Patent
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1,2,3,4-tetrahydropyrazin-2-yl acetamides and methods of use

التفاصيل البيبلوغرافية
العنوان: 1,2,3,4-tetrahydropyrazin-2-yl acetamides and methods of use
Patent Number: 7,662,811
تاريخ النشر: February 16, 2010
Appl. No: 11/182216
Application Filed: July 15, 2005
مستخلص: Selected compounds are effective for treatment of pain and diseases, such as inflammation mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving pain, inflammation, and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
Inventors: Askew, Jr., Benny C. (Marshfield, MA, US); Aya, Toshihiro (Thousand Oaks, CA, US); Biswas, Kaustav (Calabasas, CA, US); Cai, Guolin (Thousand Oaks, CA, US); Chen, Jian J. (Newbury Park, CA, US); Han, Nianhe (Thousand Oaks, CA, US); Liu, Qingyian (Camarillo, CA, US); Nguyen, Thomas (Thousand Oaks, CA, US); Nishimura, Nobuko (West Hills, CA, US); Nomak, Rana (Westlake Village, CA, US); Peterkin, Tanya (Woodland Hills, CA, US); Qian, Wenyuan (Camarillo, CA, US); Yang, Kevin (San Gabriel, CA, US); Yuan, Chester Chenguang (Newbury Park, CA, US); Zhu, Jiawang (Thousand Oaks, CA, US); D'Amico, Derin C. (Newbury Park, CA, US); Human, Jason B. (Calabasas, CA, US); Huang, Qi (Moorpark, CA, US)
Assignees: Amgen Inc. (Thousand Oaks, CA, US)
Claim: 1. A compound of Formula I [chemical expression included] wherein: t is 1; X is selected from NH, R is selected from a) 9-, 10-, or 11-membered fused bicyclic carbocyclic or heterocyclic ring substituted by 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, nitro, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8 , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; b) 3-, 4-, 5-, 6- or 7-membered carbocyclic ring substituted by 0, 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; c) 4-, 5-, 6- or 7-membered heterocyclic ring substituted by 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl,(C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; d) aralkyl substituted by 0, 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano,(C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; e) 5- or 6-membered heterocyclylalkyl substituted by 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; f) 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring substituted by 0,1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; g) —(C 1 -C 8)alkyl-R 8 , wherein the alkyl is substituted by 0, 1 or 2 groups selected from a basic moiety, phenyl, benzyl, OR 8 and NR 8 R 8′ ; h) 9-, 10-, or 11-membered fused bicyclic carbocyclic or heterocyclic ring substituted by 0, 1, 2, 3 or 4 groups independently selected from halo, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; and i) 12-, 13-, 14-, or 15-membered fused tricyclic carbocyclic or heterocyclic ring substituted by 0, 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl,substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; R 1 is selected from H, C 1-4 -alkyl, substituted C 1-4 -alkyl, aryl and substituted aryl; alternatively R and R 1 together with the nitrogen atom to which they are attached form a 4-10 membered mono- or bicyclic heterocyclyl ring, optionally containing 1-2 additional heteroatoms, optionally fused with 1 or 2 phenyl or (C 5 -C 7)cycloalkyl groups or optionally substituted with one aryl, heteroaryl or aralkyl group, wherein the heterocyclyl ring and aryl, heteroaryl or aralkyl groups are further optionally substituted with a basic moiety and futher substituted by 0, 1, 2 or 3 groups independently selected from halo, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , —Oaralkyl, —OR 8 , (C 1 -C 6)alkyl, and substituted (C 1 -C 6)alkyl; R 2 is selected from aryl, and heterocyclyl selected from thienyl, quinolinyl, isoquinolinyl, 3-pyridyl, thiazol-4-yl, 4-imidazolyl, benzofuryl, benzoxadiazolyl, benzothiadiazolyl, benzothiazolyl, 1H-pyrazolyl, isoxazolthienyl, benzothienyl, thieno[3,2-c]pyridinyl, and