# US 2003/0229079 A1 · 1-(Aromatic- or heteroaromatic-substituted)-3-(heteroaromatic substituted)-1,3-propanediones and uses thereof

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- Number: US 2003/0229079 A1
- Document ID: US20030229079A1
- Status: Published application
- Kind: A1
- Application number: 10/260,029
- Filed: 2003-06-06
- Published: 2003-12-11
- Earliest claimed: 1999-06-25
- Inventors: Linda S. Payne; Lekhanh O. Tran; Linghang H. Zhuang; Steven D. Young; Melissa S. Egbertson; John S. Wai; Mark W. Embrey; Thorsten E. Fisher; James P. Guare; H. Marie Langford; Jeffrey Y. Melamed; David L. Clark
- Web page: https://patentgrep.com/patent/US20030229079A1

## CPC

- C07D 213/30: Oxygen atoms
- A61P 31/18: for HIV
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/50: Ketonic radicals
- C07D 213/61: Halogen atoms or nitro radicals
- C07D 213/643: 2-Phenoxypyridines; Derivatives thereof
- C07D 213/65: attached in position 3 or 5
- C07D 213/68: attached in position 4
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C07D 239/26: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 241/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 277/24: Radicals substituted by oxygen atoms
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 403/10: linked by a carbon chain containing aromatic rings
- C07D 403/14: containing three or more hetero rings
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/10: linked by a carbon chain containing aromatic rings
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 417/10: linked by a carbon chain containing aromatic rings
- C07D 417/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 473/00: Heterocyclic compounds containing purine ring systems
- C07D 473/04: two oxygen atoms
- C07D 473/08: with methyl radicals in positions 1 and 3, e.g. theophylline
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Certain 1-(aromatic- or heteroaromatic-substituted-3-(heteroaromatic substituted)-1,3-propanediones are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

