Thieno[2,3-d]Pyrimidine Derivatives, Preparation Method and Use Thereof

摘要

This invention provides thieno[2,3-d]pyrimidine derivatives containing isoxazole heterocycle represented by formula (I), or pharmaceutically acceptable salts thereof;Wherein: R1 and R2 may be the same or different and is independently to each other selected from H, C1-6 alkyl, C1-6 alkoxy, halo-C1-6 alkyl or halo-C1-6 alkoxy, aryl group optionally substituted by R7 or heteroaryl group optionally substituted by R8; or R1 and R2 together with the carbon atoms to which they are attached, may form a 4- to 6-membered carbocyclic ring or heterocyclic ring; said carbocyclic ring or heterocyclic ring is optionally substituted by H, C1-6 alkyl, halogen, nitro, or amino; said heterocyclic ring contains at least one heteroatom selected from N, O or S; Z is —NR6—, C(R6)2, —S— or —O—, in which R5 is H or C1-6 alkyl, and R6 is the same or different, selected from H, C1-6 alkyl or hydroxyl substituted C1-6 alkyl; R3 is selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, halo-C1-6 alkyl or halo-C1-6 alkoxy; n is an integer of 0-5; R4 is selected from H, C1-6 alkyl, C1-6 alkoxy or halo-C1-6 alkyl, aryl group optionally substituted by R9, or heteroaryl group optionally substituted by R10; R7, R8, R9 or R10 independently to each other, is selected from H, hydroxy, mercapto, cyano, amino, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, carboxy, halo-C1-6 alkyl or halo-C1-6 alkoxy. This invention also provides the preparation method and medicinal uses of the compounds of formula (I) and pharmaceutically acceptable salts thereof. and this class of compounds can be used as medicants or lead compounds for the treatment of diseases such as tumors, cancers.

主权项

1. Thieno[2,3-d]pyrimidine derivatives represented by formula (I), pharmaceutically acceptable salts or solvates thereof, wherein: R1 and R2 may be the same or different and is independently to each other selected from H, C1-6 alkyl, C1-6 alkoxy, halo-C1-6 alkyl, halo-C1-6 alkoxy or hydroxyl substituted C1-6 alkyl, aryl group optionally substituted by R7 or heteroaryl group optionally substituted by R8; or R1 and R2 together with the carbon atoms to which they are attached, may form a 4- to 6-membered carbocyclic ring or heterocyclic ring, said carbocyclic ring or heterocyclic ring is optionally substituted by R11; said heterocyclic ring contains at least one heteroatom selected from N, O or S; Z is —NR5—, C(R6)2, —S— or —O—, in which R5 is H or C1-6 alkyl, and R6 is the same or different, selected from H, C1-6 alkyl, halo-C1-6 alkyl or hydroxyl substituted C1-6 alkyl; R3 is selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, halo-C1-6 alkyl, halo-C1-6 alkoxy or hydroxyl substituted C1-6 alkyl; n is an integer of 0-5; R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, halo-C1-6 alkyl or halo-C1-6 alkoxy, aryl group optionally substituted by R9, or heteroaryl group optionally substituted by R10; R7, R8, R9, R10 or R11 independently to each other, is selected from H, hydroxy, mercapto, cyano, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, carboxy, halo-C1-6 alkyl, halo-C1-6 alkoxy or halo-C1-6 alkylthio.