CTPS1 inhibitors and uses thereof

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from —CF3, —CHF2,
• Ring A is a 6-membered monocyclic heteroaryl ring having 1 or 2 nitrogen atoms;
• L is
• Ring B is selected from phenyl;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 5-11 membered saturated or partially unsaturated fused, bridged, or spiro, bicyclic carbocyclic ring;
• a 7-11 membered fused bicyclic aryl ring;
• a 7-11 membered saturated or partially unsaturated fused, bridged, or spiro, bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and a 7-11 membered fused bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• Ring C is selected from a 6-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms;
• and a 7-11 membered fused bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each instance of RA, RB, and RC is independently oxo, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)NR2, —N(R)S(O)2NR2, —N(R)S(O)2R, —N═S(O)R2, —S(NR)(O)R, —N(R)S(O)R, —N(R)CN, —P(O)(R)NR2, —P(O)(R)OR or —P(O)R2;
• or each instance of RC is independently an optionally substituted group selected from C1-6 aliphatic;
• phenyl;
• naphthalenyl;
• a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, phosphorous, silicon and sulfur;
• or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 5-8 membered saturated or partially unsaturated bridged bicyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 6-10 membered saturated or partially unsaturated spirocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or a 6-11 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each of which is substituted with r instances of R and s instances of RD;
• or two RC groups are optionally taken together with the atoms to which each RC is attached, to form an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• a 5-7 membered heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• each instance of RD is independently oxo, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, —N(R)C(NR)NR2, —N(R)NR2, —N(R)S(O)2NR2, —N(R)S(O)2R, —N═S(O)R2, —S(NR)(O)R, —N(R)S(O)R, —N(R)CN, —P(O)(R)NR2, —P(O)(R)OR, or —P(O)R2;
• each R is independently hydrogen, —CN, halogen, or an optionally substituted group selected from C1-6 aliphatic;
• phenyl;
• naphthalenyl;
• a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 5-8 membered saturated or partially unsaturated bridged bicyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 6-10 membered saturated or partially unsaturated spirocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• a 6-11 membered saturated or partially unsaturated bicyclic carbocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or
• two R groups are taken together with the atoms to which each R is attached, to form an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• m is 0, 1, or 2;
• n is 0, 1, or 2;
• p is 0, 1, or 2;
• each r is independently 0, 1, 2, 3, or 4;
• and
• each s is independently 0, 1, 2, 3, or 4;
• provided that when:
• R1 is
• the R group of the sulfonamide moiety
• is hydrogen or para-methoxybenzyl;
• L is not
• Ring B is phenyl or a 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• Ring C is a 6-membered monocyclic heteroaryl ring having 1-4 nitrogen atoms and is attached to Ring B in the para position relative to the L group;
• then Ring A and its RA substituents are other than
• where * denotes attachment to the
• moiety and ** denotes attachment to the
• moiety.