Methods for Treating Cognitive Disorders Using Inhibitors of Histone Deacetylase

A method for treating a cognitive disorder or deficit comprising administering an effective amount of the compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• Z is selected from the group consisting of —N(R1)OR2 and H;
• L is selected from the group consisting of a covalent bond and —N(OR2)—;
• wherein, when L is —N(OR2)—, Z is H;
• and
• wherein, when Z is H, L is —N(OR2)—;
• J is selected from the group consisting of a covalent bond, ═CH—, —C1-C8alkyl-, —C0-C3alkyl-C1-C8heteroalkyl-C0-C3alkyl-, —C0-C3alkyl-C2-C8alkenyl-C0-C3alkyl-, —C0-C3alkyl-C2-C8alkynyl-C0-C3alkyl-, —C0-C6alkyl-aryl-C0-C6alkyl-, —C0-C6alkyl-aryl-C2-C6heteroalkyl-, —C0-C3alkyl-C1-C6heteroalkyl-aryl-C0-C6alkyl-, —C0-C3alkyl-C1-C6heteroalkyl-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-cycloalkyl-C0-C6alkyl-, —C0-C6alkyl-heterocyclyl-C0-C6alkyl-, —C4-C6heterocyclyl-aryl-C0-C6alkyl-, —C4-C6heterocyclyl-aryl-C0-C6heteroalkyl-, —C0-C6alkyl-C4-C6heterocyclyl-C0-C6alkyl-, —C0-C6alkyl-heteroaryl-C0-C6alkyl-, —C0-C6alkylheteroaryl-C0-C6heteroalkyl-, —C4-C6heterocyclyl-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-aryl-C2-C6alkynyl-, —C0-C6alkyl-heteroaryl-C2-C6alkynyl-, —C0-C6alkyl-aryl-C2-C6alkynyl-C2-C6alkenyl-, —C0-C6alkyl-aryl-C2-C6alkenyl-, —C0-C6alkyl-heteroaryl-C2-C6alkenyl-, —C0-C3alkyl-C2-C6alkenyl-aryl-C0-C6alkyl-, —C0-C3alkyl-C2-C6alkenyl-heteroaryl-C0-C6alkyl-, —C0-C3alkyl-C2-C6alkynyl-aryl-C0-C6alkyl-, —C0-C3alkyl-C2-C6alkynyl-heteroaryl-C0-C6alkyl-, —C0-C6alkylaryl-aryl-C0-C6alkyl-, —C0-C6alkylaryl-heteroaryl-C0-C6alkyl-, —C0-C3alkyl-heteroaryl-heteroaryl-C0-C3alkyl-, —C0-C3alkyl-heteroaryl-aryl-C0-C3alkyl-, —C0-C3alkyl-aryl-heteroaryl-C0-C3alkyl-, —C0-C3alkyl-aryl-aryl-C0-C3alkyl-, and —C0-C6alkyl-C3-C6cycloalkyl-C0-C6alkyl-, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl moiety is optionally substituted, and wherein when J is ═CH—, Q is a covalent bond and B is attached through a carbon sp2 to J;
• Q is selected from the group consisting of an optionally substituted:
• or where possible, an (R,R) or (S,S) enantiomer or a mixture of enantiomers thereof,
• wherein G and G1 are independently selected from carbon and N;
• the variables I, m, n, o and p denote numbers that are each independently selected from 0, 1, 2 or 3 provided that the sum total of l, m, n, o and p is 4, 5, 6 or 7, such that the group represented by Q comprises a 6, 7, 8 or 9 membered bridged or fused heterocyclyl, respectively, and further provided that when G and G1 are both N then the sum total of l and o is not zero, and the sum total of m and p is not zero, and wherein n is an integer ranging from 0 to 3;
• (preferably, Q comprises a 7 or 8-membered ring;
• in one particular embodiment, n is zero, such that Q comprises a fused bicyclic ring);
• U is selected from the group consisting of —C0-C8alkyl-C(O)—C0-C3alkyl-, —C1-C8alkyl-, —C0-C8alkyl-N(R3)—C(O)—C0-C3alkyl-, —C0-C8alkyl-O—C(O)—C0-C3alkyl-, —C0-C8alkyl-N(R3)—C(S)—C0-C3alkyl-, —C0-C8alkyl-O—C(S)—C0-C3alkyl-, —C0-C8alkyl-N(R3)—S(O)2—C0-C3alkyl-, —C0-C8alkyl-heterocyclyl-C0-C3alkyl-, a covalent bond and —O—C2-C4alkyl-;
• and
• U1 is selected from the group consisting of H, —C(R1)(R2)—, —C0-C8alkyl-C(O)—C0-C3alkyl-, —C1-C8alkyl-, —C0-C8alkyl-N(R3)—C(O)—C0-C3alkyl-, —C(R1)(R2)—N(R3)—C(O)—C0-C3alkyl-, —C(R1)(R2)—C(O)—C0-C3alkyl-, —C0-C8alkyl-O—C(O)—C0-C3alkyl-, —C(R1)(R2)—O—C(O)—C0-C3alkyl-, —C0-C8alkyl-N(R3)—C(S)—C0-C3alkyl-, —C0-C8alkyl-O—C(S)—C0-C3alkyl-, —C0-C8alkyl-N(R3)—S(O)2—C0-C3alkyl-, —C0-C8alkyl-heterocyclyl-C0-C3alkyl-, a covalent bond, (R3)(R3a)N—C2-C4alkyl-, —O—C2-C4alkyl-, and R3—O—C2-C4alkyl-;
