Lsd1 inhibitor and preparation method and application thereof

A compound of formula (1), a pharmaceutically acceptable salt thereof or a tautomer thereof,

• wherein,
• f is 1 or 2;
• r is 0, 1 or 2;
• e is 0, 1, or 2;
• p is 0 or 1;
• m is 0, 1 or 2;
• n is 1 or 2;
• each of R1 and R2 is independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, NH2 and —COOH, or is a C1-3 alkyl optionally substituted by 1, 2 or 3 of R;
• or, R1 and R2 are connected together to form a 3-6-membered ring;
• R3 is selected from the group consisting of H, F, Cl, Br, I, OH, CN, NH2, —COOH, —CONH2 and -L-R5, or selected from the group consisting of a C1-6 alkyl, phenyl, a 5-12 membered heteroaryl, a C3-7 cycloalkyl and a 4-8 membered heterocycloalkyl, each of which is optionally substituted by 1, 2 or 3 of R;
• R4 is H, or selected from the group consisting of a C1-6 alkyl and a C1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 of R;
• R5 is selected from the group consisting of phenyl, a 5-10 membered heteroaryl, a C3-10 cycloalkyl, a 4-10 membered heterocycloalkyl, a 5-6 membered heterocycloalkyl-C(═O)— and a 5-6 membered heterocycloalkyl-C1-3 alkyl-, each of which is optionally substituted by 1, 2 or 3 of R;
• R6 is H, or selected from the group consisting of a C1-6 alkyl and a C1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 of R;
• L is —C(═O)—, or selected from the group consisting of —C1-6 alkyl- and -5-9 membered heteroaryl-, -4-8 membered heterocycloalkyl-, -phenyl- and —C3-6 cycloalkyl-, each of which is optionally substituted by 1, 2 or 3 of R;
• R is selected from the group consisting of H, F, Cl, Br, I, OH, NH2, CN, —COOH and NH2—C(═O)—, or selected from the group consisting of C1-6 alkyl, C1-6 heteroalkyl, phenyl-C1-6 alkyl-, phenyl, 5-6 membered heteroaryl, phenyl-C(═O)—, C3-6 cycloalkyl-C(═O)—, C3-6 cycloalkyl-C(═O)—NH, C3-6 cycloalkyl-NH—C(═O)— and C3-6 cycloalkyl-C1-3 alkyl-, each of which is optionally substituted by 1, 2 or 3 of R′;
• R′ is selected from the group consisting of F, Cl, Br, I, OH, NH2, COOH, C1-3 alkyl, C1-3 alkyl substituted by 1-3 halogen(s), C1-3 alkyl-NH—, N,N-di(C1-3 alkyl)-amino, C1-3 alkyl-O—C(═O)—, C6 cycloalkyl and C1-3 alkoxyl;
• each of the “hetero” in the 5-12 membered heteroaryl, 4-8 membered heterocycloalkyl, C1-6 heteroalkyl, 5-10 membered heteroaryl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl, 4-10 membered heterocycloalkyl is independently selected from the group consisting of —NH—, —S—, N, —O—, ═O, —C(═O)—, —NH—C(═O)—, —O—C(═O)—, —S(═O)2—, —S(═O)—, —C(═O)—NH—;
• in any above cases, the number of the heteroatom or the heteroatomic group is independently 1, 2, 3 or 4.