tetrahydroisoquinolinyl, wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6)alkylamino, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, di(C 1 -C 6)alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; R 4 and R 5 are H; or R 3 and R 3a together form oxo; R 8 and R 8′ independently in each instance are H or selected from lower alkyl, aryl heterocyclyl and heteroaryl, each of which is optionally substituted with one, two or three groups independently selected from lower alkyl, halogen, lower alkoxy, hydroxy, amino, mono- or dialkylamino, and trifluoromethyl; R x is selected from H; and wherein each substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl and substituted saturated or partially saturated heterocyclyl is substituted by 1, 2 or 3 groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6)alkylamino, (C 1 -C 6)haloalkyl, oxo, (C 1 -C 6)alkoxy, (C 1 -C 6)alkoxy(C 1 -C 6)alkyl, (C 1 -C 6)alkyl, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, di(C 1 -C 6)alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ , and wherein the basic moiety is selected from amino, clycloalkylamino(C 1 -C 6)alkyl, cycloalkyl (C 1 -C 6 alkylamino (C 1 -C 6)alkyl, heterocyclylamino(C 1 -C 6)alkyl, heterocyclyl(C 1 -C 6)alkylamino(C 1 -C 6)alkyl, arylamino(C 1 -C 6)alkyl, aryl(C 1 -C 6)alkylamino(C 1 -C 6)alkyl, (C 1 -C 6)alkylamino(C 1 -C 6)alkoxy, (C 1 -C 6)alkylamino(C 1 -C 6)alkoxy(C 1 -C 6)alkoxy,amino(C 1 -C 6) alkoxy, amino(C 1 -C 6)alkyl, (C 1 -C 6)alkylalmino(C 1 -C 6)alkyl, (C 1 -C 4)alkylamino-(C 2 -C 6)alkenyl, 4-8-membered nitrogen-containing heterocyclyl(C 2 -C 6)alkenyl, 4-8-membered nitrogen-containing heterocyclyl(C 1 -C 6)alkyl, [4-8-membered nitrogen-containing heterocyclyl]-[4-8-membered nitrogen-containing heterocyclyl], 7-12-membered bicyclic nitrogen-containing heterocyclyl(C 1 -C 6)alkyl, heterocyclyl(C 1 -C 6)alkylamino(C 2 -C 6)alkyl, 5-6 membered heterocyclyloxy, 5-6 membered nitrogen-containing heterocyclyl and 5-7 membered nitrogen-containing heterocyclyl-alkyl; where each basic moiety can be substituted by 0, 1, 2 or 3 groups independently selected from halo, —NH 2 , —OH, —CN, —CF 3 , (C 1 -C 6)alkylamino, haloalkyl,oxo, (C 1 -C 6)alkoxy, (C 1 -C 6)alkoxyalkyl, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, di(C 1 -C 6)alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8 , —NR 8 C(O)R 8′ =NCN; and (C 1 -C 6)alkyl, aryl, heteroaryl, cycloalkyl and heterocyclyl, each of which is substituted by 0, 1, 2 or 3 groups independently selected from halo, —NH 2 , —OH, —CN, —CF 3 , (C 1 -C 6)alkylamino, haloalkyl, oxo, (C 1 -C 6)alkoxy, (C 1 -C 6)alkoxyalkyl, (C 1 -C 6)alkyl, (C 2 -C 6)alkenyl, (C 2 -C 6)aalkynyl, di(C 1 -C 6)alkylamino, 13 C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8 , —NR 8 C(O)R 8′ azocan-1-ylmethyl, azepan-1-ylmethyl, (7-azabicyclo[2.2.1]hept-7-yl)methyl, (1,3,3-trimethyl-6-azaicyclo[3.2.1]oct-6-yl)methyl, wherein heteroaryl in the terms heteroaryl and substituted heteroaryl means an unsaturated 5 to 6 membered heteromonocyclyl groups containing 1 to 4 nitrogen atoms, unsaturated 5 to 6 membered heteromonocyclyl group containing a sulfur atom, unsaturated 5- to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, unsaturated 5 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, unsaturated 9 or 10-membered bicyclic heterocyclic group containing 1 to 5 nitrogen atoms, unsaturated 9 or 10-membered bicyclic heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, or unsaturated 9 or 10-membered bicyclic heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms; and wherein heterocyclyl in the terms substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl means an saturated 3 to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atoms, saturated 3 to 8-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atom, saturated 3 to 8-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, dihydrothiophene, dihydropyran, dihydrofuran, or dihydrothiazole; or a pharmaceutically acceptable salt thereof.
