US 12,435,089 B2
3-oxadiazolyl substituted pyrazolo[1,5,a]pyrimidines for ROS1, NTRK, and ALK mediated diseases
Jun Li, Zhejiang (CN); Chengshan Niu, Zhejiang (CN); Apeng Liang, Zhejiang (CN); and Yusheng Wu, Zhejiang (CN)
Assigned to TYK MEDICINES, INC., Zhejiang (CN)
Filed by TYK MEDICINES, INC., Zhejiang (CN)
Filed on Nov. 8, 2021, as Appl. No. 17/521,153.
Application 17/521,153 is a continuation in part of application No. PCT/CN2020/089067, filed on May 7, 2020.
Claims priority of application No. 201910379104.0 (CN), filed on May 8, 2019.
Prior Publication US 2022/0089603 A1, Mar. 24, 2022
Int. Cl. C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 519/00 (2013.01)] 11 Claims
 
1. A compound represented by formula I, or a tautomer thereof, or a mesomer thereof, or a racemate thereof, or a mixture of the mesomer and the racemate thereof, or an enantiomer thereof, or a diastereomer thereof, or a mixture of the enantiomer and the diastereomer thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof:

OG Complex Work Unit Chemistry
wherein * denotes R configuration, and X is independently selected from the group consisting of NR6, O, CR1R2, S, S(O) and S(O)2;
B is selected from the group consisting of phenyl, 5-6 membered heteroaryl; wherein, H on any carbon atom of the phenyl and 5-6 membered heteroaryl is optionally substituted by the following substituents: halogen, hydroxy, amino, cyano, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkylamino, C1-C6 alkoxy, C3-C6 cycloalkoxy, monosubstituted or polysubstituted C1-C6 alkyl, monosubstituted or polysubstituted C1-C6 alkoxy, monosubstituted or polysubstituted C3-C6 cycloalkyl and monosubstituted or polysubstituted C3-C6 cycloalkoxy; the substituents of the monosubstituted or polysubstituted C1-C6 alkyl, the monosubstituted or polysubstituted C1-C6 alkoxy, the monosubstituted or polysubstituted C3-C6 cycloalkyl and the monosubstituted or polysubstituted C3-C6 cycloalkoxy are independently selected from the group consisting of deuterium, halogen, amino, cyano, hydroxyl, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
or B is selected from the group consisting of

OG Complex Work Unit Chemistry
wherein, custom character is a single bond or a double bond;
Z8 and Z9 are each independently selected from CR11 or N;
P is independently selected from O, NH or S;
when custom character is a double bond, Q is independently selected from CR11 or N; when custom character is a single bond, Q is independently selected from O, S, CR11R12 or NH;
R7 is each independently selected from the group consisting of halogen, amino, cyano, hydroxy, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylamino, monosubstituted or polysubstituted C1-C6 alkyl, monosubstituted or polysubstituted C1-C6 alkoxy and monosubstituted or polysubstituted C3-C6 cycloalkyl; the substituents of the monosubstituted or polysubstituted C1-C6 alkyl, monosubstituted or polysubstituted C1-C6 alkoxy and monosubstituted or polysubstituted C3-C6 cycloalkyl are independently selected from the group consisting of deuterium, halogen, amino, cyano, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
R11 and R12 are each independently selected from the group consisting of H, hydroxy, halogen, amino, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
e is 0, 1, 2, 3 or 4;
Y is independently selected from the group consisting of O, NRA and CR1R2;
wherein R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, amino, cyano, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, monosubstituted or polysubstituted C1-C6 alkyl, monosubstituted or polysubstituted C1-C6 alkoxy and monosubstituted or polysubstituted C3-C6 cycloalkyl; the substituents of the monosubstituted or polysubstituted C1-C6 alkyl, the monosubstituted or polysubstituted C1-C6 alkoxy and the monosubstituted or polysubstituted C3-C6 cycloalkyl are independently selected from the group consisting of deuterium, halogen, amino, cyano and hydroxyl;
R3 and R4 are each independently selected from the group consisting of hydrogen, amino, hydroxy, C1-C6 alkyl, C3-C6 cycloalkyl, phenyl, 5-6 membered heteroaryl, monosubstituted or polysubstituted C1-C6 alkyl, monosubstituted or polysubstituted C1-C6 alkoxy, monosubstituted or polysubstituted C3-C6 cycloalkyl, monosubstituted or polysubstituted phenyl and monosubstituted or polysubstituted 5-6 membered heteroaryl; the substituents of the monosubstituted or polysubstituted C1-C6 alkyl, the monosubstituted or polysubstituted C1-C6 alkoxy, the monosubstituted or polysubstituted C3-C6 cycloalkyl, the monosubstituted or polysubstituted phenyl and the monosubstituted or polysubstituted 5-6 membered heteroaryl are independently selected from the group consisting of halogen, amino, cyano, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
or R3 and R4 together with the C atom attached to them form substituted or unsubstituted 3-7 membered cycloalkane, substituted or unsubstituted 3-7 membered aza-cycloalkane, substituted or unsubstituted 3-7 membered oxa-cycloalkane or substituted or unsubstituted 3-7 membered thio-cycloalkane or oxo (═O); wherein the substituted means being substituted by one or more groups selected from the group consisting of C1-C6 alkyl, —C(O)C1-C6 alkyl, —C(O)OC1-C6 alkyl, —S(O)2C1-C6 alkyl, and —S(O)C1-C6 alkyl;
R6 and RA are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, monosubstituted or polysubstituted C1-C6 alkyl and monosubstituted or polysubstituted C3-C6 cycloalkyl; the substituents of the monosubstituted or polysubstituted C1-C6 alkyl and the monosubstituted or polysubstituted C3-C6 cycloalkyl are independently selected from the group consisting of halogen, amino, cyano and hydroxy; and
each heteroaryl containing 1, 2 or 3 ring heteroatoms selected from N, O or S.