Novel cyclic dinucleotide derivative and antibody-drug conjugate thereof

An antibody-drug conjugate represented by formula (II):

• wherein
• m1 is in the range of 1 to 10;
• Ab represents an antibody or a functional fragment of the antibody, where a glycan of the antibody is optionally remodeled;
• L represents a linker linking Ab and D;
• Ab bonds directly from an amino acid residue of Ab to L, or optionally bonds via a glycan or remodeled glycan of Ab to L;
• and
• D represents a compound represented by formula (I):
• wherein
• L bonds to any —NH2 or hydroxy group included in L1 or L2;
• L1 represents a group selected from the group consisting of the following formulas:
• and optionally substituted at any position with one to three groups selected from the group consisting of a hydroxy group, —NH2, a 2-hydroxyacetylaminomethyl group, and a 2-[(2-hydroxyacetyl)amino]ethyl group,
• wherein
• R6 and R6′ each independently represent a hydrogen atom, a halogen atom, a hydroxy group, —NH2, a C1-C6 alkyl group, a C2-C6 alkenyl group, or a C2-C6 alkynyl group;
• R7 and R7′ each independently represent a hydrogen atom or a C1-C6 alkyl group, wherein the C1-C6 alkyl group is optionally substituted with one or two substituents selected from the group consisting of a halogen atom and an oxo group;
• R8 and R8′ each independently represent a hydrogen atom or a halogen atom;
• Z4 represents —CH2—, —NH—, or an oxygen atom;
• and
• Z5 represents a nitrogen atom or —CH═,
• L2 represents a group selected from (i) and (ii):
• (i) when bonding to L, L2 represents —NHR′, a hydroxy C1-C6 alkyl group, or an amino C1-C6 alkyl group, wherein R′ represents a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, or a C3-C6 cycloalkyl group, and the C1-C6 alkyl group, C2-C6 alkenyl group, or C2-C6 alkynyl group is optionally substituted with one to six halogen atoms;
• and
• (ii) when not bonding to L, L2 represents a hydrogen atom or a halogen atom;
• Q1 and Q1′ each independently represent a hydroxy group, a thiol group, or a borano group (BH3−);
• Q2 and Q2′ each independently represent an oxygen atom or a sulfur atom;
• X1 and X2 each independently represent an oxygen atom, a sulfur atom, or —CH2—;
• Y1 and Y2 each represent an oxygen atom or —CH2—;
• X3 and X4 represent a group selected from (iii) and (iv):
• (iii) when Y1 is an oxygen atom, X3—X4 represents —CH2—O—, —CH2—S—, —CH2—CH2—, or —CH2—CF2—;
• and
• (iv) when Y1 is —CH2—, X3—X4 represents —O—CH2—;
• X5 and X6 represent a group selected from (v) and (vi):
• (v) when Y2 is an oxygen atom, X5—X6 represents —CH2—O—, —CH2—S—, —CH2—CH2—, or —CH2—CF2—;
• and
• (vi) when Y2 is —CH2—, X5—X6 represents —O—CH2—;
• R1, R2 and R3 each independently represent a hydrogen atom, a halogen atom, —OR′, —OC(═O)R′, —N3, —NHR′, —NR′R″, or —NHC(═O)R′, wherein R′ is as defined above, and R″ represents a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, or a C3-C6 cycloalkyl group;
• W1 represents a nitrogen atom, an oxygen atom, a sulfur atom, or —CH—;
• W2 represents a nitrogen atom or —CH═;
• R4 represents a hydrogen atom, a halogen atom, or —NH2;
• R5 represents a group selected from (vii) to (x):
• (vii) when W1 is a nitrogen atom, R5 represents a hydrogen atom, a C1-C6 alkyl group, a hydroxy C1-C6 alkyl group, or an amino C1-C6 alkyl group;
• (viii) when W1 is an oxygen atom, R5 is absent;
• (ix) when W1 is a sulfur atom, R5 is absent;
• and
• (x) when W1 is —CH—, R5 represents a hydrogen atom, a halogen atom, a hydroxy group, —NH2, or a C1-C6 alkyl group;
• Z1-Z2-Z3 together represents —CH2—CH2—CH2—, —CH2—CH2—R′″—, —CH═CH—CH2—, —CH═CX—CH2—, —CX═CH—CH2—, —CX═CX—CH2—, —C(═O)—CH2—CH2—, —CH2—CH2—C(═O)—, —CH2—CH(CH3)—CH2—, or —CH2—CH2—CH(CH3)—, wherein R1″ represents —O— or —CH2—CH2— and X represents a halogen atom, or a group represented by either one of the following formulas:
• wherein
• each asterisk indicates bonding to W1, and each wavy line indicates bonding to the carbon atom of ═C—.