
To: SIMCERE PHARMACEUTICAL CO. LTD.
Reel/Frame 055321/0300 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 26, 2020
From: WANG, JIANFEI; SUN, JIKUI; ZHU, WENYUAN; ZHANG, YANG; LI, JIE; LI, JIAN; CHEN, SHUHUI
To: MEDSHINE DISCOVERY INC.
Reel/Frame 053607/0719 →
Priority Claims (3)
CN 201810167756.3 · Feb 28, 2018 · national
CN 201811095822.7 · Sep 19, 2018 · national
CN 201910015376.2 · Jan 7, 2019 · national
Continuity (1)
Related Publication 20200405725A1 · Dec 31, 2020
Cited By (1)
US 12,497,412