## Claims

### Claim 1

A compound of formula:
151
or a tautomer thereof; wherein
A is (i) a benzene ring; (ii) an 8- to 10-membered fused bicyclic carbocycle, wherein the ring, of the carbocycle attached to the central dione moiety is a benzene ring, and the other ring of the carbocycle is saturated or unsaturated; (iii) an 8 to 10-membered fused bicyclic heterocycle containing carbon atoms and from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, wherein the ring of the heterocycle attached to the central dione moiety is a benzene ring, and the other ring of the heterocycle is a saturated or unsaturated heteroatom-containing ring; or (iv) a 5- or 6-membered heteroaromatic ring containing from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur; and wherein A is attached to the central dione moiety via a carbon atom;
R1, R2 and R3 are substituents attached to nitrogen or carbon in A;
R1 is hydrogen, halo, nitro, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-3N(Ra)(Rb), (CH2)0-3Rc, or O(CH2)0-3Rc;
R2 is hydrogen, halo, nitro, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-3N(Ra)(Rb), (CH2)0-3Rc, O(CH2)0-3Rc, (CH2)0-3Rd, O(H2)0-3Rd, C(═O)CH2C(═O)Re, or Rf;
R3 is hydrogen, halo, nitro, oxo, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyloxy, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-4C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-4N(Ra)C(═O)Rb, SO2Ra, (CH2)1-4SO2Ra, SO2N(Ra)(Rb), (CH2)1-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, (CH2)0-3Rc, or (CH2)0-3Rg;
B is (i) a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and at least 1 carbon atom, or (ii) an 8- to 10-membered fused bicyclic heterocycle containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and carbon atoms, wherein the ring of the heterocycle attached to the central dione moiety is a 5- or 6-membered heteroaromatic ring containing at least one nitrogen or sulfur atom and the other ring of the heterocycle is a saturated or unsaturated ring; wherein B is attached to the central dione moiety via a carbon atom and at least one nitrogen or sulfur atom in B is adjacent to the point of attachment;
R4 and R5 are substituents attached to nitrogen or carbon in B, and are each independently selected from hydrogen, halo, hydroxy, (CH2)1-4OH, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-4C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-4N(Ra)C(═O)Rb, SO2Ra, (CH2)1-4SO2Ra, SO2N(Ra)(Rb), (CH2)1-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, and(CH2)0-3Rh;
Ra and Rb are each independently hydrogen, C1-C6 alkyl, or fluorinated C1-C6 alkyl;
Rc is (i) phenyl or substituted phenyl, wherein each substituent on the substituted phenyl is independently halo, cyano, hydroxy, (CH2)1-4OH, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6-alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl; or (ii) an 8- to 10-membered fused bicyclic carbocycle in which one ring is a benzene ring and the other ring is a saturated or unsaturated ring, wherein the fused carbocycle is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
Rd is (i) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains at least one carbon atom and from 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur; (ii) an 8- to 10-membered fused bicyclic heterocycle in which either ring is saturated or unsaturated and which contains carbon atoms and from 1 to 4 nitrogen atoms; wherein the heterocycle of (i) or (ii) is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, thio, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl; or (iii) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms, the heterocycle being substituted with spiro-C1-C2 alkylenedioxy or with one of pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
Re is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and at least 1 carbon atom; wherein the point of attachment of the ring is a carbon atom and at least one nitrogen or sulfur atom in the ring is adjacent to the point of attachment; wherein the ring is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
Rf is X—NH(CH2)1-3Y, wherein X is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms and which is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl; Y is pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
Rg is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains one or more carbon atoms and from 1 to 4 nitrogen atoms, the heterocycle being unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
Rh is (i) C3-C6 cycloalkyl; (ii) phenyl; (iii) substituted phenyl, wherein each substituent on the substituted phenyl is independently halo, cyano, hydroxy, (CH2)1-4OH, C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, or fluorinated C2-C8 alkoxyalkyl, or (iv) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains at least one carbon atom and from 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the heterocycle is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, or a tautomer thereof, wherein
R4 and R5 are substituents attached to nitrogen or carbon in B, and are each independently selected from hydrogen, halo, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-4C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-4N(Ra)C(═O)Rb, SO2Ra, (CH2)1-4SO2Ra, SO2N(Ra)(Rb), (CH2)1-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, and (CH2)0-3Rh;
Ra and Rb are each independently hydrogen, C1-C4 alkyl, or fluorinated C1-C4 alkyl;
Rc is (i) phenyl or substituted phenyl, wherein each substituent on the substituted phenyl is independently halo, cyano, hydroxy, C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra; C2-C8 alkoxyalkyl, or fluorinated C2-C8 alkoxyalkyl; or (ii) an 8- to 10-membered fused bicyclic carbocycle in which one ring is a benzene ring and the other ring is a saturated or unsaturated ring, wherein the fused carbocycle is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
Rd is (i) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains at least one carbon atom and from 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur; (ii) an 8- to 10-membered fused bicyclic heterocycle in which either ring is saturated or unsaturated and which contains carbon atoms and from 1 to 4 nitrogen atoms; wherein the heterocycle of (i) or (ii) is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl; or (iii) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms, the heterocycle being substituted with spiro-C1-C2 alkylenedioxy, or with one of pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, and fluorinated C1-C6 alkoxy;
Re is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and at least 1 carbon atom; wherein the point of attachment of the ring is a carbon atom and at least one nitrogen or sulfur atom in the ring is adjacent to the point of attachment; wherein the ring is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, oxo, C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, N(Ra)(Rb), (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
Rf is X—NH(CH2)1-3Y, wherein X is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms and which is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, and fluorinated C1-C6 alkoxy; Y is pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, and fluorinated C1-C6 alkoxy;
Rg is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains one or more carbon atoms and from 1 to 4 nitrogen atoms, the heterocycle being unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy and fluorinated C1-C6 alkoxy; and
Rh is C3-C6 cycloalkyl, phenyl or substituted phenyl, wherein each substituent on the substituted phenyl is independently halo, cyano, hydroxy, C1-C6 alkyl fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, C2-C8 alkoxyalkyl, or fluorinated C2-C8 alkoxyalkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound according to claim 1, or a tautomer thereof, wherein
A is a benzene ring;
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The compound according to claim 3, or a tautomer thereof, wherein
B is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and at least 1 carbon atom;
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 4)

