Novel treatment and prevention of sarcopenia-related diseases

A composition for modulating, slowing the progression of, preventing, or treating a sarcopenia related disease, disorder, or symptom, comprising a compound or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein the compound is a compound represented by [1] formula (I)

• wherein
• A is —CHR7— (wherein R7 is C1-10 alkyl optionally substituted with a substituent selected from OH, —OR8 (wherein R8 represents C1-10 alkyl), —NH2, —COOH, and —CONH2, C6-14 aryl-C1-10 alkyl optionally substituted with a substituent selected from —OH, —OP(═O)(OH)2, —OP(═O)(ONa)2, and C1-10 alkyl, heteroaryl-C1-10 alkyl, C3-10 cycloalkyl-C1-10 alkyl, C6-14 aryl, or C3-10 cycloalkyl,
• G is —NR6— or —O— (wherein R6 is independently selected from C1-10 alkyl and C2-10 alkenyl),
• R1 is —Ra—R10 (wherein Ra is C1-6 alkylene, and R10 is naphthyl or fused bicyclic heteroaryl optionally substituted with a substituent selected from —NH2 and halogen,
• R2 is —W21—W22—Rb—R20 (wherein W21 is —(CO)—, W22 is —O— or —NH—, Rb is a bond or C1-6 alkylene optionally substituted with C1-10 alkyl, and R20 is C1-10 alkyl, C6-14 aryl optionally substituted with halogen, heteroaryl, or C3-10 cycloalkyl), and
• R3 is C1-10 alkyl,
• wherein “heteroaryl” refers to a 5- to 14-membered monocyclic or polycyclic aromatic group wherein at least one ring atom is a heteroatom selected from nitrogen, oxygen, and sulfur, and the rest of the ring atoms is carbon,
• a compound represented by
• compound group [2]
• formula (II)
• wherein
• AJ is —(CHR7J)— (wherein R7J is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl),
• BJ and EJ are the same or different, independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl, or form an optionally substituted spiro ring represented by a dotted line,
• GJ is —NH—, —NR6J—, —O—, —CH2—, —CHR6J—, or —C(R6J)2— (wherein R6J is each the same or different, independently selected from optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl),
• R1J is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl,
• R2J is —W21J—W22J—RbJ—R20J (wherein W21J is —(CO)— or —(SO2)—, W22J is a bond, —O—, —NH—, or optionally substituted lower alkylene, RJ is a bond or optionally substituted lower alkylene, and R20J is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or optionally substituted heterocycloalkyl), and
• R3J is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl],
• a compound represented by
• compound group [3]
• formula (III)
• wherein
• AJ2 is —(CHR7J2)— (wherein R7J2 is C1-10 alkyl optionally substituted with OH, —OR8J2 (wherein R8J2 represents C6-14 aryl-C1-10 alkyl), —NH2, —COOH, and —CONH2, C6-14 aryl, or C6-14 aryl-C1-10 alkyl optionally substituted with OH);
• BJ2 and EJ2 are hydrogen,
• GJ2 is —O—,
• R1J2 is C1-10 alkyl optionally substituted with a substituent selected from OH, —COOH, and —COOR8J2′ (wherein R8J2′ represents C1-10 alkyl), C6-14 aryl-C1-10 alkyl, heteroaryl-C1-10 alkyl optionally substituted with —NH2, or C3-10 cycloalkyl-C1-10 alkyl,
• R2J2 is —W21J2—W22J2—RbJ2—R20J2 (wherein W21J2 is —(CO)— or —(SO2)—, W22J2 is a bond, —O—, or C1-6 alkylene, and RbJ2 is a bond or C1-6 alkylene);
• and
• R20J2 is C1-10 alkyl, C6-4 aryl optionally substituted with halogen, or heteroaryl;
• and
• R3J2 is hydrogen;
• wherein “heteroaryl” refers to a 5- to 14-membered monocyclic or polycyclic aromatic group wherein at least one ring atom is a heteroatom selected from nitrogen, oxygen, and sulfur, and the rest of the ring atoms is carbon,
• compound represented by
• compound group [4]
• formula (IV):
• wherein
• is a single bond or a double bond,
• A4 is —CHR47— (wherein R47 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl),
• E4 is a bond, —CHR45—, —O—, or —NR48— (wherein R45 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, or optionally substituted heteroarylalkyl, and R48 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl),
• B4 is absent, or an optionally substituted monocyclic ring formed together with G4 and Y4,
• D4 is absent, or an optionally substituted spiro ring formed together with Y4,
• with the proviso that not both of B4 and D4 are present,
• if B4 is present, G4 and Y4 are independently a carbon atom or a nitrogen atom,
• if D4 is present, Y4 is a carbon atom, and G4 is —NR46—, —O—, —CHR46—, or —C(R46)2—,
• if both B4 and D4 are absent, G4 and Y4 are the same or different, each —NR46—, —O—, —CHR46—, or —C(R46)2— (wherein R46 is each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, or optionally substituted heteroarylalkyl), and
• if E4 is a bond, D4 is absent, B4 is an optionally substituted monocyclic ring, and B4 and Y4 are independently a carbon atom or a nitrogen atom,
• R41 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl,
