Claims
- 1. A compound of the formula or a pharmaceutically acceptable salt thereof wherein:R1 is a) H, b) C1-8 alkyl or C1-8 alkyl substituted with one or more F, Cl, OH, C1-8 alkoxy, or C1-8 acyloxy, c) C3-6 cycloalkyl, or d) C1-8 alkoxy; L is oxygen or sulfur; A is c) a 5-membered heteroaromatic moiety having one to three hetero atoms selected from the group consisting of S, N, and O, wherein the 5-membered heteroaromatic moiety is bonded via a carbon atom and is unsubstituted or substituted with one to three R8, d) a 6-membered heteroaromatic moiety having at least one nitrogen atom, wherein the heteroaromatic moiety is bonded via a carbon atom and is unsubstituted or substituted with one to three R9, e) a β-carbolin-3-yl, or indolizinyl bonded via the 6-membered ring, said β-carbolin-3-yl or indoliziny moiety being unsubstituted or substituted with one to three R9, wherein R2 and R3 are each independently a) H, b) F, c) Cl, d) Br, e) C1-6 alkyl, f) NO2, g) I, h) C1-6 alkoxy, i) OH j) amino, k) cyano, or l) R2 and R3 taken together are —O(CH2)h—O; wherein R4 is a) H, b) C1-2 alkyl, c) F,or d) OH; R5 is a) H, b) CF3, c) C1-3 alkyl or C1-3 alkyl substituted with one or more halo, d) phenyl or phenyl substituted with one or more halo, e) R5 and R6 taken together are a 5-, 6-, or 7-membered ring of the formula, in which D is S, O or NR86 in which R86 is H or C1-6 alkyl; R6 and R7 at each occurrence are the same or different and are a) H, b) CF3, c) C1-3 alkyl or C1-3 alkyl substituted with one halo, or d) R6 and R7 taken together are a 5-, 6-, or 7-membered ring of the formula, U is a) CH2, b) O, c) S or, d) NR16; R16 is a) H or b) —C1-5 alkyl; wherein R8 is a) carboxyl, b) halo, c) —CN, d) mercapto, e) formyl, f) CF3, g) NO2, h) C1-6 alkoxy, i) C1-6 alkoxycarbonyl, j) C1-6 alkythio, k) C1-6 acyl, l) —NR17R18, in which R87 is H or C1-6 alkyl, n) C1-6 alkyl or C1-6 alkyl substituted with OH, sulfamoyl, C1-5 alkoxy, C1-5 acyl, or —NR17R18, o) C2-8 alkyl or C2-8 alkyl substituted with one or two R19, p) phenyl or phenyl substituted with one or two R19, q) a 5- or 6-membered saturated or unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, said heterocyclic moiety being unsubstituted or substituted with one or two R19, or R17 and R18 at each occurrence are the same or different and are a) H, b) C1-4 alkyl, c) C5-6 cycloalkyl, or d) R17 and R18 taken together with the nitrogen atom is a 5- or 6-membered saturated or unsaturated heterocyclic moiety said heterocyclic moiety being unsubstituted or substituted with C1-3 alkyl, formyl, a 5- or 6-membered heteroaromatic moiety containing 1-3 O, N or S, in which R88 and R89 are each independently hydrogen or C1-6 alkyl, SO2R90 in which R90 is H or C1-6 alkyl, or unsubstituted C1-3 acyl or C1-3 acyl substituted with 1 or more F, Cl or OH; R19 is a) carboxyl, b) halo, c) —CN, d) mercapto, e) formyl, f) CF3, g) NO2, h) C1-6 alkoxy, i) C1-6 alkoxycarbonyl, j) C1-6 alkythio, k) C1-6 