The compound according to claim 4, or a tautomer thereof, having the formula:
152
wherein
R1 is hydrogen, fluoro, chloro, bromo, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, N(Ra)(Rb), CH2N(Ra)(Rb), (CH2)0-2Rc, or O(CH2)0-2Rc;
R2 is hydrogen, fluoro, chloro, bromo, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, N(Ra)(Rb), CH2N(Ra)(Rb), (CH2)0-2Rc, O(CH2)0-2Rc, (CH2)0-2Rd, O(CH2)0-2Rd, C(═O)CH2C(═O)Re, or Rf;
R3is hydrogen, fluoro, chloro, bromo, oxo, methyl, ethyl, propyl, isopropyl, C3-C6 cycloalkyl, C3-C6 cycloalkyloxy, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, (CH2)0-2Rc, or (CH2)0-2Rg;
B′ is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 or 1 sulfur atoms, and one or more carbon atoms, wherein B′ is attached to the central dione moiety via a carbon atom and at least one nitrogen atom in B′ is adjacent to the point of attachment;
R4 and R5 are substituents attached to any nitrogen or carbon in B′ except for the ring carbon attached to the central dione moiety, and are each independently selected from hydrogen, fluoro, chloro, bromo, hydroxy, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-2OH, (CH2)1-2O—C1-C4 alkyl, (CH2)1-3O(CH2)0-1CF3, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, and (CH2)0-2Rh;
Ra and Rb are each independently hydrogen, C1-C4 alkyl, or fluorinated C1-C4 alkyl;
Rc is (i) phenyl or substituted phenyl, wherein each substituent on the substituted phenyl is independently fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), and (CH2)1-2N(Ra)SO2Rb; or (ii) an 8- to 10-membered fused bicyclic carbocycle in which one ring is a benzene ring and the other ring is a saturated or unsaturated ring, wherein the fused carbocycle is unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), and (CH2)1-2N(Ra)SO2Rb;
Rd is (i) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains at least one carbon atom and from 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein each ring sulfur is in a form selected from S, SO and SO2; (ii) an 8- to 10-membered fused bicyclic heterocycle in which either ring is saturated or unsaturated and which contains carbon atoms and from 1 to 4 nitrogen atoms; wherein the heterocycle of (i) or (ii) is unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, oxo, thio, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, phenyl, and benzyl; or (iii) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms, the heterocycle being substituted with spiro-C1-C2 alkylenedioxy, or with one of pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, oxo, methyl ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, phenyl, and benzyl;
Re is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and at least 1 carbon atom; wherein the point of attachment of the ring is a carbon atom and at least one nitrogen or sulfur atom in the ring is adjacent to the point of attachment; wherein the ring is unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, oxo, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, phenyl, and benzyl;
Rf is X—NH(CH2)1-2Y, wherein X is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms and which is unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, oxo, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), and (CH2)1-2N(Ra)SO2Rb; Y is pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, oxo, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), and (CH2)1-2N(Ra)SO2Rb;
Rg is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains one or more carbon atoms and from 1 to 4 nitrogen atoms, the heterocycle being unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, (CH2)1-2OH, oxo, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, phenyl, and benzyl; and
Rh is (i) C3-C6 cycloalkyl; (ii) phenyl; (iii) substituted phenyl, wherein each substituent on the substituted phenyl is independently fluoro, chloro, bromo, hydroxy, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, (CH2)1-2OH, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2N(Ra)C(═O)Rb, SO2Ra, (CH2)1-4SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, or (iv) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains at least one carbon atom and from 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur; where in the heterocycle is unsubstituted or substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, methyl, ethyl, propyl, isopropyl, OCH3, OCH2CH3, OCH2CH2CH3, OCH(CH3)2, CF3, CH2CF3, OCF3, OCH2CF3, (CH2)1-3O(CH2)0-1CH3, (CH2)1-3O(CH2)0-1CF3, CO2Ra, (CH2)1-2CO2Ra, (CH2)1-2OH, N(Ra)(Rb), (CH2)1-2N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-2C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-2(Ra)(C═O)Rb, SO2Ra, (CH2)1-2SO2Ra, SO2N(Ra)(Rb), (CH2)1-2SO2N(Ra)(Rb), (CH2)1-2N(Ra)SO2Rb, phenyl, and benzyl;
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 5)