• R42 is —W421—W422—Rb4—R420 (wherein W421 is —(CO)— or —(SO2)—, W422 is a bond, —O—, —NH—, or optionally substituted lower alkylene, Rb4 is a bond or optionally substituted alkylene, and R420 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or optionally substituted heterocycloalkyl), and
• R43 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl,
• a compound represented by
• compound group [5]
• formula (V):
• wherein
• is a single bond or a double bond,
• A5 is —(CHR57)— (wherein R57 is C1-10 alkyl optionally substituted with a substituent selected from —OH, —OR59 (wherein R59 represents C1-10 alkyl), —NH2, —COOH, and —CONH2, C6-14 aryl, or C6-14 aryl-C1-10 alkyl optionally substituted with —OH),
• B5 is a 5- or 6-membered monocyclic saturated carbon ring, or a saturated or unsaturated 4-, 5-, 6-, or 7-membered heterocyclic ring optionally substituted with a formyl group, formed together with G5, wherein a heteroatom is selected from S, N, and O, and the number of heteroatoms is an integer from 1 to 3,
• G5 is a carbon atom or a nitrogen atom,
• R51 is C1-10 alkyl, C6-14 aryl-C1-10 alkyl optionally substituted with a substituent selected from —R59′ and halogen, or 5- to 14-membered heteroaryl-C1-10 alkyl optionally substituted with —NHCOOR59′, wherein R59′ is C1-10 alkyl or C6-14 aryl,
• R52 is —W521—W522—Rb5—R520 (wherein
• W521 is —(CO)—,
• W522 is —NH—,
• Rb5 is a bond, or C1-6 alkylene optionally substituted with C6-14 aryl, and
• R520 is C1-10, alkyl optionally substituted with a substituent selected from —OH and —COOR59″ (wherein R59″ represents a hydrogen atom or C1-10 alkyl), C6-14 aryl optionally substituted with a substituent selected from halogen, methylenedioxy, and C1-10 alkyl, 5- to 14-membered heteroaryl, or C3-10 cycloalkyl), and
• R53 is hydrogen or C1-10 alkyl,
• a compound represented by
• compound group [6]
• formula (VI)
• wherein
• is a single bond or a double bond,
• A is —CHR67— (wherein R67 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl),
• E6 is —CHR65—, —O—, or —NR68— (wherein R65 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, or optionally substituted heteroarylalkyl, and R68 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl),
• B6 is absent or an optionally substituted monocyclic ring formed together with G6 and Y6,
• D6 is absent, or an optionally substituted spiro ring formed together with Y6,
• with the proviso that not both B6 and D6 are present,
• if B6 is present, G6 and Y6 are independently a carbon atom or a nitrogen atom,
• if D6 is present, Y6 is a carbon atom, and G6 is —NR66—, —O—, —CHR66—, or —C(R6)2—,
• if B6 and D6 are both absent, G6 and Y6 are the same or different, each —NR66—, —O—, —CHR66—, or —C(R66)2— (wherein R66 is each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, or optionally substituted heteroarylalkyl),
• R61 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl,
• R62 is —W621—W622—Rb6—R620 (wherein W621 is —(CO)— or —(SO2)—, W622 is a bond, —O—, —NH—, or optionally substituted lower alkylene, Rb6 is a bond or optionally substituted alkylene, and R620 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or optionally substituted heterocycloalkyl), and
• R63 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl,
• a compound represented by
• compound group [7]
• formula (VII)
• wherein
• A7 is —(CHR73)—(C═O)—, B7 is —(NR74)—, D7 is —(CHR75)— or (C═O)—, E7 is —(Z7R76)— or —(C═O)—, G7 is —(X7R77)n7—, —(CHR77)—(NR78)—, —(C═O)—(X7R79)—, or —(C═O)—, W7 is —Y7 (C═O)—, —(C═O)NH—, —(SO2)—, or absent, Y7 is oxygen or sulfur, X7 and Z7 are independently nitrogen or CH, n7=0 or 1, and R71, R72, R73, R74, R75, R76, R77, R78, and R79 are the same or different, independently selected from an amino acid side chain, a derivative of an amino acid side chain, a linker facilitating the linkage of the compound to another moiety or compound, a linker attaching the compound to a solid support, and a solid support, and stereoisomers thereof,
• a compound represented by
• compound group [8]
• formula (VIII)
• wherein
• A8 is —(CHR8′)n8—, B8 is —(CHR8″)n8—, n8 is 0, 1, or 2, m8 is 1, 2, or 3, R8′, R8″, R82, R83, and R85 are the same or different, each of R8′, R8″, R82, R83, and R83;
• that are present is independently selected from the group consisting of an amino acid side chain moiety, an amino acid side chain derivative, a linker, and a solid support, R81 and R84 represent the remaining portions of the compound, wherein R81 and R84 are the same or different, selected from the group consisting of a certain moiety, an active substance, a compound, a support, a molecule, a linker, an amino acid, a peptide, and a protein, or a compound represented by
• or a derivative thereof, or
• a compound represented by
• compound group [9]
• formula (IX)
• wherein RV1 refers to a C1-6 alkyl group, RV2 and RV3 are each the same or different, referring to a hydrogen atom or a C1-6 alkyl group, XV2, XV3, and XV4 are each the same or different, referring to a hydrogen atom or a halogen atom, and XV5 refers to a hydrogen atom or —P(═O)(OH)2.