Claim: 2. Compound of claim 1 wherein R is selected from a 9-, 10-, or 11-membered fused bicyclic carbocyclic or heterocyclic ring substituted by 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, nitro, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 3. Compound of claim 1 wherein R is selected from a 3-, 4-, 5-, 6- or 7-membered carbocyclic ring substituted by 0, 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 4. Compound of claim 1 wherein R is selected from a 4-, 5-, 6- or 7-membered heterocyclic ring substituted by 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 5. Compound of claim 1 wherein R is selected from an aralkyl substituted by 0, 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 6. Compound of claim 1 wherein R is selected from a 5- or 6-membered heterocyclylalkyl substituted by 1, 2 or 3 basic moieties, and substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 7. Compound of claim 1 wherein R is selected from a 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring substituted by 0, 1, 2 or 3 groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ ,(C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aralkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 8. Compound of claim 1 wherein R is —(C 1 -C 8)alkyl-R 8 , wherein the alkyl is substituted by 0, 1 or 2 groups selected from a basic moiety, phenyl, benzyl, OR 8 and NR 8 R 8′ .
Claim: 9. Compound of claim 1 wherein R is a 9-, 10-, or 11-membered fused bicyclic carbocyclic or heterocyclic ring substituted by 0, 1, 2, 3 or 4 groups independently selected from halo, cyano, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 10. Compound of claim 1 wherein R2 is selected from aryl substituted with 1, 2, 3, 4 or 5 groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6)alkylamino, oxo, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, di(C 1 -C 6)alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6)alkyl, substituted (C 1 -C 6)alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.
Claim: 11. Compound of claim 1 wherein the compound is selected from (3R)-3-(2-((2R)-2-(4-(hydroxymethyl)phenyl)-1-piperidinyl)-2-oxoethyl)-4-((4-methylphenyl)sulfonyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-3-(2-((2S)-2-(4-(hydroxymethyl)phenyl)-1-piperidinyl)-2-oxoethyl)-4-((4-methylphenyl)sulfonyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-3-(2-(1-azepanyl)-2-oxoethyl)-4-((3,4-dichlorophenyl)sulfonyl)-3,4-dihydro-2(1H) -pyrazinone; (3R)-3-(2-(1-azetidinyl)-2-oxoethyl)-4-((4-methylphenyl)sulfonyl)-3,4-dihydro-2(1H) -pyrazinone; (3R)-3-(2-(1-azocanyl)-2-oxoethyl)-4-((3,4-dichlorophenyl)sulfonyl)-3,4-dihydro-2(1H) -pyrazinone; (3R)-3-(2-(1-azonanyl)-2-oxoethyl)-4-((3,4-dichlorophenyl)sulfonyl)-3,4-dihydro-2(1H) -pyrazinone; (3R)-3-(2-(1H-benzo[de]isoquinolin-2(3H)-yl)-2-oxoethyl)-4-((3,4-dichlorophenyl)sulfonyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-3-(2-(3,4-dihydro-2(1H)-isoquinolinyl)-2-oxoethyl)-4-((4-methylphenyl)sulfonyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-3-(2-(3-azabicyclo[3.2.2]non-3-yl)-2-oxoethyl)-4-((3,4-dichlorophenyl)sulfonyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-3-(2-(4-(2-hydroxyethyl)-1-piperazinyl)-2-oxoethyl)-4-((4-methylphenyl)sulfonyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((2R)-2-(hydroxymethyl)-1-piperidinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((2R)-2-methyl-1-piperidinyl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((2S)-2-(hydroxymethyl)-1-piperidinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((2S)-2-methyl-1-piperidinyl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((3R)-3-(hydroxymethyl)-1-piperidinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((3R)-3-methyl-1-piperidinyl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((3S)-3-(hydroxymethyl)-1-piperidinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((3S)-3-methyl-1-piperidinyl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aR,8aR)-octahydro-1 (2H)-quinolinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aR,8aR)-octahydro-2(1H)-isoquinolinyl) -2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aR,8aS)-octahydro-1(2H)-quinolinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aR,8aS)-octahydro-2(1H)-isoquinolinyl) -2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aS,8aR)-octahydro-1(2H)-quinolinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aS,8aR)-octahydro-2(1H)-isoquinolinyl) -2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aS,8aS)-octahydro-1(2H)-quinolinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4aS,8aS)-octahydro-2(1H)-isoquinolinyl) -2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4R)-4-hydroxy-1-azepanyl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4R)-4-hydroxy-4-methyl-1-azepanyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4S)-4-hydroxy-1-azepanyl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-((4S)-4-hydroxy-4-methyl-1-azepanyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-(1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-(1,4-oxazepan-4-yl)-2-oxoethyl)-3,4-dihydro -2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-(3,4-dihydro-1(2H)-quinolinyl)-2-oxoethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-(3,4-dihydro-2(1H)-isoquinolinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-(4-(hydroxymethyl)-1-piperidinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-(4-methyl-1-piperidinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((1R,5S)-1,3,3-trimethyl-6-azabicyclo[3.2.1 ]oct-6-yl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2R)-2-(phenylmethyl)-1-pyrrolidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2R)-2-(phenylmethyl)-1-piperidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2R)-2-phenyl-1-pyrrolidinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2R)-2-phenyl-1-piperidinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2R)-2-phenyl-1-azepanyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2S)-2-(phenylmethyl)-1-pyrrolidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2S)-2-(phenylmethyl)-1-piperidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2S)-2-phenyl-1-pyrrolidinyl)ethyl) -3,4-dihydro2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2S)-2-phenyl-1-piperidinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((2S)-2-phenyl-1-azepanyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((3R)-3-(phenylmethyl)-1-pyrrolidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((3R)-3-phenyl-1-piperidinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((3R)-3-phenyl-1-pyrrolidinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((3S)-3-(phenylmethyl)-1-pyrrolidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((3S)-3-phenyl-1-piperidinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-((3S)-3-phenyl-1-pyrrolidinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-(1-piperidinyl)ethyl)-3,4-dihydro -2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-(1-pyrrolidinyl)ethyl)-3,4-dihydro -2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-(4-(2-pyridinyl)-1-piperazinyl)ethyl) -3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-(4-(phenylmethyl)-1-piperidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((3,4-dichlorophenyl)sulfonyl)-3-(2-oxo-2-(4-phenyl-1-piperidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((4-methylphenyl)sulfonyl)-3-(2-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl) -2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((4-methylphenyl)sulfonyl)-3-(2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl) -2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((4-methylphenyl)sulfonyl)-3-(2-((4aR,8aS)-octahydro-2(1H)-isoquinolinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((4-methylphenyl)sulfonyl)-3-(2-((4aS,8aR)-octahydro-2(1H)-isoquinolinyl)-2-oxoethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((4-methylphenyl)sulfonyl)-3-(2-(4-morpholinyl)-2-oxoethyl)-3,4-dihydro-2(1H) -pyrazinone; (3R)-4-((4-methylphenyl)sulfonyl)-3-(2-oxo-2-((2R)-2-(4-(1-piperidinylmethyl)phenyl) -1-piperidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (3R)-4-((4-methylphenyl)sulfonyl)-3-(2-oxo-2-((2S)-2-(4-(1-piperidinylmethyl)phenyl) -1-piperidinyl)ethyl)-3,4-dihydro-2(1H)-pyrazinone; (4-(((2S)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl) -1-piperazinyl)acetonitrile; 1-(((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl) -1,4-diazepan-5-one; 1-(((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl) -4-azepanone; 1,1-dimethylethyl (1R)-6-(((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenylcarbamate; 1,1-dimethylethyl 4-(1-((5R)-5-((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)ethyl)-1-piperazinecarboxylate; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4-(1-piperidinylmethyl)phenyl)methyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -1-(4-fluorophenyl)ethyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(3-pyridinylmethyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((2-(2-thienyl)-1,3-thiazol-4-yl)methyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -1-phenylethyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1S) -1-(3,3′-difluoro-2′-(3-methyl-1,2,4-oxadiazol-5-yl)-1,1′-biphenyl-4-yl)ethyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-pyridinylmethyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(2-pyridinylmethyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N -(phenylmethyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((2,3-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((3-fluorophenyl)methyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -6-(hydroxymethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R) -7-(hydroxymethyl)-3,4-dihydro-2H-chromen-4-yl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -6-(((1-methylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R) -7-(((1-methylethyl)amino)methyl)-3,4-dihydro-2H-chromen-4-yl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((5R) -5,6,7,8-tetrahydro-5-quinolinyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4-(1-piperidinylmethyl)phenyl)methyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -6-(2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(2,3-dihydro-1H-inden-2-yl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N -(phenylmethyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(2-phenylethyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N -phenylacetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)acetamide; 2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(3 -(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)acetamide; 2-((2R)-1-((3-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1 R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-(methyloxy)phenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N -((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R)-7-(hydroxymethyl)-3,4-dihydro-2H-chromen-4-yl)acetamide 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(hydroxymethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1-phenylethyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R)-7-((cyclopentylamino)methyl)-3,4-dihydro-2H-chromen-4-yl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-((cyclopentylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R)-7-(((1,1-dimethylethyl)amino)methyl)-3,4-dihydro -2H-chromen-4-yl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4-(1-piperidinylmethyl)phenyl)methyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((3R)-6(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R)-7-(1-piperidinylmethyl)-3,4-dihydro-2H-chromen-4-yl)acetamide; 2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-((cyclopropylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(((3R)-3-hydroxy-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(((2-(methyloxy)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(((2-hydroxyethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1-phenylethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-(1-piperidinylmethyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R) -1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((5S)-2-(2-(1-piperidinyl)ethyl)-5,6,7,8-tetrahydro-5-quinazolinyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(3-(1-piperidinyl)propyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(3-(4-methyl-1-piperazinyl)propyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-((1S)-1-((2-methylpropyl)amino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-5-(1-piperidinylmethyl)-2,3-dihydro-1H-inden-1-yl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(2-(4-morpholinyl)ethyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(2-(4-(1-piperidinylmethyl)phenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(3-(1-pyrrolidinyl)propyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(2-(1-pyrrolidinyl)ethyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1-methyl-2-(3-(1-piperidinylmethyl)phenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1-(4-(1-piperidinylmethyl)phenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(1-piperidinyl)butyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(1-pyrrolidinyl)butyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(5-(1-piperidinyl)pentyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(5-(1-pyrrolidinyl)pentyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1-phenylethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4S)-1-(2-(1-piperidinyl)ethyl)-4,5,6,7-tetrahydro-1H-indazol-4-yl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(3-(3-(1-piperidinyl)propyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(3-(3-(1-pyrrolidinyl)propyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(3-(3-((2-methylpropyl)amino)propyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-((4-(2-pyridinyl)-1-piperazinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(2-(4-((4-methyl-1-piperazinyl)methyl)phenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(2-(4-(((2-methylpropyl)amino)methyl)phenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R)-7-(1-pyrrolidinylmethyl)-3,4-dihydro-2H-chromen-4-yl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4-(1-piperidinylmethyl)phenyl)methyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-pyrrolidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4-(1-piperidinylmethyl)phenyl)methyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(4-pyridinylmethyl)phenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((8R) -2,6,6-trimethyl-3-oxo-2,3,5,6,7,8-hexahydro-8-isoquinolinyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((8S) -2,6,6-trimethyl-3-oxo-2,3,5,6,7,8-hexahydro-8-isoquinolinyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(4-morpholinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(((2S)-2-(1-pyrrolidinylmethyl)-1-pyrrolidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(2-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1S)-1-(2-naphthalenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1-(2-naphthalenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((3S)-2-oxo-3-azepanyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-(1-piperazinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-((4-methyl-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(1-(phenylmethyl)-4-piperidinyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((3S)-2-oxo-3-azepanyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((3R)-2-oxo-3-azepanyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N -tricyclo[3.3.1.1˜3,7˜]dec-1-ylacetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R,2R) -2-((phenylmethyl)oxy)cyclohexyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1S,2S) -2-((phenylmethyl)oxy)cyclohexyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R)-7-(1-pyrrolidinylmethyl)-3,4-dihydro-2H-chromen-4-yl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-pyrrolidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-7-nitro-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-5-nitro-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-(2-(4-(4H-1,2,4-triazol-3-yl)phenyl)ethyl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((7R)-3-(2-methylpropyl)-1,2,3,4,7,8,9,10-octahydrobenzo[f]isoquinolin-7-yl)acetamide; 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-4-oxo-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-1-(cyclopropylsulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)-N -(phenylmethyl)acetamide; 2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((4R)-7-(1-piperidinylmethyl)-3,4-dihydro-2H-chromen-4-yl)acetamide; 2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1-phenylethyl)acetamide; 2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1S)-1-phenylethyl)acetamide; 2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2R)-4-methyl-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N -((1R)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2S)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; 2-((2S)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((6R)-2-(2-methylpropyl)-1,2,3,4,6,7,8,9-octahydrobenzo[g]isoquinolin-6-yl)acetamide; 2-((2S)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((7R)-3-(2-methylpropyl)-1,2,3,4,7,8,9,10-octahydrobenzo[f]isoquinolin-7-yl)acetamide; 2-((4S)-4-((2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)-4,5,6,7-tetrahydro-1H-indazol-1-yl)ethyl methanesulfonate; 2-((5R)-5-((2-((2S)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-quinazolinyl)ethyl methanesulfonate; 2-(1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((2R)-1,2,3,4-tetrahydro-2-naphthalenyl)acetamide; 2-(1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)-N-((2S)-1,2,3,4-tetrahydro-2-naphthalenyl)acetamide; ethyl (1R,2R)-2-((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)cyclohexanecarboxylate; ethyl (1R,2S)-2-((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)cyclohexanecarboxylate; ethyl (1S,2R)-2-((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)cyclohexanecarboxylate; ethyl (1S,2S)-2-((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)cyclohexanecarboxylate; methyl (2S)-((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)(phenyl)ethanoate; methyl 2-((1R)-1-((((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)amino)-2,3-dihydro-1H-inden-5-yl)benzoate; methyl 4-((2R)-1-(((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)-2-piperidinyl)benzoate; methyl 4-((2S)-1-(((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetyl)-2-piperidinyl)benzoate; N-(((5R)-5-((1-methylethyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)methyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(((5R)-5-amino-5,6,7,8-tetrahydro-2-naphthalenyl)methyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-1-(3,3′-difluoro-2′-(3-methyl-1,2,4-oxadiazol-5-yl)-1,1′-biphenyl-4-yl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-1-(4-(hydroxymethyl)phenyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-1-cyclohexylethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-2-((2,6-dimethylphenyl)oxy)-1-methylethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-2,3-dihydro-1H-inden-1-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-5-(hydroxymethyl)-2,3-dihydro-1H-inden-1-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(((2R)-2-(hydroxymethyl)-1-pyrrolidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(((2S)-2-(hydroxymethyl)-1-pyrrolidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(((cyclopropylmethyl)(propyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(((cyclopropylmethyl)(propyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R) -1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((1S)-1-(cyclobutylamino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R) -1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((1S)-1-(cyclopentylamino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R) -1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((1S)-1-(cyclopropylamino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R) -1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((4-fluoro-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R) -3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((cyclopentylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((cyclopentylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((cyclopentylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((cyclopropylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-((dimethylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(1-azepanylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(aminomethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-(hydroxymethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-acetyl-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R)-6-acetyl-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R,2R)-2-hydroxycyclohexyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R,2R)-2-methylcyclohexyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1R,5R,7S)-3-hydroxytricyclo[3.3.1.1˜3,7˜]dec-1-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S)-2-((2,6-dimethylphenyl)oxy)-1-methylethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S)-2-(3-(hydroxymethyl)phenyl)-1-methylethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S)-2,3-dihydro-1H-inden-1-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo -1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S)-2-cyclohexyl-1-(hydroxymethyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S)-2-hydroxy-1-phenylethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S)-3-methylcyclohexyl)-2-(1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro -2-pyrazinyl)acetamide; N-((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S,2R)-2-methylcyclohexyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S,2S)-2-hydroxycyclohexyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((1S,2S)-2-methylcyclohexyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((2-fluorophenyl)methyl)-2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((2R)-5-(methyloxy)-1,2,3,4-tetrahydro-2-naphthalenyl)-2-(1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((2R)-6-(methyloxy)-1,2,3,4-tetrahydro-2-naphthalenyl)-2-(1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((2R)-6-bromo-1,2,3,4-tetrahydro-2-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((2R)-7-(methyloxy)-1,2,3,4-tetrahydro-2-naphthalenyl)-2-(1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((2R)-8-bromo-1,2,3,4-tetrahydro-2-naphthalenyl)-2-(1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((2S)-6-bromo-1,2,3,4-tetrahydro-2-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((3-fluorophenyl)methyl)-2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4-cyanophenyl)methyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4-fluorophenyl)methyl)-2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-1,1-dioxido-3,4-dihydro-2H-1-benzothiopyran-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-(methyloxy)phenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-6-chloro-1,1-dioxido-3,4-dihydro-2H-1-benzothiopyran-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-6-chloro-7-methyl-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-(((2,2-dimethylpropyl)amino)methyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R) -1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-(((2,2-dimethylpropyl)amino)methyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R) -3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-(((2,2-dimethylpropyl)amino)methyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R) -1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-((cyclopentylamino)methyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-((cyclopentylamino)methyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-((cyclopentylamino)methyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-((cyclopropylamino)methyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-(hydroxymethyl)-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4R)-7-cyano-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl) -3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4S)-1-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-4,5,6,7-tetrahydro-1H -indazol-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4S)-1-(2-((2,2-dimethylpropyl)amino)ethyl)-4,5,6,7-tetrahydro-1H-indazol-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4S)-1-(2-(cyclopropylamino)ethyl)-4,5,6,7-tetrahydro-1H-indazol-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4S)-1-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1H-indazol-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4S)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((4S)-3,4-dihydro-2H-chromen-4-yl)-2-((2R)-1-((4-(methyloxy)phenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-((5S)-2-(2-hydroxyethyl)-5,6,7,8-tetrahydro-5-quinazolinyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(1,1-dimethylethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2-(3-formylphenyl)propyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2-(4-((cyclopentylamino)methyl)phenyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl) -3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2-(4-((cyclopropylamino)methyl)phenyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl) -3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2-(4-(hydroxymethyl)phenyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo -1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2-(4-(hydroxymethyl)phenyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo -1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2-(4-aminophenyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2-(4-cyanophenyl)ethyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(2,3-dihydro-1H-inden-2-yl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(3-(3-hydroxypropyl)phenyl)-2-((2R)-1-((4-methyl-2,4-cyclohexadien-1-yl)sulfonyl) -3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(3-(cyclohexylamino)propyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(4-(1,4′-bipiperidin-1′-yl)phenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(4-(2-(dimethylamino)ethyl)phenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo -1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(4-(3-hydroxypropyl)phenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(4-hydroxybutyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(5-hydroxypentyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(cis-4-methylcyclohexyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-(trans-4-methylcyclohexyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-cyclobutyl-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-cycloheptyl-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-cyclohexyl-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-cyclooctyl-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-cyclopentyl-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-cyclopropyl-2-((2R)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl)acetamide; N-methyl-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl) -N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide; and N-methyl-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-1,2,3,4-tetrahydro-2-pyrazinyl) -N-((4R)-7-(1-piperidinylmethyl)-3,4-dihydro-2H-chromen-4-yl)acetamide.
Claim: 12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1 .
Claim: 13. A method of treating pain comprising administering an effective amount a compound according to claim 1 .
Current U.S. Class: 5142/102
Patent References Cited: 2005/0014749 January 2005 Chen et al.
WO 03/007958 January 2003
WO 03/093245 November 2003
WO 2004/033436 April 2004
2004/054854 July 2004
2004/083173 September 2004
WO 2005/061467 July 2005
Other References: Dorwald F. A. Side Reactions in Organic Synthesis, 2005, Wiley: VCH, Weinheim p. IX of Preface. cited by examiner
Assistant Examiner: Murray, Jeffrey H
Primary Examiner: Wilson, James O
Attorney, Agent or Firm: Bansal, Rekha P.
رقم الانضمام: edspgr.07662811
قاعدة البيانات: USPTO Patent Grants
الوصف
الوصف غير متاح.