Quinolyl-containing Hydroxamic Acid Compound and Preparation Method Thereof, and Pharmaceutical Composition Containing This Compound and Use Thereof

摘要

Provided in the present invention is a quinolyl-containing hydroxamic acid compound as shown in formula (I), at the same time also disclosed is the preparation method of the compound and the use thereof, and a pharmaceutical composition containing the quinolyl-containing hydroxamic acid compound. Such compounds are inhibitors of protein kinases and/or histone deacetylases, and can be used in the treatment of diseases caused by the abnormal activity of protein kinases and/or histone deacetylases, for example, tumors, etc.

主权项

1. A quinolyl-containing hydroxamic acid compound, having the molecular structure of formula (I) below:wherein,
either of V1 or V2 is a hydrogen, halogen, —OCF3, —CF3, —NO2, —CN, —OH, —NH2, —NMe2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-12 heteroalicyclyl, C1-6 alkoxy, C3-6 cycloalkyloxy or C3-12 heteroalicyclyloxy group; either of R or R′ is a hydroxamic acid-containing Q group and the other is a hydrogen, methoxy, methoxyethoxy or the hydroxamic acid-containing Q group, wherein the hydroxamic acid-containing Q group is A is O, —NH, S(═O)m, C1-6 alkyl, or A is absent, and the hydrogen of A may be substituted with G1; L is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6 aryl, C5-6 heteroaryl, C3-12 heteroalicyclyl, or L is absent, and the hydrogen of L may be substituted with G2; J is O, —NH, S(═O)m, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6 aryl, C5-6 heteroaryl, C3-12 heteroalicyclyl, or J is absent, and the hydrogen of J may be substituted with G3; X is C(═O)—, —S(O)m, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6 aryl, C5-6 heteroaryl, C3-12 heteroalicyclyl, or X is absent, and the hydrogen of X may be substituted with G4; Y is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6 aryl, C5-6 heteroaryl, C3-12 heteroalicyclyl, or Y is absent, and the hydrogen of Y may be substituted with G5; wherein, each of G1, G2, G3, G4 and G5 is H, —CN, —CF3, —CO2H, halogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6 aryl, C5-6 heteroaryl, C3-12 heteroalicyclyl, R1O—, R1R2N—, R1S(═O)m—, R1R2NS(═O)m—, R3C(═O)—, R1R2NC(═O)—, R1OC(═O)—, R3C(═O)O—, R1R2NC(═O)O—, R3C(═O)NR1—, R1R2NC(═O)NR4—, R1OC(═O)NR4—, R1S(═O)mNR4—, R1R2NS(═O)mNR4—, R1R2NC(═NR5)NR4—, R1R2NC(═CHNO2)NR4—, R1R2NC(═N—CN)NR4—, R1R2NC(═NR5)—, R1S(═O)(═NR5)NR4— or R1R2NS(═O)(═NR5)—; each of R1, R2, R3, R4 and R5 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6 aryl, C5-6 heteroaryl or C3-12 heteroalicyclyl; when R1 and R2 are connected with the same nitrogen atom, they may form a C3-12 heteroalicyclyl ring together with the nitrogen atom they are attached to, and this C3-12 heteroalicyclyl ring may further comprise one or more hetero atom selected from O, N, or S(═O)m; the hydrogen of R1, R2, R3, R4 and R5 may be substituted with halogen, —CN, C1-6 alkyl or C3-6 cycloalkyl; and m=0-2.