Glycopeptide antibiotic derivatives
AssigneeEli Lilly and Company
InventorsRobin D. G. Cooper, Bret E. Huff, Thalia I. Nicas, John T. Quatroche, Michael J. Rodriguez, Nancy J. Snyder, Michael A. Staszak, Richard C. Thompson, Stephen C. Wilkie, Mark J. Zweifel
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Abstract
The present invention provides glycopeptide antibiotic derivative compounds. These derivative compounds possess antibacterial activity aginst a wide variety of bacteria, including activity against vancomycin-resistant isolates. Methods of making and using these glycopeptide antibiotic derivative compounds are also provided.
Claims9
A compound of the formula:
- ##STR9## or salt thereof, wherein:
- R.sup.6 is vancosaminyl;
- and
- R.sup.7 is (C.sub.1 -C.sub.12 alkyl)--R.sub.8 and is attached to the amino group of R.sup.6 ;
- R.sup.8 is a group of the formula:
- ##STR10## wherein q is 0 to 4;
- R.sup.12 is independently selected from the group consisting of:
- (i) halo,
- (ii) nitro,
- (iii) (C.sub.1 -C.sub.6)alkyl,
- (iv) (C.sub.1 -C.sub.6)alkoxy,
- (v) halo-(C.sub.1 -C.sub.6)alkyl,
- (vi) halo-(C.sub.1 -C.sub.6)alkoxy,
- (vii) hydroxy, and
- (vii) (C.sub.1 -C.sub.6)thioalkyl;
- r is 1 to 5;
- provided that the sum of q and r is no greater than 5;
- Z is selected from the group consisting of:
- (i) a single bond,
- (ii) divalent (C.sub.1 -C.sub.6)alkyl unsubstituted or substituted with hydroxy, (C.sub.1 -C.sub.6)alkyl, or (C.sub.1 -C.sub.6)alkoxy,
- (iii) divalent (C.sub.2 -C.sub.6)alkenyl,
- (iv) divalent (C.sub.2 -C.sub.6)alkynyl, and
- (v) a group of the formula --(C(R.sup.14).sub.2).sub.s --R.sup.15 -- or --R.sup.15 -- (C(R.sup.4).sub.2).sub.s --, wherein s is 0-6;
- wherein each R.sup.14 substituent is independently selected from hydrogen, (C.sub.1 -C.sub.6)-alkyl, and (C.sub.4 -C.sub.10) cycloalkyl;
- and R.sup.15 is selected from --O--, --S--, --SO--, --SO.sub.2 --, --SO.sub.2 --O--, --C(O)--, --OC(O)--, --C(O)O--, --NH--, --N(C.sub.1 -C.sub.6 alkyl)-, --C(O)NH--, --NHC(O)--, and N.dbd.N;
- R.sup.13 is independently selected from the group consisting of:
- (i) (C.sub.4 -C.sub.10) heterocyclyl,
- (ii) heteroaryl,
- (iii) (C.sub.4 -C.sub.10) cycloalkyl unsubstituted or substituted with (C.sub.1 -C.sub.6) alkyl, and
- (iv) phenyl unsubstituted or substituted with 1 to 5 substituents independently selected from:
- halo, hydroxy, nitro, (C.sub.1 -C.sub.10) alkyl, (C.sub.1 -C.sub.10)alkoxy, halo-(C.sub.1 -C.sub.3)alkoxy, halo-(C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxyphenyl, phenyl, phenyl-(C.sub.1 -C.sub.3) alkyl, (C.sub.1 -C.sub.6)alkoxyphenyl, phenyl-(C.sub.2 -C.sub.3)alkynyl, and (C.sub.1 -C.sub.3) alkylphenyl.
A pharmaceutical composition comprising a compound of claim 11 with one or more pharmaceutically acceptable carriers therefor.
Dependencies are inferred from the claim text.