The compound according to claim 5, or a tautomer thereof, wherein
B′ is pyridyl, pyrazinyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl or thiazolyl
Rc is (i) phenyl or substituted phenyl or (ii) an unsubstituted or substituted fused bicyclic carbocycle selected from
153
Rd is (i) an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle selected from pyrazolyl, imidazolyl, pyrrolyl, pyrrolidinyl, pyridyl, piperidinyl, pyrazinyl, piperazinyl, pyridazinyl, pyrimidinyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, morpholinyl, tetrahydrothienyl, tetrahydrodioxothienyl, thiadiazinanyl dioxothiazinanyl, thiazinanyl, dioxothiazinanyl, thiazolidinyl, dioxothiazolidinyl, isothiazolidinyl, isodioxothiazolidinyl, thiazolyl, and isothiazolyl; (ii) an unsubstituted or substituted fused bicyclic heterocycle selected from
154
155
(iii) a monocyclic heterocycle selected from pyridyl, piperidinyl, pyrazinyl, piperazinyl, and pyrimidinyl, the heterocycle being substituted with spiro-C1-C2 alkylenedioxy or with one of unsubstituted or substituted piperidinyl, unsubstituted or substituted piperazinyl, or unsubstituted or substituted morpholinyl;
Re is an unsubstituted or substituted heteroaromatic ring selected from pyridyl, pyrazinyl, and pyrimidinyl;
Rf is X—NH(CH2)1-2Y, wherein X is selected from unsubstituted or substituted pyridyl, unsubstituted or substituted pyrazinyl, and unsubstituted or substituted pyrimidinyl; and Y is unsubstituted or substituted pyrrolidinyl, unsubstituted or substituted piperidinyl, unsubstituted or substituted piperazinyl, or unsubstituted or substituted morpholinyl;
Rg is an unsubstituted or substituted monocyclic heterocycle selected from pyridyl, pyrrolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, pyrazolyl, imidazolyl, tetrazolyl, piperidinyl, and piperazinyl; and
Rh is C3-C6 cycloalkyl, phenyl, substituted phenyl, or an unsubstituted or substituted monocyclic heterocycle selected from pyridyl, pyrrolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, pyrazolyl, imidazolyl, tetrazolyl, piperidinyl, piperazinyl, and tetrahydrofuranyl;
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 6)

