wherein:

each W₁ and W₂ is independently CH, CF or N;

W₃ is independently, CR₂ or N;

U is N or CR₆;

A is selected from the group consisting of H, D, halogen, CN, —CHO, —COOH, —COOR, —C(O)NH₂, —C(O)NHR, R′S(O)₂—, —O(CH₂)_nC(O)R′, R′S(O)—, heteroaryl, —SOMe, —SO₂Me,

wherein X and Y are independently in each occurrence C, N, NR′, S, and O, provided that the ring containing X and Y cannot have more than 4 N or NH atoms or more than one S or O atoms, and wherein the S and O are not contiguous;

R and R′ at each occurrence are independently selected from the group consisting of H, OH, CN, —CH₂CN, halogen, —NR₇R₈, CHCF₂, CF₃, C₁-C₆ alkyl, R₇S(O)₂—, C₁-C₆ alkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₃-C₈ cycloalkylalkyl, 3- to 8-membered heterocyclyl, aryl, and heteroaryl, wherein each R and R′ are optionally substituted with one or more substituents selected from the group consisting of OH, halogen, C₁-C₆ alkoxy, NH₂, R₇S(O)₂—, CN, C₃-C₈ cycloalkyl, 3- to 8-membered heterocyclyl, aryl, heteroaryl, and R₇S(O)—;

R₁ is independently OH, CN, halogen, CHCF₂, CF₃, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₂-C₆ alkenyl, C₂-C₆ alkenyl, C₃-C₈ cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl, wherein each C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl is optionally substituted one or more times with substituents selected from the group consisting of halogen, OH, NH₂, CN, C₁-C₆ alkyl, and C₁-C₆ alkoxy;

each R₂ is independently H, OH, CN, halogen, CF₃, CHF₂, benzyl, C₁-C₆ alkyl, C₁-C₆ alkoxy, NH₂, —O(CH₂)_nR′, —O(CH₂)_nC(O)NHR′, —O(CH₂)_nC(O)R′, NHR₇, —N(R₇)(R₈), NHC(O)R₇, NHS(O)R₇, NHS(O)₂R₇, NHC(O)OR₇, NHC(O)NHR₇, —S(O)₂NHR₇, NHC(O)N(R₈)R₇, OCH₂R₇, CHRR′ or OCHR′R₇, wherein C₁-C₆ alkyl, C₁-C₆ alkoxy is optionally substituted with one or more substituents selected from the group consisting of C₁-C₆ alkyl, C₁-C₆ alkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, C₃-C₈ cycloalkyl substituted with one or more halogen, 3- to 8-membered heterocyclyl, aryl, -heteroaryl-C(O)NH₂, and heteroaryl;

or R₁ and R₂ can combine to form a C₄-C₆ cycloalkyl or a 3- to 8-membered heterocyclyl containing at least one atom selected from the group consisting of N, O, and S;

R₃ is H, C₁-C₆ alkyl, or —OH;

R₄ and R₅ are independently H, halogen, CH₂OH, C₁-C₃ alkyl, or C₁-C₃ alkyl substituted with halogen, or R₄ and R₅ when combined can form a C₃-C₆ cycloalkyl or C₃-C₆ heterocyclyl;

each R₆ is H, halogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₁-C₆ alkoxy substituted with one or more halogen, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, 3- to 8-membered heterocyclyl, aryl, or heteroaryl, or C₁-C₆ alkyl substituted with one or more of halogen, oxo, or C₁-C₆ alkoxy;

R₇ and R₈ are independently H, C₁-C₆ alkyl, C₁-C₆ alkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₈ cycloalkyl, 3- to 8-membered heterocyclyl, aryl, and heteroaryl; or when combined R₇ and R₈ can form a 3- to 8-membered heterocyclyl or heteroaryl ring, wherein each of R₇ and R₈ are optionally substituted with halogen;

R₉ is independently H, D, CD3, CF₃, C₁-C₆ alkyl, C₂-6 alkenyl, C₃-6 alkynyl, C₃-C₈ cycloalkyl, wherein the alkyl, alkenyl, alkynyl, and cycloalkyl is optionally substituted with amino, OH, halo, or alkoxy;

n is 0, 1, or 2; and

r is 0, 1, or 2;