• or
• Q is selected from the group consisting of a covalent bond, —C1-C8alkyl-, —C1-C8alkyl-, —C1-C8heterocyclyl-, ═N—O—, —C0-C6alkyl-N(R3)—C0-C3alkyl-, —C0-C6alkyl-O—C0-C3alkyl-, —C0-C6alkyl-S(O)0-2-C0-C3alkyl-, —C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C0-C6alkyl-C(O)—C0-C3alkyl-, —C0-C6alkyl-O—C0-C3alkyl-, —C0-C6alkyl-cycloalkyl-C0-C3alkyl-, —C0-C6alkyl-N(R3)—C(O)-cycloalkyl-C0-C3alkyl-, —C0-C6alkyl-N(R3)-cycloalkyl-C0-C3alkyl-, —C0-C6alkyl-S(O)0-2—N(R3)-cycloalkyl-C0-C3alkyl-, —C0-C6alkyl-N(R3)—C(O)—N(R3)-cycloalkyl-C0-C3alkyl-, —C0-C6alkyl-O—C(O)—O-cycloalkyl-C0-C3alkyl-, —C0-C6alkyl-N(R3)—C(O)—O-cycloalkyl-C0-C3alkyl-, —C0-C6alkyl-(CR3═CR3)1-2-C0-C6alkyl-, —C0-C6alkyl-(C≡C)1-2—C0-C6alkyl-, —C0-C6alkyl-N(R3)—C(O)—C0-C3alkyl-, —C0-C6alkyl-N(R3)—C(O)-alkenyl-C0-C4alkyl-, —C0-C6alkyl-C(O)—N(R3)—C0-C4alkyl-, —C0-C6alkyl-SO2—N(R3)—C0-C3alkyl-, —C0-C6alkyl-N(R3)—SO2—C0-C3alkyl-, —C0-C3alkyl-N(R3)—S(O)2—N(R3)—C0-C3alkyl-, —C0-C6alkyl-S—C0-C3alkyl-, —C0-C6alkyl-S(O)—C0-C3alkyl-, —C0-C6alkyl-S(O)2—C0-C3alkyl-, —C0-C6alkyl-N(R3)—C(O)—N(R3)—C0-C3alkyl-, ═N—O—C0-C3alkyl-, -heterocyclyl-C0-C3alkyl-heterocyclyl-C0-C3alkyl-, —SO2—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C(O)—C0-C6alkyl-bridged heterocyclyl-C0-C3alkyl-, —N(R3)—C(O)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —O—C(O)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —N(R3)—C(S)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —O—C(S)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —N(R3)—S(O)2—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C0-C6alkyl-heterocyclyl-C0-C3alkyl-SO2—N(R3)—, —C0-C6 alkyl-heterocyclyl-C0-C3alkyl-C(O)—N(R3)— and —C0-C6alkyl-heterocyclyl-C0-C3alkyl-C(O)—O—, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl moiety is optionally substituted;
• wherein
• is selected from the group consisting of b-1a to b-1k and b-1 to b-125, and wherein when Q is attached to
• via ═N—O—, or ═N—O—C0-3alkyl, it is attached through carbon sp2 in
• and wherein each alkyl, heteroalkyl, cycloalkyl, heterocyclyl and alkenyl moiety is optionally substituted;
• and wherein when Q is a covalent bond and J is attached to
• via ═CH—, then it is attached through carbon sp2 in
• or
• when
• is selected from the group consisting of b-1 to b-121 and is attached to Q via a N in
• then Q is selected from the group consisting of a covalent bond, —C(O)—C1-C3alkyl-O—, —C1-C8alkyl-, —C2-C6alkyl-N(R3)—C0-C3alkyl-, —C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C0-C6alkyl-C(O)—C0-C3alkyl-, —C0-C6alkyl-O—C0-C3alkyl-, —C1-C6alkyl-(CR3═CR3)1-2-C0-C6alkyl-, —C1-C6alkyl-(C≡C)1-2-C0-C6alkyl-, —C2-C6alkyl-N(R3)—C(O)—C0-C3alkyl, —C2-C6alkyl-N(R3)—C(O)-alkenyl-C0-C3alkyl, —C0-C6alkyl-C(O)—N(R3)—C0-C4alkyl-, —C(O)—O—C0-C4alkyl, —C0-C6alkyl-S(O)2—N(R3)—C0-C3alkyl, —C2-C6alkyl-N(R3)—S(O)2—C0-C3alkyl, —C2-C3alkyl-N(R3)—S(O)2—N(R3)—C0-C3alkyl-, —C2-C6alkyl-S—C0-C3alkyl, —C2-C6alkyl-S(O)—C0-C3alkyl, —C0-C6alkyl-S(O)2—C0-C3alkyl, —C2-C6alkyl-N(R3)—C(O)—N(R3)—C0-C3alkyl, —C2-C3alkyl-C═N—O—C0-C3alkyl, —SO2—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C(O)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C2-C4alkyl-N(R3)—C(O)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C2-C4alkyl-O—C(O)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C2-C4alkyl-N(R3)—C(S)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C2-C4alkyl-O—C(S)—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C2-C4alkyl-N(R3)—S(O)2—C0-C6alkyl-heterocyclyl-C0-C3alkyl-, —C0-C6alkyl-heterocyclyl-C0-C3alkyl-S(O2)—N(R3)—, —C0-C6alkyl-heterocyclyl-C0-C3alkyl-C(O)—N(R3)— and —C0-C6alkyl-heterocyclyl-C0-C3alkyl-C(O)—O—, wherein each alkyl, heterocyclyl and alkenyl moiety is optionally substituted, and wherein the heterocyclyl moiety is optionally bridged with —(CH2)0-3—;
• R1 and R2 are independently selected from the group consisting of —H, C1-C6alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl and a protecting group;
• each R3 is independently selected from the group consisting of —H, alkyl, C0-C3alkyl-heterocyclyl, C1-C3alkyl-C2-C6alkenyl, C1-C3alkyl-C2-C3alkynyl, —C2-C4alkyl-OR1, —C2-C4alkyl-NR3bR3c, —C2-C4alkyl-NR1R2, heteroalkyl, C0-C6alkylheteroaryl, C(O)CF3, —C(O)—NH2, —C(O)—NR3bR3c, —C(O)—NR1R2, —C(O)—OR1, —S(O)2—NR1R2, —S(O)2—R1, —C(O)—R1, —C3-C6cycloalkyl, —C0-C3alkyl-C3-C7cycloalkyl, —C1-C6alkylaryl, aryl, C0-C3alkyl-heteroaryl and heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl moiety is optionally substituted with from one to three independently selected substituents;
• each R3a is independently selected from the group consisting of —H, alkyl, heterocyclyl, C2-C6alkenyl, C2-C3alkynyl, C2-C4alkyl-OR1, heteroalkyl, heteroaryl, C0-C6alkylheteroaryl, C(O)CF3, —C(O)—NH2, —C3-C6cycloalkyl, -alkyl-C3-C6cycloalkyl, —C1-C6alkylaryl, aryl, alkylheteroaryl and heteroaryl, covalent bond, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl moiety is optionally substituted;
• wherein R3 and R3a, together with the atom to which they are attached, optionally form a heterocyclic ring, wherein the heterocyclyl moiety is optionally substituted;
• wherein R3b and R3c, together with the atom to which they are attached, optionally form a heterocyclic ring, wherein the heterocyclyl moiety is optionally substituted;
• provided that
• is absent when Q is structure (a-1), (a-2), (a-3), (a-20) or when U1 is H, N(R3)(R3a)—C2-C4alkyl- or R3—O—C2-C4alkyl-;
• is selected from the group consisting of hydrogen, aryl, aryl-alkyl-, heteroaryl, heteroaryl-alkyl-, heterocyclyl, cycloalkyl, heterocyclyl-alkyl, cycloalkyl-alkyl, C1-C10alkyl, (aryl)2-CH—C0-C6alkyl-, (aryl)(heteroaryl)CH—C0-C6alkyl- and (heteroaryl)2CH—C0-C6alkyl-, each of which is optionally substituted;
• or
• is a radical selected from the group consisting of
• wherein
• and are independently selected from phenyl or a 5- or 6-membered heteroaryl, wherein each of which is optionally substituted with one to three substituents;
• provided that when
• is selected from the group consisting of hydrogen, aryl, aryl-alkyl-, heteroaryl, heteroaryl-alkyl-, heterocyclyl, cycloalkyl, heterocyclyl-alkyl, cycloalkyl-alkyl, C1-C10alkyl, (aryl)2-CH—C0-C6alkyl-, (arylXheteroaryl)CH—C0-C6alkyl- and (heteroaryl)2CH—C0-C6alkyl-, each of which is optionally substituted, then Q is selected from the group consisting of a-3, a-4, a-5, a-6, a-7, a-8, a-9, a-10, a-11, a-12, a-13 and a-14,
• wherein
• each A is independently selected from the group consisting of N, —N-oxide, —CH═ and —C(R4)═, wherein no more than two A per 5 or 6 membered ring are N in a
• group, and wherein no more than one A is —N-oxide;