The compound according to claim 6, or a tautomer thereof wherein B′ is pyridyl;
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The compound according to claim 7, selected from the group consisting of
1-(3-Benzyl-5-pyrazin-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-5-pyrazin-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
3-[3-(2-Chlorobenzyl)-5-pyridin-2-ylmethylphenyl]-1-(4-methylpyridin-2-yl)propane-1,3-dione;
3-[3-(3-Chlorobenzyl)-5-pyridin-2-ylmethylphenyl]-1-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-Benzyl-5-(2-oxo-2H-pyridin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3dione;
1-[3-Benzyl-5-(2-oxo-pyridin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3dione;
1-[3-Benzyl-5-(4-methylpiperazin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3dione;
1-(3-Benzylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[(2,6-difluoro-benzyl)-phenyl]-3-(4methoxy-pyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-phenyl)-3-(4-methoxy-pyridin-2-yl)-propane-1,3-dione;
1-[3-(2,6-Difluoro-benzyl)-phenyl]-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-{3-Benzyl-5-[6-(2-morpholin-4-yl-ethylamino)-pyrazin-2-yl]-phenyl}-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-[3-Benzyl-5-(6-methoxypyridin-2-yl)-phenyl]-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;)
1-[3-Benzyl-5-(6-morpholin-4-yl-pyrazin-2-yl)-phenyl]-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-[3-Benzyl-5-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-6′-yl)-phenyl]-3-(4-methyl-pyridin-2yl)-propane-1,3-dione;
1-[5-(4-Fluoro-benzyl)-2,3-dimethoxy-phenyl]-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-[2,3-Dimethoxy-5-(2-methyl-benzyl)-phenyl]-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-(5-Benzyl-2-methoxy-3-morpholin-4-ylmethylphenyl)-3-(4-methyl-pyridin-2-yl)propane-1,3-dione;
1-(5-Benzyl-2-isopropoxy-3-pyrrolidin-1-ylmethyl-phenyl)-3-(4-methyl-pyridin-2-yl)propane-1,3-dione;
1-(5-Benzyl-2-isopropoxy-3-[1,2,4]triazol-1-ylmethylphenyl)-3-(4-methyl-pyridin-2-yl)propane-1,3-dione;
1-[5-Benzyl-2-(pyridin-2-yloxy)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-Benzyl-5-(4-methylpiperazin-1-yl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-5-[1,2,4]triazol-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-5-imidazol-1-ylphenyl)-3-(4-methylpyridin-2yl)-propane-1,3-dione;
1-(3-Benzyl-5-[1,2,3]triazol-1-ylmethylphenyl)-3-(4-methylpyridin-yl)propane-1,3-dione;
1-(3-Benzyl-5-[1,2,3]triazol-1-ylmethylphenyl)-3-(6-chloropyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-5-tetrazol-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-5-[1,2,3]triazol-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-5-tetrazol-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-Benzyl-5-pyrrolo[2,3]pyridin-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-Benzylphenyl)-3-(3-isopropoxypyridin-2-yl)-propane-1,3-dione;
1-(3-Benzylphenyl)-3-(3-propoxypyridin-2-yl)-propane-1,3-dione;
1-(3,5-Bis-pyrazol-1-ylmethyl-phenyl)-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-(4-Methyl-pyridin-2-yl)-3-(3pyrazol-1-ylmethyl-phenyl)-propane-1,3-dione;
1-(4-Methyl-pyridin-2-yl)-3-(3-pyrrol-1-ylmethyl-phenyl)-propane-1,3-dione;
1-(4-Methyl-pyridin-2-yl)-3-(3-tetrazol-2-ylmethyl-phenyl)-propane1,3-dione;
1-(4-Methyl-pyridin-2-yl)-3-(3-[1,2,3]triazol-2-ylmethyl-phenyl)-propane-1,3-dione;
1-[3-(3-Methyl-pyrazol-1-ylmethyl)-phenyl]-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-[3-(5-Methyl-pyrazol-1-ylmethyl)-phenyl]-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-(4-Methyl-pyridin-2-yl)-3-(3-[1,2,3]triazol-2-ylmethyl-5-[1 2,3]triazol-1-ylmethylphenyl)-propane-1,3-dione;
1-(3,5-Bis-pyrrol-1-ylmethyl-phenyl)-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-(3-Indazol-1-ylmethyl-phenyl)-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-(4-methyl-pyridin-2-yl)-3-(3-pyrimidin-2-ylmethyl-phenyl)-propane-1,3-dione;
1-(3-Benzylphenyl)-3-(5-dimethylaminopyridin-2-yl)-propane1,3-dione;
1-(3-benzyl-5-pyrazin-2-yl-phenyl)-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
1-(3-benzyl-5-pyrimidin-2-yl-phenyl)-3-(4-methyl-pyridin-2-yl)-propane-1,3-dione;
tautomers thereof;
and pharmaceutically acceptable salts thereof.

### Claim 9 (depends on 7)

The compound according to claim 7, selected from the group consisting of
1-(3,5-bis-pyridin-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3,5-bis-(2-methyl-2H-pyrazol-3-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-Pyridin-2-ylmethyl)phenyl-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-(1,1-Dioxoisothiazolin-2-ylmethyl)-5-(pyridin-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[5-(2,6-Difluorobenzyl)-2,3-dimethoxyphenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(5-benzyl-2-fluorophenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(2-Methoxy-5-[1,2,3]triazol-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-indazol-1-ylmethyl)phenyl-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-pyrazol-1-ylmethyl)phenyl-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-[1,2,3]triazolo[4,5,b]pyridin-1-ylmethyl)phenyl-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[3-benzyl-5-(3-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(2-oxo-1,2-dihydro-2H-pyrimidin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-purin-9-ylmethyl)phenyl-3-(4-methylpyridin-2-yl )propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxoisothiazolidin-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxothiazinan-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxo-[1,2,6]-thiadiazinan-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(2-oxo-2H-pyrimidin-1-ylmethyl)phenyl]-3-(pyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxotetrahydrothiophen-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxotetrahydrothiophen-2-ylmethyl)-2-isopropoxyphenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(1,3-dimethyl-2,3,6,1-tertrahydro-2,6-dioxopurin-9-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(6-dimethylaminoylpurin-7-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[3-benzyl-5-(4-methyl-5-thioxo-3-trifluoromethyl-4,5-dihydro-[1,24]-triazol-1-ylmethyl)phenyl]-3-(4-methylpyidin-2-yl)propane1,3-dione;
1-[3-benzyl-5-(3,7-dimethyl-3,7-dihydro-2,6-dioxopurin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(2-oxo-2H-pyridin-1-ylmethyl)phenyl]3-(4-methylpyridin-2-methylpyridin-1,3-dione;
1-[3-benzyl-5-([1,2,3]triazolo[4,5-b]pyridinyl-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3,5-bis-pyrazol-1-ylmethylphenyl)-3-pyridin-2-yl-propane-1,3-dione;
1-(4-Methylpyridin-2-yl)-3-(3-pyrazol-1-ylmethyl-5-[1,2,4]triazol-1-ylmethylphenyl)-propane-1,3-dione;
1-[3,5bis(3,5-dimethylpyrazol-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-benzylphenyl)-3-(5-bromopyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(5-methoxypyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(4-imidazol-1-ylmethylpyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(4-(1,2,4-triazol-1-yl)methyl)pyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(4-(pyrazol-1-ylmethylpyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(4-(1,2,3,4-tetrazol-2-yl)methyl)pyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-2-[1,2,3]-triazol-1-ylmethyl)phenyl)-3-(4-imidazol-1-ylmethylpyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(4-methoxymethylpyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(4-hydroxymethylpyridin-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-[4-(tetrahydrofuran-2-yl)-pyridin-2-yl]propane-1,3-dione;
1-(3,5-bis-pyrazol-1-ylmethyl-phenyl)-3-(4-[1,2,4]triazol-1-ylmethyl-pyridin-2-yl)-propane-1,3-dione;
1-(3,5-bis-pyridin-2-ylmethylphenyl)-3-(4-imidazol-1-ylmethyl-pyridin-2-yl)propane-1,3-dione;
tautomers thereof;
and pharmaceutically acceptable salts thereof.

