IP Library Granted Patent US 12,331,044
Granted Patent B2
US 12,331,044 · App. 17/261,982 · Granted Jun 17, 2025

Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection

Inventors: Jian Liu (Edison, NJ); Dane James Clausen (Rahway, NJ); Wensheng Yu (Edison, NJ); Joseph M. Kelly (Parlin, NJ); Hyunjin M. Kim (Livingston, NJ); Joseph A. Kozlowski (Princeton, NJ)
Assignee: Merck Sharp & Dohme LLC
C07D413/14C07D413/12C07D417/14C07D471/04C07D487/04C07D498/04C07D498/10C07D513/04
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Quick Facts
Patent No.
US 12,331,044
App. No.
17/261,982
Granted
Jun 17, 2025
Kind
B2
Abstract

The present invention relates to Compounds of Formula (I): Formula (I) and pharmaceutically acceptable salts or prodrug thereof, wherein R 1 , R 2 , R 3 , R a , R b , A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula (I), and methods of using the compounds of Formula (I) for treating or preventing HIV infection in a subject.

Claims (182)

1. A compound of the formula:

wherein

 is a five-membered heteroaryl ring which is optionally substituted with halo, cyano or C 1-3 alkyl;

 is a-five-membered heteroaryl ring selected from the group consisting of isoxazolyl, oxazolyl, or thiazolyl, which is optionally substituted with C 1-3 alkyl;

R 1 is phenyl or heteroaryl, which may be monocyclic or bicyclic, wherein said phenyl and heteroaryl groups are optionally substituted with one to three groups independently selected from the group consisting of halo, oxo, cyano, R 4 , R 6 , OR 4 , OR 6 and SO 2 R 4 ;

R 2 is selected from the group consisting of hydrogen, NH(C═O)R 6 , NH(C═O)CH 2 R 6 , NH(C═O)R 4 , NH(C═O)R 5 , NH(C═O)OR 5 , NH 2 , NHR 4 , NHR 6 , NHCH 2 R 6 and R 6 ;

R 3 is selected from hydrogen or C 1-6 alkyl;

or R 2 and R 3 can be taken together with the atoms to which they are attached to form a 5, 6 or 7 membered heterocyclyl group which is optionally substituted with oxo;

each R 4 is independently hydrogen or C 1-6 alkyl, which is optionally substituted with one to three halo;

each R 5 is independently hydrogen or C 1-6 alkyl, which is optionally substituted with N(R 4 ) 2 or OR 4 ;

R 6 is

(a) heterocyclyl, which may be monocyclic or bicyclic,

(b) C 3-6 cycloalkyl, or

(c) heteroaryl, which may be monocyclic or bicyclic,

wherein said R 6 heterocyclyl, cycloalkyl, and heteroaryl groups are optionally substituted with one to two groups independently selected from the group of oxo, R 5 , OR 4 and heteroaryl;

R a is hydrogen or halo;

R b is hydrogen or halo;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein

 is selected from imidazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl or triazolyl, wherein said groups are optionally substituted with halo, cyano or C 1-3 alkyl; or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 wherein R 1 is imidazolyl, isoquinolinyl, napthyridinyl, phenyl, pyrazinyl, pyridinyl, quinolinyl or quinoxalinyl, wherein said groups are optionally substituted with one to three groups optionally selected from the group consisting of halo, oxo, cyano, R 4 , R 6 , OR 4 , OR 6 and SO 2 R 4 ; or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 wherein R 2 is NH(C═O)R 6 or NH(C═O)CH 2 R 6 , and R 6 is selected from the group consisting of azaindolyl, azaspirononanyl, azaspirooctanyl, azetidinyl, benzisoxazolyl, cyclobutyl, cyclopentyl, cyclopropyl, dihydrobenzodioxinyl, dihydropyrazoloxazinyl, dihydropyrazolyothiazinedioxidyl, dioxanyl, morpholinyl, oxadiazaspirodecenyl, oxaspirooctanyl, oxazolidinonyl, oxazolyl, piperazinyl, piperidinyl, pyrazolopyrimidinyl, pyrazolyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, tetrahydrofuranyl, tetrahydropyranyl and thiazolyl; or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 wherein R 2 is NH 2 , or a pharmaceutically acceptable salt thereof.

