Acylsulfonamide derivatives for treating senescence-associated diseases and disorders

A compound represented by Formula (I):

• or a salt thereof, wherein:
• Z1 is a piperidine or piperazine substituted with —X—C1-6 alkyl-R3 and Z1 is further optionally substituted with one or more R6;
• Z2 is C3-12 carbocycle optionally substituted with one or more R6;
• R1 is hydrogen;
• Z3 is C3-12 carbocycle optionally substituted with one or more R6;
• L1 is selected from —(CH2)s—X10—(CH2)r—, —(CH2)r—X10—(CH2)r—X10—(CH2)r—, and —(CH2)r—X10—(CH2)r—X10—(CH2)r—X10—(CH2)r—, wherein s is selected from 0 to 3, each r is selected from 1 to 6, each X10 is selected from —O—, —S—, or —N(R4)—, and L1 may be optionally substituted with one or more R6;
• L2 is Y-alkylene;
• Y is 3- to 12-membered heterocycle;
• W and W1 are independently selected from —O—, —S— and —NR10—;
• R2 and R2* are independently selected from R7, or R2 and R2* are taken together with the atoms to which they are attached to form a heterocycle, optionally substituted with one or more R6;
• R3 is C3-12 carbocycle or 3- to 12-membered heterocycle, each of which is optionally substituted with one or more R6;
• R4 is independently selected at each occurrence from hydrogen, —C(O)R10, —C(O)OR10 and —C(O)N(R4)—;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, —NO2, —CN, —OR10, —SR10, —N(R10)2, —S(═O)R10, —S(═O)2R10, —S(═O)2N(R10)2, —NR10S(═O)2R10, —C(O)R10, —C(O)OR10, —OC(O)R10, —OC(O)OR10, —OC(O)N(R10)2, —NR10C(O)R10, —C(O)N(R10)2, ═O, ═S, ═N(R10), —P(O)(OR7)2, —OP(O)(OR7)2, C3-10 carbocycle and 3- to 12-membered heterocycle;
• and C3-12 carbocycle and 3- to 12-membered heterocycle, wherein each C3-12 carbocycle and 3- to 12-membered heterocycle in R4 is independently optionally substituted with one or more substituents selected from halogen, —NO2, —CN, —OR10, —SR10, —N(R10)2, —S(═O)R10, —S(═O)2R10, —S(═O)2N(R10)2, —NR10S(═O)2R10, —C(O)R10, —C(O)OR10, —OC(O)R10, —OC(O)OR10, —OC(O)N(R10)2, —NR10C(O)R10, —C(O)N(R10)2, ═O, ═S, ═N(R10), —P(O)(OR7)2, —OP(O)(OR7)2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
• R6 is independently selected at each occurrence from halogen, —NO2, —CN, —OR10, —SR10, —N(R10)2, —S(═O)R10, —S(═O)2R10, —S(═O)2N(R10)2, —NR10S(═O)2R10, —C(O)R10, —C(O)OR10, —OC(O)R10, —OC(O)OR10, —OC(O)N(R10)2, —NR10C(O)R10, —C(O)N(R10)2, ═O, ═S, ═N(R10), —P(O)(OR7)2, —OP(O)(OR7)2;
• C1-10 alkyl, C2-10 alkenyl, and C2-10 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, —NO2, —CN, —OR10, —SR10, —N(R10)2, —S(═O)R10, —S(═O)2R10, —S(═O)2N(R10)2, —NR10S(═O)2R10, —C(O)R10, —C(O)OR10, —OC(O)R10, —OC(O)OR10, —OC(O)N(R10)2, —NR10C(O)R10, —C(O)N(R10)2, ═O, ═S, ═N(R10), —P(O)(OR10)2, —OP(O)(OR10)2, C3-12 carbocycle and 3- to 12-membered heterocycle;
• and C3-12 carbocycle and 3- to 12-membered heterocycle, wherein each C3-12 carbocycle and 3- to 12-membered heterocycle in R6 is independently optionally substituted with one or more substituents selected from halogen, —NO2, —CN, —OR10, —SR10, —N(R10)2, —S(═O)R10, —S(═O)2R10, —S(═O)2N(R10)2, —NR10S(═O)2R10, —C(O)R10, —C(O)OR10, —OC(O)R10, —OC(O)OR10, —OC(O)N(R10)2, —NR10C(O)R10, —C(O)N(R10)2, ═O, ═S, ═N(R10), —P(O)(OR7)2, —OP(O)(OR7)2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
• R7 is independently selected at each occurrence from hydrogen, —C(O)R10, —C(O)OR10 and —C(O)N(R4)—;
• C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-12 carbocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, —NO2, —CN, —OR10, —SR10, —S—S—R10, —N(R10)2, —S(═O)R10, —S(═O)2R10, —S(═O)2N(R10)2, —NR10S(═O)2R10, —S—C(O)R10, —C(O)R10, —C(O)OR10, —OC(O)R10, —OC(O)OR10, —OC(O)N(R10)2, —NR10C(O)R10, —C(O)N(R10)2, ═O, ═S, ═N(R10), —P(O)(OR10)2, —OP(O)(OR10)2, C3-12 carbocycle and 3- to 12-membered heterocycle;
• and C3-12 carbocycle and 3- to 12-membered heterocycle, wherein each C3-12 carbocycle and 3- to 12-membered heterocycle in R7 is independently optionally substituted with one or more substituents selected from halogen, —NO2, —CN, —OR10, —SR10, —N(R10)2, —S(═O)R10, —S(═O)2R10, —S(═O)2N(R10)2, —NR10S(═O)2R10, —C(O)R10, —C(O)OR10, —OC(O)R10, —OC(O)OR10, —OC(O)N(R10)2, —NR10C(O)R10, —C(O)N(R10)2, ═O, ═S, ═N(R10), —P(O)(OR10)2, —OP(O)(OR10)2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
• R10 at each occurrence is independently selected from hydrogen;
• and C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, C3-12 carbocycle and 3- to 12-membered heterocycle, each of which may be optionally substituted by halogen, —CN, —NO2, —OH and —OCH3;
• and
• X at each occurrence is independently selected from bond, —O—, —S—, —N(R4)—, —C(O)—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R4)—, —C(O)N(R4)C(O)—, —C(O)N(R4)C(O)N(R4)—, —N(R4)C(O)—, —N(R4)C(O)N(R4)—, —N(R4)C(O)O—, —OC(O)N(R4)—, —C(NR4)—, —N(R4)C(NR4)—, —C(NR4)N(R4)—, —N(R4)C(NR4)N(R4)—, —S(O)2—, —OS(O)—, —S(O)O—, —S(O)—, —OS(O)2—, —S(O)2O—, —N(R4)S(O)2—, —S(O)2N(R4)—, —N(R4)S(O)—, —S(O)N(R4)—, —N(R4)S(O)2N(R4)—, and —N(R4)S(O)N(R4)—.