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US 6,992,087 B2Granted
Substituted aryl 1,4-pyrazine derivatives
AssigneePfizer Inc.
InventorsPatrick R. Verhoest, Robert Louis Hoffman, Jeffrey W. Corbett, Michael Dalton Ennis, Kristine E. Frank, Jian-Min Fu
Life of this patent
Estimating the term…
Abstract
Substituted aryl 1,4-pyrazine derivatives of formula I as defined herein and their use in treating anxiety disorders, depression and stress related disorders are disclosed.
Claims20
A compound of Formula I
- or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, wherein in Formula I,
- X is —NR3R4,
- Ar is selected from aryl or substituted aryl;
- R1, R2, and are independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- R3 and R4 are independently selected from heteroaryl, substituted heteroaryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, substituted heteroaryl heterocycloalkyl, Ra and
- wherein W is O, NRp, or S(O)m,
- Rp is independently selected from —Ra, —S(O)mRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —C(O)ORa, or —C(S)ORa;
- m is 0,1 or 2, and Rs each is independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- substituted heteroaryl, substituted aryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, or substituted heteroaryl heterocycloalkyl provided at least one of R3 and R4 is
- Ra each is selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, NRtRt, oxo (═O), thione (═S), phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
- and
- Rt each is selected from H, halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Oalkyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen, provided that the compound is not.
9 more elements
A compound of Formula II
- or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, wherein in Formula II,
- Ar is selected from aryl or substituted aryl;
- m is 0,1 or 2;
- R1 and R2 are independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- R3 and R4 are independently selected from heteroaryl, substituted heteroaryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, substituted heteroaryl heterocycloalkyl and
- wherein W is O, NRp, or S(O)m, Rp is independently selected from —Ra, —S(O)mRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —C(O)ORa, or —C(S)ORa;
- m is 0,1 or 2, and Rs each is independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- substituted heteroaryl, substituted aryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroalkyl, cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, or substituted heteroaryl heterocycloalkyl provided at least one of R3 and R4 is
- Ra each is independently selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, NRtRt, oxo (═O), thione (═S) phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
- and
- Rt each is independently selected from H, halogen, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Olakyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen.
8 more elements
A compound of Formula III
- or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, wherein in Formula III,
- Ar is selected from aryl or substituted aryl;
- m is 0,1 or 2;
- R1 and R2 are independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- R3 is selected from heteroaryl, substituted heteroaryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, substituted heteroaryl heterocycloalkyl, or
- wherein W is O, NRp, or S(O)m, Rp is independently selected from —Ra, —S(O)mRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —C(O)ORa, or —C(S)ORa;
- m is 0,1 or 2, and Rs each is independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- Ra each is independently selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, NRtRt, oxo (═O), thione (═S) phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
- and
- Rt each is independently selected from H, halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Oalkyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen.
7 more elements
A compound of Formula VII
- or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, wherein in Formula VII,
- Ar is selected from aryl or substituted aryl;
- W is O, NRp, or S(O)m;
- m is 0,1 or 2;
- Rs each is independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- R1 and R2 are independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- Rp each is independently selected from —Ra, —S(O)mRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —C(O)ORa, or —C(S)ORa;
- Ra each is independently selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, —NRtRt, oxo (═O), thione (═S), phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
- and
- Rt each is independently selected from H, halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Olakyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen.
7 more elements
A compound of Formula VIII
- or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, wherein in Formula VIII,
- Ar is selected from aryl or substituted aryl;
- W is O, NRp, or S(O)m,
- m is 0,1 or 2;
- Ra each is independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRa—C(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- Rp is independently selected from —Ra, —S(O)mRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —C(O)ORa, or —C(S)ORa;
- Ra each is independently selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, NRtRt, oxo (═O), thione (═S), phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
- and
- Rt each is independently selected from H, halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Olakyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen.
6 more elements
A compound of Formula IX
- or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, wherein in Formula IX,
- Ar is selected from aryl or substituted aryl;
- m is 0,1 or 2;
- Y=O or S
- Rm is C1-C6 alkyl substituted with from 1-2 of halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Oalkyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, oxo (═O), thione (═S), heterocycloalkyl, or substituted heterocycloalkyl;
- Ra each is independently selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, —NRtRt, oxo (═O), thione (═S), phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
- and
- Rt each is independently selected from H, halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Oalkyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen.