### Claim 10 (depends on 7)

The compound according to claim 7, selected from the group consisting of
1-(3,5-bis-pyrazol-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-tetrazol-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-[1,2,4]triazol-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3-benzyl-5-tetrazol-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-[1,2,3]triazol-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[3-benzyl-5-(4-methylpiperazin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione
1-(3-benzyl-5-[1,2,3]triazol-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-pyrazin-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(2-oxopiperidin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-Benzyl-5-[1,2,4]triazol-1-ylmethylphenyl)-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-(3,5-bis-pyridin-2-ylmethylphenyl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3benzyl]-5-(3-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[3-benzyl-5-(2-oxo-1,2-dihydro-2H-pyrimidin-1-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(3-benzyl-5-([1,1-dioxoisothiazolidin-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxothiazinan-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)-propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxo-[1,2,6]-thiadiazinan-2-ylmethyl)phenyl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
tautomers thereof;
and pharmaceutically acceptable salts thereof.

### Claim 11 (depends on 6)

The compound according to claim 6 or a tautomer thereof, wherein B is pyrazinyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, or thiazolyl; or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 11)

The compound according to claim 11, selected from the group consisting of
1-(3-benzylphenyl)-3-(1H-imidazol-2-yl)-propane-1,3-dione;
1-(3-benzylphenyl)-3-(1-benzyl-1H-imidazol-2-yl)propane-1,3-dione TFA salt;
1-(3-benzylphenyl)-3-(1H-imidazol-4-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-pyrazin-2-ylpropane-1,3-dione;
1-(3-benzylphenyl)-3-(2-methylthiazol-4-yl)-propane-1,3-dione;
1-[3-benzyl-5-(5-methylpyrazin-2-ylmethyl)phenyl]-3-(5-methylpyrazin-2-yl)-propane-1,3-dione;
1-(3-benzylphenyl)-3-(4H-[1,2,4]triazol-3-yl)propane-1,3-dione;
tautomers thereof;
and pharmaceutically acceptable salts thereof.

