Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors

A compound of Formula I

• or a pharmaceutically salt thereof, wherein
• Y is N or C—CN;
• Z is N or CH;
• X is N or CR3;
• provided that at least one of Y, Z, or X is N;
• R1 is C3-7cycloalkyl or a 4- to 7-membered heterocyclic moiety, wherein the heterocyclic moiety contains 1 to 2 atoms independently selected from nitrogen, oxygen and sulfur, and wherein the cycloalkyl or heterocyclic moiety has 0 to 3 substitutuents independently selected from —C1-3alkyl, and —OH, provided that there is no more than one —OH substituent;
• or
• N(C1-3alkyl)2, NH(C1-3alkyl), or NH(C3-4cycloalkyl), wherein each C1-3alkyl is substituted with 0 to 1 OH;
• R2 is -(L)m-CON(RN)2, -(L)m-SO2Rs, -L-(CH2)nSO2Rs, -L-(CH2)nCO2H, -L -(CH2)nC(O)Rc, -L-(CH2)nCONHSO2Rs, -L-(CH2)nSO2NHCORs, -L-(CH2)nSO2NHCONH2, or -L-(CH2)ntetrazol-5-yl;
• m is 0 or 1;
• n is 0 or 1;
• RN is H or —C1-3alkyl;
• Rs is H or —C1-3alkyl;
• L is CH2, CHF, or CF2;
• Rc is —C1-4alkyloxy, —C1-4alkyloxycarbonyloxy-C1-4alkyloxy, or —C1-4alkylcarbonyloxy-C1-4alkyloxy;
• R3 is H, halogen, —CN, —C1-3alkyl, —OC1-3alkyl, —C1-3alkyl substituted with 1 to 3 halogen atoms, or —C3-4cycloalkyl;
• and
• R4 is cyclopropyl, cyclobutyl, or —C1-3alkyl substituted with 0 to 5 halogen atoms as valency allows.