Patent CA-1337526-C (CA)
Inventor: CARLSON RANDALL KENT
IPC: C07D413/10
Filed: 1989-07-28
Granted: 1995-11-07
Abstract: Antibacterial arylbenzene oxazolidone pharmaceutical of the following formula:       (I) wherein, for the ?, and mixtures of the d and ? stereoisomers of the compound Ar is an aromatic group selected from the group consisting of         ,             , a diazinyl group optionally substituted with X and Y, a triazinyl group optionally substituted with X and Y,     ,                   ,              ,            and               ;            Z is O, S, or NR5, W is CH or N, or also can be S or O when Z is NR5; X independently is H, -NO2, -S(O)nRI, tetrazoyl,   -S(O)2-N=S(O)pR2R3, -SH,      , -COR23,   -CONR5R6,       ,   ,    , R6R5N-(CH2),  , -CN, -OR5, halogen, -NR5R6,      ,        , -CR23(OR16)OR17,    alkyl of 1 to 8 carbons optionally substituted with one or more halogen atoms, OH, =O other than at alpha position, S(O)nR24, or NR5R6, alkenyl of 2-5 carbons or cycloalkyl of 3-8 carbons; R1 is C1-C4 alkyl, optionally substituted with one or more halogen atoms, OH, CN, NR5R6 or CO2R8;             C2-C4 alkenyl; -NR9R10; -N3;   -NHCR4   ; -NMCR4 ; -NG2; NR9G-NGM+; R2 and R3 are independently C1-C2 alkyl or, taken together are -(CH2)q-; R4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens; R5 and R6 are independently H, alkyl of 1-8 carbons, cycloalkyl of 3-8 carbons -(CH2)tOR8, - (CH2)tNR11R11a, or -O(CH2)tNR11R11a; or taken together are -(CH2)2O(CH2)2-, -(CH2)tCH(COR4)-, or     R7 is -NR5R6, -OR5 or R8 is H or alkyl of 1-4 carbons; R9 is H, C1-C4 alkyl or C3-C8 cycloalkyl; R10 is H, C1-C4 alkyl, C2-C4 alkenyl, C3-C4 cycloalkyl, -OR8 or -NR11R11A; R11 and R11A are independently H or C1-C4 alkyl, or taken together, are -(CH2)t-; G is Cl, Br or I; Y independently is H, F, Cl, Br, OR8, alkyl of 1-3 carbons, or NO2;            X and Y taken together (a) when Ar is         or   to form a fused six-membered carbocyclic ring, or (b) when Ar is   to form   M is a physiologically acceptable cation; n is 0, 1 or 2 p is 0 or 1; q is 3, 4 or 5; r is 4 or 5; t is 1, 2 or 3;                     B is -NH2, or N3; R12 is H, C1-C10 alkyl or C3-C8 cycloalkyl; R13 is H; C1-C4 alkyl optionally substituted with one or more halogen atoms; C2-C4 alkenyl; C3-C4 cycloalkyl; phenyl, -CH2OR15; -CH(OR16)OR11;              -CH2S(O)vR14;     ; -OR18; -SR14; -CH2N3; the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine; -NR19R20; or -C(NH2)R21R22; R14   is C1-C4 alkyl, optionally substituted with one or more halogen atoms; R15   is H or C1-C4 alkyl, optionally substituted with one or  more halogen atoms; R16   and R17 are independently C1-C4 alkyl or, taken together, are -(CH2)m-; R18   is C1-C4 alkyl or C7-C11 aralkyl; R19 and R20 are independently H or C1-C2 alkyl;-R21 and R22 are independently H, C1-C4 alkyl, C3-C6 cycloalkyl, phenyl or, taken together, are -(CH2)s-; u is 1 or 2; v is 0, 1 or 2; m is 2 or 3; s is 2, 3, 4 or 5; R23   is H, alkyl of 1-8 carbons optionally substituted with one or more halogens, cycloalkyl of 3-8 carbons, alkyl of 1-4 carbons substituted with one or more of - S (O)nR24, -OR8   , or -NR5R6; or alkenyl of 2-5 carbons optionally substituted with CHO or CO2R8; R24   is alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons; and R25   is R6 or NR5R6; or a pharmaceutically suitable salt thereof; provided that:                                . 1)   when B is NH2, then Ar is not phenyl optionally substituted with halogen or CF3.