Ring-fused thiazolino 2-pyridones, methods for preparation thereof and their use in the treatment and/or prevention of tuberculosis

A method for treatment of tuberculosis comprising administering to a mammal in need of treatment thereof an effective amount of a drug against tuberculosis,

• or a pharmaceutically acceptable salt thereof;
• and an effective amount of a compound of Formula H
• or a pharmaceutically acceptable salt thereof,
• wherein
• R1 is selected from the group consisting of:
• a) C(O)OH,
• b) tetrazolyl,
• c) CH2OH,
• d) C(O)NR6aR6b,
• e) C(O)NHSO2R7,
• f) C(O)OR8,
• g) NH2,
• h) H,
• i)
• j)
• and
• k)
• R2 is selected from the group consisting of:
• a) H
• b) Cl, F, Br or I,
• c) CH2OH,
• d) C1-C4alkyl, and
• e) NY1Y2,
• R3 is selected from the group consisting of:
• a) 1-naphtyl, 2-naphtyl, and 1-naphtyloxy, each independently substituted with 0, 1, 2 or 3 substituents selected from the group consisting of methyl, fluoro, chloro, bromo, cyano, and methoxy,
• b) phenyl substituted with 0,1, 2 or 3 substituents independently selected from the group consisting of methyl, fluoro, chloro, cyano, and trifluoromethyl,
• c) aminophenyl substituted with 0,1, 2 or 3 substituents independently selected from the group consisting of methyl, fluoro, chloro, and trifluoromethyl,
• d) 2-(3-methyl)phenylmethylene,
• e) benzothiophen-2-yl,
• f) H or C1-C4-alkyl,
• g) 2-methyl-1-aza-2-bora-1H-naphth-5-yloxy, and
• h) 2-methyl-1-aza-2-bora-1H-naphth-5-yl,
• R4 is selected from the group consisting of:
• a) C1-C4alkyl substituted by 0, 1, 2, 3 or 4 fluoro;
• b) C3-C6cycloalkyl,
• c) C1-C4alkoxy substituted by 0, 1, 2, 3 or 4 fluoro,
• d) C3-C6cycloalkoxy,
• e) a 3-, 4-, 5-or 6-membered heterocycle,
• f) N-methyl 3-indolyl, and
• g) NR9R10,
• R5 is selected from the group consisting of:
• a) H
• b) phenyl substituted with 0, 1, 2 or 3 methyl group(s),
• c) benzyl,
• d) thienyl,
• e) C1-C4alkoxy, and
• f) 3-, 4-, 5-or 6-membered heterocycle, and in the above definitions:
• R6a is selected from the group consisting of H and C1-C4alkyl,
• R6b is selected from the group consisting of H, C1-C4alkoxy, and isonicotinoylamino;
• R7 is C1-C4alkyl or phenyl,
• R8 represents 2-{2-[1-(hydroxymethyl)propylamino]ethylamino}butyl),
• R9a represents C1-C4 alkyl,
• R9b represents C1-C4alkyl,
• R10 represents C1-C4alkyl, or
• R9 and R10 together form CH2(CH2)m CH2,
• Y1 and Y2 each independently represents hydrogen, methyl, CH3S(O)2 or C(O)CH3, or
• Y1 and Y2 together form CH2CH2CH2CH2 or CH2CH2CH2CH2CH2,
• m is 1, 2 or 3, and
• X is S, SO or SO2, thereby treating tuberculosis.