Antibacterial cephalosporins

Details Antibacterial cephalosporins Antibacterial cephalosporins

2001-05-21

2003-03-11

Berch, Mark L. (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S203000, C514S204000, C514S205000, C514S206000, C514S208000, C540S215000, C540S222000, C540S224000, C540S225000, C540S226000, C540S229000

Reexamination Certificate

active

06531465

ABSTRACT:

The present invention relates to antibacterial compounds which are 7-acylamino-3-(imino)methyl cephalosporins.
Particularly the present invention provides a compound of formula
wherein
R
1
denotes hydrogen or an ester moiety,
R
2
denotes a group of formula
 wherein
Y denotes hydrogen, alkyl, alkenyl, acyl, carbamoyl or aryl
R
4
denotes hydrogen, alkyl, alkenyl, cycloalkyl, aryl, acyl or heterocyclyl
R
5
denotes hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, or a group of formula
 wherein
R
7
denotes alkyl or aryl
R
8
denotes hydrogen, cycloalkyl or alkyl
R
9
denotes hydrogen or alkyl
R
10
denotes hydrogen, alkyl, hydroxy, amino, phenyl, alkenyl, cycloalkyl,aryl, heterocyclyl or a group of formula
—N═CH-Phe
 wherein Phe denotes aryl
R
9
and R
10
together with the nitrogen atom denote heterocyclyl,
Z denotes oxygen, sulphur or N—R
13
, wherein
R
13
denotes hydrogen, alkyl or cycloalkyl
R
11
denotes hydrogen, alkyl, aryl, cycloalkyl or heterocyclyl, or
R
4
and R
5
together with the nitrogen atom denote heterocyclyl,
R
6
denotes heterocyclyl, and
Ac denotes
(i) a group
(ii) a group of formula
 wherein
B denotes N or CH
Z
1
denotes aryl, cycloalkyl, 1,4-cyclohexadienyl or heterocyclyl
Z
2
denotes hydrogen, alkyl or —CH
2
COOZ
5
, wherein
Z
5
denotes hydrogen, alkyl or cycloalkyl
Z
3
denotes hydrogen or alkyl
Z
4
denotes hydrogen or an organic radical
D denotes oxygen or CH
2
.
A subgroup of the invention comprises any of the individual groups of significances mentioned therein.
R
1
may be hydrogen or an ester moiety. An ester moiety includes alkyl, preferably C
1-6
alkyl; arylalkyl, for example benzyl, alkoxybenzyl, such as 4-methoxybenzyl; indanyl, phthalidyl, alkoxymethyl, e.g. methoxymethyl; (C
1-6
)alkanoyloxy(C
1-6
)alkyl, (C
1-6
)alkoxycarbonyl-oxy(C
1-6
)alkyl, glycyloxymethyl, phenylglycyloxymethyl, (5-methyl-2-oxo-1,3-dioxolen4-yl)methyl and ester moieties which form with the COO— group a physiologically hydrolysable and acceptable ester, e.g. such known to be hydrolysable ester groups in the field of cephalosporins. A compound of formula I may thus be in the form of an physiologically-hydrolysable and -acceptable ester. By physiologically-hydrolysable and -acceptable esters as used herein is meant an ester in which the COO— group is esterified and which is hydrolysable under physiological conditions to yield an acid which is itself physilogically tolerable at dosages to be administered. The term is thus to be understood as defining regular pro-drug forms. An ester moiety may be preferably a group which is easily hydrolysable under physiological conditions. Such esters may be administered preferably orally. Parenteral administration may be indicated if the ester per se is an active compound or, if hydrolysis occurs in the blood.
Y may be preferably hydrogen, unsubstituted alkyl or alkyl substituted by e.g. hydroxy or, preferably the residue of a carboxylic acid. The residue of a carboxylic acid includes the residue of a carboxylic acid in free form or in salt form, of a carboxylic acid ester and of a carboxylic acid amide. The carboxylic acid is, for example, a C
1-7
carboxylic acid, preferably a C
1-5
aliphatic carboxylic acid, an alkyl part thereof including lower alkyl. The alkoxy group of a carboxylic acid ester includes C
1-6
, preferably C
1-4
alkoxy. Alkyl is preferably lower alkyl. The alkyl group is preferably unsubstituted or substituted by carboxylic acid residues.
R
4
may be preferably hydrogen or alkyl, for example lower alkyl.
R
5
may be preferably hydrogen; unsubstituted alkyl; alkyl substituted for example by oxo, alkyl or halogenated alkyl; amino; one or several fold substituted heterocyclyl; or a group of formulae IId, IIe, IIf. Heterocyclyl includes unsaturated or saturated heterocyclyl having, e.g. 5 or 6 ring members and, for example, 1 to 3 hetero atoms, such as N, O, S, preferably N, or condensed heterocyclyl, such as benzothiazolyl.
R
4
and R
5