6. A compound selected from the group consisting of

(S)-N-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)thiazole-5-carboxamide,

(S)-N-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)methylpiperidine-4-carboxamide,

(S)-N-((S)-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspirol[2.5]octane-1-carboxamide,

N-((S)-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-oxaspiro[2.5]octane-1-carboxamide,

(S)-N-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-oxo-7-(thiazol-2-yl)heptyl)-1-methylpiperidine-4-carboxamide,

(S)-N-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-oxo-7-(thiazol-2-yl)heptyl)thiazole-5-carboximide,

(S)-N-(1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(4-methyloxazol-2-yl)-7-oxoheptyl)-1-methylpiperdine-4-carboxamide,

(S)-7-amino-7-(4-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-6-(2-(1-amino-7-(oxazol-2-yl)-7-oxoheptyl)-1H-imidazol-4-yl)-2-ethylisoquinolin-1(2H)-one,

(S)-7-amino-1-(oxazol-2-yl)-7-(5-(quinoline-6-yl)-1H-imidazol-2-yl)heptan-1-one, 16

(S)-7-amino-7-(4-(7-methoxyquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-amino-7-(4-(6-cyclopropyl-2-methoxypyridin-3-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-amino-7-(4-chloro-2-(4_fluorophenyl)-1H-imidazol-5-yl)-1-(oxazol-2-yl)heptan-1-one,

7-amino-7-(5-(2-methylquinonlin-6-yl)oxazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-amino-7-(5-(7-methoxy-2-methylquinolin-6-yl_oxazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-amino-7-(5-(2-methoxypiperdin-3-yl)oxazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-amino-7-(-methyl-4-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-amino-(1-ethyl-4-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-amino-1-(isoxazole-3-yl)-7-(4-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)heptan-1-one,

(S)-6-(2-(I-amino-7-(isoxazol-3-yl)-7-oxoheptyl)-1H-imidazol-4-yl)-1-methylquinolin-2(1H)-one,

(S)-7-amino-1-(isoxazol-3-yl)-7-(4-(2-methoxypyridin-3-yl)-1H-imidazol-2-yl)heptan-1-one,

(S)-7-amino-1-(isoxazol-3-yl)-7-(4-(7-methoxyquinolin-6-yl)-1H-imidazol-2-yl)heptan-1-one,

(S)-6-(2-(1-amino-7-(isoxazol-3-yl)-7-oxoheptyl)-1H-imidazol-5-yl)-7-methoxy-1-methylquinolin-2(1H)-one,

(S)-7-amino-7-(5-(2-fluorophenyl)-1H-imidazol-2-yl)-1-(oxazol-4-yl)heptan-1-one,

(S)-7-amino-7-(5-(2-fluorophenyl)-1H-imidazol-2-yl)-1-(isoxazol-3-yl)heptan-1-one,

(S)-N-(1-(5-(2-fluorophenyl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(R)-5-(5-(4-fluorophenyl)-1H-imidazol-2-yl)-5-(6-(oxazol-2-yl)-6-oxohexyl)pyrrolidin-2-one,

4-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-4-(6-(oxazol-2-yl)-6-oxohexyl)oxazolidin-2-one,

(S)-5-(4-(2-fluoro-4-(oxazol-2-yl)phenyl)-1H-imidazol-2-yl)-5-(6-(isoxazol-3-yl)-6-oxohexyl)pyrrolidin-2-one,

(S)-5-(4-(4-cyclopropyl-2-fluorophenyl)-1H-imidazol-2-yl)-5-(6-(isoxazol-3-yl)-6-oxohexyl)pyrrolidin-2-one,

(S)-5-(4-(2-fluorophenyl)-1H-imidazol-2-yl)-5-(6-(isoxazol-3-yl)-6-oxohexyl)pyrrolidin-2-one,

(R)-5-(6-(isoxazol-3-yl)-6-oxohexyl)-5-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)pyrrolidin-2-one,

