What is claimed is:
1. A compound having the following formula:
61
wherein:
(a) X is selected from the group consisting of
62
(b) R1 is selected from the group consisting of C3 to about C5 cycloalkyl, C1 to about C2 alkanyl, C2 to about C3 linear alkenyl, C3 to about C4 branched alkanyl or alkenyl, all such alkyl or cycloalkyl moieties being unsubstituted or substituted with from 1 to about 3 fluoro; and phenyl, unsubstituted or substituted with from 1 to about 3 fluoro, or with one hydroxy in the 4-position;
(c) R3 is hydrogen or hydroxy;
(d) R5 is selected from the group consisting of hydrogen, hydroxy, amino, halo, C1 to about C2 alkanyl, C2 alkenyl, and methoxy, all such alkyl and methoxy moieties being unsubstituted or substituted with from 1 to about 3 fluoro;
(e) R8 is selected from the group consisting of fluoro, chloro and bromo;
(f) R7 is amino which is attached to a ring carbon of X which is not adjacent to the ring nitrogen, the amino being unsubstituted or substituted with one or two C1 to about C3 alkanyl; or aminoalkanyl which is attached to any ring carbon of X and is C1 to about C3 alkanyl substituted with one amino, the amino being unsubstituted or substituted with one or two C1 to about C3 alkanyl;
(g) each R9 is independently selected from the group consisting of hydrogen, C1 to about C4 alkanyl, C2 to about C6 alkenyl or alkynyl, and a C3 to about C6 fused or spirocycle alkyl ring; or one R9 may optionally be selected from the group consisting of hydroxy, C1 to about C4 alkoxy, aryl and heteroaryl, all other R9 being hydrogen; all alkyl and aryl portions of R9 moieties being unsubstituted or substituted with one hydroxy or with from 1 to about 3 fluoro; and
(h) a R7 moiety described in (f) and a R9 moiety described in (g) may optionally be connected thus forming a fused or spirocycle ring with the N-containing ring shown in (a), the fused or spirocycle ring comprising from 2 to about 5 ring carbons and 0 or 1 ring nitrogen;
or an optical isomer, diastereomer or enantiomer thereof; a pharmaceutically-acceptable salt, hydrate, or biohydrolyzable ester, amide or imide thereof.
2. The compound of claim 1 wherein R3 is hydroxy, and X is
63
3. The compound of claim 2 wherein each R9 is independently selected from the group consisting of hydrogen, C1 to about C4 alkanyl, C2 to about C6 alkenyl or alkynyl, and a C3 to about C6 fused or spirocycle alkyl ring; all such alkyl moieties being unsubstituted or substituted with from 1 to about 3 fluoro.
4. The compound of claim 3 wherein:
(a) R1 is selected from the group consisting of C3 to C5 cycloalkanyl, methyl, ethyl, ethenyl, isopropyl, isopropenyl, isobutyl, isobutenyl, t-butyl, all such alkyl or cycloalkanyl moieties being unsubstituted or substituted with from 1 to 3 fluoro; and phenyl, unsubstituted or substituted with from 1 to 3 fluoro, or with one hydroxy in the 4-position;
(b) R5 is selected from the group consisting of hydrogen, hydroxy, amino, fluoro, chloro, bromo, and methyl, the methyl being unsubstituted or substituted with from 1 to 3 fluoro;
(c) R7 is attached to a ring carbon of X which is not adjacent to the ring nitrogen; and
(d) no more than two ring carbons of X have non-hydrogen R9’s attached thereto.
5. The compound of claim 4 wherein:
(a) R7 is amino which is attached to a ring carbon of X which is not adjacent to the ring N, the amino being unsubstituted or substituted with one or two C1 to about C3 alkanyl; or is C1 to about C3 alkanyl substituted with one amino;
(b) R9 is selected from the group consisting of hydrogen, C1 to about C4 alkanyl, C2 to about C6 alkenyl or alkynyl, and a C3 to about C6 spirocycle alkyl ring; all such alkyl moieties being unsubstituted or substituted with from 1 to about 3 fluoro.
6. The compound of claim 5 wherein R8 is chloro.
7. The compound of claim 4 wherein;
(a) R1 is selected from the group consisting of cyclopropyl, ethyl, phenyl substituted with 1 to 3 fluoro, and 4-hydroxyphenyl;
(b) R5 is selected from the group consisting of hydrogen, hydroxy, amino, and methyl;
(c) X comprises the piperidinyl ring;
(d) R7 is amino in the 3-position of the piperidinyl ring; and
(e) all R9 are hydrogen, or one non-hydrogen R9 is in the 4-position or 5-position of the piperidinyl ring.