5 more elements
A compound of Formula II
- or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, wherein in Formula II,
- Ar is selected from aryl or substituted aryl;
- m is 0,1 or 2;
- R1 and R2 are independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- R3 and R4 are independently selected from heteroaryl, substituted heteroaryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, substituted heteroaryl heterocycloalkyl and
- wherein W is O, NRp, or S(O)m, Rp is independently selected from —Ra, —S(O)mRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —C(O)ORa, or —O(S)ORa;
- m is 0,1 or 2, and Rs each is independently selected from halogen, —NO2, —CN, —Ra, —ORa, —S(O)mRa, —NRaRa, —C(O)NRaRa, —C(S)NRaRa—S(O)mNRaRa, —NRaS(O)mRa, —NRaC(O)ORa, —OC(O)NRaRa, —NRaC(O)NRaRa, —NRaC(S)NRaRa, —C(O)ORa, —C(S)ORa, or —OC(O)ORa;
- substituted heteroaryl, substituted aryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, or substituted heteroaryl heterocycloalkyl
- provided at least one of R3 and R4 are heteroaryl, substituted heteroaryl, aryl cycloalkyl, substituted aryl cycloalkyl, heteroaryl cycloalkyl, substituted heteroaryl cycloalkyl, aryl heterocycloalkyl, substituted aryl heterocycloalkyl, heteroaryl heterocycloalkyl, or substituted heteroaryl heterocycloalkyl,
- and provided that at least one of R3 and R4 is
- Ra each is independently selected from H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, or heterocycloalkyl optionally substituted with 1 to 5 of Rt, —ORt, —S(O)mRt, NRtRt, oxo (═O), thione (═S), phenyl, heteroaryl, or heterocycloalkyl where phenyl, heteroaryl, and heterocycloalkyl are optionally substituted with 1 to 5 independently taken from Rt;
- and
- Rt each is independently selected from H, halogen, —NO2, —NH2, —OH, —SH, —CN, —C(O)NH2, —C(O)—NHalkyl, —C(O)Nalkylalkyl, —Oalkyl, NHalkyl, Nalkylalkyl, —S(O)malkyl, SO2NH2, SO2NHalkyl and SO2Nalkylalkyl, alkyl, cycloalkyl, haloalkyl, phenyl, benzyl, heteroaryl, or heterocycloalkyl where phenyl, benzyl heteroaryl and heterocycloalkyl may be optionally substituted with alkyl or halogen.
10 more elements
A compound which is:
- benzyl (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate;
- 5-(2,4-dichlorophenyl)-N-[(cis)-4-ethoxypyrrolidine-3-yl]-3,6-diethylpyrazin-2-amine;
- N-[(cis)-1-acetyl-4-ethoxypyrrolidine-3-yl]-5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-amine;
- methyl (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate;
- 5-(2,4-dichlorophenyl)-N-[(cis)-4-ethoxy-1-(methylsulfonyl)pyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine;
- (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxy-N,N-dimethylpyrrolidine-1-carboxamide;
- (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxy-N,N-dimethylpyrrolidine-1-carbothioamide;
- isopropyl (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate;
- (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxy-N-methylpyrrolidine-1-carbothioamide;
- 5-(2,4-dichlorophenyl)-N-[(cis)-4-ethoxy-1-(morpholin-4-ylcarbonyl)pyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine;
- 2-fluoroethyl (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate;
- 5-(2,4-dichlorophenyl)-N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine;
- 5-(2,4-dichlorophenyl)-3,6-diethyl-N-[(3R,4S)-4-(2-fluoroethoxy)pyrrolidin-3-yl]pyrazin-2-amine;
- methyl(3R,4S)-3-{[3,6-diethyl-5-(4-methoxy-2-methylphenyl)pyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-({5-[2-chloro-4-(dimethylamino)phenyl]-3,6-diethylpyrazin-2-yl}amino)-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- benzyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-hydroxypyrrolidine-1-carboxylate;
- 5-(2-chloro-4-methoxyphenyl)-N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine;
- 5-(2-chloro-4-methoxyphenyl)-3,6-diethyl-N-[(3R,4S)-4-(2-fluoroethoxy)pyrrolidin-3-yl]pyrazin-2-amine;
- trans-(+/−)-N-[4-ethoxytetrahydrofuran-3-yl]-3,6-diethyl-5-(4-methoxy-2-methylphenyl)pyrazin-2-amine;
- cis-(+/−)-N-[4-ethoxytetrahydrofuran-3-yl]-3,6-diethyl-5-(4-methoxy-2-methylphenyl)pyrazin-2-amine;
- cis-(+/−)-5-(2-chloro-4-methoxyphenyl)-3,6-diethyl-N-[4-methoxytetrahydrofuran-3-yl]pyrazin-2-amine;
- cis-(+/−)-5-(2-chloro-4-methoxyphenyl)-N-[4-ethoxytetrahydrofuran-3-yl]-3,6-diethylpyrazin-2-amine;
- 5-(2-chloro-4-methoxyphenyl)-3,6-diethyl-N-[(3S,4S)-4-propoxytetrahydrofuran-3-yl]pyrazin-2-amine;
- 5-(2-chloro-4-methoxyphenyl)-3,6-diethyl-N-[(3S,4S)-4-propoxytetrahydrofuran-3-yl]pyrazin-2-amine;
- (+/−)-5-(2-chloro-4-methoxyphenyl)-3,6-diethyl-N-[cis-4-(3-fluoropropoxy)tetrahydrofuran-3-yl]pyrazin-2-amine;
- methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-propoxypyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(3-fluoropropoxy)pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(3-fluoropropoxy)pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}4-propoxypyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(propionyloxy)pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(propionyloxy)pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(propionylamino)pyrrolidine-1-carboxylate;
- methyl (3S,4R)-3-(acetylamino)-4-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(ethylamino)pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(propylamino)pyrrolidine-1-carboxylate;
- O-methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-2-fluoroethoxy)pyrrolidine-1-carbothioate;
- O-methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carbothioate;
- O-methyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(3-fluoropropoxy)pyrrolidine-1-carbothioate;
- pyridin-2-ylmethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- pyridin-3-ylmethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- pyridin-4-ylmethyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-piperidin-1-ylethyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-morpholin-4-ylethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-morpholin-4-ylethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(propionyloxy)pyrrolidine-1-carboxylat;
- 2-(dimethylamino)ethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(3-fluoropropoxy)pyrrolidine-1-carboxylate;
- 2-pyrrolidin-1-ylethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(3-fluoropropoxy)pyrrolidine-1-carboxylate;
- 2-(1H-imidazol-1-yl)ethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-(methylamino)ethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-aminoethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-hydroxyethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-methoxyethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- 2-(2-oxopyrrolidin-1-yl)ethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate;
- 2-(2-oxopyridin-1(2H)-yl)ethyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate;
- (3S,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxypyrrolidin-2-one
- (3S,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxy-1-methylpyrrolidin-2-one;
- (3S,4S)-1-benzyl-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidin-2-one;
- (3R,4R)-4-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-3-(2-fluoroethoxy)pyrrolidin-2-one;
- (3R,4R)-4-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-3-(2-fluoroethoxy)-1-methylpyrrolidin-2-one;
- (3R,4R)-1-benzyl-4-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-3-(2-fluoroethoxy)pyrrolidin-2-one;
- 5-(2,4-dichlorophenyl)-3,6-diethyl-N-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]pyrazin-2-amine;
- 5-(2,4-dichlorophenyl)-3,6-diethyl-N-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]pyrazin-2-amine;
- 5-(2,4-dichlorophenyl)-N-[(2R)-2-(ethoxymethyl)pyrrolidin-1-yl]-3,6-diethylpyrazin-2-amine;
- 5-(2,4-dichlorophenyl)-3,6-diethyl-N-[(2R)-2-(propoxymethyl)pyrrolidin-1-yl]pyrazin-2-amine;
- 5-(2-chloro-4-methoxyphenyl)-3,6-diethyl-N-{(2R)-2-[(2-fluoroethoxy)methyl]pyrrolidin-1-yl}pyrazin-2-amine;
- 5-(2-chloro-4-methoxyphenyl)-N-[(2R)-2-(ethoxymethyl)pyrrolidin-1-yl]-3,6-diethylpyrazin-2-amine;
- methyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-bis(methoxymethyl)pyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- methyl (3R,4S)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-bis(methoxymethyl)pyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate;
- (3R,4R)-4-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}tetrahydrofuran-3-yl acetate;
- (3R,4R)-4-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}tetrahydrofuran-3-yl acetate;
- (3R,4R)-4-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}tetrahydrofuran-3-yl propionate;
- (3R,4R)-4-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}tetrahydrofuran-3-yl propionate;
- 5-(2,4-dichlorophenyl)-3,6-diethyl-N-[(3R,4R)-4-propoxytetrahydrofuran-3-yl]pyrazin-2-amine;
- 5-(2,4-dichlorophenyl)-3,6-diethyl-N-[(3R,4R)-4-(3-fluoropropoxy)tetrahydrofuran-3-yl]pyrazin-2-amine;
- (3S,4R)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)dihydrofuran-2(3H)-one;
- (3S,4R)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-ethoxydihydrofuran-2(3H)-one;
- (3R,4S)-4-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-5-oxotetrahydrofuran-3-yl acetate;
- (3R,4S)-4-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-5-oxotetrahydrofuran-3-yl propionate;
- (3S,4R)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-propoxydihydrofuran-2(3H)-one;
- (3S,4R)-3-{[5-(2-chloro-4-methoxyphenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(3-fluoropropoxy)dihydrofuran-2(3H)-one;
- or
- a pharmaceutically acceptable salt of any said compound.
78 more elements
Dependencies are inferred from the claim text.