(S)-6-(6-(isoxazol-3-yl)-6-oxohexyl)-6-(4-(2-methoxypyridin-3-yl)-1H-imidazol-2-yl)piperidin-2-one,

(S)-7-(4-(2-fluorophenyl)-1H-imidazol-2-yl)-7-(6-(isoxazol-3-yl)-6-oxohexyl)azepan-2-one,

7-(5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-(ethyl amino)-7-(5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-(methylamino)-7-(5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-methoxy-1-methyl-6-(2-(1-(methylamino)-7-(oxazol-2-yl)-7-oxoheptyl)-1H-imidazol-5-yl)quinolin-2(1H)-one,

(S)-6-(2-(1-(ethyl amino)-7-(oxazol-2-yl)-7-oxoheptyl)-1H-imidazol-5-yl)-7-methoxy-1-methylquinolin-2(1H)-one,

(S)-7-((1-methylpiperidin-4-yl)amino)-7-(5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-(5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)-7-((tetrahydro-2H-pyran-4-yl)amino)heptan-1-one,

(S)-7-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)-7-((tetrahydro-2H-pyran-4-yl)amino)heptan-1-one,

(S)-7-(benzylamino)-7-(5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-(benzylamino)-7-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(S)-7-(5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-morpholino-1-(oxazol-2-yl)heptan-1-one,

(S)-7-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)-7-(pyrimidin-2-ylamino)heptan-1-one,

(S)-N-(1-(5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)acetamide,

(S)-N-(1-(4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)thiazole-5-carboxamide,

(S)-N-(1-(4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-2-(dimethylamino)acetamide,

(S)-2-(dimethylamino)-N-(1-(5-(2-ethyl-7-methoxy-1-oxo-1,2-dihydroisoquinolin-6-yl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)acetamide,

(S)-2-(dimethylamino)-N-(7-(oxazol-2-yl)-7-oxo-1-(5-(quinoxalin-6-yl)-1H-imidazol-2-yl)heptyl)acetamide,

(S)-2-(dimethylamino)-N-(1-(5-(2-ethyl-7-methoxy-1-oxo-1,2-dihydroisoquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)acetamide,

(S)-N-((S)-1-(4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-ethyl-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-(1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methyl piperidine-4-carboxamide,

(S)-N-(1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(1-(5-(7-methoxy-2-methylquinolin-6-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(1-(4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-1-methyl-2-oxo-1,2-dihydroquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

N-(1-(5-(2-methoxypyridin-3-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(1-(4-chloro-2-(2-fluorophenyl)-1H-imidazol-5-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(1-(5-(2-fluorophenyl)-1,3,4-oxadiazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

N-(1-(5-(2-fluorophenyl)oxazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide,

(S)-6-methyl-N-((S)-1-(5-(2-methylquinolin-6-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-((S)-7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide,

(1S)-6-methyl-N-(1-(5-(2-methylquinolin-6-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-((S)-1-(4-chloro-2-(2-fluorophenyl)-1H-imidazol-5-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-((S)-1-(5-(7-methoxy-2-methylquinolin-6-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.S]octane-1-carboxamide,

(1S)-N-(1-(5-(2-methoxypyridin-3-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-((S)-1-(4-(6-cyclopropyl-2-methoxypyridin-3-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide,

(S)-8-methyl-N-(1-(5-(2-methylquinolin-6-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-3-carboxamide,

(S)-N-(1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-2-methyl-2-azaspiro[3.5]nonane-7-carboxamide,

(S)-7-amino-7-(5-(4-fluorophenyl)isoxazol-3-yl)-1-(isoxazol-3-yl)heptan-1-one,

(R)-7-amino-7-(5-(4-fluorophenyl)isoxazol-3-yl)-1-(isoxazol-3-yl)heptan-1-one,

(7S)-7-amino-7-[1-(4-fluorophenyl)-1H-pyrazol-3-yl]-1-isoxazol-3-ylheptan-1-one,

7-amino-7-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-1-isoxazol-3-vlheptan-1-one,

