NOVEL COMPOUNDS FOR SELECTIVE HISTONE DEACETYLASE INHIBITORS, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

摘要

The present invention relates to novel urea derivatives and, more particularly, to novel urea derivatives with histone deacetylase (HDAC) inhibitory activity, isomers thereof, pharmaceutically acceptable salts thereof, their use for the preparation of a medicaments comprising the same, a pharmaceutical composition comprising the same, a treatment method using the composition, and a method for preparing novel urea derivatives. The novel urea derivatives as selective histone deacetylase (HDAC) inhibitors are effective for the treatment of histone deacetylase-mediated diseases such as malignant tumors, inflammatory diseases, rheumatoid arthritis, neurodegeneration, etc.

主权项

1. A compound of Formula I: or an optical isomer thereof or pharmaceutically acceptable salt thereof, wherein: A is Xa and Xb are each independently C or N; L1 and L2 are each independently hydrogen, —F, —Cl, —Br, —I, —CF3, or —C1-3 straight or branched chain alkyl; Q is C(═O), S((═O)2), S(═O), or C(═NH); Y is selected from the group consisting of: M is C, O, N, S(═O)2, or S; l and m are each independently an integer of 0 or 1; Ra1 and Ra2 are each independently hydrogen, hydroxy, —C1-4 straight or branched chain alkyl, substituted with one or more F, Cl, Br or I or unsubstituted, a —C1-4 straight or branched chain alcohol, benzhydryl, a —C1-4 straight or branched chain alkyl substituted with a saturated or unsaturated 5- to 7-membered heterocyclic compound comprising 1 to 3 heteroatoms selected from N, O, and S as a ring member (wherein the heterocyclic compound may be unsubstituted or at least one hydrogen may be optionally substituted with OH, OCH3, CH3, CH2CH3, F, Cl, Br, or I), a saturated or unsaturated 5- to 7-membered heterocyclic compound comprising 1 to 3 heteroatoms selected from N, O, and S as a ring member (wherein the heterocyclic compound may be unsubstituted or at least one hydrogen may be optionally substituted with OH, OCH3, CH3, CH2CH3, F, Cl, Br, or I), phenyl, substituted with one or more F, Cl, Br, I, C1-4 alkoxy, C1-2 alkyl, or hydroxy or unsubstituted, benzyl, substituted with one or more F, Cl, Br, I, C1-4 alkoxy, C1-2 alkyl, or hydroxy or unsubstituted, —S((═O)2)CH3, —F, —Cl, —Br, —I, a —C1-6 straight or branched chain alkoxy, —C2-6 alkyl alkoxy, —C(═O)Rx, wherein Rx is a straight or branched C1-3 alkyl or C3-10 cycloalkyl;wherein Rc and Rd are each independently hydrogen, a C1-3 straight or branched chain alkyl, n is an integer of 0, 1, or 2; Rb is hydrogen, hydroxy, a —C1-6 straight or branched chain alkyl, substituted with one or more F, Cl, Br, or I or unsubstituted, —C(═O)CH3, a —C1-4 straight or branched chain alcohol, a —C1-6 straight or branched chain alkoxy a —C2-6 straight or branched chain alkyl alkoxy, —CF3, —F, —Cl, —Br, —I, orwherein Re and Rf are each independently hydrogen or a —C1-3 straight or branched chain alkyl; and
Z is selected from the group consisting of the following substituents: wherein Pa and Pb are each independentlyhydrogen, hydroxy, a —C1-4 straight or branched chain alkyl, substituted with one or more F, Cl, Br or I or unsubstituted, —F, —Cl, —Br, —I, —CF3, —OCF3, —CN, a —C1-6 straight or branched alkoxy, a —C2-6 straight or branched alkyl alkoxy, —CH2F, or a —C1-3 alcohol,
whereinis selected from among phenyl, pyridine, pyrimidine, thiazole, indole, indazole, piperazine, quinoline, furan, tetrahydropyridine, piperidine, x, y and z are each independently an integer of 0 or 1; and Rg1, Rg2 and Rg3 are each independently selected from among hydrogen, hydroxy, a —C1-3 alkyl, —CF3, a —C1-6 straight or branched chain alkoxy, a —C2-6 straight or branched chain alkyl alkoxy, —C(═O)CH3, a —C1-4 straight or branched chain alcohol, —N(CH3)2, —F, —Cl, —Br, —I, phenyl, —S((═O)2)CH3,