• the group M1-M2 is selected from the group consisting of a covalent bond, —N(R3)CH2—, —CH2N(R3)—, —S(O)0-2—CH2—, —CH2S(O)0-2—, —O—CH2—, —CH2—O—, —C(O)N(R3)—, —C(O)—O—, —C(O)—CH2—, —CH(OH)—CH2—, —CH(F)—CH2—, —CH2—C(O)—, —CH2—CH(OH)—, —CH2—CH(F)—, —N(R3)—C(O)—, —SO2N(R3)—, —N(R3)SO2—, —CH(R4)CH2—, —CH2CH(R4)—, —N═C(R4)—, —C(R4)═N—, —CH2—CH2—, —CH═CH—, —CH(R3)—CH(R3)—, —C(R3)═C(R3)—, —C(R4)═C(R4)—, —CF═CH—, —CH═CF—,
• —CH2—, —C(R3)(R3a)—, —S(O)0-2—, —N(R3)—, or absent;
• M3 is selected from the group consisting of
• or M3 is
• wherein Q is attached to
• via ═N—O—, or ═N—O—C0-3alkyl, or J is attached to
• via ═CH—,
• wherein * represents the point of attachment to Q;
• M4 is selected from the group consisting of
• and covalent bond;
• wherein, when M1-M2 is a covalent bond, M4 is selected from the group consisting of
• the groups D1-D2 and D1a-D2a are selected from the group consisting of
• wherein, * represents the point of attachment to Q;
• D3 is selected from the group consisting of a covalent bond,
• wherein the
• optionally substituted;
• D4 is selected from the group consisting of
• wherein the
• is optionally substituted;
• the group E1-E2 is selected from the group consisting of
• wherein * represents the point of attachment to Q;
• and
• E3 is selected from the group consisting of —C(O)—, —C(S)—, —CH2—, —C(OH)2— and —C═N(R3)—;
• and
• R4 is independently selected from the group consisting of —H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyl-R3, —C0-C6alkyl-OR3, —C0-C6alkyl-OR1, —C0-C6alkyl-C(O)—OR3, —C0-C6alkyl-C(O)NR3R3a, —CH═CH—C(O)—OR3, —CH═CH—C(O)—N(R3)(R3a), —N(R3)—C(O)—CF3, —N(R3)—C2-C6alkyl-N(R3)(R3a), —C0-C6alkyl-N(R3)(R3a), —N(R3)—C(O)—C1-C6alkyl-R3, —N(R3)—S(O)2—C1-C6alkyl-R3, —S(O)2—N(R3)R3a, —O—C2-C6alkyl-N(R3)(R3a), —O—C2-C6alkyl-OR1, —S—R3, —S(O)—C1-C6alkyl-R3, —S(O)2—C1-C6alkyl-R3, C3-C6cycloalkyl, heterocyclyl, C4-C7heterocyclyl-R3, —O—C2-C4alkyl-heterocyclyl, —O-heterocyclyl-C(O)—OR3, —O—C0-C4alkyl-aryl, —O—C0-C4alkyl-heteroaryl, —O—C(O)—NR3-C0-C4alkyl-aryl, —O—C(O)—NR3-C0-C4alkyl-heteroaryl, —O—C0-C4alkyl-heterocyclylaryl, —O—C0-C4alkyl-heterocyclyl-heteroaryl, —N(R3)—C2-C4alkyl-heterocyclyl, —N(R3)C(O)N(R3)—C0-C4alkyl-heterocyclyl-R3, —C0-C4alkyl-OC(O)—R3, —C0-C4alkyl-N(R3)C(O)—O—R3, —C0-C4alkyl-heterocyclyl-C(O)—O—R3, —N(R3)—C2-C4alkyl-heterocyclyl, F, Cl, Br, I, NO2, —CF3, —OCF3, —OCHF2, —SCF3, —SF5, —SO3H, —CN, —C1-C6 alkylaryl, aryl, heteroaryl, cycloalkyl, —C1-C6 alkylheteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl moeity of the aformentioned R4 is optionally substituted;
• or
• is selected from the group consisting of structures b-1a to b-1k and (b-1) to (b-125) and Q-J-L taken together is selected from the group consisting of —C3-C8alkyl-, —C(O)—C3-C8alkyl-, —C0-C3alkyl-O—C3-C8alkyl-, —C0-C3alkyl-C1-C4alkenyl-C0-C3alkyl-, ═N—O—C1-C8alkyl-, ═N—O—C0-C3alkyl-aryl-C0-C3alkyl-, ═N—O—C0-C3alkyl-aryl-C0-C3alkenyl-, ═N—O—C0-C3alkyl-aryl-C0-C3alkynyl-, ═N—O—C0-C3alkyl-heteroaryl-C0-C3alkyl-, ═N—O—C0-C3alkyl-heteroaryl-C0-C3alkenyl-, ═N—O—C0-C3alkyl-heteroaryl-C0-C3alkynyl-, —C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-aryl-C2-C4alkenyl-, —C0-C3alkyl-aryl-C2-C4alkynyl-, —C0-C3alkyl-heteroaryl-C0-C3alkyl-, —C0-C3alkyl-heteroaryl-C1-C3alkenyl-, —C0-C3alkyl-heteroaryl-C1-C3alkynyl-, —C0-C3alkyl-N(R3)—C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-N(R3)—C0-C3alkyl-aryl-C2-C3alkenyl-, —C0-C3alkyl-N(R3)—C0-C3alkyl-aryl-C2-C3alkynyl-, —C0-C3alkyl-N(R3)—C0-C3alkyl-heteroaryl-C0-C3alkyl-, —C0-C3alkyl-N(R3)—C0-C3alkyl-heteroaryl-C2-C3alkenyl-, —C0-C3alkyl-N(R3)—C0-C