7-amino-7-[2-(4-fluorophenyl)-2H-1,2,3-triazol-4-yl]-1-isoxazol-3-vlheptan-1-one,

(7S)-7-amino-7-(5-(2-fluorophenyl)isoxazol-3-yl]-1-isoxazol-3-ylheptan-1-one,

(7S)-7-amino-1-isoxazol-3-yl-7-[5-(2-methyl-2H-indazol-5-yl)isoxazol-3-yl]heptan-1-one, (7R)-7-amino-7-[1-(2-methyl-2H-indazol-5-yl)-1H-pyrazol-3-yl]-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-[1-(2-methyl-2H-indazol-5-yl)-1H-pyrazol-3-yl]-1-(1,3-oxazol-2-yl)heptan-1-one,

(S)-7-amino-7-(5-(5-fluoro-2-methoxypyridin-4-yl)-1H-imidazol-2-yl)-1-(oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-{5-[5-(cyclobutyloxy)-2-fluorophenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-[5-(5-cyclopropyl pyrazin-2-yl)-1H-imidazol-2-yl]-1-(1,3-oxazol-2-yl)heptan-1-one,

5-{2-[(1S)-1-amino-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1H-imidazol-5-yl}pvrazine-2-carbonitrile,

6-{2-[(1S)-1-amino-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1H-imidazol-5-yl}pyrazine-2-carbonitrile,

(7S)-7-amino-7-{5-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-[5-(2,5-difluorophenyl)-1H-imidazol-2-yl]-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-{5-[2-fluoro-5-(trifluoromethyl)phenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-{5-[2-fluoro-3-(trifluoromethyl)phenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-{5-[2-fluoro-4-(trifluoromethyl)phenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-[5-(2-fluoro-4-methoxyphenyl)-1H-imidazol-2-yl]-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-{5-[2-fluoro-4-(trifluoromethoxy)phenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-{5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-{5-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl}-1-(1,3-oxazol-2-yl)heptan-1-one,

(7S)-7-amino-7-(5-{2-fluoro-3-methoxy-5-[(trans-3-methoxycyclobutyl)oxy]phenyl}-1H-imidazol-2-yl)-1-(1,3-oxazol-2-yl)heptan-1-one,

(S)-6-ethyl-N-((S)-7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)isoxazol-3-yl)-7-oxoheptyl)-6-azaspiro[2.5]octane-1-carboxamide,

6-(difluoromethoxy)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]pyridine-3-carboxamide,

2-methoxy-N-[(1S)-1-(5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-vi)-7-oxoheptyl lacetamide,

2,2-difluoro-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]propenamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]pyrimidine-4-carboxamide,

N-[(1S)-1-(5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(1H-pyrrol-1-yl)acetamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1-pyridin-4-ylcyclopropanecarboxamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1,4-dioxane-2-carboxamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1,3-benzoxazole-2-carboxamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1-pyrazin-2-ylcyclopropanecarboxamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-5-oxo-D-prolinamide,

N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-5-oxo-L-prolinamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(3-oxomorpholin-4-yl)acetamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(2-oxopiperazin-1-yl)acetamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(1H-pyrazol-1-yl)acetamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]pyrazolo[1,5-a]pyrimidine-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(1H-pyrrol-1-yl)acetamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]thiazine-2-carboxamide 5,5-dioxide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(3-methyl-1H-pyrazol-1-yl)acetamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]pyrazolo[1,5-a]pyridine-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]tetrahydro-2H-pyran-2-carboxamide,

N N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-methyltetrahydro-2H-pyran-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]tetrahydrofuran-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2,3-dihydro-1,4-benzodioxine-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-5-phenyl-1,4-dioxane-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1,4-dioxane-2-carboxamide,

N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1,4-dioxane-2-carboxamide,

(1S)-6-ethyl-N-{(1S)-1-[5-(2-fluorophenyl)isoxazol-3-yl]-7-isoxazol-3-yl-7-oxoheptyl}-6-azaspiro[2.5]octane-1-carboxamide,

