Substituted bridged urea analogs as sirtuin modulators

A method for treating acne, rosacea or Inflammatory Bowel Disease, which comprises administering a compound or a pharmaceutically acceptable salt thereof according to Formula (I), to a subject in need thereof;

• wherein Formula (I) is
• wherein:
• m is 1 or 2;
• n is 2 or 3;
• p is 0 to 4;
• R1 is selected from the group consisting of a carbocycle and heterocycle, wherein R1 is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C4 alkyl, fluoro-substituted C1-C4 alkyl, —C≡N, —Y, —X—C(═O)—Y, —X—O—Y, —X—OR4, —X—C(═O)—NR3R3, —X—NH—C(═O)—Y—NR3R3, —X—NH—C(═O)—O—Y, —X—NR3R3, ═O, —NH—S(═O)2—R3, —S(═O)2—R3, —S—R3, —(C3-C7) cycloalkyl, —C(═N)—NR3R3, —C(═N)—NH—X —NR3R3, —X—NH—C(═O)—Y, —C(═O)—NH—X, —NH—X, phenyl, —O-phenyl, 3- to 6-membered saturated or unsaturated heterocycle and —O-(5- to 6-membered saturated heterocycle), wherein any phenyl, 3- to 6-membered saturated or unsaturated heterocycle or —O-5- to 6-membered saturated heterocycle substituent of R1 is optionally substituted at any substitutable carbon atom with one or more substituents selected from the group consisting of halo, —OR4, —X—O—Y, —CF3, —Y, —X—R3R3, —X—NH—C(═O)—Y—NR3R3, —X—NH—C(═O)—O—Y-(5- to 6-membered saturated heterocycle or carbocycle), —X—C(═N)—NR3R3 and —S—Y and optionally substituted at any substitutable nitrogen atom with —Y, —C(═O)—Y, —C(═O)—O—Y, —C(═O)—OR4, —Y—C(═O)—Y—NR3R3, —Y—NH—C(═O)—O—Y, —Y—NH—C(═O)—OR4, —Y—NH2, —C(═O)—NH—Y or —C(═O)-3- to 5-membered saturated carbocycle;
• R2 is selected from the group consisting of a carbocycle and a heterocycle, wherein R2 is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C4 alkyl, fluoro-substituted C1-C4 alkyl, —C≡N, —Y, —X—OR4, —X—O—Y, —SO2—R3, —X—NR3R3, —NH—S(═O)2R3, —C(═O)—NR3R3, —C(═O)—Y, —C(═O)—O—Y, —SO2—Ry, —SO2—NH—Ry, —SO2—NR3R3, 3- to 6-membered saturated carbocycle or heterocycle and phenyl, wherein any 3- to 6-membered saturated heterocycle substituent of R2 is optionally substituted at any carbon atom with one or more substituents selected from the group consisting of halo, —CF3, —Y, —X—O—Y, —NH—Y and —N(Y)2, and is optionally substituted at any nitrogen atom with one or more substituents selected from the group consisting of —C(═O)—O—Y, —Y and —C(═O)—Y, and when R2 is an N-linked 5- to 7-membered saturated or unsaturated heterocycle it is further substituted at any nitrogen atom with one or more substituents selected from the group consisting of —C(═O)—O—Y, —Y and —C(═O)—Y;
• each R3 is independently selected from the group consisting of hydrogen, —C(═N)—NH2, —C(═O)—Y, —Y, —Y—NH—C(═O)—O—Y, —Y—NH—C(═O)—OH, —Y—NH—C(═O)—CF3, —C(═O)—Y-3- to 5-membered saturated heterocycle, —C(═O)—O—Y-(3- to 5-membered saturated heterocycle), —C(═O)—CF3, —C(═O)—O—Y, —C(═O)—OH, —C(═O)—O—CF3, —S(═O)2—Y, —S(═O)2—OH;
• two R3 are taken together with the nitrogen or carbon atom to which they are bound to form a 4- to 8-membered saturated heterocycle optionally comprising one additional heteroatom selected independently from the group consisting of N, S, S(═O), S(═O)2, and O, wherein the heterocycle formed by two R3 is optionally substituted at any carbon atom with one or more of OH, halo, Y, NH2, NH—Y, N(Y)2, O—Y, and optionally substituted at any substitutable nitrogen atom with C(═O)—O—Y, Y or C(═O)—Y;
• each R4 is independently selected from hydrogen, Y, —CF3, —C(═O)—Y, —C(═O)—O—Y, —Y—C(═O)—Y or —Y—C(═O)—O—Y;
• R5 and R6 are independently selected from hydrogen, —OH, —OCF3, —O—Y, —O—C(═O)—Y, —O—C(═O)—O—Y, —O—C(═O)—NH—Y, —O—C(═O)—N(Y)2, —O—C(═O)-5- to 6-membered saturated or unsaturated heterocycle or carbocycle, wherein only one of R5 and R6 is O—C(═O)-5- to 6-membered saturated or unsaturated heterocycle or carbocycle, and when R5 or R6 is O—C(═O)-5- to 6-membered saturated or unsaturated heterocycle or carbocycle it is further substituted with halo, —OH, Y, —O—Y, —OCF3 or —O—C(═O)—Y;
• or
• R5 and R6 can be taken together to the carbon atom to which they are bound to form ═O;
• R7 and R8 are independently selected from the group consisting of hydrogen, halo, —OH, —O—Y and Y;
• R9 is selected from hydrogen, the group consisting of halo, —OH, —OCF3, —O—Y, Y, —O—C(═O)—Y, —NH—Y and —N(Y)2;
• each X is C0-C5 straight chain or branched alkyl, alkenyl or alkynyl;
• and
• each Y is C1-C5 straight chain or branched alkyl, alkenyl or alkynyl;
• wherein any Y or X is optionally substituted with one or more of —OH, —C1-C4 straight chain or branched alkyl, —C1-C4 alkene, —C1-C4 alkynyl, —O—(C1-C4 alkyl), —O—(C1-C4 alkene), —O—(C1-C4 alkynyl), —C(═O)—C1-C4 straight chain or branched alkyl, —C(═O)—C1-C4 alkene, —C(═O)—C1-C4 alkynyl, —C(═O)—O—C1-C4 straight chain or branched alkyl, —C(═O)—O—C1-C4 alkene, —C(═O)—O—C1-C4 alkynyl, halo, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —(C1-C3 straight chain or branched alkyl)-NH—(=NH)—NH2, —NH(alkoxy-substituted C1-C4 alkyl), —NH(hydroxy-substituted C1-C4 alkyl), —N(alkoxy-substituted C1-C4 alkyl)(hydroxy-substituted C1-C4 alkyl), —N(hydroxy-substituted C1-C4 alkyl)2 or —N(alkoxy-substituted C1-C4 alkyl)2;
• or
• a pharmaceutically acceptable salt thereof.