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US 2009/0022694 A1Published application
Sirt1 inhibition
OwnerPeter Distefanoinventor
Life of this patent
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Abstract
A method of culturing cells in the presence of a SIRT1 inhibitor is described.
Claims29
A method of culturing cells in culture medium, the method comprising
- inhibiting SIRT1 activity in cells in vitro, wherein the culture medium comprises a SIRT1 inhibitor having Formula (I)
- wherein,
- R1 and R2, together with the carbons to which they are attached, form C5-C10 cycloalkyl, C5-C10 heterocyclyl, C5-C10 cycloalkenyl, C5-C10 heterocycloalkenyl, C6-C10 aryl, or C6-C10 heteroaryl, each of which may be optionally substituted with 1-5 R5;
- or R1 is H, S-alkyl, or S-aryl, and R2 is amidoalkyl wherein the nitrogen is substituted with alkyl, aryl, or arylalkyl, each of which is optionally further substituted with alkyl, halo, hydroxy, or alkoxy;
- R3 and R4, together with the carbons to which they are attached, form C5-C10 cycloalkyl, C5-C10 heterocyclyl, C5-C10 cycloalkenyl, C5-C10 heterocycloalkenyl, C6-C10 aryl, or C6-C10 heteroaryl, each of which are optionally substituted with 1-5 R6;
- each of R5 and R6 is, independently, halo, hydroxy, C1-C10 alkyl, C1-C6 haloalkyl, C1-C10 alkoxy, C1-C6 haloalkoxy, C6-C10 aryl, C5-C10 heteroaryl, C7-C12 aralkyl, C7-C12 heteroaralkyl, C3-C8 heterocyclyl, C2-C12 alkenyl, C2-C12 alkynyl, C5-C10 cycloalkenyl, C5-C10 heterocycloalkenyl, carboxy, carboxylate, cyano, nitro, amino, C1-C6 alkyl amino, C1-C6 dialkyl amino, mercapto, SO3H, sulfate, S(O)NH2, S(O)2NH2, phosphate, C1-C4 alkylenedioxy, oxo, acyl, aminocarbonyl, C1-C6 alkyl aminocarbonyl, C1-C6 dialkyl aminocarbonyl, C1-C10 alkoxycarbonyl, C1-C10 thioalkoxycarbonyl, hydrazinocarbonyl, C1-C6 alkyl hydrazinocarbonyl, C1-C6 dialkyl hydrazinocarbonyl, hydroxyaminocarbonyl;
- alkoxyaminocarbonyl;
- or one of R5 or R6 and R7 form a cyclic moiety containing 4-6 carbons, 1-3 nitrogens, 0-2 oxygens and 0-2 sulfurs, which are optionally substituted with oxo or C1-C6 alkyl;
- X is NR7, O, or S;
- Y is NR7′, O or S;
- ———— represent optional double bonds;
- each of R7 and R7′ is, independently, hydrogen, C1-C6 alkyl, C7-C12 arylalkyl, C7-C12 heteroarylalkyl;
- or R7 and one of R5 or R6 form a cyclic moiety containing 4-6 carbons, 1-3 nitrogens, 0-2 oxygens and 0-2 sulfurs, which are optionally substituted with oxo or C1-C6 alkyl;
- and
- n is 0 or 1.
12 more elements
Dependencies are inferred from the claim text.