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US 5,854,242 AGranted
Benzoxazine antimicrobial agents
AssigneeOrtho Pharmaceutical Corporation
InventorsRoger Frechette, Michele Ann Weidner-Wells
Life of this patent
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Abstract
The invention relates to benzoxazine and pyrido-oxazine antibacterial compounds of the general formula: ##STR1## wherein the moiety Q is a fused phenyl or fused pyridyl moiety as herein described, pharmaceutical compositions containing the compounds, methods for their production and their use in treating bacterial infections.
Claims9
A compound selected from those of Formula 1:
- ##STR170## wherein the moiety Q is a fused pyridyl moiety;
- Z.sub.1 is hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, phenyl, hydroxy, amino, nitro, sulfonylamino or trifluoromethyl;
- Z.sub.2 is hydrogen or a halogen;
- X is hydrogen or oxygen;
- A is C.sub.1 -C.sub.5 alkyl, --CH.sub.2 phenyl, --CH.sub.2 thienyl, --CH.sub.2 pyridyl, --CH.sub.2 furyl, or -ethyl piperidine;
- wherein said phenyl, thienyl, pyridyl, furyl or piperidine moiety is optionally substituted with (C.sub.1 -C.sub.6)alkyl, benzyl, oxybenzyl, phenoxy, hydroxy, alkoxy, halogen, dihalogen, nitro, amino, carboxyl or carbomethoxy;
- n is an integer from 0-3;
- Y is a moiety selected from:
- (a) --NHR.sub.1 R.sub.2,--N.sup.+ R.sub.1 R.sub.2 R.sub.3 ;
- ##STR171## (c) --CO.sub.2 H, --CHO;
- (d) --CH(R.sub.6)CO.sub.2 H, --CH(R.sub.6)CO.sub.2 CH.sub.3, --CH.dbd.CHR.sub.7, --CH.dbd.C(CO.sub.2 H).sub.2 ;
- (e) a moiety of the formula:
- ##STR172## (f) 5-tetrazolyl;
- wherein
- R.sub.1, R.sub.2 and R.sub.3 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or t-butoxycarbonyl;
- R.sub.4 and R.sub.5 are independently t-butoxycarbonyl or hydrogen or R.sub.4 and R.sub.5 may be joined together to form an imnidazoline, imidazolyl or pyrimidine ring;
- R.sub.6 is hydrogen, hydroxy or chloro;
- R.sub.7 is CO.sub.2 H or C(O)NH(CH.sub.2).sub.p OH wherein p is an integer from 1-4;
- and the pharmaceutically acceptable salts, esters and pro-drug forms thereof.
16 more elements
The compound according to claim 1, 4-(3-Chlorobenzyl)-3,4-dihydro-2-2-4-(2-guanidinoethyl)phenoxy!ethyl!-3- oxo-2H-pyrido3,2-b!-1,4-oxazine.
A method of preparing a compound of the Formula 1:
- ##STR175## wherein the moiety Q is a fused pyridyl moiety;
- Z.sub.1 is hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, phenyl, hydroxy, amino, nitro, sulfonylamino or trifluoromethyl;
- Z.sub.2 is hydrogen or a halogen;
- X is hydrogen or oxygen;
- A is C.sub.1 -C.sub.5 alkyl, --CH.sub.2 phenyl, --CH.sub.2 thienyl, --CH.sub.2 pyridyl, --CH.sub.2 furyl, or -ethyl piperidine;
- wherein said phenyl, thienyl, pyridyl, furyl or piperidine moiety is optionally substituted with (C.sub.1 -C.sub.6)alkyl, benzyl, oxybenzyl, phenoxy, hydroxy, alkoxy, halogen, dihalogen, nitro, amino, carboxyl or carbomethoxy;
- n is an integer from 0-3;
- Y is a moiety selected from:
- (a) --NHR.sub.1 R.sub.2, --N.sup.+ R.sub.1 R.sub.2 R.sub.3 ;
- ##STR176## (c) --CO.sub.2 H, --CHO;
- (d) --CH(R.sub.6)CO.sub.2 H, --CH(R.sub.6)CO.sub.2 CH.sub.3, --CH.dbd.CHR.sub.7, --CH.dbd.C(CO.sub.2 H).sub.2 ;
- (e) a moiety of the formula:
- ##STR177## (f) 5-tetrazolyl;
- wherein
- R.sub.1, R.sub.2 and R.sub.3 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or t-butoxycarbonyl;
- R.sub.4 and R.sub.5 are independently t-butoxycarbonyl or hydrogen or R.sub.4 and R.sub.5 may be joined together to form an imidazoline, imidazolyl or pyrimidine ring;
- R.sub.6 is hydrogen, hydroxy or chloro;
- R.sub.7 is CO.sub.2 H or C(O)NH(CH.sub.2).sub.p OH wherein p is an integer from 1-4;
- and the pharmaceutically acceptable salts, esters and pro-drug forms thereof, which comprises reacting a compound of the formula:
- ##STR178## wherein Q is fused pyridyl with a compound of the formula:
- ##STR179## wherein the moiety Y is protected or unprotected, in a suitable solvent in the presence of an appropriate phosphine and azodicarbonyl reagent, and where Y is protected, removing the protecting group and recovering the compound of formula 1.
18 more elements
A compound of the formula:
- ##STR180## wherein the Q moiety is fused pyridyl;
- Z.sub.1 is hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, phenyl, hydroxy, amino, nitro, sulfonylamino or trifluoromethyl;
- Z.sub.2 is hydrogen or a halogen;
- X is hydrogen or oxygen;
- A is C.sub.1 -C.sub.5 alkyl, --CH.sub.2 phenyl, --CH.sub.2 thienyl, --CH.sub.2 pyridyl, --CH.sub.2 furyl, or -ethyl piperidine;
- wherein said phenyl, thienyl, pyridyl, furyl or piperidine moiety is optionally substituted with (C.sub.1 -C.sub.6)alkyl, benzyl, oxybenzyl, phenoxy, hydroxy, alkoxy, halogen, dihalogen, nitro, amino, carboxyl or carbomethoxy;
- and R.sub.8 is hydrogen or a hydroxy protecting group.
4 more elements
Dependencies are inferred from the claim text.