Anacetrapib and other CETP inhibitors

摘要

A compound having Formula 1 or a pharmaceutically acceptable salt thereof, wherein: Y is - (CRR1) -; X is selected from the group consisting of -O-, -NH-, and -N (C1-C3); Z is -C ( = O) -; Each R is independently selected from the group consisting of H and C1-C2 alkyl; B is selected from the group consisting of A1 and A2, wherein A1 has the structure: R1 is selected from the group consisting of H, -C1-C3 alkyl, and - (C (R) 2) NA2, in the -C1-C3 that is optionally substituted with 1-5 halogens; R2 is selected from the group consisting of H, -C1-C3, A1, and - (C (R) 2) NA2, wherein -C1-C3 is optionally substituted with 1-5 halogens; Wherein one of B and R2 is A1; and one of B, R1, and R2 is A2 or - (C (R) 2) NA2; so that the compound of Formula I comprises one group A1 and A2 group; A3 is selected from the group consisting of: (a) phenyl; (B) an aromatic heterocyclic ring having 1-2 5-6 membered independently selected from N, S, O, and -N (O) heteroatoms -, wherein the point of attachment of A3 to the phenyl ring to which A3 is attached is a carbon atom; and (c) a benzoheterocyclic ring comprising a phenyl ring fused with an aromatic heterocyclic ring having 1-2 members independently selected from O, N, and -S (O) x heteroatoms, wherein the point of attachment of A3 the phenyl ring to which A3 is attached is a carbon atom; A2 is selected from the group consisting of: (a) phenyl; (B) a heterocyclic 5-6 membered ring having 1-4 heteroatoms independently selected from N, S, O, and -N (O) -, and optionally also comprising 1-3 double bonds; (C) a benzoheterocyclic ring comprising a phenyl ring fused with a heterocyclic ring members having 1-2 heteroatoms independently selected from O, N, and S; and (d) -cycloalkyl ring C5-C6; wherein A3 and A2 are each optionally substituted with 1-4 substituent groups independently selected from Ra; Each Ra is independently selected from the group consisting of -C1-C4, alkenyl C2-C4, cyclopropyl, C1-C2 -Oalkyl, -C ( = O) C1-C2, -C ( = O) H, -CO 2 alkyl C1-C4, -OH, -NR3R4, -NR3C ( = O) OC1-C4 alkyl, -S (O) xalquilo C1-C2, halogen, -CN, -NO2, and a heterocyclic ring of 5 -6 members having 1-2 independently selected from N, S heteroatoms, and O, wherein the point of attachment of said heterocyclic ring to the ring to which Ra is attached is a carbon atom, wherein said heterocyclic ring is optionally substituted with 1-5 substituent groups independently selected from halogen; wherein for compounds in which Ra is selected from the group consisting of -C1-C4 alkyl, -C2-C4, C1-C2 -Oalkyl, -C ( = O) C1-C2 alkyl, -CO 2 C1-C4, -NR3C ( = O) OC1-C4 alkyl, and -S (O) xalquilo C1-C2, alkyl group of Ra is optionally substituted with 1-5 halogens and is optionally substituted with a substituent selected between (a) -OH, (b) -NR3R4, (c) -OCH3 optionally substituted with 1-3 fluorine atoms and optionally substituted with a phenyl group, and (d) phenyl which is optionally substituted with 1-3 groups independently selected from halogen, -CH3, -CF3, -OCH3, -OCF3 and; n is 0 or 1; p is an integer of 0-2; x is 0, 1 or 2; and R3, R4, and R5 are each independently selected from H and -C1-C3.