Peptidomimetic compounds and antibody-drug conjugates thereof

An antibody-drug conjugate represented by Formula (I)

• Ab-(L-D)p, (I), wherein
• Ab is an antibody;
• L is a peptidomimetic linker represented by the following formula
• -Str-(PM)-Sp-;
• wherein
• Str is a stretcher unit covalently attached to Ab;
• Sp is a bond or spacer unit covalently attached to a drug moiety;
• PM is a non-peptide chemical moiety selected from the group consisting of:
• each R1 is independently C1-C10alkyl, (C1-C10alkyl)NHC(NH)NH2 or (C1-C10alkyl)NHC(O)NH2;
• R4 and R5 together form a C3-C7cycloalkyl ring;
• p is an integer from 1 to 8;
• D is a drug moiety of formula A or of formula B:
• or a pharmaceutically acceptable salt and/or solvate thereof, wherein:
• the wavy line indicates the covalent attachment site to the linker;
• the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3;
• R22 is independently selected from H, OH, ═O, ═CH2, CN, Rm, ORm, ═CH-RD, ═C(RD)2, O—SO2— Rm, CO2Rm and CO Rm, and optionally further selected from halo or dihalo, wherein RD is independently selected from Rm, CO2Rm, CO Rm, CHO, CO2H, and halo;
• R66 and R99 are independently selected from H, Rm, OH, ORm, SH, S Rm, NH2, NH Rm, NRmRp, NO2, Me3Sn and halo;
• R77 is independently selected from H, Rm, OH, ORm, SH, S Rm, NH2, NH Rm, NRmRP, NO2, Me3Sn and halo;
• Q is independently selected from O, S and NH;
• R11 is either H, or Rm or, where Q is O, SO3M, where M is a metal cation;
• Rm and Rp are each independently selected from optionally substituted C1-8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalyl, C3-8 heterocyclyl, C5-20 aryl and C5-20 heteroaryl groups, and optionally in relation to the group NRmRp, Rm and Rp together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 7-membered heterocyclic ring;
• R12, R16, R19, R21 and R17 are as defined for R22, R66, R99, R11 and R77 respectively;
• R″ is a C3-C12 alkylene group, which chain may be interrupted by one or more heteroatoms, selected from O, S, N(H), or NMe and/or an aromatic ring, which rings are optionally substituted;
• X and X′ are independently selected from O, S and N(H);
• and
• RC is a capping group.