acyl, l) C1-6 alkyl or C1-6 alkyl substituted with OH, C1-5 alkoxy, C1-5 acyl, or —NR17R1-8, m) phenyl, n) —C(═O)NR20R21, o) —N R17R18, p) —N(R20)(—SO2R22), q) —SO2—NR20R21, or r) —S(═O)iR22; R20 and R21 at each occurrence are the same or different and are a) H, b) C1-6 alkyl, or c) phenyl; R22 is a) C1-4 alkyl, or b) phenyl or phenyl substituted with C1-4 alkyl; wherein R9 is a) carboxyl, b) halo, c) —CN, d) mercapto, e) formyl, f) CF3, g) NO2, h) C1-6 alkoxy, i) C1-6 alkoxycarbonyl, j) C1-6 alkythio, k) C1-6 acyl, l) —NR23R24, m) C1-6 alkyl or C1-6 alkyl substituted with OH, C1-5 alkoxy, C1-5 acyl, or —NR23R24, n) C2-8 alkenylphenyl unsubstituted or substituted with one or two R25, o) phenyl or phenyl substituted with one or two R25, p) a 5- or 6-membered saturated or unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, said moiety being unsubstituted or substituted with one or two R25, or R23 and R24 at each occurrence are the same or different and are a) H, b) formyl, c) C1-4 alkyl, d) C1-4 acyl, e) phenyl, f) C3-6 cycloalkyl, or g) R23 and R24 taken together with the nitrogen atom is a 5- or 6-membered saturated heterocyclic moiety said heterocyclic moiety being unsubstituted or substituted with phenyl, pyrimidyl, C1-3 alkyl, or C1-3 acyl; R25 is a) carboxyl, b) halo, c) —CN, d) mercapto, e) formyl, f) CF3, g) NO2, h) C1-6 alkoxy, i) C1-6 alkoxycarbonyl, j) C1-6 alkythio, k) C1-6 acyl, l) phenyl, m) C1-6 alkyl or C1-6 alkyl substituted with OH, azido, C1-5 alkoxy, C1-5 acyl, —NR32R33, —SR34, —O—SO2R35, or n) —C(═O)NR26R27, o) —NR23R24, p) —N(R26)(—SO2R22), q) —SO2—NR26R27, or r) —S(═O)iR22, s) —CH═N—R28, or t) —CH(OH)—SO3R31; R22 is the same as defined above; R26 and R27 at each occurrence are the same or different and are a) H, b) C1-6 alkyl, c) phenyl, or d) tolyl; R28 is a) OH, b) benzyloxy, c) —NH—C(═O)—NH2, d) —NH—C(═S)—NH2, or e) —NH—C(═NH)—NR29R30; R29 and R30 at each occurrence are the same or different and are a) H, or b) C1-4 alkyl or C1-4 alkyl substituted with phenyl or pyridyl; R31 is a) H, or b) a sodium ion; R32 and R33 at each occurrence are the same or different and are a) H, b) formyl, c) C1-4 alkyl, d) C1-4 acyl, e) phenyl, f) C3-6 cycloalkyl, g) R32 and R33 taken together are a 5- or 6-membered saturated heterocyclic moiety having one to three atoms selected from the group consisting of S, N, O, said heterocyclic moiety being unsubstituted or substituted on a carbon or nitrogen atom with phenyl, pyrimidyl, C1-3 alkyl, or C1-3 acyl, h) —P(O)(OR37)(OR38), or i) —SO2—R39; R35 is C1-3 alkyl; R36 is a) C1-6 alkoxycarbonyl, or b) carboxyl; R37 and R38 at each occurrence are the same or different and are a) H, or b) C1-3 alkyl; R39 is a) methyl, b) phenyl, or c) tolyl; wherein K is a) O, b) S, or c) NR40 in which R40 is hydrogen, formyl, C1-4 alkyl, C1-4 acyl, phenyl, C3-6 cycloalkyl, —P(O)(OR37)(OR38) or —SO2—R39 in which R37, R38 and R39 are as defined above; R10, R11, R12, R13, R14 and R15 at