IP Library Patent Application 13079458
Patent Application
App. No. 13/079,458

INHIBITORS OF HISTONE DEACETYLASE

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Patent No.
US None
App. No.
13/079,458
Abstract

This invention relates to compounds for the inhibition of histone deacetylase. More particularly, the invention provides for compounds of formula (I) wherein Q, J, L and Z are as defined in the specification.

Claims (181)

1 . A compound represented by Formula (I):

and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic mixtures, diastereomers and enantiomers thereof, wherein

Z is selected from the group consisting of —N(R 1 )OR 2 and H;

L is selected from the group consisting of a covalent bond and —N(OR 2 )—;

wherein, when L is —N(OR 2 )—, Z is H; and

wherein, when Z is H, L is —N(OR 2 )—;

J is selected from the group consisting of a covalent bond, ═CH—, —C 1 -C 8 alkyl-, —C 0 -C 3 alkyl-C 1 -C 8 heteroalkyl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-C 2 -C 8 alkenyl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-C 2 -C 8 alkynyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-aryl-C 0 -C 6 alkyl-, —C 0 -C 6 alkyl-aryl-C 2 -C 6 heteroalkyl-, —C 0 -C 3 alkyl-C 1 -C 6 heteroalkyl-aryl-C 0 -C 6 alkyl-, —C 0 -C 3 alkyl-C 1 -C 6 heteroalkyl-heteroaryl-C 0 -C 6 alkyl-, —C 0 -C 6 alkyl-cycloalkyl-C 0 -C 6 alkyl-, —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 6 alkyl-, —C 4 -C 6 heterocyclyl-aryl-C 0 -C 6 alkyl-, —C 4 -C 6 heterocyclyl-aryl-C 0 -C 6 heteroalkyl-, —C 0 -C 6 alkyl-C 4 -C 6 heterocyclyl-C 0 -C 6 alkyl-, —C 0 -C 6 alkyl-heteroaryl-C 0 -C 6 alkyl-, —C 0 -C 6 alkylheteroaryl-C 0 -C 6 heteroalkyl-, —C 4 -C 6 heterocyclyl-heteroaryl-C 0 -C 6 alkyl-, —C 0 -C 6 alkyl-aryl-C 2 -C 6 alkynyl-, —C 0 -C 6 alkyl-heteroaryl-C 2 -C 6 alkynyl-, —C 0 -C 6 alkyl-aryl-C 2 -C 6 alkynyl-C 2 -C 6 alkenyl-, —C 0 -C 6 alkyl-aryl-C 2 -C 6 alkenyl-, —C 0 -C 6 alkyl-heteroaryl-C 2 -C 6 alkenyl-, —C 0 -C 3 alkyl-C 2 -C 6 alkenyl-aryl-C 0 -C 6 alkyl-, —C 0 -C 3 alkyl-C 2 -C 6 alkenyl-heteroaryl-C 0 -C 6 alkyl-, —C 0 -C 3 alkyl-C 2 -C 6 alkynyl-aryl-C 0 -C 6 alkyl-, —C 0 -C 3 alkyl-C 2 -C 6 alkynyl-heteroaryl-C 0 -C 6 alkyl-, —C 0 -C 6 alkylaryl-aryl-C 0 -C 6 alkyl-, —C 0 -C 6 alkylaryl-heteroaryl-C 0 -C 6 alkyl-, —C 0 -C 3 alkyl-heteroaryl-heteroaryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-heteroaryl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-aryl-heteroaryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-aryl-aryl-C 0 -C 3 alkyl-, and —C 0 -C 6 alkyl-C 3 -C 6 cycloalkyl-C 0 -C 6 alkyl-, 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 sp 2 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 G 1 are independently selected from carbon and N; the variables l, 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 G 1 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;

U is selected from the group consisting of —C 0 -C 8 alkyl-C(O)—C 0 -C 3 alkyl-, —C 1 -C 8 alkyl-, —C 0 -C 8 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-O—C(O)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-N(R 3 )—C(S)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-O—C(S)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-N(R 3 )—S(O) 2 —C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-heterocyclyl-C 0 -C 3 alkyl-, a covalent bond and —O—C 2 -C 4 alkyl-; and

