CETP inhibitors

A compound having Formula I, or a pharmaceutically acceptable salt thereof, wherein

• Y is selected from the group consisting of —C(═O)— and —(CRR1)—;
• X is selected from the group consisting of —O—, —NH—, —N(C1-C5alkyl)-, and —(CRR6)—;
• Z is selected from the group consisting of —C(═O)—, —S(O)2—, and —C(═N—R9)—, wherein R9 is selected from the group consisting of H, —CN, and C1-C5alkyl optionally substituted with 1-11 halogens;
• Each R is independently selected from the group consisting of H, —C1-C5 alkyl, and halogen, wherein —C1-C5 alkyl is optionally substituted with 1-11 halogens;
• B is selected from the group consisting of A1 and A2, wherein A1 has the structure:
• R1 and R6 are each selected from the group consisting of H, —C1-C5 alkyl, halogen, and —(C(R)2)nA2, wherein —C1-C5 alkyl is optionally substituted with 1-11 halogens;
• R2 is selected from the group consisting of H, —C1-C5 alkyl, halogen, A1, and —(C(R)2)nA2, wherein —C1-C5 alkyl is optionally substituted with 1-11 halogens;
• Wherein one of B and R2 is A1;
• and one of B, R1, R2, and R6 is A2 or —(C(R)2)nA2;
• so that the compound of Formula I comprises one group A1 and one group A2;
• A3 is selected from the group consisting of:
• (a) an aromatic ring selected from phenyl and naphthyl;
• (b) a phenyl ring fused to a 5-7 membered non-aromatic cycloalkyl ring, which optionally comprises 1-2 double bonds;
• (c) a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, O, and —N(O)—, and optionally also comprising 1-3 double bonds and a carbonyl group, wherein the point of attachment of A3 to the phenyl ring to which A3 is attached is a carbon atom;
• and
• (d) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-6-membered heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and —S(O)x— and optionally 1-2 double bonds, wherein the point of attachment of A3 to the phenyl ring to which A3 is attached is a carbon atom;
• A2 is selected from the group consisting of:
• (a) an aromatic ring selected from phenyl and naphthyl;
• (b) a phenyl ring fused to a 5-7 membered non-aromatic cycloalkyl ring, which optionally comprises 1-2 double bonds;
• (c) a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, O, and —N(O)—, and optionally also comprising 1-3 double bonds and a carbonyl group;
• (d) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-6-membered heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and S and optionally 1-2 double bonds;
• and
• (e) a —C3-C8 cycloalkyl ring optionally having 1-3 double bonds;
• wherein A3 and A2 are each optionally substituted with 1-5 substituent groups independently selected from Ra;
• Each Ra is independently selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl optionally having 1-3 double bonds, —OC1-C6alkyl, —OC2-C6 alkenyl, —OC2-C6 alkynyl, —OC3-C8 cycloalkyl optionally having 1-3 double bonds, —C(═O)C1-C6alkyl, —C(═O)C3-C8 cycloalkyl, —C(═O)H, —CO2H, —CO2C1-C6alkyl, —C(═O)SC1-C6alkyl, —OH, —NR3R4, —C(═O)NR3R4, —NR3C(═O)OC1-C6 alkyl, —NR3C(═O)NR3R4, —S(O)xC1-C6 alkyl, —S(O)yNR3R4, —NR3S(O)yNR3R4, halogen, —CN, —NO2, and a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, and O, said heterocyclic ring optionally also comprising a carbonyl group and optionally also comprising 1-3 double bonds, 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, —C1-C3 alkyl, and —OC1-C3 alkyl, wherein —C1-C3 alkyl and —OC1-C3 alkyl are optionally substituted with 1-7 halogens;
• wherein for compounds in which Ra is selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl optionally having 1-3 double bonds, —OC1-C6alkyl, —OC2-C6 alkenyl, —OC2-C6 alkynyl, —OC3-C8 cycloalkyl optionally having 1-3 double bonds, —C(═O)C1-C6alkyl, —C(═O)C3-C8 cycloalkyl, —CO2C1-C6alkyl, —C(═O)SC1-C6alkyl, —NR3C(═O)OC1-C6 alkyl, and —S(O)xC1-C6 alkyl, then Ra is optionally substituted with 1-15 halogens and is optionally also substituted with 1-3 substituent groups independently selected from (a) —OH, (b) —CN, (c) —NR3R4, (d) —C3-C8 cycloalkyl optionally having 1-3 double bonds and optionally substituted with 1-15 halogens, (e) —OC1-C4alkyl optionally substituted with 1-9 halogens and optionally also substituted with 1-2 substituent groups independently selected from —OC1-C2 alkyl and phenyl, (f) —OC3-C8 cycloalkyl optionally having 1-3 double bonds and optionally substituted with 1-15 halogens, (g) —CO2H, (h) —C(═O)CH3, (i) —CO2C1-C4alkyl which is optionally substituted with 1-9 halogens, and (j) phenyl which is optionally substituted with 1-3 groups independently selected from halogen, —CH3, —CF3, —OCH3, and —OCF3;
• with the proviso that when B is A1, and X and Y are —CH2—, and Z is —C(═O)—, and R2 is phenyl which has a substituent Ra in the 4-position, wherein Ra is —OC1-C6alkyl which is optionally substituted as described above, then there are no other Ra substitutents on R2 in which Ra is selected from —OH, —OC1-C6alkyl, —OC2-C6 alkenyl, —OC2-C6 alkynyl, and —OC3-C8 cycloalkyl optionally having 1-3 double bonds, optionally substituted as described above.
• n is 0 or 1;
• p is an integer from 0-4;
• x is 0, 1, or 2;
• y is 1 or 2;
• R3 and R4 are each independently selected from H, —C1-C5 alkyl, —C(═O)C1-C5 alkyl and —S(O)yC1-C5 alkyl, wherein —C1-C5 alkyl in all instances is optionally substituted with 1-11 halogens;
• and
• R5 is selected from the group consisting of H, —OH, —C1-C5 alkyl, and halogen, wherein —C1-C5 alkyl is optionally substituted with 1-11 halogens.