Peptide amide composition and preparation method therefor

A pharmaceutical composition consisting of a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pH regulator, wherein the composition has a pH value of 3-5.5, and the pH regulator is a buffer consisting of acids and corresponding salts thereof and has a pH value of 3-5.5,

• wherein
• R1 is selected from
• m1 and m2 are each independently selected from 1, 2, 3 or 4;
• m3 and m4 are each independently selected from 0, 1, 2, 3 or 4, provided that m3 and m4 are not both 0;
• n1 and n2 are each independently selected from 0, 1, 2, 3 or 4;
• Z is selected from CRz1Rz2 or NRz3;
• Rz1 and Rz2 are each independently selected from H, F, Cl, Br, I, OH, CF3, nitro, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, —C(═O)—C1-6alkyl, —(CH2)q—C(═O)O—C1-6alkyl, —(CH2)q—NR1eR1f, —(CH2)q—COOH, —(CH2)q—CONH2, C3-8carbocyclyl, or 3- to 8-membered heterocyclyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally further substituted with 0-5 substituents selected from F, Cl, Br, I, OH, CF3, ═O, carboxyl, nitro, cyano, amino, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-8carbocyclyl or 3- to 8-membered heterocyclyl, the heterocyclyl contains 1 to 3 heteroatoms optionally selected from N, O or S, and when the heteroatom is S, the heterocyclyl can optionally contain S, S═O or S(═O)2;
• R1e and R1f are each independently selected from H, C1-6alkyl, —C(═O)O—C1-6alkyl, —C(═O)O—(CH2)q—C3-8carbocyclyl, or —C(═O)O—(CH2)q-3- to 8-membered heterocyclyl, wherein the alkyl, carbocyclyl or heterocyclyl is optionally further substituted with 0-5 substituents selected from F, Cl, Br, I, OH, CF3, cyano, nitro, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-8carbocyclyl or 3- to 8-membered heterocyclyl, and the heterocyclyl contains 1 to 3 heteroatoms selected from N, O or S;
• or Rz1 and Rz2 together with the carbon atoms to which they are attached form a 3- to 10-membered nitrogen-containing heterocyclic ring, wherein the ring is optionally further substituted with a substituent selected from F, Cl, Br, I, OH, CF3, cyano, nitro, ═O, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-8carbocyclyl or 3- to 8-membered heterocyclyl;
• R1a and R1b are each independently selected from F, CF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl or 3- to 8-membered heterocyclyl, wherein the alkyl, alkenyl, alkynyl or heterocyclyl is optionally further substituted with 0-5 substituents selected from F, Cl, Br, I, OH, CF3, nitro, cyano, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-8carbocyclyl or 3- to 8-membered heterocyclyl, and the heterocyclyl contains 1 to 3 heteroatoms optionally selected from N, O or S;
• Rz3 is independently selected from H, —C(═O)—C1-6alkyl, —C(═O)O—C1-6alkyl, —C(═O)—C3-8carbocyclyl, —C(═O)O—C3-8carbocyclyl, —C(═O)O-(3- to 8-membered heterocyclyl), —S(═O)p—C1-6alkyl, —S(═O)p—C3-8carbocyclyl, —S(═O)p-(3- to 8-membered heterocyclyl), —C(═O)NR1gR1h, —S(═O)p—NR1iR1j or 3- to 8-membered heterocyclyl, wherein the alkyl, carbocyclyl or heterocyclyl is optionally further substituted with 0-5 substituents selected from F, Cl, Br, I, OH, CF3, nitro, cyano, amino, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-8carbocyclyl or 3- to 8-membered heterocyclyl, and the heterocyclyl contains 1 to 3 heteroatoms optionally selected from N, O or S;
• R1g, R1h, R1i, and R1j are each independently selected from H or C1-6alkyl;
• or R1g and R1h together with the nitrogen atoms to which they are attached form a 3- to 10-membered heterocyclic ring, wherein the ring is optionally further substituted with a substituent selected from F, Cl, Br, I, OH, CF3, cyano, nitro, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl or —S(═O)p—C1-6alkyl, and the heterocyclic ring contains 1 to 3 heteroatoms selected from N, O or S;
• q is selected from 0, 1, 2, 3 or 4;
• p is selected from 0, 1 or 2;
• a is selected from 0, 1, 2 or 3;
• R4 is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl or —(CH2)q—C3-8carbocyclyl, wherein the alkyl, alkenyl, alkynyl or carbocyclyl is optionally further substituted with 0-5 substituents selected from F, Cl, Br, I, OH, CN, CF3, NO2, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-8carbocyclyl or 3- to 8-membered heterocyclyl, and the heterocyclyl contains 1 to 3 heteroatoms selected from N, O or S;
• R2, R3, R7 and R8 are each independently selected from H, C1-6alkyl, —C(═O)O—C1-4alkyl, —C(═O)O—(CH2)q—C3-8carbocyclyl, —C(═O)O—(CH2)q-3- to 8-membered heterocyclyl or
• wherein the alkyl, carbocyclyl or heterocyclyl is optionally further substituted with 0-5 substituents selected from F, Cl, Br, I, OH, CF3, nitro, cyano, C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-8carbocyclyl or 3- to 8-membered heterocyclyl, and the heterocyclyl contains 1 to 3 heteroatoms optionally selected from N, O or S;
• b is selected from 0, 1, 2, 3, 4 or 5;
• c is selected from 0, 1, 2, 3, 4 or 5;
• R5 and R6 are each independently selected from F, Cl, Br, I, CF3, cyano, nitro, C1-4alkyl, —OR5a, —C(O)OR5b, —SR5c, —S(O)R5d, +S(O)2R5e or —NR5fR5g;
• R5a, R5b, R5c, R5d, R5e, R5f and R5g are each independently selected from H or C1-4alkyl;
• or R5f and R5g together with the nitrogen atoms to which they are attached form a 5- to 6-membered heterocyclic ring, wherein the heterocyclic ring contains 1 to 3 heteroatoms optionally selected from N, O or S.