Inhibitors of cytochrome p450 (cyp3a4)

A compound of formula I:

• wherein:
• A1 is (C1-C6)alkyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C6)carbocyclyl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl, wherein any (C1-C6)alkyl of A1 is optionally substituted with one or more Z1 groups and wherein any aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C6)carbocyclyl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl of A1 is optionally substituted with one or more Z2 groups;
• A2 is (C1-C6)alkyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C6)carbocyclyl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl, wherein any (C1-C6)alkyl of A2 is optionally substituted with one or more Z1 groups and wherein any aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, (C3-C6)carbocyclyl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl of A2 is optionally substituted with one or more Z2 groups;
• X is —C(O)NRaRb, —C(O)NRa1Rb1, —C(O)ORc, —S(O)2Rd or —C(O)Re;
• Y is —C(O)O— or —C(O)NRf—;
• R1 is H or (C1-C6)alkyl, and R2 is heterocyclyl(C1-C6)alkyl, aryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl or (C1-C6)alkyl, wherein any heterocyclyl(C1-C6)alkyl, aryl, aryl(C1-C6)alkyl or heteroaryl(C1-C6)alkyl of R2 is optionally substituted with one or more Z3 groups and wherein any (C1-C6)alkyl of R2 is optionally substituted with one or more Z4 groups;
• or R1 and R2 taken together with the atoms to which they are attached form a heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more Z5 groups;
• R3 is H or (C1-C6)alkyl;
• R4 is H or (C1-C6)alkyl;
• R5 is aryl, aryl(C1-C6)alkyl, heteroaryl, heteroaryl(C1-C6)alkyl, heterocyclyl or heterocyclyl(C1-C6)alkyl, wherein any aryl, aryl(C1-C6)alkyl, heteroaryl, heteroaryl(C1-C6)alkyl, heterocyclyl or heterocyclyl(C1-C6)alkyl of R5 is optionally substituted with one or more Z6 groups;
• Ra is H or (C1-C6)alkyl;
• Rb is (C1-C6)alkyl, aryl(C1-C6)alkyl or carbocyclyl, wherein any (C1-C6)alkyl of Rb is optionally substituted with one or more Z7 groups and wherein any carbocyclyl or aryl(C1-C6)alkyl of Rb is optionally substituted with one or more Z8 groups;
• Ra1 and Rb1 together with the nitrogen to which they are attached form a heterocyclyl, wherein the heterocyclyl is optionally substituted with one or more Z8 groups;
• Rc is (C1-C6)alkyl, aryl(C1-C6)alkyl or carbocyclyl, wherein any (C1-C6)alkyl of Rc is optionally substituted with one or more Z7 groups and wherein any carbocyclyl or aryl(C1-C6)alkyl of Rc is optionally substituted with one or more Z8 groups;
• Rd is (C1-C6)alkyl, aryl(C1-C6)alkyl, carbocyclyl, heteroaryl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl, wherein any (C1-C6)alkyl of Rd is optionally substituted with one or more Z7 groups and wherein any carbocyclyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl of Rd is optionally substituted with one or more Z8 groups;
• Re is (C1-C6)alkyl, aryl(C1-C6)alkyl, carbocyclyl, heteroaryl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl, wherein any (C1-C6)alkyl of Re is optionally substituted with one or more Z7 groups and wherein any carbocyclyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl or heterocyclyl(C1-C6)alkyl of Re is optionally substituted with one or more Z8 groups;
• Rf is H or (C1-C6)alkyl;
• each Rg and Rh is independently selected from H and (C1-C6)alkyl;
• Ri is H or (C1-C6)alkyl;
• Rj is (C1-C6)alkyl;
• each Z1 is independently selected from OH, oxo, halogen, OCF3, CN, —O(C1-C6)alkyl, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —S(O)2(C1-C6)alkyl, —NRgRh, —NRiC(O)Rj and —NRiS(O)2Rj;
• each Z2 is independently selected from OH, oxo, halogen, CF3, OCF3, NO2, CN, (C1-C6)alkyl, —O(C1-C6)alkyl, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —S(O)2(C1-C6)alkyl, —NRgRh, —NRiC(O)Rj and —NRiS(O)2Rj;
• each Z3 is independently selected from OH, oxo, halogen, CF3, OCF3, NO2, CN, (C1-C6)alkyl, —O(C1-C6)alkyl, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —S(O)2(C1-C6)alkyl, —NRgRh, —NRiC(O)Rj, —NRiS(O)2Rj, —NRiC(O)NRgRh, —NRiC(═NRi)NRgRh, —C(═NRi)NRgRh, —CO2H, —CO2Rj and —C(O)NRgRh;
• each Z4 is independently selected from OH, oxo, halogen, OCF3, NO2, CN, —O(C1-C6)alkyl, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —S(O)2(C1-C6)alkyl, —NRgRh, —NRiC(O)Rj, —NRiS(O)2Rj, —NRiC(O)NRgRh, —NRiC(═NRi)NRgRh, —C(═NRi)NRgRh, —CO2H, —CO2Rj and —C(O)NRgRh;
• each Z5 is independently selected from OH, oxo, halogen, CF3, OCF3, NO2, CN, (C1-C6)alkyl, —O(C1-C6)alkyl, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —S(O)2(C1-C6)alkyl, —NRgRh, heterocyclyl, —NRiC(O)Ri, —NRiS(O)2Rj, —NRiC(O)NRgRh, —NRiC(═NRi)NRgRh, —C(═NRi)NRgRh, —CO2H, —CO2Rj and —C(O)NRgRh;
• each Z6 is independently selected from OH, oxo, halogen, —CF3, —OCF3, —NO2, —CN, (C1-C6)alkyl, —O(C1-C6)alkyl and —NRgRh;
• each Z7 is independently selected from OH, oxo, halogen, —OCF3, —CN, —O(C1-C6)alkyl and —NRgRh;
• and
• each Z8 is independently selected from OH, oxo, halogen, —CF3, —OCF3, —NO2, —CN, (C1-C6)alkyl, —O(C1-C6)alkyl and —NRgRh;
• or a salt thereof;
• provided that when X is —C(O)NRaRb, Ra is H, R1 is H, R2 is 2-(4-morpholino)ethyl, R3 is H, R4 is H, R5 is thiazol-5-ylmethyl, Y is —C(O)O—, A1 is benzyl and A2 is benzyl;
• then Rb is other than methyl.