| 摘要 |
Melanocortin receptor-specific linear peptides of the formula;;where R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined in the specification, compositions and formulations including peptides of the foregoing formula or salts thereof, and pharmaceutical compositions for preventing, ameliorating or treating melanocortin-1 receptor-mediated or responsive diseases, indications, conditions and syndromes. |
| 主权项 |
1. A linear peptide of formula (I):or a pharmaceutically acceptable salt thereof,
wherein:
R1 is —R11—R12;R2 is —H, —CH3 or —CH2—, and if it is —CH2— forms with R3 a ring of the general structure R3 is —H, —(CH2)z— if R2 is —CH2—, and if it is —(CH2)z— forms the ring with R2, or R3 is —(CH2)w—R14—(CH2)w—R15, wherein any H in either (CH2)w is optionally substituted with —(CH2)w—CH3;R4 is —(CH2)w—R16;R5 is —H, —CH3 or —CH2—, and if it is —CH2— forms with R6 a ring of the general structure wherein the ring is optionally substituted;R6 is —(CH2)z— if R5 is —CH2—, and if it is —(CH2)z— forms the ring with R5, or R6 is —(CH2)w—R17;R7 is —H or —CH3;R8 is —H or a C1-C10 linear or branched alkyl, cycloalkyl or alkyl cycloalkyl;R9 is —(CH2)w—R18;R10 is —R11—R19;R11 is in each instance independently optionally present, and if present, is in each instance independently from one to three L- or D-isomer amino acids, or a combination thereof;R12 is in each instance independently H or a C1 to C7 acyl group comprising a linear or branched alkyl, cycloalkyl, alkyl cycloalkyl, aryl or aralkyl;R13 is —H or —R14—(CH2)w—R15;R14 is optionally present, and if present is
—O—,—S—,—NH—,—S(═O)2—,—S(═O)—,—S(═O)2—NH—,—NH—S(═O)2—,—C(═O)—,—C(═O)—O—,—O—C(═O)—,—NH—C(═O)—O—,—O—C(═O)—NH—,—NH—C(═O)—, or—C(═O)—NH—;R15 is
—H,—CH3,—N(R20a)(R20b),—NH—(CH2)z—N(R20a)(R20b),—NH—C(═NH)—N(R20a)(R20b),—NH—C(═O)—N(R20a)(R20b),—O(R20a),—(R20a)(R20b),—S(═O)2(R20a),—C(═O)—O(R20a), wherein any ring in R15 is optionally substituted with one or more ring substituents, and when one or more are present, are the same or different and independently hydroxyl, halogen, sulfonamide, alkyl, —O-alkyl, aryl, —O-aryl, C(═O)—OH, or C(═O)—N(R20a)(R20b);
R16 is substituted or unsubstituted aryl or heteroaryl;R17 is
—H,—N(R20a)(R20b),—NH—(CH2)z—N(R20a)(R20b),—NH—C(═NH)—N(R20a)(R20b),—NH—C(═O)—N(R20a)(R2b),—O(R20a),—C1 to C17 linear, branched or cyclic alkyl chain,—C(═O)—N(R20a)(R20b),—S(═O)2(R20a), wherein any ring is optionally substituted with one or more optional ring substituents, and when one or more are present, are the same or different and independently hydroxyl, halogen, sulfonamide, alkyl, —O-alkyl, aryl, aralkyl, O-aralkyl, or —O-aryl;
R18 is optionally substituted with one or more ring substituents, and when one or more are present, are the same or different and independently hydroxyl, halogen, sulfonamide, alkyl, —O-alkyl, aryl, or —O-aryl;
R19 is —OH, —N(R20a)(R20b), —N(R20a)(CH2)w-cycloalkyl, or —O—(CH2)w-cycloalkyl;R20a and R20b are each independently H or a C1 to C4 linear, branched or cyclic alkyl chain;w is in each instance independently 0 to 5; andz is in each instance independently 1 to 5. |