U 1 is selected from the group consisting of H, —C(R 1 )(R 2 )—, —C 0 -C 8 alkyl-C(O)—C 0 -C 3 alkyl-, —C 1 -C 8 alkyl-, —C 0 -C 8 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-, —C(R 1 )(R 2 )—N(R 3 )—C(O)—C 0 -C 3 alkyl-, —C(R 1 )(R 2 )—C(O)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-O—C(O)—C 0 -C 3 alkyl-, —C(R 1 )(R 2 )—O—C(O)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-N(R 3 )—C(S)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-O—C(S)—C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-N(R 3 )—S(O) 2 —C 0 -C 3 alkyl-, —C 0 -C 8 alkyl-heterocyclyl-C 0 -C 3 alkyl-, a covalent bond, (R 3 )(R 3a )N—C 2 -C 4 alkyl-, —O—C 2 -C 4 alkyl-, and R 3 —O—C 2 -C 4 alkyl-;

or

Q is selected from the group consisting of a covalent bond, —C 1 -C 8 alkyl-, —C 1 -C 8 alkyl-, —C 1 -C 8 heterocyclyl-, ═N—O—, —C 0 -C 6 alkyl-N(R 3 )—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-O—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-S(O) 0-2 —C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-C(O)—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-O—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-cycloalkyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-N(R 3 )—C(O)-cycloalkyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-N(R 3 )-cycloalkyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-S(O) 0-2 —N(R 3 )-cycloalkyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-N(R 3 )—C(O)—N(R 3 )-cycloalkyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-O—C(O)—O-cycloalkyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-N(R 3 )—C(O)—O-cycloalkyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-(CR 3 ═CR 3 ) 1-2 —C 0 -C 6 alkyl-, —C 0 -C 6 alkyl-(C≡C) 1-2 —C 0 -C 6 alkyl-, —C 0 -C 6 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-N(R 3 )—C(O)-alkenyl-C 0 -C 4 alkyl-, —C 0 -C 6 alkyl-C(O)—N(R 3 )—C 0 -C 4 alkyl-, —C 0 -C 6 alkyl-SO 2 —N(R 3 )—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-N(R 3 )—SO 2 —C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-N(R 3 )—S(O) 2 —N(R 3 )—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-S—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-S(O)—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-S(O) 2 —C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-N(R 3 )—C(O)—N(R 3 )—C 0 -C 3 alkyl-, ═N—O—C 0 -C 3 alkyl-, -heterocyclyl-C 0 -C 3 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —SO 2 —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C(O)—C 0 -C 6 alkyl-bridged heterocyclyl-C 0 -C 3 alkyl-, —N(R 3 )—C(O)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —O—C(O)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —N(R 3 )—C(S)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —O—C(S)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —N(R 3 )—S(O) 2 —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-SO 2 —N(R 3 )—, —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-C(O)—N(R 3 )— and —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-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—C 0-3 alkyl, it is attached through carbon Sola-Penna et al. 2 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 sp 2 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)—C 1 -C 3 alkyl-O—, —C 1 -C 8 alkyl-, —C 2 -C 6 alkyl-N(R 3 )—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-C(O)—C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-O—C 0 -C 3 alkyl-, —C 1 -C 6 alkyl-(CR 3 ═CR 3 ) 1-2 —C 0 -C 6 alkyl-, —C 1 -C 6 alkyl-(C≡C) 1-2 —C 0 -C 6 alkyl-, —C 2 -C 6 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl, —C 2 -C 6 alkyl-N(R 3 )—C(O)-alkenyl-C 0 -C 3 alkyl, —C 0 -C 6 alkyl-C(O)—N(R 3 )—C 0 -C 4 alkyl-, —C(O)—O—C 0 -C 4 alkyl, —C 0 -C 6 alkyl-S(O) 2 —N(R 3 )—C 0 -C 3 alkyl, —C 2 -C 6 alkyl-N(R 3 )—S(O) 2 —C 0 -C 3 alkyl, —C 2 -C 3 alkyl-N(R 3 )—S(O) 2 —N(R 3 )—C 0 -C 3 alkyl-, —C 2 -C 6 alkyl-S-C 0 -C 3 alkyl, —C 2 -C 6 alkyl-S(O)—C 0 -C 3 alkyl, —C 0 -C 6 alkyl-S(O) 2 —C 0 -C 3 alkyl, —C 2 -C 6 alkyl-N(R 3 )—C(O)—N(R 3 )—C 0 -C 3 alkyl, —C 2 -C 3 alkyl-C═N—O—C 0 -C 3 alkyl, —SO 2 —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C(O)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 2 -C 4 alkyl-N(R 3 )—C(O)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 2 -C 4 alkyl-O—C(O)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 2 -C 4 alkyl-N(R 3 )—C(S)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 2 -C 4 alkyl-O—C(S)—C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 2 -C 4 alkyl-N(R 3 )—S(O) 2 —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-, —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-S(O 2 )—N(R 3 )—, —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-C(O)—N(R 3 )— and —C 0 -C 6 alkyl-heterocyclyl-C 0 -C 3 alkyl-C(O)—O—, wherein each alkyl, heterocyclyl and alkenyl moiety is optionally substituted, and wherein the heterocyclyl moiety is optionally bridged with —(CH 2 ) 0-3 —;

R 1 and R 2 are independently selected from the group consisting of —H, C 1 -C 6 alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl and a protecting group;

each R 3 is independently selected from the group consisting of —H, alkyl, C 0 -C 3 alkyl-heterocyclyl, C 1 -C 3 alkyl-C 2 -C 6 alkenyl, C 1 -C 3 alkyl-C 2 -C 3 alkynyl, —C 2 -C 4 alkyl-OR 1 , —C 2 -C 4 alkyl-NR 3b R 3c , —C 2 -C 4 alkyl-NR 1 R 2 , heteroalkyl, C 0 -C 6 alkylheteroaryl, C(O)CF 3 , —C(O)—NH 2 , —C(O)—NR 3b R 3c , —C(O)—NR 1 R 2 , —C(O)—OR 1 , —S(O) 2 —NR 1 R 2 , —S(O) 2 —R 1 , —C(O)—R 1 , —C 3 -C 6 cycloalkyl, —C 0 -C 3 alkyl-C 3 -C 7 cycloalkyl, —C 1 -C 6 alkylaryl, aryl, C 0 -C 3 alkyl-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 R 3a is independently selected from the group consisting of —H, alkyl, heterocyclyl, C 2 -C 6 alkenyl, C 2 -C 3 alkynyl, C 2 -C 4 alkyl-OR 1 , heteroalkyl, heteroaryl, C 0 -C 6 alkylheteroaryl, C(O)CF 3 , —C(O)—NH 2 , —C 3 -C 6 cycloalkyl, -alkyl-C 3 -C 6 cycloalkyl, —C 1 -C 6 alkylaryl, aryl, alkylheteroaryl and heteroaryl, covalent bond, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl moiety is optionally substituted;

wherein R 3 and R 3a , together with the atom to which they are attached, optionally form a heterocyclic ring, wherein the heterocyclyl moiety is optionally substituted;

wherein R 3b and R 3c , 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 U 1 is H, N(R 3 )(R 3a )—C 2 -C 4 alkyl- or R 3 —O—C 2 -C 4 alkyl-;

is selected from the group consisting of hydrogen, aryl, aryl-alkyl-, heteroaryl, heteroaryl-alkyl-, heterocyclyl, cycloalkyl, heterocyclyl-alkyl, cycloalkyl-alkyl, C 1 -C 10 alkyl, (aryl) 2 -CH—C 0 -C 6 alkyl-, (aryl)(heteroaryl)CH—C 0 -C 6 alkyl- and (heteroaryl) 2 CH—C 0 -C 6 alkyl-, each of which is optionally substituted; or

is a radical selected from the group consisting of

wherein

are independently selected from phenyl, a 5- or 6-membered heteroaryl and a heterocyclyl, wherein each of which is optionally substituted with one to three independently selected substituents;

provided that when

is selected from the group consisting of hydrogen, aryl, aryl-alkyl-, heteroaryl, heteroaryl-alkyl-, heterocyclyl, cycloalkyl, heterocyclyl-alkyl, cycloalkyl-alkyl, C 1 -C 10 alkyl, (aryl) 2 -CH—C 0 -C 6 alkyl-, (aryl)(heteroaryl)CH—C 0 -C 6 alkyl- and (heteroaryl) 2 CH—C 0 -C 6 alkyl-, 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(R 4 )═, 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 M 1 -M 2 is selected from the group consisting of a covalent bond, —N(R 3 )CH 2 —, —CH 2 N(R 3 )—, —S(O) 0-2 —CH 2 —, —CH 2 S(O) 0-2 —, —O—CH 2 —, —CH 2 —O—, —C(O)N(R 3 )—, —C(O)—O—, —C(O)—CH 2 —, —CH(OH)—CH 2 —, —CH(F)—CH 2 —, —CH 2 —C(O)—, —CH 2 —CH(OH)—, —CH 2 —CH(F)—, —N(R 3 )—C(O)—, —SO 2 N(R 3 )—, —N(R 3 )SO 2 —, —CH(R 4 )CH 2 —, —CH 2 CH(R 4 )—, —N═C(R 4 )—, —C(R 4 )═N—, —CH 2 —CH 2 —, —CH═CH—, —CH(R 3 )—CH(R 3 )—, —C(R 3 )═C(R 3 )—, —C(R 4 )═C(R 4 )—, —CF═CH—, —CH═CF—,

—CH 2 —, —C(R 3 )(R 3a )—, —S(O) 0-2 —, —N(R 3 )—, or absent;

M 3 is selected from the group consisting of

or M 3 is

wherein Q is attached to

via ═N—O—, or ═N—O—C 0-3 alkyl, or J is attached to

via ═CH—,

wherein * represents the point of attachment to Q;

M 4 is selected from the group consisting of

and covalent bond;

wherein, when M 1 -M 2 is a covalent bond, M 4 is selected from the group consisting of

the groups D 1 -D 2 and D 1a -D 2a are selected from the group consisting of

wherein, * represents the point of attachment to Q;

D 3 is selected from the group consisting of a covalent bond,

wherein the

are optionally substituted;

D 4 is selected from the group consisting of

wherein the

is optionally substituted;

the group E 1 -E 2 is selected from the group consisting of

wherein * represents the point of attachment to Q; and

E 3 is selected from the group consisting of —C(O)—, —C(S)—, —CH 2 —, —C(OH) 2 — and —C═N(R 3 )—;

and

R 4 is independently selected from the group consisting of —H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl-R 3 , —C 0 -C 6 alkyl-OR 3 , —C 0 -C 6 alkyl-OR 1 , —C 0 -C 6 alkyl-C(O)—OR 3 , —C 0 -C 6 alkyl-C(O)NR 3 R 3a , —CH═CH—C(O)—OR 3 , —CH═CH—C(O)—N(R 3 )(R 3a ), —N(R 3 )—C(O)—CF 3 , —N(R 3 )—C 2 -C 6 alkyl-N(R 3 )(R 3a ), —C 0 -C 6 alkyl-N(R 3 )(R 3a ), —N(R 3 )—C(O)—C 1 -C 6 alkyl-R 3 , —N(R 3 )—S(O) 2 —C 1 -C 6 alkyl-R 3 , —S(O) 2 —N(R 3 )R 3a , —O—C 2 -C 6 alkyl-N(R 3 )(R 3a ), —O—C 2 -C 6 alkyl-OR 1 , —S—R 3 , —S(O)—C 1 -C 6 alkyl-R 3 , —S(O) 2 —C 1 -C 6 alkyl-R 3 , C 3 -C 6 cycloalkyl, heterocyclyl, C 4 -C 7 heterocyclyl-R 3 , —O—C 2 -C 4 alkyl-heterocyclyl, —O-heterocyclyl-C(O)—OR 3 , —O—C 0 -C 4 alkyl-aryl, —O—C 0 -C 4 alkyl-heteroaryl, —O—C(O)—NR 3 —C 0 -C 4 alkyl-aryl, —O—C(O)—NR 3 —C 0 -C 4 alkyl-heteroaryl, —O—C 0 -C 4 alkyl-heterocyclylaryl, —O—C 0 -C 4 alkyl-heterocyclyl-heteroaryl, —N(R 3 )—C 2 -C 4 alkyl-heterocyclyl, —N(R 3 )C(O)N(R 3 )—C 0 -C 4 alkyl-heterocyclyl-R 3 , —C 0 -C 4 alkyl-OC(O)—R 3 , —C 0 -C 4 alkyl-N(R 3 )C(O)—O—R 3 , —C 0 -C 4 alkyl-heterocyclyl-C(O)—O—R 3 , —N(R 3 )—C 2 -C 4 alkyl-heterocyclyl, F, Cl, Br, I, NO 2 , —CF 3 , —OCF 3 , —OCHF 2 , —SCF 3 , —SF 5 , —SO 3 H, —CN, —C 1 -C 6 alkylaryl, aryl, heteroaryl, cycloalkyl, —C 1 -C 6 alkylheteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl moeity of the aformentioned R 4 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 —C 3 -C 8 alkyl-, —C(O)—C 3 -C 8 alkyl-, —C 0 -C 3 alkyl-O—C 3 -C 8 alkyl-, —C 0 -C 3 alkyl-C 1 -C 4 alkenyl-C 0 -C 3 alkyl-, ═N—O—C 1 -C 8 alkyl-, ═N—O—C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, ═N—O—C 0 -C 3 alkyl-aryl-C 0 -C 3 alkenyl-, ═N—O—C 0 -C 3 alkyl-aryl-C 0 -C 3 alkynyl-, ═N—O—C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl-, ═N—O—C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkenyl-, ═N—O—C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkynyl-, —C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-aryl-C 2 -C 4 alkenyl-, —C 0 -C 3 alkyl-aryl-C 2 -C 4 alkynyl-, —C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-heteroaryl-C 1 -C 3 alkenyl-, —C 0 -C 3 alkyl-heteroaryl-C 1 -C 3 alkynyl-, —C 0 -C 3 alkyl-N(R 3 )—C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-N(R 3 )—C 0 -C 3 alkyl-aryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-N(R 3 )—C 0 -C 3 alkyl-aryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-N(R 3 )—C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-N(R 3 )—C 0 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-N(R 3 )—C 0 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-C(O)—N(R 3 )—C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-C(O)—N(R 3 )—C 0 -C 3 alkyl-aryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-aryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-C(O)—N(R 3 )—C 0 -C 3 alkyl-aryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-aryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-C(O)—N(R 3 )—C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-C(O)—N(R 3 )—C 0 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-C(O)—N(R 3 )—C 0 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)—C 0 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-heterocyclyl-C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-O—C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 0 -C 3 alkyl-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkenyl, —C 0 -C 3 alkyl-C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkenyl, —C 0 -C 3 alkyl-N(R 3 )—C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkenyl, —C 0 -C 3 alkyl-O—C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkenyl, —C 0 -C 3 alkyl-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkynyl, —C 0 -C 3 alkyl-C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkynyl, —C 0 -C 3 alkyl-N(R 3 )—C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkynyl, —C 0 -C 3 alkyl-O—C(O)-heterocyclyl-C 0 -C 3 alkyl-aryl-C 2 -C 4 alkynyl, —C 0 -C 3 alkyl-heterocyclyl-C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl, —C 0 -C 3 alkyl-C(O)-heterocyclyl-C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl, —C 0 -C 3 alkyl-N(R 3 )—C(O)-heterocyclyl-C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl, —C 0 -C 3 alkyl-O—C(O)-heterocyclyl-C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl, —C 0 -C 3 alkyl-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-C(O)-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-O—C(O)-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 0 -C 3 alkyl-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-C(O)-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-N(R 3 )—C(O)-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-, —C 0 -C 3 alkyl-O—C(O)-heterocyclyl-C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-, —C 2 -C 4 alkyl-O—C 0 -C 3 alkyl-aryl-, —C 2 -C 4 alkyl-O—C 0 -C 3 alkyl-aryl-C 0 -C 3 alkyl-, —C 2 -C 4 alkyl-O—C 0 -C 3 alkyl-aryl-C 2 -C 4 alkenyl, —C 2 -C 4 alkyl-O—C 0 -C 3 alkyl-aryl-C 2 -C 4 alkynyl, —C 2 -C 4 alkyl-O—C 0 -C 3 alkyl-heteroaryl-C 0 -C 3 alkyl, —C 2 -C 4 alkyl-O—C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkenyl-, —C 2 -C 4 alkyl-O—C 1 -C 3 alkyl-heteroaryl-C 2 -C 3 alkynyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-heteroaryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-N(R 3 )-heteroaryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-U—N(R 3 )-bridged heterocyclyl-heteroaryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-aryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-N(R 3 )-aryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-U—N(R 3 )-bridged heterocyclyl-aryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-aryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-N(R 3 )-aryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-U—N(R 3 )-bridged heterocyclyl-aryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-heteroaryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-U-bridged heterocyclyl-N(R 3 )-heteroaryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-U—N(R 3 )-bridged heterocyclyl-heteroaryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-bridged heterocyclyl-U-heteroaryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-N(R 3 )-bridged heterocyclyl-U-heteroaryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-bridged heterocyclyl-N(R 3 )—U-heteroaryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-bridged heterocyclyl-U-aryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-N(R 3 )-bridged heterocyclyl-U-aryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-bridged heterocyclyl-N(R 3 )—U-aryl-C 0 -C 6 alkyl-,

—C 0 -C 6 alkyl-bridged heterocyclyl-U-aryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-N(R 3 )-bridged heterocyclyl-U-aryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-bridged heterocyclyl-N(R 3 )—U-aryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-bridged heterocyclyl-U-heteroaryl-C 2 -C 6 alkenyl-,

—C 0 -C 6 alkyl-N(R 3 )-bridged heterocyclyl-U-heteroaryl-C 2 -C 6 alkenyl-, and

—C 0 -C 6 alkyl-bridged heterocyclyl-N(R 3 )—U-heteroaryl-C 2 -C 6 alkenyl-,

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 —C 1 -C 13 alkyl-N(R 3 )—C 0 -C 6 alkyl-aryl-C 2 alkenyl-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 R 906 is selected from the group consisting of aryl and heteroaryl;

T 906 is selected from the group consisting of —C 0-6 alkyl-S(O) 2 —C 0-6 alkyl-, —C 0-6 alkyl-C(O)—C 0-6 alkyl- and C 1-3 alkyl, wherein T 906 is substituted at the carbon atom attached to R 906 with a moiety selected from the group consisting of aryl, heteroaryl, cycloalkyl and heterocycle;

A 906 is an optionally substituted unbridged heterocycle;

Q 906 is a bond;

Het is an optionally substituted 5-membered aryl ring;

L 906 is a bond or —C 1-4 alkyl-; and

R 906a is —N(R 906b )OH, wherein R 906b 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 —C 0 -C 4 alkyl-X—C 1 -C 4 alkyl-phenyl-C 2 alkenyl-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 C 1-4 alkyl, a benzyl group or a pyridylmethyl group; and

X is a moiety having a structure selected from the group consisting of —C(O)N(R A1 )—, —O—C(O)—N(R A1 )—, —SO 2 —, —N(R A2 )SO 2 —, wherein R A1 and R A2 are independently —H or optionally substituted C 1 -C 4 alkyl;

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 —CH 2 —; and

provided that Formula (I) excludes compounds of Formula (B)

wherein

R B is H or phenyl;

A B 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, aminoC 1 -C 4 alkyl, mono- or di(C 1 -C 4 )alkyl-aminoC 1 -C 4 alkyl, halogen, C 1 -C 4 alkyl and tri(C 1 -C 4 )alkylammoniumC 1 -C 4 alkyl;

is a chain of 1 to 5 carbon atoms optionally containing a double bond or an NR group, wherein R is H or C 1 -C 4 alkyl;

X B is absent, an oxygen atom or an NR group, wherein R is H or C 1 -C 4 alkyl; and

B B is a phenylene or cyclohexylene ring;

and

provided that Formula (I) excludes compounds of Formula (D)

wherein

A D is selected from the group consisting of a 4- to 10-membered aromatic or non-aromatic heterocyclyl;

X D is C═O or S(O) 2 ;

R D1 is H or C 1 -C 6 alkyl;

R D2 is independently selected from the group consisting of oxo, (C═O)—NH 2 , C 1 -C 6 alkyl-aryl and heterocyclyl, when A D is a non-aromatic heterocycle, wherein said alkyl, and aryl moieties are optionally substituted with one to three R b ; or

R D2 is independently selected from the group consisting of OH, NO 2 , (C═O) 0-1 —O 0-1 —C 1 -C 6 alkyl, CN, (C═O) 0-1 —O 0-1 —C 3 -C 10 cycloakyl, halogen, (C═O) 0-1 —N(R a ) 2 , CF 3 , NH—S(O) 0-2 —R a , (C═O) 0-1 —O 0-1 -heterocyclyl, (C═O) 0-1 —O 0-1 -aryl, S(O) 0-2 —R a , NH(C═O)R a , C 1 -C 6 alkyl-aryl and heterocyclyl, when A D is an aromatic heterocyclyl, wherein said alkyl, cycloalkyl, aryl and heterocyclyl are optionally substituted with one to three R b ;

R a is independently H or C 1 -C 6 alkyl; and

R b is independently selected from the group consisting of oxo, NO 2 , N(R a ) 2 , OH, CN, halogen, CF 3 and C 1 -C 6 alkyl;

and

provided that Formula (I) excludes compounds of Formula (E)

wherein

A E is selected from the group consisting of —CH 2 —O—, —CH 2 —S—, —CH 2 —CH 2 — and —NH—CO—;

X E is selected from the group consisting of —N(R E3 )—, ═C(O) and —CH(OH)—;

Y E is selected from the group consisting of O, S and —N(R E4 )—;

Z E is selected from the group consisting of a straight chain C 4 -C 8 alkylene, wherein one CH 2 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 C 1 -C 4 alkyl and halogen;

R E1 and R E2 are independently selected from the group consisting of H, halogen, C 1 -C 4 alkyl, trifluoromethyl, hydroxy, C 1 -C 4 alkoxy, benzyloxy, C 1 -C 3 alkylenedioxy, nitro, amino, C 1 -C 4 alkylamino, di[(C 1 -C 4 )alkyl]-amino, and C 1 -C 4 alkanoylamino; and

R E3 and R E4 are independently selected from H and C 1 -C 4 alkyl; and

provided that Formula (I) excludes compounds of Formula (F)

A F -Q 1F -J F -Q 2F -C(O)—NH—OH  (F)

wherein

A F is a C 5 -C 20 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;

Q 1F is a linker group having a backbone length of at least 2 carbon atoms, the linker being optionally substituted;

J F is —N(R F )—C(O)— or —C(O)—N(R F )—;

Q 2F is selected from the group consisting of C 1 -C 10 alkyl, C 5 -C 20 aryl, 5 to 20 membered heteroaryl, C 5 -C 20 aryl-C 1 -C 10 alkyl, 5 to 20 membered heteroaryl-C 1 -C 10 alkyl, C 1 -C 10 alkyl-C 5 -C 20 aryl and C 1 -C 10 alkyl-5 to 20 membered heteroaryl, each of which is optionally substituted; and