together with the nitrogen atom may be heterocyclyl, having preferably 5 or 6 ring members and having preferably 1 to 3 heteroatoms, for example N atoms; which may be unsubstituted heterocyclyl; or one or several fold substituted heterocyclyl, for example by oxo, amino, alkyl.
R
6
may be saturated or unsaturated heterocyclyl; having preferably 5 or 6 ring members and having for example 1 or 2 nitrogen hetero atoms; for example unsubstituted heterocylclyl; or one or several fold substituted heterocyclyl, for example by amino, alkyl or thiono.
R
7
may be preferably alkyl.
R
8
may be preferably alkyl or cycloalkyl.
R
9
may be preferably hydrogen or lower alkyl.
R
13
may be preferably alkyl.
R
10
may be preferably hydrogen; aryl; alkenyl; cycloalkyl; unsubstituted alkyl; substituted alkyl, for example by hydroxy, halogen, heterocyclyl, such as pyridyl, amino, for example N(alkyl)
2
or N
+
(alkyl)
3
; or a group
—N═/CH-Ar
wherein Ar denotes heterocyclyl; unsubstituted aryl; or substituted aryl, for example by hydroxy or alkoxy; preferably aryl which may be preferably phenyl.
R
9
and R
10
together with the nitrogen atom may be heterocyclyl having preferably 5 or 6 ring members and 1 to 3 hetero atoms such as N, S, O, for example N, O; preferably saturated heterocyclyl. Heterocyclyl includes unsubstituted heterocyclyl, or substituted heterocyclyl, for example by acyl, formyl, alkyl, for example lower alkyl. Examples include pyrrolidine, morpholine, piperazine, preferably piperazine.
R
11
may be preferably hydrogen; unsubstituted alkyl; substituted alkyl, for example by aminoalkyl, diaminoalkyl, triaminoalkyl; aryl, such as dihydroxyphenyl; cycloalkyl; or unsubstituted heterocyclyl; or substituted heterocyclyl, for example by alkyl, thiono heterocyclyl; heterocyclyl having preferably 5 or 6 ring members and 1 to 3 hetero, preferably N atoms.
If not otherwise stated therein any carbon containing group may contain up to 20 carbon atoms, e.g. alkyl includes C
1-20
, e.g. C
1-8
alkyl. Lower alkyl includes e.g. C
1-4
alkyl, preferably C
1-2
alkyl. Alkenyl includes C
2-20
, e.g. C
2-8
alkenyl. Lower alkenyl includes e.g. C
3-5
alkenyl, preferably C
3
alkyl. Cycloalkyl includes, for example, C
3-6
Cycloalkyl, particularly C
3
, C
5
or C
6
cycloalkyl. Alkyl, alkenyl and cycloalkyl include unsubstituted alkyl, alkenyl and cycloalkyl; and, substituted alkyl, alkenyl and cycloalkyl, for example, by halogen, a sulphonic acid derivative, such as SO
3
H, CF
3
, hydroxy, alkoxy, acyl, alkylamino, pyridyl. Cycloalkyl is preferably unsubstituted. Acyl includes C
1-12
, e.g. C
1-6
acyl, particularly C
1-4
acyl. Acyl includes unsubstituted acyl and substituted acyl, for example, by hydroxy, alkoxy, amino. Aryl includes phenyl. Aryl may be unsubstituted aryl or substituted aryl, for example by alkyl, alkoxy, acyl, halogen, hydroxy, unprotected or protected amino. Alkoxy includes alkoxy wherein the alkyl part is as defined above.
Heterocyclyl includes heterocyclyl having 5 or 6 ring members and 1 to 3 nitrogen, sulphur and/or oxygen hetero atoms including, for example, condensed heterocyclyl, such as for example benzthiazolyl. Heterocyclyl includes further unsubstituted hetercyclyl and substituted heterocyclyl, for example by oxo, alkoxy, hydroxy, thiono, mercapto, alkylthio, imino, alkylamino, alkylimino, amino, halogen, acyl, CF
3
, CHO, alkyl, cycloalkyl.
Carbamoyl includes the carbamoyl group or carbamoyl having alkyl and aryl residues.
Z
1
denotes unsubstituted cycloalkyl, 1,4-cyclohexadienyl, heterocyclyl or aryl; and one or several fold substituted cycloalkyl, 1,4-cyclohexadiene, heterocyclyl or aryl; for example by carboxyl, amino, nitro, cyano, lower alkyl, lower alkoxy, hydroxy, halogen, —CO—N(Z
5
Z
6
), —N(Z
6
)—COOZ, Z
6
CO—, Z
6
OCO—, Z
6
COO—.
Z
2
denotes hydrogen; CH
2
COOZ
5
; unsubstituted lower alkyl; one or several fold substituted lower alkyl, for example by carboxyl, amino, nitro, cyano, lower alkyl, lower alkoxy, hydroxy, halogen, —COZ
5
Z
6
, —N(Z
6
)—COOZ
7
, Z
6
CO—, Z
6
OCO— or Z
6
COO—.
Z
3
denotes hydrogen or lower a

Affiliated with

Also associated with

Rating

Antibacterial cephalosporins does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Antibacterial cephalosporins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antibacterial cephalosporins will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3049856