US 4,705,799 AGranted

Aminomethyl oxooxazolidinyl benzenes useful as antibacterial agents

AssigneeE. I. Du Pont de Nemours and Company

InventorWalter A. Gregory

Life of this patent

Estimating the term…

Abstract

Novel aminomethyl oxooxazolidinyl benzene derivatives, including the sulfides, sulfoxides, sulfones and sulfonamides, such as (l)-N-[3-[4-(methylsulfinyl)phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide, possess useful antibacterial activity.

Claims100

Dependent claims

A compound of the formula ##STR89## wherein, for the l, and mixtures of the d and l stereoisomers of the compound, ##STR90## alkyl of 1 to 8 carbons, optionally substituted with one or more halogen atoms, OH, .dbd.O other than at alpha position, S(O).sub.n R.sub.24, NR.sub.5 R.sub.6, alkenyl of 2-5 carbons, alkynyl of 2-5 carbons or cycloalkyl of 3-8 carbons;

R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, OH, CN, NR.sub.5 R.sub.6
or CO.sub.2 R.sub.8 ;
C.sub.2 -C.sub.4 alkenyl;
--NR.sub.9 R.sub.10 ;
--N.sub.3 ;
##STR91## --NX.sub.2 ;
NR.sub.9 X --.sup.- NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --;
R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens;
R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.7 is --NR.sub.5 R.sub.6, --OR.sub.5 or ##STR92## R.sub.8 is H or alkyl of 1-4 carbons;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --;
X is Cl, Br or I;
Y is H, F, Cl, Br, alkyl of 1-3 carbons, or NO.sub.2, or A and Y taken together can be --O--(CH.sub.2).sub.t O--;
Z 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 --NH.sub.2, ##STR93## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CH.sub.2 S(O).sub.v R.sub.14 ;
##STR94## --OR.sub.18 ;
--SR.sub.14 ;
--CH.sub.2 N.sub.3 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
--NR.sub.19 R.sub.20 ;
or C(NH.sub.2)R.sub.21 R.sub.22 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s --;
u is 1 or 2;
v is 0, 1 or 2;
m is 2 or 3;
s is 2, 3, 4 or 5;
and
R.sub.23 is H, alkyl of 1-8 carbons optionally substituted with one or more halogens, or cycloalkyl of 3-8 carbons;
R.sub.24 is alkyl of 1-4 carbons or cycloalkyl of
- 8carbons;
R.sub.25 is alkyl of 1-4 carbons substituted with
one or more of --S(O).sub.n R.sub.24, --OR.sub.8, ##STR95## --NR.sub.5 R.sub.6, or alkenyl of 2-5 carbons optionally substituted with CHO;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR96## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR97## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR98## then R.sub.12 is H;
(4) when A is --CN, B is not --N.sub.3 ;
(5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl;
(6) when A is OR.sub.5, then B is not NH.sub.2 ;
(7) when A is F, then B is not NHCO.sub.2 CH.sub.3.

58 more elements

A compound of the formula ##STR99## wherein, for the l, and mixtures of the d and l stereoisomers of the compound,

A is --NO.sub.2, --S(O).sub.n R.sub.1, --S(O).sub.2 --N.dbd.S(O).sub.p R.sub.2 R.sub.3, --SH, ##STR100## alkyl of 1 to 5 carbons, optionally substituted with one or more halogen atoms, alkenyl of 2-5 carbons, alkynyl of 2-5 carbons or cycloalkyl of 3-8 carbons;
R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, CN, NR.sub.5 R.sub.6 or CO.sub.2 R.sub.8 ;
C.sub.2 -C.sub.4 alkenyl;
--NR.sub.9 R.sub.10 ;
--N.sub.3 ;
##STR101## --NX.sub.2 ;
NR.sub.9 X --.sup.-NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --;
R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens;
R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.7 is --NR.sub.5 R.sub.6, --OR.sub.5 or ##STR102## R.sub.8 is H or alkyl of 1-4 carbons;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --;
X is Cl, Br or I;
Y is H, F, Cl, Br or NO.sub.2, or A and Y taken together can be --O--(CH.sub.2).sub.t O--;
Z 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 --NH.sub.2, ##STR103## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CH.sub.2 S(O).sub.v R.sub.14 ;
##STR104## --OR.sub.18 ;
--SR.sub.14 ;
--CH.sub.2 N.sub.3 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
--NR.sub.19 R.sub.20 ;
or C(NH.sub.2)R.sub.21 R.sub.22 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s ;
u is 1 or 2;
v is 0, 1 or 2;
m is 2 or 3;
s is 2, 3, 4 or 5;
and
R.sub.23 is H, alkyl of 1-4 carbons optionally substituted with one or more halogens, or cycloalkyl of 3-8 carbons;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR105## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR106## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR107## when R.sub.12 is H;
(4) when A is --CN, B is not --N.sub.3 ;
(5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl;
(6) when A is OR.sub.5, then B is not NH.sub.2 ;
(7) when A is F, then B is not NHCO.sub.2 CH.sub.3.