3alkyl-heteroaryl-C2-C3alkynyl-, —C0-C3alkyl-C(O)—N(R3)—C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-N(R3)—C(O)—C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-C(O)—N(R3)—C0-C3alkyl-aryl-C2-C3alkenyl-, —C0-C3alkyl-N(R3)—C(O)—C0-C3alkyl-aryl-C2-C3alkenyl-, —C0-C3alkyl-C(O)—N(R3)—C0-C3alkyl-ayl-C2-C3alkynyl-, —C0-C3alkyl-N(R3)—C(O)—C0-C3alkyl-aryl-C2-C3alkynyl-, —C0-C3alkyl-C(O)—N(R3)—C0-C3alkyl-heteroaryl-C0-C3alkyl-, —C0-C3alkyl-N(R3)—C(O)—C0-C3alkyl-heteroaryl-C0-C3alkyl-, —C0-C3alkyl-C(O)—N(R3)—C0-C3alkyl-heteroaryl-C2-C3alkenyl-, —C0-C3alkyl-N(R3)—C(O)—C0-C3alkyl-heteroaryl-C2-C3alkenyl-, —C0-C3alkyl-C(O)—N(R3)—C0-C3alkyl-heteroaryl-C2-C3alkynyl-, —C0-C3alkyl-N(R3)—C(O)—C0-C3alkyl-heteroaryl-C2-C3alkynyl-, —C0-C3alkyl-heterocyclyl-C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-C(O)-heterocyclyl-C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-N(R3)—C(O)-heterocyclyl-C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-O—C(O)-heterocyclyl-C0-C3alkyl-aryl-C0-C3alkyl-, —C0-C3alkyl-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkenyl, —C0-C3alkyl-C(O)-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkenyl, —C0-C3alkyl-N(R3)—C(O)-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkenyl, —C0-C3alkyl-O—C(O)-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkenyl, —C0-C3alkyl-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkynyl, —C0-C3alkyl-C(O)-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkynyl, —C0-C3alkyl-N(R3)—C(O)-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkynyl, —C0-C3alkyl-O—C(O)-heterocyclyl-C0-C3alkyl-aryl-C2-C4alkynyl, —C0-C3alkyl-heterocyclyl-C0-C3alkyl-heteroaryl-C0-C3alkyl, —C0-C3alkyl-C(O)-heterocyclyl-C0-C3alkyl-heteroaryl-C0-C3alkyl, —C0-C3alkyl-N(R3)—C(O)-heterocyclyl-C0-C3alkyl-heteroaryl-C0-C3alkyl, —C0-C3alkyl-O—C(O)-heterocyclyl-C0-C3alkyl-heteroaryl-C0-C3alkyl, —C0-C3alkyl-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkenyl-, —C0-C3alkyl-C(O)-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkenyl-, —C0-C3alkyl-N(R3)—C(O)-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkenyl-, —C0-C3alkyl-O—C(O)-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkenyl-, —C0-C3alkyl-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkynyl-, —C0-C3alkyl-C(O)-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkynyl-, —C0-C3alkyl-N(R3)—C(O)-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkynyl-, —C0-C3alkyl-O—C(O)-heterocyclyl-C1-C3alkyl-heteroaryl-C2-C3alkynyl-, —C2-C4alkyl-O—C0-C3alkyl-aryl-, —C2-C4alkyl-O—C0-C3alkyl-aryl-C0-C3alkyl-, —C2-C4alkyl-O—C0-C3alkyl-aryl-C2-C4alkenyl, —C2-C4alkyl-O—C0-C3alkyl-aryl-C2-C4alkynyl, —C2-C4alkyl-O—C0-C3alkyl-heteroaryl-C0-C3alkyl, —C2-C4alkyl-O—C1-C3alkyl-heteroayl-C2-C3alkenyl-, —C2-C4alkyl-C1-C3alkyl-heteroaryl-C2-C3alkynyl-, —C0-C6alkyl-U-bridged heterocyclyl-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-U-bridged heterocyclyl-N(R3)-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-U—N(R3)-bridged heterocyclyl-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-U-bridged heterocyclyl-aryl-C0-C6alkyl-, —C0-C6alkyl-U-bridged heterocyclyl-N(R3)-aryl-C0-C6alkyl-, —C0-C6alkyl-U—N(R3)-bridged heterocyclyl-aryl-C0-C6alkyl-, —C0-C6alkyl-U-bridged heterocyclyl-aryl-C2-C6alkenyl-, —C0-C6alkyl-U-bridged heterocyclyl-N(R3)-aryl-C2-C6alkenyl-, —C0-C6alkyl-U—N(R3)-bridged heterocyclyl-aryl-C2-C6alkenyl-, —C0-C6alkyl-U-bridged heterocyclyl-heteroaryl-C2-C6alkenyl-, —C0-C6alkyl-U-bridged heterocyclyl-N(R3)-heteroaryl-C2-C6alkenyl-, —C0-C6alkyl-U—N(R3)-bridged heterocyclyl-heteroaryl-C2-C6alkenyl-, —C0-C6alkyl-bridged heterocyclyl-U-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-N(R3)-bridged heterocyclyl-U-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-bridged heterocyclyl-N(R3)—U-heteroaryl-C0-C6alkyl-, —C0-C6alkyl-bridged heterocyclyl-U-aryl-C0-C6alkyl-, —C0-C6alkyl-N(R3)-bridged heterocyclyl-U-aryl-C0-C6alkyl-, —C0-C6alkyl-bridged heterocyclyl-N(R3)—U-aryl-C0-C6alkyl-, —C0-C6alkyl-bridged heterocyclyl-U-aryl-C2-C6alkenyl-, —C0-C6alkyl-N(R3)-bridged heterocyclyl-U-aryl-C2-C6alkenyl-, —C0-C6alkyl-bridged heterocyclyl-N(R3)—U-aryl-C2-C6alkenyl-, —C0-C6alkyl-bridged heterocyclyl-U-heteroaryl-C2-C6alkenyl-, —C0-C6alkyl-N(R3)-bridged heterocyclyl-U-heteroaryl-C2-C6alkenyl-, and —C0-C6alkyl-bridged heterocyclyl-N(R3)—U-heteroaryl-C2-C6alkenyl-,
• wherein each alkyl, alkenyl, aryl, alkynyl, heteroaryl and heterocyclyl moiety is optionally substituted;
• and wherein the bridge is methylene or propylene;
• provided that Formula (I) excludes those compounds wherein
• -Q-J-L-C(O)Z is optionally substituted —C1-C13alkyl-N(R3)—C0-C6alkyl-aryl-C2alkenyl-C(O)NHOH;
• and
• is selected from the group consisting of aromatic polycycles, non-aromatic polycycles, mixed aryl and non-arylpolycycles, polyheteroaryl, non-aromatic polyheterocycles, and mixed aryl and non-aryl polyheterocycles, each of which is optionally substituted;
• and
• provided that Formula (I) excludes compounds of Formula (A)
• wherein R906 is selected from the group consisting of aryl and heteroaryl;
• T906 is selected from the group consisting of —C0-6alkyl-S(O)2—C0-6alkyl-, —C0-6alkyl-C(O)—C0-6alkyl- and C1-3alkyl, wherein T906 is substituted at the carbon atom attached to R906 with a moiety selected from the group consisting of;
• aryl, heteroaryl, cycloalkyl and heterocycle;
• A906 is an optionally substituted unbridged heterocycle;
• Q906 is a bond;
• Het is an optionally substituted 5-membered aryl ring;
• L906 is a bond or —C1-4alkyl-;
• and
• R906a is —N(R906b)OH, wherein R906b is selected from the group consisting of H, optionally substituted alkyl and optionally substituted aryl;
• and
• provided that Formula (I) excludes those compounds wherein
• -Q-J-L-C(O)Z is optionally substituted —C0-C4alkyl-X—C1-C4alkyl-phenyl-C2alkenyl-C(O)NHOH;
• is a 5- or 6-membered aromatic heterocyclic group condensed with a carbon ring or other heterocyclic ring, which
• is substituted with 1 to 4 substituents selected from phenyl, another 5- or 6-membered aromatic heterocyclic group and a heterocyclic group, said heterocyclic group being optionally substituted with C1-4alkyl, a benzyl group or a pyridylmethyl group;
• and
• X is a moiety having a structure selected from the group consisting of —C(O)N(RA1)—, —O—C(O)—N(RA1)—, —SO2—, —N(RA2)SO2—, wherein RA1 and RA2 are independently —H or optionally substituted C1-C4alkyl;
• and
• provided that Formula (I) excludes compounds wherein B-Q- is
• and
• -J-L- is
• wherein R is directly attached or attached through a linker, and is selected from the group consisting of substituted or unsubstituted aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, 9-purine-6-amine, thiazoleamino group, hydroxyl, branched or unbranched alkyl, alkenyl, alkyoxy, aryloxy, arylalkyloxy and pyridine group, wherein the linker is selected from the group consisting of an amide moiety, —O—, —S—, —NH— and —CH2—;