8. The compound of claim 7 wherein:
(a) R1 is cyclopropyl;
(b) R5 is hydrogen, and
(c) all R9 are hydrogen, or one non-hydrogen R9 is selected from the group consisting of methyl, ethyl, dimethyl, spirocyclopropyl, methoxy, 2-thienyl and 2-furyl.
9. The compound of claim 8 wherein R8 is chloro.
10. The compound of claim 4 wherein:
(a) R1 is selected from the group consisting of cyclopropyl, ethyl, phenyl substituted with 1 to 3 fluoro, and 4-hydroxyphenyl;
(b) R5 is selected from the group consisting of hydrogen, hydroxy, chloro, bromo, amino, and methyl, the methyl being unsubstituted or substituted with from 1 to 3 fluoro;
(c) when X comprises the piperidinyl ring, R7 is amino unsubstituted or substituted with one C1 to C3 alkanyl or two methyl; when X comprises the pyrrolidinyl ring, R7 is aminoalkanyl which is methyl or ethyl or isopropyl substituted with one amino unsubstituted or substituted with one methyl or ethyl or dimethyl.
11. The compound of claim 10 wherein:
(a) R1 is cyclopropyl or ethyl, unsubstituted or substituted with from 1 to about 3 fluoro;
(b) R5 is selected from the group consisting of hydrogen, hydroxy, amino, and methyl;
(c) when X comprises the piperidinyl ring, R7 is amino or methylamino in the 3-position or 4-position of the ring; when X comprises the pyrrolidinyl ring, R7 is selected from the group consisting of aminomethyl, methylaminomethyl, 1-aminoethyl, 1-methylaminoethyl, 1-amino-1-methylethyl and 1-methylamino-1-methylethyl in the 3-position of the ring.
(d) all R9 are hydrogen or only one ring carbon of X has a non-hydrogen R9 attached thereto, such non-hydrogen R9 being selected from the group consisting of methyl, ethyl, dimethyl and spirocyclopropyl.
12. The compound of claim 11 wherein X comprises the pyrrolidinyl ring.
13. The compound of claim 12 wherein R1 is cyclopropyl, R5 is hydrogen, and all R9 are hydrogen.
14. The compound of claim 13 wherein R8 is chloro.
15. A compound selected from the group consisting of:
7-3R-(1S-aminoethylpyrrolidinyl)-1-ethyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo -3-quinolinecarboxylic acid;
7-3R-(1S-aminoethylpyrrolidinyl)-1-(2-fluoroethyl)-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3R-(1S-aminoethylpyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3R-(1S-methylaminoethylpyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3R-(1-amino-methylethylpyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3R-(1-methylamino-methylethylpyrrolidinyl)1-cyclopropyl-1,4-dihydro-8-chloro -6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1S-aminoethyl-5-methyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro -6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1S-aminoethyl-5,5-dimethyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro -6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1-aminomethylethyl-5,5-dimethyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro -8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1S-methylaminoethyl-5,5-dimethyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro -8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1-methylaminomethylethyl-5,5-dimethyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro -8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1S-aminoethyl-5-ethyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1-aminomethylethyl-5-ethyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro -6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1S-methylaminoethyl-5-ethyl-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro -6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1-methylaminom ethylethyl-5-ethyl-pyrrolidinyl)1-cyclopropyl-1,4-dihydro -8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3R-(1-amino-1-cyclopropyl-methylpyrrolidinyl)-1-cyclopropyl-1,4-dihydro-8-chloro -6-hydroxy-4-oxo-3 -quinolinecarboxylic acid;
7-6R-(1S-aminoethyl)-4-azaspiro2.4heptanyl-1-cyclopropyl-1,4-dihydro-8-chloro -6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-6R-(1S-methylaminoethyl)-4-azaspiro2.4heptanyl-1-cyclopropyl-1,4-dihydro -8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-6R-(1S-amino-methylethyl)-4-azaspiro2.4heptanyl-1-cyclopropyl-1,4-dihydro -8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-6R-(1S-methylamino-methylethyl)-4-azaspiro2.4heptanyl-1-cyclopropyl-1,4-dihydro -8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
or a pharmaceutically-acceptable salt thereof.