54 more elements

A compound of the formula ##STR108## wherein, for the l, and mixtures of the d and l stereoisomers of the compound,

A is --NO.sub.2, --S(O).sub.n R.sub.1, --S(O).sub.2 --N.dbd.S(O).sub.p R.sub.2 R.sub.3, --SH, ##STR109## alkyl of 1 to 5 carbons, optionally substituted with one or more halogen atoms, alkenyl of 2-5 carbons or cycloalkyl of 3-8 carbons;
R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, CN, NR.sub.5 R.sub.6 or CO.sub.2 R.sub.8 ;
C.sub.2 -C.sub.4 alkenyl;
--NR.sub.9 R.sub.10 ;
--N.sub.3 ;
##STR110## --NX.sub.2 ;
NR.sub.9 X --.sup.- NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --;
R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens;
R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.7 is --NR.sub.5 R.sub.6 or --OR.sub.5 ;
R.sub.8 is H or alkyl of 1-4 carbons;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --;
X is Cl, Br or I;
Y is H, F, Cl, Br or NO.sub.2, or A and Y taken together can be --O(CH.sub.2).sub.t O--;
Z 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 --NH.sub.2, ##STR111## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CH.sub.2 S(O).sub.v R.sub.14 ;
##STR112## --OR.sub.18 ;
--SR.sub.14 ;
--CH.sub.2 N.sub.3 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
--NR.sub.19 R.sub.20 ;
or C(NH.sub.2)R.sub.21 R.sub.22 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s --;
u is 1 or 2;
v is 0, 1 or 2;
m is 2 or 3;
s is 2, 3, 4 or 5;
and
R.sub.23 is independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR113## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR114## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR115## then R.sub.12 is H;
(4) when A is --CN, B is not --N.sub.3 ;
(5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl;
(6) when A is OR.sub.5, then B is not NH.sub.2.

54 more elements

A compound of the formula ##STR116## wherein, for the l, and mixtures of the d and l stereoisomers of the compound,

A is --NO.sub.2, --S(O).sub.n R.sub.1, or --S(O).sub.2 --N.dbd.S(O).sub.p R.sub.2 R.sub.3 ;
R.sub.1 is C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms, C.sub.2 -C.sub.4 alkenyl, --NR.sub.9 R.sub.10, --N.sub.3, --NX.sub.2, --NR.sub.9 X or --.sup.- NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together, are --(CH.sub.2).sub.q --;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
X is Cl, Br or I;
Z is a physiologically acceptable cation;
R.sub.8 is H or C.sub.1 -C.sub.4 alkyl;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or, taken together, are --(CH.sub.2).sub.r --;
n is 0, 1 or 2;
p is 0 or 1;
q is 3, 4 or 5;
r is 4 or 5;
B is --NH.sub.2, ##STR117## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CH.sub.2 S(O).sub.v R.sub.14 ;
--OR.sub.18 ;
--SR.sub.14 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
or --NR.sub.19 R.sub.20 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
u is 1 or 2;
v is 0, 1 or 2;
and
m is 2 or 3;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR118## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR119## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR120## then R.sub.12 is H.

36 more elements

A method for alleviating bacterial infection in a mammal which comprises administering to the mammal an antibacterially effective amount of at least one compound having the formula:

