Substituted oxetanes, method of making, and method of use thereof

A compound, comprising:

• an oxetane of Formula 1,
• a pharmaceutically acceptable salt, diastereomer, or mixture thereof wherein:
• B is a purin-9-yl or a heterocyclic isostere of a purin-9-yl,
• wherein the purin-9-yl or heterocyclic isostere of a purin-9-yl comprises
• wherein J, L, and M are each independently
• hydrogen;
• hydroxy;
• halogen;
• C1-C12 alkyl;
• C1-C6 perhaloalkyl;
• azido;
• cyano;
• —COOR21 wherein R21 is hydrogen or C1-C12 alkyl;
• —CONR22R23 wherein R22 and R23 are each independently hydrogen or C1-C12 alkyl;
• —OR24 wherein R24 is C1-C6 alkyl, C1-C6 perhaloalkyl, phenyl, benzyl, or heterocyclic;
• —SR25 wherein R25 is hydrogen, C1-C6 alkyl, C1-C6 perhaloalkyl, phenyl, benzyl, or heterocyclic;
• —NR26R27 wherein R26 and R27 are independently hydrogen or C1-C12 alkyl;
• —SO2NR26R27 wherein R26 and R27 are defined above;
• —NHC(O)R28 wherein R28 is hydrogen, C1-C12 alkyl, carboxyalkyl, or aminoalkyl;
• —NC(═NR29)NR30 wherein R29 and R30 are each independently hydrogen or C1-C12 alkyl;
• —N(R31)OR32 wherein R31 and R32 are each independently hydrogen or C1-C12 alkyl;
• —N(R33)NR34R35 wherein R33, R34, and R35 are each independently hydrogen or C1-C12 alkyl;
• hydroxyamino;
• phenyl, —O(phenyl), benzyl, —O(benzyl), heterocyclic or —O(heterocyclic) group which may be unsubstituted, or mono-, di- or trisubstituted with one or more of hydroxy, amino, azido, nitro, cyano, halogen, sulfonamide, carboxyl, C1-C6 perfluoroalkyl, —OR24 wherein R24 is as defined above, —NR26R27 wherein R26 and R27 are as defined above, —N(R33)NR34R35 wherein R33, R34, and R35 are as defined above;
• or
• wherein m is 1-5;
• R2, R3, R4, and R5 are each independently
• hydrogen;
• hydroxy;
• amino;
• azido;
• nitro;
• cyano;
• halogen;
• sulfonamide;
• —COOR6 wherein R6 is hydrogen or C1-C12 alkyl;
• —CONR7R8 wherein R7 and R8 are each independently hydrogen or C1-C12 alkyl;
• straight or branched C1-C12 alkyl wherein the branched alkyl chains may form a 3 to 7 member heteroalkyl ring, alkyl ring, or alkenyl ring, and wherein the straight or branched C1-C12 alkyl is optionally substituted with a hydroxy, halogen, —COOR6 wherein R6 is defined above, —CONR7R8 wherein R7 and R8 are defined above, cyclo(C3-C6 alkyl)methyl, —OR9 wherein R9 is C1-C6 alkyl, C1-C6 perhaloalkyl, phenyl, benzyl, or heterocyclic, —SR9, —OR10OR9 wherein R10 is C1-C6 alkylene, C1-C6 perhaloalkylene, phenyl, or heterocyclic and R9 is as defined above, C1-C6 perhaloalkyl, —NR11R12 wherein R11 and R12 are independently hydrogen or C1-C6 alkyl, —NHC(O)R13 wherein R13 is hydrogen, C1-C6 alkyl, carboxyalkyl, or aminoalkyl, —NC(═NR14)NR15 wherein R14 and R15 are each independently hydrogen or C1-C6 alkyl, —N(R16)OR17 wherein R16 and R17 are each independently hydrogen or C1-C6 alkyl, —N(R18)NR19R20 wherein R18, R19, and R20 are each independently hydrogen or C1-C6 alkyl;
• —C1-C12 perhaloalkyl;
• —OR9 wherein R9 is as defined above;
• —SR9 wherein R9 is as defined above;
• —O—R10OR9 wherein R9 and R10 are as defined above;
• —NR11R12 wherein R11 and R12 are as defined above;
• —N(R18)NR19NR20 wherein R18, R19, and R20 are as defined above;
• or
• phenyl, —O(phenyl), —O(benzyl), heterocyclic, or —O(heterocyclic) group which may be unsubstituted, or mono-, di-, or trisubstituted with one or more of hydroxy, amino, —NHC(O)R13 wherein R13 is defined above, azido, nitro, cyano, halogen, sulfonamide, —COOR6 wherein R6 is defined above, —CONR7R8 wherein R7 and R8 are defined above, C1-C6 alkyl, C1-C6 perfluoroalkyl, —OR9 wherein R9 is as defined above, —SR9, —NR11R12 wherein R11 and R12 are as defined above, or —N(R18)NR19R20 wherein R18, R19, and R20 are as defined above;
• and
• wherein R1 is
• hydroxy;
• amino;
• azido;
• nitro;
• cyano;
• halogen;
• sulfonamide;
• —COOR6 wherein R6 is hydrogen or C1-C12 alkyl;
• —CONR7R8 wherein R7 and R8 are each independently hydrogen or C1-C12 alkyl;
• —OR9 wherein R9 is as defined above;
• —SR9 wherein R9 is as defined above;
• —O—R10OR9 wherein R9 and R10 are as defined above;
• —NR11R12 wherein R11 and R12 are as defined above;
• —N(R18)NR19R20 wherein R18, R19, and R20 are as defined above;
• or
• phenyl, —O(phenyl), —O(benzyl), heterocyclic, or —O(heterocyclic) group which may be unsubstituted, or mono-, di-, or trisubstituted with one or more of hydroxy, amino, —NHC(O)R13 wherein R13 is defined above, azido, nitro, cyano, halogen, sulfonamide, —COOR6 wherein R6 is defined above, —CONR7R8 wherein R7 and R8 are defined above, C1-C6 alkyl, C1-C6 perfluoroalkyl, —OR9 wherein R9 is as defined above, —SR9, —NR11R12 wherein R11 and R12 are as defined above, or —N(R18)NR19R20 wherein R18, R19 and R20 are as defined above;
• wherein any two of R1, R2, R3, R4, and R5 may form a substituted or unsubstituted 5 to 7 member carbocyclic ring or a substituted or unsubstituted 5 to 7 member heterocyclic ring wherein the substitution is hydroxy, amino, nitro, halogen, sulfonamide, —COOR6, —CONR7R8, cyclo(C3-C6 alkyl)methyl, C1-C6 alkyl, C1-C6 perfluoroalkyl, —OR9, —SR9, —OR10OR9, —NR11R12, —NHC(O)R13, —NC(═NR14)NR15, —N(R16)OR17, or —N(R18)NR19R20 wherein R6 to R20 are defined above;
• and with the proviso that
• at least one of R2, R3, R4 and R5 is not hydrogen;
• and
• when R2 and R4 are both hydrogen and either R3 or R5 is C1 alkyl substituted with a hydroxy or —O-benzyl group and the other R3 or R5 is hydrogen, then B is not purin-9-yl-6-amine.