16. A compound selected from the group consisting of:
7-3S-aminopiperidinyl-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo-3-quinolinecarboxylic acid;
7-3S-methylaminopiperidinyl-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy-4-oxo -3-quinolinecarboxylic acid;
7-3S-amino-4R-methyl-piperidinyl-1-cyclopropyl- 1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3S-amino-5S-methyl-piperidinyl-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3S-amino-5R-methyl-piperidinyl-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3S-amino-4R-ethyl-piperidinyl-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3S-amino-6,6-dimethyl-piperidinyl-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-3S-amino-6-methyl-piperidinyl-1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-7-amino-5-azaspiro2.5-octanyl1-cyclopropyl-1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
7-4-amino-6-azaspiro2.5-octanyl-1-cyclopropyl- 1,4-dihydro-8-chloro-6-hydroxy -4-oxo-3-quinolinecarboxylic acid;
or a pharmaceutically-acceptable salt thereof.
17. A pharmaceutical composition comprising:
(a) a safe and effective amount of a compound of claim 1 or 14; and
(b) a pharmaceutically-acceptable excipient.
18. A method for preventing or treating microbial infection comprising administering to a host in need of such a treatment a safe and antimicrobially effective amount of a compound of claim 1 or 14.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An angular ball bearing comprising:
an outer ring having an inner peripheral surface, an outer peripheral surface, and a radially inwardly-facing outer raceway groove formed in said inner peripheral surface of said outer ring;
an inner ring disposed within said outer ring and having an inner peripheral surface, an outer peripheral surface, and a radially outwardly-facing inner raceway groove formed in said outer peripheral surface of said inner ring; and
a plurality of rolling elements disposed in said inner raceway groove and said outer raceway groove and radially between said inner ring and said outer ring;
wherein said inner peripheral surface of said outer ring includes a first annular inner peripheral surface portion on a first axial side of said outer raceway groove, and a second annular inner peripheral surface portion on a second axial side of said outer raceway groove;
wherein said outer peripheral surface of said inner ring includes a first annular outer peripheral surface portion on a first axial side of said inner raceway groove, and a second annular outer peripheral surface portion on a second axial side of said inner raceway groove;
wherein said first annular inner peripheral surface portion of said inner peripheral surface of said outer ring is disposed to face said first annular outer peripheral surface portion of said outer peripheral surface of said inner ring across a first annular radial gap that has an annular opening that opens axially outwardly on said first axial side of said inner and outer raceway grooves;
wherein said second annular inner peripheral surface portion of said inner peripheral surface of said outer ring is disposed to face said second annular outer peripheral surface portion of said outer peripheral surface of said inner ring across a second annular radial gap that has an annular opening that opens axially outwardly on said second axial side of said inner and outer raceway grooves;
wherein an inner diameter of said first annular inner peripheral surface portion of said inner peripheral surface of said outer ring is greater than an inner diameter of said second annular inner peripheral surface portion of said inner peripheral surface of said outer ring;
wherein an outer diameter of said first annular outer peripheral surface portion of said outer peripheral surface of said inner ring is greater than an outer diameter of said second annular outer peripheral surface portion of said outer peripheral surface of said inner ring;
wherein a first annular seal is press fit into one of said first and second radial gaps so as to be press fit between one of (a) said first annular inner peripheral surface portion of said inner peripheral surface of said outer ring and said first annular outer peripheral surface portion of said outer peripheral surface of said inner ring, and (b) said second annular inner peripheral surface portion of said inner peripheral surface of said outer ring and said second annular outer peripheral surface portion of said outer peripheral surface of said inner ring;
wherein said inner peripheral surface of said outer ring has no inner peripheral surface portion that both protrudes radially inwardly further than an inner peripheral contact surface portion at which said first annular seal contacts said inner peripheral surface of said outer ring, and is disposed closer than said inner peripheral contact surface portion to the annular opening of said one of said first and second radial gaps in which said first annular seal is press fit;
wherein said outer peripheral surface of said inner ring has no outer peripheral surface portion that both protrudes radially outwardly further than an outer peripheral contact surface portion at which said first annular seal contacts said outer peripheral surface of said inner ring, and is disposed closer than said outer peripheral contact surface portion to the annular opening of said one of said first and second radial gaps in which said first annular seal is press fit;
wherein a portion of said inner peripheral surface of said outer ring extending between said inner peripheral contact surface portion and said radially inwardly-facing outer raceway groove constitutes a conical surface; and
wherein said inner diameter of said first annular inner peripheral surface portion of said inner peripheral surface of said outer ring is substantially uniform over the entire axial length of said first annular inner peripheral surface portion.