Rifabutin analogs for the treatment of disease

A compound of the Formula I or a pharmaceutically acceptable salt, tautomer, solvate, hydrate or enantiomer thereof:

• wherein:
• Y1 is (CR1R2)n, wherein n is an integer from 1 to 6 and R1 and R2 are independently, at each occurrence, selected from the group consisting of hydrogen, —C1-C6 alkyl, and —C1-C6 alkoxy, wherein each alkyl is optionally substituted with one or more halogen or —C3-C6 cycloalkyl, and wherein each cycloalkyl is further optionally substituted with one or more halogen;
• X1 is —OR11 or —NR51R52;
• R11 is independently —C1-C6 alkyl, —C1-C6 alkylene-R12A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, or 5-membered heteroaryl, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one or more R12;
• R12 and R12A are each independently —C1-C6 alkyl, —C1-C6 alkylene-R16A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, halogen, cyano, oxo, —OR13, —CO2R13, or —NR14R15, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R16.
• R13, R14 and R15 are each independently hydrogen, —C1-C6 alkyl, —C1-C6 alkylene-R20A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, —S(O)2(C1-C6 alkyl), or —S(O)2NR18R19, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R20;
• R16 and R16A are each independently —C1-C6 alkyl, —C1-C6 alkylene-R20A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, halogen, cyano, oxo, —OR17, —S(O)2(C1-C6 alkyl), or —S(O)2NR18R19, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R20;
• R17, R18 and R19 are each independently hydrogen, halogen, —OH, —C1-C6 alkyl, —C1-C6 alkylene-R23A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, —S(O)2(C1-C6 alkyl), or S(O)2NR21R22, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R23;
• R20 and R20A are each independently halogen, —OH, —C1-C6 alkyl, —C1-C6 alkylene-R23A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, halogen, cyano, oxo, —S(O)2(C1-C6 alkyl), or S(O)2NR21R22, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R23;
• R21 and R22 are each independently hydrogen or —C1-C6 alkyl;
• and
• R23 and R23A are each independently —C1-C6 alkyl, —C1-C6 alkoxy, —C1-C6 haloalkyl, halogen, or cyano;
• R51 and R52 are each independently hydrogen, —C1-C6 alkyl, —C1-C6 alkylene-R53A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, or 5-10 membered heteroaryl, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one or more R53;
• or R51 and R52, together with the nitrogen atom to which they are attached, combine to form a 3-15 membered heterocycloalkyl or 5-15 membered heteroaryl, wherein the heterocycloalkyl or heteroaryl are optionally substituted with one or more R53;
• R53 and R53A are each independently —C1-C6 alkyl, —C1-C6 alkylene-R57A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, halogen, cyano, oxo, —OR54, —C(O)R54, —CO2R4, or —NR55R56, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R57;
• R54, R55 and R56 are each independently hydrogen, —C1-C6 alkyl, —C1-C6 alkylene-R61A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, —CO2R58, —S(O)2(C1-C6 alkyl), —S(O)2(C6-C10 aryl), or —S(O)2NR59R60, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R61;
• R57 and R57A are each independently —C1-C6 alkyl, —C1-C6 alkylene-R61A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, halogen, cyano, oxo, —OR58, NR59R60, —S(O)2(C1-C6 alkyl), or —S(O)2NR59R60, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R61;
• R58, R59 and R60 are each independently hydrogen, —C1-C6 alkyl, —C1-C6 alkylene-R64, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, —S(O)2(C1-C6 alkyl), or S(O)2NR62R63, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R64;
• R61 and R61A are each independently halogen, —OH, —C1-C6 alkyl, —C1-C6 alkylene-R64A, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C6 cycloalkyl, —C5-C8 cycloalkenyl, 3-10 membered heterocycloalkyl, —C6-C10 aryl, 5-10 membered heteroaryl, —C1-C6 alkoxy, —C1-C6 haloalkyl, halogen, cyano, oxo, —S(O)2(C1-C6 alkyl), or S(O)2NR62R63, wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl and alkoxy is optionally substituted with one or more R64;
• and
• R62 and R63 are each independently hydrogen and —C1-C6 alkyl;
• and
• R64 and R64A are each independently —C1-C6 alkyl, —C1-C6 alkoxy, —C1-C6 haloalkyl, phenyl, halogen, or cyano.