each occurrence are the same or different and are a) H, b) formyl, c) carboxyl, d) C1-6 alkoxycarbonyl, e) C1-8 alkyl, f) C2-8 alkenyl, wherein the substituents (e) and (f) are unsubstituted or substituted with OH, halo, C1-6 alkoxyl, C1-6 acyl, C1-6 alkylthio or C1-6 alkoxycarbonyl, or phenyl or phenyl substituted with halo, g) phenyl or naphthyl being unsubstituted or substituted with carboxyl, halo, —CN, formyl, CF3, NO2, C1-6 alkyl, C1-6 alkoxy, C1-6 acyl, C1-6 alkylthio, or C1-6 alkoxycarbonyl; h) —NR42R43, i) OR44, j) —S(═O)i—R45, k) —SO2—N(R46)(R47), or l) a radical having the formula: R19 is the same as defined above; T is a) O, b) S, or c) SO2; R42 and R43 at each occurrence are the same or different and are a) H, b) C3-6 cycloalkyl, c) phenyl, d) C1-6 acyl, e) C1-8 alkyl or C1-8 alkyl substituted with OH, C1-6 alkoxy which is unsubstituted or substituted with OH, a 5- or 6-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, phenyl or phenyl substituted with OH, CF3, halo, —NO2, C1-4 alkoxy, —NR48R49, or V is a) O, b) CH2, or c) NR56; R48 and R49 at each occurrence are the same or different and are a) H, or b) C1-4 alkyl; R54 is a) OH, b) C1-4 alkoxy, or c) —NR57R58; R55 is a) H, or b) C1-7 alkyl or C1-7 alkyl substituted with indolyl, OH, mercaptyl, imidazolyl, methylthio, amino, phenyl optionally substituted with OH, —C(═O)—NH2, —CO2H, or —C(═NH)—NH2; R56 is a) H, b) phenyl, or c) C1-6 alkyl or C1-6 alkyl substituted by OH; R57 and R58 at each occurrence are the same or different and are a) H, b) C1-5 alkyl, c) C1-3 cycloalkyl, or d) phenyl; R44 is a) C1-8 alkyl or C1-8 alkyl substituted with C1-6 alkoxy or C1-6 hydroxy, C3-6 cycloalkyl, a 6-membered aromatic moiety or a 6-membered aromatic benzo-fused heterocyclic moiety having one to three nitrogen atoms, said aromatic moiety being unsubstituted or substituted with one or two —NO2, CF3, halo, —CN, OH, C1-5 alkyl, C1-5 alkoxy, or C1-5 acyl, c) phenyl, or d) pyridyl; R45 is a) C1-16 alkyl, b) C2-16 alkenyl, wherein the substituents (a) and (b) are unsubstituted or substituted with C1-6 alkoxycarbonyl, or a 5-, 6-, or 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, c) phenyl or naphthyl, or d) a 5-, 6-, or 7-membered aromatic heterocyclic moiety having one to three atoms selected from the group of S, N, and O, wherein the substituents (c) and (d) are unsubstituted or substituted with carboxyl, halo, —CN, formyl, CF3, —NO2, C1-6 alkyl, C1-6 alkoxy, C1-6 acyl, C1-6 alkylthio, or C1-6 alkoxycarbonyl; R46 and R47 at each occurrence are the same or different and are a) H, b) phenyl, c) C1-6 alkyl, or d) benzyl; R50 and R51 at each occurrence are the same or different and are a) H, b) OH, c) C1-6 alkyl or C1-6 alkyl substituted with —NR48R49 in which R48 and R49 are as defined above, d) R50 and R51 taken together are ═O; R52 is a) phenyl or naphthyl, b) a 5- or 6-membered aromatic heterocyclic moiety or 5- or 6-membered benzo-fused heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, wherein the substituents (a) and (b) are be unsubstituted or substituted with one or three —NO2, CF3, halo, —CN, OH, phenyl, C1-5 alkyl, C1-5 alkoxy, or C1-5 acyl, c) morpholinyl, d) OH, e) C1-6 alkoxy, f) —NR48R49 in which R48 and R49 are as defined above, g) —C(═O)—R59, or R53 is a) H, b) formyl, c) C1-4 alkyl, d) C1-4 acyl, e) phenyl, f) C3-6 cycloalkyl, g) —P(O)(OR37)(OR38), or h) —SO2R39, in which R37, R38 and R39 are as defined above; R59 is a) morpholinyl, b) OH, or c) C1-6 alkoxy; h is 1, 2, or 3; i is 0, 1, or 2; j is 0, or 1; r is 1, 2, 3, 4, 5 or 6; t is 0, 1, 2, 3, 4, 5, or 6; u is 1 or 2; and Q is a) hydrogen, b) halo, c) NO2, d) N3, e) C1-C6 alkylthio, h) C1-C6 alkyl, i) C1-C6 alkoxy, j) formyl, m) -sulfamoyl (H2NSO2—), n) —NHOH, in which heteroaryl is a 5- or 6-membered aromatic heterocyclic group having 1-3 hetero atoms selected from O, N or S, r) amino, s) C1-C6 alkylamino, t) di(C1-C6 alkyl)amino-, in which R60 and R61 are each independently hydrogen or C1-C6 alkyl, v) OH, w) cyano, x) hydroxy (C1-C6 alkyl), in which r is 1-6, in which R84 is hydrogen or C1-6 alkyl, in which R85 is hydrogen, C1-8 alkyl or C1-8 alkyl substituted with one or more F, Cl, OH, C1-8 alkoxy or C1-8 acyloxy, C3-6 cycloalkyl or C1-8 alkoxy; in which R84 is hydrogen or C1-6 alkyl, ff) a substituted or unsubstituted C6-C10 aryl moiety, gg) a substituted or unsubstituted monocyclic or bicyclic, saturated or unsaturated, heterocyclic moiety having 1-3 atoms selected from O, N or S, said ring being bonded via a ring carbon or nitrogen to the phenyl substituent, hh) a monocyclic or bicyclic substituted or unsubstituted heteroaromatic moiety having 1-3 hetero atoms selected from O, N or S, said ring being bonded via a ring carbon or nitrogen to the phenyl substituent; the substituents for such p, q, ff, gg and hh moieties being selected from 1 or 2 of the following: 1) halo, 2) C1-6 alkyl, 3) NO2, 4) N3, 7) formyl, in which heteroaryl is a 5- or 6-membered aromatic heterocyclic group having 1-3 hetero atoms selected from O, N or S, in which R60 and R61 are each independently hydrogen or C1-C6 alkyl, 13) OH, 14) hydroxy (C1-C6 alkyl), in which r is 1-6, 18) —CH2—R80 in which R80 is a) —OR32 in which R32 is as defined above, b) —SR32 in which R32 is as defined above, c) —NR32R33 in which R32 and R33 are as defined above, or d) 5- or 6-membered heteroaromatic containing 1-4 O, S or N atoms, in which R84 is as defined above, 20) cyano, 21) carboxyl, 22) CF3, in which the phenyl moiety may be unsubstituted or substituted by halo or (C1-C6)alkyl, in which R60 and R61 are as defined above, in which R91 is a 5- or 6-membered aromatic heterocyclic group having 1-3 O, N or S, in which R85 is as defined above, in which R99, R100 and R101 are each independently C1-6 alkyl; or Q and either R1 and R2 taken together form —O—CH2—O.
- 2. A compound of claim 1 wherein A is in which Q, R2 and R3 are as defined in claim 1.