(1S)-6-ethyl-N-{(1S)-7-isoxazol-3-yl-1-[5-(2-methyl-2H-indazol-5-yl)isoxazol-3-yl]-7-oxoheptyl}-6-azaspiro[2.5]octane-1-carboxamide,

N-{(1S)-7-isoxazol-3-yl-1-[5-(2-methyl-2H-indazol-5-yl)isoxazol-3-yl]-7-oxoheptyl}-8-methyl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-3-carboxamide,

N-[(1S)-1-[5-(5-fluoro-2-methoxypyridin-4-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide,

(1S)-6-ethyl-N-[(1S)-1-[5-(5-fluoro-2-methoxypyridin-4-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-6-azaspiro[2.5]octane-1-carboxamide,

(1S)-6-ethyl-N-[(1S)-1-[1-(2-methyl-2H-indazol-5-yl)-1H-pyrazol-3-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-6-azaspiro[2.5]octane-1-carboxamide,

N-[(1S)-1-{5-[5-(cyclobutyloxy)-2-fluorophenyl]-1H-imidazol-2-yl}-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide,

(1S)-N-[(1S)-1-{5-[5-(cyclobutyloxy)-2-fluorophenyl]-1H-imidazol-2-yl}-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-6-ethyl-6-azaspiro[2.5]octane-1-carboxamide,

(S)-6-ethyl-N-((S)-2-(5-(2-fluorophenyl)-1H-imidazol-2-yl)-8-(isoxazol-3-yl)-8-oxooctan-2-yl)-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-(2-(5-(2-fluorophenyl)-1H-imidazol-2-yl)-8-(isoxazol-3-yl)-8-oxooctan-2-yl)-1-10

methylazetidine-3-carboxamide,

(S)-5-(1-amino-7-(oxazol-2-yl)-7-oxoheptyl)-2-(4-fluorophenyl)-1H-imidazole-4-carbonitrile,

(S)-N-(1-(4-cyano-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-2-(dimethylamino)acetamide,

(S)-N-((S)-1-(4-cyano-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-(1-(4-cyano-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)thiazole-5-carboxamide,

(S)-5-(1-amino-7-(oxazol-2-yl)-7-oxoheptyl)-2-(4-fluorophenyl)oxazole-4-carbonitrile,

(S)-N-(1-(4-cyano-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-2-(dimethylamino)acetamide,

(S)-N-((S)-1-(4-cyano-2-(4-fluorophenyl)oxazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide,

(S)-N-(1-(4-cyano-2-(4-fluorophenyl)oxazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)thiazole-5-carboxamide,

(S)-7-amino-7-(4-chloro-5-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(isoxazol-3-yl)heptan-1-one,

(S)-N-(1-(4-chloro-5-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-2-25 (dimethylamino)acetamide,

(S)-N-((S)-1-(4-chloro-5-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide 2,3-dihydroxysuccinate,

(S)-N-(1-(4-chloro-5-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide 2,3-dihydroxysuccinate,

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. A method for the inhibition of HDAC in a subject in need thereof which comprises administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

9. A method for the treatment of infection by HIV or for the treatment of AIDS in a subject in need thereof, which comprises administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

10. The pharmaceutical composition of claim 7 , further comprising one or more additional therapeutic agents selected from raltegravir, lamivudine, abacavir, ritonavir, darunavir, atazanavir, emtricitabine, tenofovir, rilpivirine, doravirine, EFdA and lopinavir.

11. The method of claim 9 , further comprising administering to the subject one or more additional therapeutic agents selected from raltegravir, lamivudine, abacavir, ritonavir, darunavir, atazanavir, emtricitabine, tenofovir, rilpivirine, doravirine, EFdA and lopinavir, wherein the amounts administered of the compounds are B together effective to treat infection by HIV or to treat AIDS.

12. A compound of claim 1 , selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

Assignments (2)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 21, 2021
From: LIU, JIAN; CLAUSEN, DANE JAMES; YU, WENSHENG; KELLY, JOSEPH M.; KIM, HYUNJIN M.; KOZLOWSKI, JOSEPH A.
To: MERCK SHARP & DOHME CORP.
Reel/Frame 054985/0079 →