### Claim 13 (depends on 11)

The compound according to claim 11, selected from the group consisting of
1-[3-(1,1-Dioxoisothiazolin-2-ylmethyl)-5-(pyridin-2-ylmethyl)phenyl]-3-(1-methyl-1H-imidazol-4-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(1-N-methyl-imidazole-4-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-[1-N-(pyridin-4-yl)methylimidazole-4-yl]propane-1,3-dione;
1-(3-benzylphenyl)-3-[1-N-(pyridin-2-yl)methylimidazole-4-yl]propane-1,3-dione;
1-(3-benzylphenyl)-3-[1-N-(pyridin-3-yl)methylimidazole-4-yl]propane-1,3-dione;
1-(3-benzylphenyl)-3-{1-N-[(1-N-tert-butylcarbamyl)-piperidine-4-yl]methylimidazole-4-yl}propane-1,3-dione;
1-(3-benzylphenyl)-3[1-N-(piperidine-4-yl)methylimidazole-4-y]propane-1,3-dione;
1-(3-benzylphenyl)-3-{1-N-[(1-N-methanesulfonyl)piperidine-4-yl]methylimidazole-4-yl}propane-1,3-dione;
1-(3-benzylphenyl)-3-{1-N-[2-(1-N-tert-butylcarbamylpipeniazin-4-yl)ethyl]imidazole-4-yl}propane-1,3-dione;
1-(3-benzylphenyl)-3-{1-N-[2-(piperiazin-1-yl)ethyl]imidazole-4-yl}propane-1,3-dione;
1-(3-benzylphenyl)-3-{1-N-[2-(1-N-methansufonyl-piperazin-4-yl)ethyl]-imidazole-4-yl}propane-1,3-dione;
1-(3-benzylphenyl)-3-{1-N-[2-(1-N-benzylpiperiazin-4-yl)ethyl]imidazole-4-yl}propane-1,3-dione;
1-[3-benzyl-5-(6-oxo-6H-pyrimidin-1-ymethyl)phenyl]-3-(1-methylimidazole-4-yl)propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxoisothiazolidin-2-ylmethyl)phenyl]-3-(1-methylimidazole-4-yl)propane-1,3-dione;
1-(3-benzylphenyl-pyrimidin-2yl-propane-1,3-dione;
1-(3-benzylphenyl)-3-(4-methylpyrimidin-2-yl)propane-1,3-dione;
1-(3,5-bis-pyrazol-1-ylmethylphenyl)-3-pyrimidin-2yl-propane-1,3-dione;
1-(3,5-bis-pyrazol-1-ylmethylphenyl)-3-(4-methylpyrimidin-2-yl)propane-1,3-dione;
1-(3,5-bis-pyrazol-1-ylmethyl-phenyl)-3-(1H-imidazol-2-yl)propane-1,3-dione;
1-(3,5-bis-pyrazol-1-ylmethyl-phenyl)-3-(1-methyl-1H-imidazol-4-yl)propane-1,3-dione;
1{3-benzyl-5-[(1,1-dioxido-1,2-thiazinan-2-yl)methyl]phenyl}-3-(1,3-thiazol-2-yl)-1,3-propanedione;
1-{3-benzyl-5-[(1,1-dioxido-2-isothiazolidinyl)methyl]phenyl)}-3-(1,3-thiazol-2-yl)-1,3-propanedione;
1-{3-benzyl-5-[(6-oxo-1(6H)-pyrimidinyl)methyl]phenyl}-3-(1,3-thiazol-2-yl)-1,3-propanedione;
tautomers thereof,
and pharmaceutically acceptable salts thereof.

### Claim 14 (depends on 11)

The compound according to claim 11, selected from the group consisting of
1-(3-benzylphenyl)-3-(1H-imidazol-2-yl)propane-1,3-dione;
1-(3-benzylphenyl)-3-(1H-imidazol-4-yl)propane-1,3-dione;
1-[3-benzyl-5-(1,1-dioxoisothiazolidin-2-ylmethyl)phenyl]-3-(1-methylimidazole-4-yl)propane-1,3-dione;
1-{3-benzyl-5-[(6-oxo-1(6H)-pyrimidinyl)methyl]phenyl}-3-(1,3-thiazol-2-yl)-1,3-propanedione;
tautomers thereof;
and pharmaceutically acceptable salts thereof.

### Claim 15 (depends on 3)

The compound according to claim 3, or a tautomer thereof, wherein
B is an 8- to 10-membered fused bicyclic heterocycle containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and carbon atoms, wherein the ring of the heterocycle attached to the central dione moiety is a 5- or 6-membered heteroaromatic ring containing at least one nitrogen or sulfur atom and the other ring of the heterocycle is a saturated or unsaturated ring;
or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 15)

The compound according to claim 15, or a tautomer thereof, wherein the compound is
1-(3-benzylphenyl)-3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propane-1,3-dione;
or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The compound according to claim 1, or a tautomer thereof, wherein
A is an 8- to 10-membered fused bicyclic heterocycle containing carbon atoms and from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur; wherein the ring of the heterocycle attached to the central dione moiety is a benzene ring, and the other ring of the heterocycle is a saturated or unsaturated heteroatom-containing ring;
or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 17)

