Sirtuin modulating compounds

A compound of the formula:

• or a salt thereof wherein
• R19 is
• wherein:
• each Z10, Z11, Z12 and Z13 is independently selected from CR20 or CR1′;
• wherein:
• zero to one R20 is a solubilizing group;
• and
• zero to one R1′ is an optionally substituted C1-C3 straight or branched alkyl;
• each R20 is independently selected from H or a solubilizing group;
• R20a is independently selected from H or a solubilizing group;
• R21 is —NR1′—C(O)—;
• wherein
• each R1′ is independently selected from H or optionally substituted C1-C3 straight or branched alkyl;
• and
• R31 is selected from an optionally substituted monocyclic or bicyclic aryl, or an optionally substituted monocyclic or bicyclic heteroaryl, wherein when Z10, Z11, Z12 and Z13 are each CH, R20a is a solubilizing group.

A compound of the formula:

• or a salt thereof, wherein
• R21 is —NR1′—C(O)—;
• wherein
• R1′ is H or optionally substituted C1-C3 straight or branched alkyl;
• and
• R32 is an optionally substituted monocyclic or bicyclic heteroaryl, or an optionally substituted bicyclic aryl, wherein:
• when R21 is —NH—C(O)—, R32 is not furan-2-yl, 5-bromofuran-2-yl, or 2-phenyl-4-methylthiazol-5-yl.

A compound of the formula:

• or a salt thereof, wherein:
• R21 is —NR1′—C(O)—,
• wherein R1′ is optionally substituted C1-C3 straight or branched alkyl;
• and
• R33 is an optionally substituted phenyl.

A compound of the formula:

• or a salt thereof wherein:
• R21 is —NH—C(O)—;
• and
• R33 is phenyl substituted with
• a) one —N(CH3)2 group;
• b) one CN group at the 3 position;
• c) one —S(CH3) group;
• or
• d)
• bridging the 3 and 4 positions.

A composition comprising a compound of the formula:

• or a salt thereof, wherein
• R19 is selected from:
• wherein:
• each Z10, Z11, Z12 and Z13 is independently selected from CR20 or CR1′;
• wherein:
• zero to one R20 is a solubilizing group;
• and
• zero to one R1′ is an optionally substituted C1-C3 straight or branched alkyl;
• each R20 is independently selected from H or a solubilizing group;
• R21 is —NR1′—C(O)—;
• each R1′ is independently selected from H or optionally substituted C1-C3 straight or branched alkyl;
• and
• R31 is selected from an optionally substituted monocyclic or bicyclic aryl, or an optionally substituted monocyclic or bicyclic heteroaryl, with the proviso that when R19 is
• Z10, Z11, Z12 and Z13 are each CH, R20 is H, and R21 is —NHC(O)—, R31 is not an optionally substituted phenyl,
• wherein the composition is pyrogen-free.

A pharmaceutical composition comprising:

• a) a compound of the formula:
• or a pharmaceutically acceptable salt thereof, wherein
• R19 is selected from:
• wherein:
• each Z10, Z11, Z12 and Z13 is independently selected from CR20 or CR1′;
• wherein:
• zero to one R20 is a solubilizing group;
• and
• zero to one R1′ is an optionally substituted C1-C3 straight or branched alkyl;
• each R20 is independently selected from H or a solubilizing group;
• R21 is —NR1′—C(O)—;
• each R1′ is independently selected from H or optionally substituted C1-C3 straight or branched alkyl;
• and
• R31 is selected from an optionally substituted monocyclic or bicyclic aryl, or an optionally substituted monocyclic or bicyclic heteroaryl, with the proviso that
• when R19 is
• Z10, Z11, Z12 and Z13 are each CH, R20 is H, and R21 is —NHC(O)—, R31 is not an optionally substituted phenyl;
• and
• b) a pharmaceutically acceptable carrier or diluent.

A packaged pharmaceutical comprising a compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein
• R19 is selected from:
• wherein:
• each Z10, Z11, Z12 and Z13 is independently selected from CR20 or CR1′;
• zero to one R20 is a solubilizing group;
• and
• zero to one R1′ is an optionally substituted C1-C3 straight or branched alkyl;
• each R20 is independently selected from H or a solubilizing group;
• R21 is —NR1′—C(O)—;
• each R1′ is independently selected from H or optionally substituted C1-C3 straight or branched alkyl;
• and
• R31 is selected from an optionally substituted monocyclic or bicyclic aryl, or an optionally substituted monocyclic or bicyclic heteroaryl, with the proviso that when R19 is
• Z10, Z11, Z12 and Z13 are each CH, R20 is H and R21 is —NHC(O)—, R31 is not an optionally substituted phenyl.