Substituted thiadiazolyl derivatives as dna polymerase theta inhibitors

A compound of Formula (II)

• wherein:
• X1 is selected from the group consisting of CH2 and C2-4 alkylene substituted with from 0 to 1 —OH;
• ring A is selected from the group consisting of phenyl and a 5- to 10-membered heteroaryl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S;
• the subscripts m and n are each independently 0 or 1;
• each R1 and R2, when present, are each independently selected from C1-4 alkyl, C1-4 alkoxy, halo, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 hydroxyalkyl, —C(O)OH, and cyano;
• Ar1 is selected from the group consisting of phenyl, 5- to 6-membered heteroaryl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, 5- to 6-membered heterocycloalkyl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, 6- to 10-membered bicyclic heterocyclyl having 1 to 4 heteroatoms as ring vertices independently selected from N, O, and S, 6- to 10-membered bridged heterocyclyl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, and 6- to 12-membered spiroheterocyclyl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, wherein Ar1 is substituted with 0 to 3 R3;
• each R3 is independently selected from the group consisting of C1-4 alkyl, halo, C1-4 haloalkyl, C1-4haloalkoxy, C3-6 cycloalkyl, C3-6 cycloalkyloxy, —X2—OH, —X2—O—C1-4 alkyl, —C(O)—C1-4 alkyl, and —X2-cyano;
• or two R3 on adjacent ring vertices, combine to form a C3-6 cycloalkyl, or two R3 on the same ring vertex, combine to form oxo, wherein each X2 is independently selected from a bond and C1-4 alkylene;
• Ar2 is selected from the group consisting of phenyl, 5- to 10-membered heteroaryl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, and C3-6cycloalkyl,
• wherein each Ar2 is substituted with an R4a substituent selected from the group consisting of —X3—OH, —X3—O—C1-4 alkyl, C3-6 cycloalkyl, —X5—C(O)OH, —C2-4 alkylene-cyano, —S(O)(NH)—C1-4 alkyl, —S(O)2—C1-4 alkyl, and —X4-heterocycloalkyl comprising 4- to 6-ring members and 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S wherein
• each cycloalkyl is independently substituted with from 1 to 2 substituents independently selected from —X3—O—C1-4 alkyl, —X5—C(O)OH and —X3—OH;
• and wherein each Ar2 is also substituted with 0 to 2 R4 substituents each of which is independently selected from the group consisting of C1-4 alkyl, halo, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, —X5—OH, C3-6 cycloalkyl, —X5-cyano, and C3-6 cycloalkyloxy;
• each X3 is independently C1-4 alkylene;
• each X4 is selected from —O— and C1-4 alkylene;
• and
• each X5 is independently selected from a bond and C1-4 alkylene;
• or a pharmaceutically acceptable salt thereof.

A compound of Formula (IV)

• wherein
• X1 is selected from the group consisting of CH2 and C2-4 alkylene substituted with from 0 to 1 —OH;
• ring A is selected from the group consisting of phenyl and a 5- to 10-membered heteroaryl having 1 to 4 heteroatoms as ring vertices independently selected from N, O, and S;
• the subscripts m and n are each independently 0 or 1;
• R1 and R2, when present, are each independently selected from the group consisting of C1-4 alkyl, C1-4 alkoxy, halo, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 hydroxyalkyl, —Xa—O—C3-6 cycaloalkyl, —C(O)OH, and cyano, wherein Xa is independently selected from a bond and C1-4 alkylene;
• Ar1 is selected from the group consisting of phenyl, 5- to 6-membered heteroaryl having 1 to 4 heteroatoms as ring vertices independently selected from N, O, and S, 5- to 6-membered heterocycloalkyl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, 6- to 10-membered bicyclic heterocyclyl having 1 to 4 heteroatoms as ring vertices independently selected from N, O, and S, 6- to 10-membered bridged heterocyclyl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, and 6- to 12-membered spiroheterocyclyl having 1 to 3 heteroatoms as ring vertices independently selected from N, O, and S, wherein Ar1 is substituted with 0 to 3 R3;
• each R3 is independently selected from the group consisting of C1-4 alkyl, halo, C1-4 haloalkyl, C1-4haloalkoxy, C3-6 cycloalkyl, C3-6 cycloalkyloxy, —X2—OH, —X2—O—C1-4 alkyl, —C(O)—C1-4alkyl, and —X2-cyano;
• or two R3 on adjacent ring vertices, combine to form a C3-6cycloalkyl, or two R3 on the same ring vertex, combine to form oxo, wherein each X2 is selected from a bond and C1-4 alkylene;
• and
• Z1 is C3-6 cycloalkyl substituted with 1 to 3 R5 substituents,
• wherein each R5 is independently selected from —OH, cyano, C1-4 alkyl, halo, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• or a pharmaceutically acceptable salt thereof.