Cytotoxicity targeting chimeras for CCR2-expressing cells

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is C1-4 alkyl or C3-6 cycloalkyl;
• R2 is hydrogen or C1-4 alkyl;
• R3 is hydrogen or C1-4 alkyl;
• L is a divalent linker of Formula (L-a), (L-b), (L-c), (L-f), (L-g), (L-h), (L-i), (L-j), (L-k), (L-m), (L-n-i), (L-n-ii), (L-n-iii), or (L-n-iv):
• or a stereoisomer thereof,
• wherein:
• Ring A and Ring B are each independently C4-6 cycloalkylene;
• L1a is C3-5 linear alkylene, wherein 1 or 2 methylene units are replaced with —O— or —NRa—;
• each Ra is independently hydrogen or C1-3 alkyl;
• and
• L2a is —O—, —NHC(O)—, or —CH2—O—;
• or a stereoisomer thereof,
• wherein:
• Ring A is C4-6 cycloalkylene or C7-9 bridged bicyclic cycloalkylene;
• L1b is —CH2—NH—C(O)—, —NHC(O)—, or —C(O)NH—;
• L2b is C6-12 linear alkylene, wherein 1, 2, 3, or 4 methylene units are replaced with —O—, —NR1b—, —C(O)NR1b—, or —NR1bC(O)—;
• or
• L2b is
• wherein n is 1, 2, 3, or 4, and
• represents a covalent bond to L1b;
• and
• each R1b is independently hydrogen or C1-3 alkyl;
• or a stereoisomer thereof,
• wherein:
• L1c is C2-10 linear alkylene, wherein 1, 2, or 3 methylene units are replaced with —O—, —NH—, —NHC(O)—, or —C(O)NH—;
• Ring A is C4-6 cycloalkylene or C7-9 bridged bicyclic cycloalkylene;
• and
• L2c is —O— or a saturated C2-10 linear alkylene, wherein 1, 2, or 3 methylene units are replaced with —O—, —NH—, —NHC(O)—, or —C(O)NH—;
• or a stereoisomer thereof,
• wherein:
• L1f is a bond;
• C1-6 linear alkylene, wherein 0, 1, or 2 methylene units are replaced with —O—, —NH—, or —C(O)—;
• or —(C3-6 cycloalkylene)-NHC(O)—;
• L2f is a bond, —NHC(O)—, —C(O)NH—, or a C1-6 linear alkylene, wherein 0, 1, or 2 methylene units are replaced with —O—;
• and
• each of Z1 and Z2 is independently N or CH;
• wherein:
• Ring A is a 5 to 6 membered heteroarylene having 1 or 2 nitrogen ring atoms;
• L1g is a bond, —CH2—, —NH—, or —O—;
• and
• L2g is
• wherein n is 1, 2, 3, 4, or 5, and
• represents a covalent bond to L1g;
• or a stereoisomer thereof,
• wherein:
• each Z1 is independently N or CH;
• L1h is a bond, —C(O)—, —C(O)—NH—, or —NHC(O)—;
• L2h is C2-10 linear alkylene or
• wherein n is 1, 2, 3, or 4, and
• represents a covalent bond to L1h and
• represents a covalent bond to L3h;
• L3h is a bond, —C(O) CH2—, —O—(C3-6 cycloalkylene)-O—, or —C(O)NH(CH2)3OCH2—;
• L4h is a bond, —C(O)—, —CH2C(O)—, or —C(O) CH2—;
• and
• m is 1, 2, or 3;
• wherein:
• L1i is a bond, C1-12 linear alkylene, or
• wherein n is
• 1, 2, 3, 4, or 5, and
• represents a covalent bond to L3i and
• represents a covalent bond to NH;
• L2i is a bond, C1-12 linear alkylene, or
• wherein n is 1, 2, 3, 4, or 5, and
• represents a covalent bond to HN;
• and
• L3i is a bond or —C(O)—;
• or a stereoisomer thereof,
• wherein:
• Z1 is C, CH, or N;
• each of Z2, Z3, Z4 and Z5 is independently CH or N, provided that no more than two of Z2, Z3, Z4 and Z5 are N;
• L1j is —NH—, —C(O)NH—, —NHC(O)—, or —O—;
• L2j is C1-6 linear alkylene or
• wherein n is 1 or 2, and
• represents a covalent bond to L1j;
• and
• represents a single bond or a double bond;
• or a stereoisomer thereof,
• wherein:
• Ring A is phenyl or a 5 or 6 membered heteroarylene having 1 or 2 nitrogen ring atoms;
• each of Z1 and Z2 is independently CH or N;
• L1k is a bond, —C(O)—, —C(O)NH— or —NHC(O)—;
• and
• L2k is a C3-8 straight chain alkylene or
• wherein n is 1, 2, or 3, and
• represents a covalent bond to L1k;
• or a stereoisomer thereof,
• wherein:
• Z1 is CH or N;
• m is 1 or 2;
• p is 1 or 2;
• 0, 1, or 2 hydrogen atoms of
• are replaced with F;
• L1m is a bond, —C(O)—, —C(O)NH—, —NHC(O)—, —S(O)2NH— or —NHS(O)2—;
• and
• L2m is C3-6 linear alkylene, C3-6 cycloalkylene, or
• wherein
• n is 1 or 2, and
• represents a covalent bond to L1m;
• wherein each
• represents a covalent bond to the NH group of Formula (I), and each
• represents a covalent bond to the methylene group of Formula (I).