Acyl phosphonamidates and acyl benzylamines that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer

A compound of Formula (I):

• wherein:
• X1 is O or S;
• R1 is selected from SH, SR21, OH, OR21, NH2 and NR21R22;
• R2 is selected from H and R11;
• or R1 and R2 together with the atoms through which they are connected form a 5- or 6-membered heterocyclic ring optionally substituted with one or more R23;
• Z1 is O and R32 is R12;
• or Z1 and R32 together with the atoms through which they are connected form a 5- or 6-membered fused carbocyclic, heterocyclic, aryl or heteroaryl ring optionally substituted with one or more R12 groups;
• R3 is selected from hydrogen, alkyl and substituted alkyl;
• R4 is selected from hydrogen, alkyl, substituted alkyl, nitro, alkylsulfonyl, substituted alkylsulfonyl, alkylsulfinyl, substituted alkylsulfinyl, cyano, alkylcarbonyl, substituted alkylcarbonyl, C(O)OH, C(O)NH2, halogen, SO2NH2, alkylaminosulfonyl, substituted alkylaminosulfonyl, alkylsulfonylamino and substituted alkylsulfonylamino, alkyloxycarbonyl and substituted alkyloxycarbonyl;
• each R21 is independently selected from alkyl and substituted alkyl;
• R22 is selected from hydrogen, alkyl and substituted alkyl;
• or R21 and R22 together with the N atom through which they are connected form a 5- or 6-membered heterocyclic ring, optionally substituted with one or more R23;
• each R23 is independently selected from alkyl, substituted alkyl, hydroxyl, halogen, alkoxy and substituted alkoxy;
• Z2 is selected from —NR5R6, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, alkylsulfanyl, substituted alkylsulfanyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkoxy, substituted arylalkoxy, aryloxy, substituted aryloxy, aryloxyalkoxy, substituted aryloxyalkoxy, arylsulfanyl, substituted arylsulfanyl, arylsulfanylalkoxy, substituted arylsulfanylalkoxy, cycloalkylalkoxy, substituted cycloalkylalkoxy, cycloalkyloxy, substituted cycloalkyloxy, halogen, carbonyloxy, haloalkoxy, haloalkyl, hydroxy and nitro;
• R5 and R6 are independently selected from hydrogen, alkyl and substituted alkyl;
• Z3 is selected from —NR5R6, aryl, substituted aryl, heteroaryl, substituted heteroaryl, carbocycle, substituted carbocycle, heterocycle and substituted heterocycle;
• R11 and R12 are each independently one or more optional substituents each independently selected from alkyl, substituted alkyl, alkoxy, substituted alkoxy, halogen, cyano, nitro, carboxy, C(O)NH2, SO2NH2, sulfonate, hydroxyl, alkylsulfonyl, substituted alkylsulfonyl, alkylaminosulfonyl, substituted alkylaminosulfonyl, alkylsulfonylamino, substituted alkylsulfonylamino, alkyloxycarbonyl, substituted alkyloxycarbonyl and —NR5R6;
• and
• R31 is selected from H, R12 and L3-Y3 wherein L3 is a linker and Y3 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl.