Acrylamide derivatives as Fab I inhibitors

A compound of formula Ia:

• wherein, independently for each occurrence,
• A is a bicyclic ring of 8-12 atoms containing 0-4 heteroatoms or a tricyclic ring of 8-12 atoms containing 0-6 heteroatoms wherein the rings are independently aliphatic, aromatic, heteroaryl or heterocyclic in nature, the heteroatoms are selected from the group consisting of N, S, and O, and the rings are optionally substituted with one or more groups selected from the group consisting of C1-4 alkyl, OR″, CN, OCF3, F, Cl, Br, and I;
• wherein R″ is selected from the group consisting of H, alkyl, aralkyl, and heteroaralkyl, wherein the heteroaryl group of the heteroaralkyl is a 3-10 membered ring structure containing 1-4 heteroatoms selected from the group consisting of N, S, and O;
• R′ is selected from the group consisting of H and alkyl;
• wherein, independently for each occurrence,
• R3 is selected from the group consisting of H, alkyl, carbonyl, sulfonyl, and aryl;
• or
• a pharmaceutically acceptable salt thereof;
• wherein:
• carbonyl is —C(O)—X50—R55 or —X50—C(O)—R56, where X50 is a bond, oxygen, or sulfur;
• R55 and R56 are hydrogen, alkyl, alkenyl, or —(CH2)m—R61;
• R61 is aryl, cycloalkyl, cycloalkenyl, or heterocyclyl;
• and m is zero or an integer in the range of 1 to 8;
• and sulfonyl is —S(O)2—R58, where R58 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or hetero aryl.

A compound of formula Io:

• wherein:
• R′ is selected from the group consisting of H and alkyl;
• R3 is, independently for each occurrence, selected from the group consisting of H, alkyl, carbonyl, sulfonyl, and aryl;
• or a pharmaceutically acceptable salt thereof;
• wherein:
• carbonyl is —C(O)—X50—R55 or —X50—C(O)—R56, where X50 is a bond, oxygen, or sulfur;
• R55 and R56 are hydrogen, alkyl, alkenyl, or —(CH2)m—R61;
• R61 is aryl, cycloalkyl, cycloalkenyl, or heterocyclyl;
• and m is zero or an integer in the range of 1 to 8;
• and sulfonyl is —S(O)2—R58, where R58 is alkyl, alkenyl, alkenyl, cycloalkyl, heterocyclyl, aryl, or hetero aryl.

A compound selected from the group consisting of:

• (R,E)-(3,3-dimethyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-8-yl)-N-(1(3-ethylbenzofuran-2-yl)ethyl)-N-methylacrylamide;
• (E)-N-((1,3-dimethyl-1H-indol-2-yl)methyl)-N-methyl-3-(2-oxo-4-phenyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide;
• and
• (E)-N-((3-ethylbenzofuran-2-yl)methyl)-N-methyl-3-(8-oxo-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepin-3-yl)acrylamide, and pharmaceutically acceptable salts thereof.