R F is selected from the group consisting of H, C 1 -C 7 alkyl, C 3 -C 20 heterocyclyl and C 5 -C 20 aryl, each of which is optionally substituted; and

provided that Formula (I) excludes compounds wherein

Z is —N(R 1 )(OR 2 );

R 1 and R 2 are independently selected from the group consisting of H, C 1 -C 6 alkyl, 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, C 1 -C 10 alkyl, (aryl) 2 -CH—C 0 -C 6 alkyl-, (aryl)(heteroaryl)CH—C 0 -C 6 alkyl- and (heteroaryl) 2 CH—C 0 -C 6 alkyl-, each of which is optionally substituted; and

Q comprises a ring selected from the group consisting of

wherein Y F is nitrogen or —CH<, and Z F is oxygen, NH or —CH 2 — if Z F is not bonded to

or Z F is nitrogen or —CH< if Z F is bonded to

or

is selected from the group consisting of b-53, b-62 (wherein D 3 is

b-69 (wherein R 4 is H), b-70, b-72 (wherein D 3 is

b-92 and b-93; and

Q-J is selected from the group consisting of —X F —C 0-4 alkyl-aryl-C 0-4 alkyl-, —X F —C 0-4 alkyl-heteroaryl-C 0-4 alkyl-, and —X F —C 0-4 alkyl-heterocyclyl-C 0-4 alkyl-, wherein said alkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted, and wherein said heterocyclyl is a mono- or bi-saturated or mono- or bi-unsaturated heterocyclic ring, and wherein

X F 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; R 4A is H, C 1-6 alkyl or phenyl; Y F is nitrogen or —CH<, and Z F is oxygen, NH or —CH 2 — if Z F is not bonded to

or Z F is nitrogen or —CH< if Z F is bonded to

and

provided that Formula (I) excludes those compounds having the following structure:

wherein

X 9 is selected from the group consisting of CO, SO 2 and CH 2 ;

Y 9 is selected from the group consisting of N—R 9f , CH—OR 9f , CH—NR 9f R 9i and C═CH—CO—R 9g ;

A 9 and B 9 are independently selected from 5- or 6-membered rings;

R 9a , R 9b , R 9c and R 9d are independently selected from the group consisting of H, halogen, CF 3 , NO 2 , NR 9i R 9j , CN, COOH, (CH 2 ) 0-2 —CONR 9i R 9j , C 1-6 alkyl, OH, O—C 1-6 alkyl, O-cyclopropyl, O—(CH 2 ) 2 —O—C 1-6 alkyl, O—(CH 2 ) 2 —NR 9i R 9j , O—CONHR 9i , CH 2 -Z 9 -R 9h , COR 9i , CR 9i R 9m R 9n , SR 9i , SO 2 R 9o , CR 9i NOR 9i , CR 9i NNR 9i R 9 j, a Q 9 -(CH 2 ) 2-9 CONHOH 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;

R 9e and R 9f are Q 9a -(CH 2 ) 2-9 CONHOH;

R 9g is NH—(CH 2 ) 2-9 CONHOH;

R 9h is a (CH 2 )P—R 9k group, wherein R 9k can be methyl or hydroxyl;

Z 9 is selected from the group consisting of O, NR 9L and S;

Q 9 is selected from the group consisting of a chemical bond, —O—, —S—, —NR 9L —, —NR 9i CO—, —CONR 9i —, —W 9 —, —COW 9 —, wherein W 9 is piperidine or pyrrolidine;

Q 9a is a bond or a —CO—;

R 9i and R 9j are independently H or a C 1-6 alkyl;

R 9L is H or R 9h ;

R 9m and R 9n can either be a fluorine atom or oxygen atoms linked together by an alkyl chain consisting of 2 or 3 CH 2 ; and

1. R 9o is a C 1-6 alkyl; provided that (1) only one (CH 2 ) 2-9 CONHOH is present in the molecule and (2) when X 9 is CO and A 9 and B 9 are both benzene then R 9c and R 9d cannot signify Q 9 -(CH 2 ) 2-9 CONHOH.

2 - 25 . (canceled)

Assignments (1)
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