- 3. A compound of the formula or a pharmaceutically acceptable salt thereof, in whichR1 is H, C1-8 alkyl unsubstituted or substituted with one or more F, Cl, OH, C1-8 alkoxy, or C1-8 acyloxy, C3-6 cycloalkyl or C1-8 alkoxy; R2 and R3 are each independently a) H, b) F, c) Cl, d) Br, e) C1-6 alkyl, f) NO2, g) I, h) C1-6 alkoxy, i) OH j) amino, or k) cyano; and Q is a) hydrogen, b) halo, c) NO2, d) N3, e) C1-C6 alkylthio, h) C1-C6 alkyl, i) C1-C6 alkoxy, j) formyl, in which heteroaryl is a 5- or 6-membered aromatic heterocyclic group having 1-3 hetero atoms selected from O, N or S, p) amino, q) C1-C6 alkylamino-, r) di(C1-C6 alkyl)amino-, in which R60 and R61 are each independently hydrogen or C1-C6 alkyl, t) OH, u) cyano, v) hydroxy (C1-C6 alkyl), in which r is 1-6, wherein R84 is hydrogen or C1-6 alkyl, in which R85 is hydrogen, C1-8 alkyl or C1-8 alkyl substituted with one or more F, Cl, OH, C1-8 alkoxy or C1-8 acyloxy, C3-6 cycloalkyl or C1-8 alkoxy, in which R84 is as defined above, in which R92 is H or C1-6 alkyl, M is a) H, b) C1-8 alkyl, c) C3-8 cycloalkyl, d) —(CH2)mOR66, or e) —(CH2)nNR67R68; Z is a) O, b) S or c) NM; W is a) CH, b) N or c) S or O when Z is NM; X and Y are each independently a) hydrogen, b) halo, c) NO2, d) N3, e) C1-6 alkythio, h) C1-C6 alkyl, i) C1-C6 alkoxy, j) formyl, in which heteroaryl is a 5- or 6-membered aromatic heterocyclic group having 1-3 hetero atoms selected from O, N or S, o) amino, p) C1-C6 alkylamino-, q) di(C1-C6 alkyl)amino-, in which R60 and R61 are each independently hydrogen or C1-C6 alkyl, s) OH, t) hydroxy (C1-C6 alkyl), in which r is 1-6, in which R84 is as defined above, z) cyano, aa) carboxyl, bb) CF3, cc) mercapto, in which the phenyl moiety is unsubstituted or substituted by halo or C1-C6 alkyl, in which R85 is as defined above, or in which R99, R100 and R101 are each independently C1-6 alkyl; or Q and either R1 and R3 taken together form —O—CH2—O; R62 is a) H, b) C1-8 alkyl or C1-8 alkyl substituted with one or more halos, or c) C1-8 alkyl or C1-8 alkyl substituted with one or more OH, or C1-8 alkoxy; E is a) NR69, b) —S(═O)i in which i is 0, 1 or 2, or c) O; R63 is a) H, b) C1-6 alkyl, c) —(CH2)q-aryl, or d) halo; R66 is H or C1-4 alkyl; R67 and R68 are each independently H or C1-4 alkyl, or NR67R68 taken together are —(CH2)m—; R69 is a) H, b) C1-6 alkyl, c) —(CH2)q-aryl, d) —CO2R81, e) COR82, f) —C(═O)—(CH2)q—C(═O)R81, g) —S(═O)z—C1-6 alkyl, h) —S(═O)z—(CH2)q-aryl, or i) —(C═O)j-Het in which j is 0 or 1 and Het represents a 5 to 10 membered saturated, unsaturated or aromatic heterocyclic ring containing at least one O, S or N; Z1 is a) —CH2—, or b) —CH(R70)—CH2—; Z2 is a) —O2S—, b) —O—, c) —S—, d) —SO—, or e) —N(R71)—; Z3 is a) S, b) SO, c) SO2, or d) O; A1 is H or CH3; A2 is a) H, b) OH—, c) CH3CO2—, d) CH3—, e) CH3O—, f) R72O—CH2—C(O)—NH—, g) R73O—C(O)—NH—, h) R73—C(O)—NH—, i) (C1-C2)alkyl-O—C(O)—, or j) HO—CH2; or A1 and A2 taken together are b) O═; R64 is H or CH3—; m is 4 or 5; n is 0, 1, 2, 3, 4 or 5; y is 0 or 1; p is 0, 1, 2, 3, 4 or 5; w is 1, 2 or 3; q is 1, 2, 3 or 4; z is 0 or 1; R65 is a) R74OC(R75)(R76)—C(O)—, b) R77OC(O)—, c) R78(O)—, d) R79—SO2—, or e) R80—NH—C(O)—; R70 