The compound according to claim 17, or a tautomer thereof, wherein the compound is
1-(6-benzyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-3-(4-methylpyridin-2-yl)propane-1,3-dione;
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

The compound according to claim 1, or a tautomer thereof; wherein
A is a 5- or 6-membered heteroaromatic ring containing 0, 1 or 2 nitrogen atoms and 0 or 1 sulfur atoms;
or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 19)

The compound according to claim 19, or a tautomer thereof, wherein
B is (i) a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 or 1 sulfur atoms, and at least 1 carbon atom, or (ii) an 8- to 10-membered fused bicyclic heterocycle containing from 1 to 3 nitrogen atoms and carbon atoms, wherein the ring of the heterocycle attached to the central dione moiety is a 5- or 6-membered heteroaromatic ring containing at least one nitrogen atom and the other ring of the heterocycle is a saturated or unsaturated ring; wherein B is attached to the central dione moiety via a carbon atom and at least once nitrogen or sulfur atom in B is adjacent to the point of attachment;
or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 20)

The compound according to claim 20, or a tautomer thereof wherein
A is pyrrolyl, thienyl, or pyridyl; and
B is (i) a heteroaromatic ring selected from pyridyl, pyrazinyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, and thiazolyl, or (ii), a fused bicyclic heterocycle selected from
156
or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 21)

The compound according to claim 21, selected from the group consisting of
1-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-3-pyrimidin-4-yl-propan-1,3-dione;
1-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-3-thiazol-2-yl-propan-1,3-dione;
1-[1-(4-Fluorobenzyl)-1H-pyrrol-2-yl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-(1-Benzyl-1H-imidazol-2-yl)-3-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl)propan-1,3-dione;
1-[1-(4-Fluorobenzyl)-1H-pyrrol-3-yl]-3-pyridin-2ylpropan-1,3-dione;
1-(1-(4-Fluorobenzyl)-1H-imidazol-2-yl)-3-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl)propan-1,3-dione;
1-[1-(4-Fluorobenzyl)-1H-pyrrol-2-yl]-3-(4H-[1,2,4]triazol-3-yl-propan-1,3-dione;
1-[1-(4-Fluorobenzyl)-4-(2-oxo-2H-pyridin-1-yl)-1H-pyrrol-2-yl]-3-pyridin-2-yl-propan-1,3-dione;
1-(1H-Imidazol-2-yl)-3-(5-phenethylthiophen-2-yl)propane-1,3-dione;
1-(5-Benzyl-thiophen-2-yl)-3-pyridin-2-yl-propane-1,3-dione;
1-(5-Benzylthiophen-2yl)-3-(4-methyl-pyridin-2-yl)propane-1,3-dione;
1-[5-(3-Chlorobenzyl)thiophen-2-yl]-3-pyridin-2-yl-propane-1,3-dione;
1-[5-(4-Fluorobenzyloxy)thiophen-2-yl]-3-(4-methylpyridin-2-yl)propane-1,3-dione;
1-[5-(4-Fluorobenzyloxy)thiophen-2-yl]-3-pyridin-2-yl-propane-1,3-dione;
tautomers thereof;
and pharmaceutically acceptable salts thereof.

### Claim 23 (depends on 1)

A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.

### Claim 24 (depends on 23)

The pharmaceutical composition according to claim 23, wherein the composition further comprises at least one anti viral selected from the group consisting of HIV pro tease inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, and nucleoside HIV reverse transcriptase inhibitors.

### Claim 25 (depends on 1)

A method of inhibiting HIV integrase in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1.

### Claim 26 (depends on 1)

A method for preventing or treating infection by HIV or treating AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1.

### Claim 27 (depends on 26)

The method according to claim 26, wherein the compound is administered in combination with a therapeutically effective amount of at least one antiviral selected from the group consisting of HIV protease inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, and nucleoside HIV reverse transcriptase inhibitors

### Claim 28 (depends on 23)

A method of inhibiting HIV integrase in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition according to claim 23.

### Claim 29 (depends on 23)

A method for preventing or treating infection by HIV or for treating AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition according to claim 23.

### Claim 30 (depends on 24)

A method for preventing or treating HIV infection or for treating AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition according to claim 24.