##STR139## wherein, for the l, and mixtures of the d and l stereoisomers of the compound,
A is --NO.sub.2, --S(O).sub.n R.sub.1, --S(O).sub.2 --N.dbd.S(O).sub.p R.sub.2 R.sub.3, --SH, ##STR140## alkyl of 1 to 8 carbons, optionally substituted with one or more halogen atoms, OH, .dbd.O other than at alpha position, S(O).sub.n R.sub.24, NR.sub.5 R.sub.6, alkenyl of 2-5 carbons, alkynyl of 2-5 carbons or cycloalkyl of 3-8 carbons;
R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, OH, CN, NR.sub.5 R.sub.6
or CO.sub.2 R.sub.8 ;
C.sub.2 -C.sub.4 alkenyl;
--NR.sub.9 R.sub.10 ;
--N.sub.3 ;
##STR141## --NX.sub.2 ;
NR.sub.9 X--.sup.- NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --;
R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens;
R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.7 is --NR.sub.5 R.sub.6, --OR.sub.5 or ##STR142## R.sub.8 is H or alkyl of 1-4 carbons;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --;
X is Cl, Br or I;
Y is H, F, Cl, Br, alkyl of 1-3 carbons, or NO.sub.2, or A and Y taken together can be --O--(CH.sub.2).sub.t O--;
Z 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 --NH.sub.2, ##STR143## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally subsituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CH.sub.2 S(O).sub.v R.sub.14 ;
##STR144## --OR.sub.18 ;
--SR.sub.14 ;
--CH.sub.2 N.sub.3 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
--NR.sub.19 R.sub.20 ;
or C(NH.sub.2)R.sub.21 R.sub.22 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s --;
u is 1 or 2;
v is 0, 1 or 2;
m is 2 or 3;
s is 2, 3, 4 or 5;
and
R.sub.23 is H, alkyl of 1-8 carbons optionally substituted with one or more halogens, or cycloalkyl of 3-8 carbons;
R.sub.24 is alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.25 is alkyl of 1-4 carbons substituted with one or more of --S(O).sub.n R.sub.24, --OR.sub.8, ##STR145## --NR.sub.5 R.sub.6, or alkenyl of 2-5 carbons optionally substituted with CHO;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR146## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR147## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR148## then R.sub.12 is H;
(4) when A is --CN, B is not --N.sub.3 ;
(5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl;
(6) when A is F, then B is not NHCO.sub.2 CH.sub.3.

57 more elements

A method for alleviating bacterial infection in a mammal which comprises administering to the mammal an antibacterially effective amount of at least one compound having the formula ##STR149## wherein, for the l, and mixtures of the d and l stereoisomers of the compound,

A is --NO.sub.2, --S(O).sub.n R.sub.1, --S(O).sub.2 --N.dbd.S(O).sub.p R.sub.2 R.sub.3, --SH, ##STR150## alkyl of 1 to 5 carbons, optionally substituted with one or more halogen atoms, alkenyl of 2-5 carbons, alkynyl of 2-5 carbons or cycloalkyl of 3-8 carbons;
R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, CN, NR.sub.5 R.sub.6 or CO.sub.2 R.sub.8 ;
C.sub.2 -C.sub.4 alkenyl;
--NR.sub.9 R.sub.10 ;
--N.sub.3 ;
##STR151## --NX.sub.2 ;
NR.sub.9 X --.sup.- NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --;
R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens;
R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.7 is --NR.sub.5 R.sub.6, --OR.sub.5 or ##STR152## R.sub.8 is H or alkyl of 1-4 carbons;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --;
X is Cl, Br or I;
Y is H, F, Cl, Br or NO.sub.2, or A and Y taken together can be --O--(CH.sub.2).sub.t O--;
Z 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 --NH.sub.2, ##STR153## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CH.sub.2 S(O).sub.v R.sub.14 ;
##STR154## --OR.sub.18 ;
--SR.sub.14 ;
--CH.sub.2 N.sub.3 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
--NR.sub.19 R.sub.20 ;
or C(NH.sub.2)R.sub.21 R.sub.22 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s ;
u is 1 or 2;
v is 0, 1 or 2;
m is 2 or 3;
s is 2, 3, 4 or 5;
and
R.sub.23 is H, alkyl of 1-4 carbons optionally substituted with one or more halogens, or cycloalkyl of 3-8 carbons;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR155## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR156## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR157## then R.sub.12 is H;
(4) when A is --CN, B is not --N.sub.3 ;
(5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl;
(6) when A is F, then B is not NHCO.sub.2 CH.sub.3.

53 more elements

A method for alleviating bacterial infection in a mammal which comprises administering to the mammal an antibacterially effective amount of at least one compound having the formula:

##STR158## wherein, for the l, and mixtures of the d and l stereoisomers of the compound,
A is --NO.sub.2, --S(O).sub.n R.sub.1, --S(O).sub.2 --N.dbd.S(O).sub.p R.sub.2 R.sub.3, --SH, ##STR159## alkyl of 1 to 5 carbons, optionally substituted with one or more halogen atoms, alkenyl of 2-5 carbons or cycloalkyl of 3-8 carbons;
R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, CN, NR.sub.5 R.sub.6 or CO.sub.2 R.sub.8 ;
C.sub.2 -C.sub.4 alkenyl;
--NR.sub.9 R.sub.10 ;
--N.sub.3 ;
##STR160## --NX.sub.2 ;
NR.sub.9 X--.sup.- NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --;
R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens;
R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.7 is --NR.sub.5 R.sub.6 or --OR.sub.5 ;
R.sub.8 is H or alkyl of 1-4 carbons;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --;
X is Cl, Br or I;
Y is H, F, Cl, Br or NO.sub.2, or A and Y taken together can be --O(CH.sub.2).sub.t O--;
Z 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 --NH.sub.2, ##STR161## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CN.sub.2 S(O).sub.v R.sub.14 ;
##STR162## --OR.sub.18 ;
--SR.sub.14 ;
--CH.sub.2 N.sub.3 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
--NR.sub.19 R.sub.20 ;
or C(NH.sub.2)R.sub.21 R.sub.22 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s --;
u is 1 or 2;
v is 0, 1 or 2;
m is 2 or 3;
s is 2, 3, 4 or 5;
and
R.sub.23 is independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR163## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR164## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR165## then R.sub.12 is H;
(4) when A is --CN, B is not --N.sub.3 ;
(5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl.

54 more elements

Dependencies are inferred from the claim text.

Facts

Application: 06/803,191Filed 2 Dec 1985 · continuation in part
Priority: 7 Jun 1983
Granted: 10 Nov 1987
Term ends: Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07D 263/20
Oxygen atoms: attached in position 2
C07D 263/24
Attached in position 2: with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
C07D 413/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
C07D
Heterocyclic compounds

Family

Serial501,897Parent of this continuation-in-part · filed 7 Jun 1983
Serial578,332Parent of this continuation-in-part · filed 14 Feb 1984
Serial676,745Parent of this continuation-in-part · filed 5 Dec 1984
US 4,705,799 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, OH, CN, NR.sub.5 R.sub.6
or CO.sub.2 R.sub.8 ;
C.sub.2 -C.sub.4 alkenyl;
--NR.sub.9 R.sub.10 ;
--N.sub.3 ;
##STR91## --NX.sub.2 ;
NR.sub.9 X --.sup.- NXZ.sup.+ ;
R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --;
R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens;
R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
R.sub.7 is --NR.sub.5 R.sub.6, --OR.sub.5 or ##STR92## R.sub.8 is H or alkyl of 1-4 carbons;
R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ;
R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --;
X is Cl, Br or I;
Y is H, F, Cl, Br, alkyl of 1-3 carbons, or NO.sub.2, or A and Y taken together can be --O--(CH.sub.2).sub.t O--;
Z 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 --NH.sub.2, ##STR93## or N.sub.3 ;
R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl;
R.sub.13 is H;
C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms;
C.sub.2 -C.sub.4 alkenyl;
C.sub.3 -C.sub.4 cycloalkyl;
phenyl;
--CH.sub.2 OR.sub.15 ;
--CH(OR.sub.16)OR.sub.17 ;
--CH.sub.2 S(O).sub.v R.sub.14 ;
##STR94## --OR.sub.18 ;
--SR.sub.14 ;
--CH.sub.2 N.sub.3 ;
the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine;
--NR.sub.19 R.sub.20 ;
or C(NH.sub.2)R.sub.21 R.sub.22 ;
R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms;
R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --;
R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl;
R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl;
R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s --;
u is 1 or 2;
v is 0, 1 or 2;
m is 2 or 3;
s is 2, 3, 4 or 5;
and
R.sub.23 is H, alkyl of 1-8 carbons optionally substituted with one or more halogens, or cycloalkyl of 3-8 carbons;
R.sub.24 is alkyl of 1-4 carbons or cycloalkyl of
- 8carbons;
R.sub.25 is alkyl of 1-4 carbons substituted with
one or more of --S(O).sub.n R.sub.24, --OR.sub.8, ##STR95## --NR.sub.5 R.sub.6, or alkenyl of 2-5 carbons optionally substituted with CHO;
or a pharmaceutically suitable salt thereof;
provided that:
(1) when A is CH.sub.3 S--, then B is not ##STR96## (2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR97## (3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR98## then R.sub.12 is H;
(4) when A is --CN, B is not --N.sub.3 ;
(5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl;
(6) when A is OR.sub.5, then B is not NH.sub.2 ;
(7) when A is F, then B is not NHCO.sub.2 CH.sub.3.

58 more elements

Facts

Application

06/803,191Filed 2 Dec 1985 · continuation in part

Priority

7 Jun 1983

Granted

10 Nov 1987

Term ends

Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07D 263/20
Oxygen atoms: attached in position 2
C07D 263/24
Attached in position 2: with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
C07D 413/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
C07D
Heterocyclic compounds