is H or (C1-C3)alkyl; R71 is a) R74OC(R75)(R76)—C(O)—, b) R77O—C(O)—, c) R78—C(O)—, f) H3C—C(O)—(CH2)2—C(O)—, g) R79—SO2—, i) R80—NH—C(O)—, R72 is a) H, b) CH3, c) phenyl —CH2—, or d) CH3C(O)—; R73 is (C1-C3)alkyl or phenyl; R74 is H, CH3, phenyl-CH2— or CH3—C(O)—; R75 and R76 are each independently H or CH3, or R75 and R76 taken together are —CH2CH2—; R77 is (C1-C3)alkyl or phenyl; R78 is H, (C1-C4)alkyl, aryl-(CH2)n1, ClH2C, Cl2HC, FH2C—, F2HC— or (C3-C6)cycloalkyl; R79 is CH3; —CH2Cl, —CH2CH═CH2, aryl or —CH2CN; R80 is —(CH2)n1-aryl where n1 is 0 or 1; R81 is a) H, b) C1-6 alkyl or C1-6 alkyl substituted with one or more OH, halo or CN, c) —(CH2)q-aryl in which q is as defined above, or d) —(CH2)q—OR83 in which q is as defined above; R82 is a) C1-6 alkyl or C1-6 alkyl substituted with one or more OH, halo or CN, b) —(CH2)q-aryl in which q is as defined above, or c) —(CH2)q—OR83 in which q is as defined above; R83 is a) H, b) C1-6 alkyl, c) —(CH2)q-aryl in which q is as defined above; or d) —C(═O) C1-6 alkyl; and aryl is phenyl, pyridyl or naphthyl, said phenyl, pyridyl or naphthyl moieties being unsubstituted or substituted by one or more halo, —CN, OH, SH, C1-6 alkoxy or C1-6 alkylthio.
- 4. A compound of the formula or a pharmaceutically acceptable salt thereof, in whichR1 is H, C1-8 alkyl unsubstituted or substituted with one or more F, Cl, OH, C1-8 alkoxy or C1-8 acyloxy, C3-6 cycloalkyl or C1-8 alkoxy; R2 and R3 are each independently H or F; or R2 and R3 taken together represent Q is a) hydrogen, b) halo, c) N3, d) NO2, e) C1-C6 alkylthio, h) C1-C6 alkyl, i) C1-C6 alkoxy, j) formyl, n) (C1-C6 alkoxy)2N—, o) 5- or 6-membered saturated or unsaturated heterocyclic containing 1-3 O, N or S and linked to the phenyl substituent via a carbon or nitrogen, said heterocycle moiety being unsubstituted or substituted by R96, q) phenyl or phenyl substituted by R96, and R96 is a) C1-C6 alkyl-OH, d) cyano, e) formyl, in which R84, R85 and R86 are each independently C1-C6 alkyl, where the phenyl is unsubstituted or substituted by halo, m) (C1-C6 alkyl)2N—, n) C1-C6 alkyl-NH—, o) amino, in which R98 is phenyl, 5- or 6-membered heteroaryl containing 1-3 O, N or S and linked to the phenyl substituent via a ring carbon atom or 5- or 6-membered saturated or unsaturated heterocyclic containing 1-4 O, N or S and linked to the phenyl substituent via a ring carbon atom.
- 5. A compound selected from the group consisting of:
- 6. A pharmaceutical composition comprising a compound of claim 1 in admixture with a pharmaceutically acceptable carrier.
- 7. A method of treating a bacterial infection in a mammal which comprises administering a therapeutically effective amount of a compound of claim 1 to a mammal in need thereof.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of application Ser. No. 09/379,222 filed Aug. 23, 1999, now abandoned, which claims the benefit of U.S. Provisional Application Ser. No. 60/097,574 filed Aug. 24, 1998.
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Continuations (1)
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| Child |
09/782120 |
|
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Patent Grant
6420349