• and
• provided that Formula (I) excludes compounds of Formula (B)
• wherein
• RB is H or phenyl;
• AB is a bi- or tricyclic residue optionally partially or totally unsaturated, and which optionally contains one or more heteroatoms selected from the group consisting of N, S and O, and optionally substituted by hydroxy, alkanoyloxy, primary, secondary or tertiary amino, aminoC1-C4alkyl, mono- or di(C1-C4)alkyl-aminoC1-C4alkyl, halogen, C1-C4alkyl and tri(C1-C4)alkylammoniumC1-C4alkyl;
• is a chain of 1 to 5 carbon atoms optionally containing a double bond or an NR group, wherein R is H or C1-C4alkyl;
• XB is absent, an oxygen atom or an NR group, wherein R is H or C1-C4alkyl;
• and
• BB is a phenylene or cyclohexylene ring;
• and
• provided that Formula (I) excludes compounds of Formula (D)
• wherein
• AD is selected from the group consisting of a 4- to 10-membered aromatic or non-aromatic heterocyclyl;
• XD is C═O or S(O)2;
• RD1 is H or C1-C6alkyl;
• RD2 is independently selected from the group consisting of oxo, (C═O)—NH2, C1-C6alkyl-aryl and heterocyclyl, when AD is a non-aromatic heterocycle, wherein said alkyl, and aryl moieties are optionally substituted with one to three Rb;
• or
• RD2 is independently selected from the group consisting of OH, NO2, (C═O)0-1—O0-1—C1-C6alkyl, CN, (C═O)0-1—O0-1—C3-C10cycloakyl, halogen, (C═O)0-1—N(Ra)2, CF3, NH—S(O)0-2—Ra, (C═O)0-1—O0-1-heterocyclyl, (C═O)0-1—O0-1-aryl, S(O)0-2—Ra, NH(C═O)Ra, C1-C6alkyl-aryl and heterocyclyl, when AD is an aromatic heterocyclyl, wherein said alkyl, cycloalkyl, aryl and heterocyclyl are optionally substituted with one to three Rb;
• Ra is independently H or C1-C6alkyl;
• and
• Rb is independently selected from the group consisting of oxo, NO2, N(Ra)2, OH, CN, halogen, CF3 and C1-C6alkyl;
• and
• provided that Formula (I) excludes compounds of Formula (E)
• wherein
• AE is selected from the group consisting of —CH2—O—, —CH2—S—, —CH2—CH2— and —NH—CO—;
• XE is selected from the group consisting of —N(RE3)—, ═C(O) and —CH(OH)—;
• YE is selected from the group consisting of O, S and —N(RE4)—;
• ZE is selected from the group consisting of a straight chain C4-C8alkylene, wherein one CH2 group may be replaced by an oxygen or a sulfur atom, or wherein 2 carbon atoms form a C═C double bond, and which is either unsubstituted or substituted by one or two substituents selected from C1-C4alkyl and halogen;
• RE1 and RE2 are independently selected from the group consisting of H, halogen, C1-C4alkyl, trifluoromethyl, hydroxy, C1-C4alkoxy, benzyloxy, C1-C3alkylenedioxy, nitro, amino, C1-C4alkylamino, di[(C1-C4)alkyl]-amino, and C1-C4alkanoylamino;
• and
• RE3 and RE4 are independently selected from H and C1-C4alkyl;
• and
• provided that Formula (I) excludes compounds of Formula (F)
• AF-Q1F-JF-Q2F-C(O)—NH—OH (F)
• wherein
• AF is a C5-C20 aryl group or a 5-20 membered heteroaryl group, each having one ring or two or more fused rings, wherein at least one ring is aromatic, said ary and heteroaryl groups being optionally substituted;
• Q1F is a linker group having a backbone length of at least 2 carbon atoms, the linker being optionally substituted;
• JF is —N(RF)—C(O)— or —C(O)—N(RF)—;
• Q2F is selected from the group consisting of C1-C10alkyl, C5-C20aryl, 5 to 20 membered heteroaryl, C5-C20aryl-C1-C10alkyl, 5 to 20 membered heteroaryl-C1-C10alkyl, C1-C10alkyl-C5-C20aryl and C1-C10alkyl-5 to 20 membered heteroaryl, each of which is optionally substituted;
• and
• RF is selected from the group consisting of H, C1-C7alkyl, C3-C20heterocyclyl and C5-C20aryl, each of which is optionally substituted;
• and
• provided that Formula (I) excludes compounds wherein
• Z is —N(R1)(OR2);
• R1 and R2 are independently selected from the group consisting of H, C1-C6alkyl, aryl and heteroaryl;
• L is a bond;
• and
• is selected from the group consisting of hydrogen, aryl, aryl-alkyl-, heteroaryl, heteroaryl-alkyl-, heterocyclyl, cycloalkyl, heterocyclyl-alkyl, cycloalkyl-alkyl, C1-C10alkyl, (aryl)2-CH—C0-C6alkyl-, (aryl)(heteroaryl)CH—C0-C6alkyl- and (heteroaryl)2CH—C0-C6alkyl-, each of which is optionally substituted;
• and
• Q comprises a ring selected from the group consisting of
• wherein YF is nitrogen or —CH<, and ZF is oxygen, NH or —CH2— if ZF is not bonded to
• or ZF is nitrogen or —CH< if ZF is bonded to
• or
• is selected from the group consisting of b-53, b-62 (wherein D3 is
• b-69 (wherein R4 is H), b-70, b-72 (wherein D3 is
• b-92 and b-93;
• and
• Q-J is selected from the group consisting of —XF—C0-4alkyl-aryl-C0-4alkyl-, —XF—C0-4alkyl-heteroaryl-C0-4alkyl-, and —XF—C0-4alkyl-heterocyclyl-C0-4alkyl-, wherein said alkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted, and wherein said hetercyclyl is a mono- or bi-saturated or mono- or bi-unsaturated heterocyclic ring, and wherein
• XF is selected from the group consisting of
• wherein the left side attaches to
• and wherein r and s are each independently 0, 1, 2, 3, 4 or 5, wherein r and s cannot be both 0 and when r or s are 0 then a direct bound in intended;
• each r′ is independently 0, 1, 3, 3 or 4 and r′ cannot be 0 when s is 0;
• R4A is H, C1-6alkyl or phenyl;
• YF is nitrogen or —CH<, and ZF is oxygen, NH or —CH2— if ZF is not bonded to
• or ZF is nitrogen or —CH< if ZF is bonded to
• and
• provided that Formula (I) excludes those compounds having the following structure:
• wherein
• X9 is selected from the group consisting of CO, SO2 and CH2;
• Y9 is selected from the group consisting of N—R9f, CH—OR9f, CH—NR9fR9i and C═CH—CO—R9g;
• A9 and B9 are independently selected from 5- or 6-membered rings;
• R9a, R9b, R9c and R9d are independently selected from the group consisting of H, halogen, CF3, NO2, NR9iR9j, CN, COOH, (CH2)0-2-CONR9iR9j, C1-6alkyl, OH, O—C1-6alkyl, O-cyclopropyl, O—(CH2)2—O—C1-6alkyl, O—(CH2)2—NR9iR9j, O—CONHR9i, CH2—Z9—R9h, COR9i, CR9iR9mR9n, SR9i, SO2R9o, CR9iNOR9i, CR9iNNR9iR9j, a Q9-(CH2)2-9CONHOH group, furan, thiophene, pyrrole, oxazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, 1,2,3-oxathiazole, 1,2,3-triazole, pyridine, pyridazine, pyrimidine, pyrazine, morpholine thiomorpholine, piperidine and pyrrolidine;
• R9e and R9f are Q9a-(CH2)2-9CONHOH;
• R9g is NH—(CH2)2-9CONHOH;
• R9h is a (CH2)P—R9k group, wherein R9k can be methyl or hydroxyl;
• Z9 is selected from the group consisting of O, NR9L and S;
• Q9 is selected from the group consisting of a chemical bond, —O—, —S—, —NR9L—, —NR9iCO—, —CONR9i—, —W9—, —COW9—, wherein W9 is piperidine or pyrrolidine;
• Q9a is a bond or a —CO—;
• R9i and R9j are independently H or a C1-6alkyl;
• R9L is H or R9h
• R9m and R9n can either be a fluorine atom or oxygen atoms linked together by an alkyl chain consisting of 2 or 3 CH2;
• and
• R9o is a C1-6alkyl;
• provided that (1) only one (CH2)2-9CONHOH is present in the molecule and (2) when X9 is CO and A9 and B9 are both benzene then R9c and R9d cannot signify Q9-(CH2)2-9CONHOH.