US20050033064A1 - Intermediates for the production of quinolone carboxylic acid derivatives - Google Patents
Intermediates for the production of quinolone carboxylic acid derivatives Download PDFInfo
- Publication number
- US20050033064A1 US20050033064A1 US10/935,357 US93535704A US2005033064A1 US 20050033064 A1 US20050033064 A1 US 20050033064A1 US 93535704 A US93535704 A US 93535704A US 2005033064 A1 US2005033064 A1 US 2005033064A1
- Authority
- US
- United States
- Prior art keywords
- carboxylic acid
- formula
- aminomethyl
- production
- acid derivatives
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 0 *O/N=C1/C(C[N+])C*C1 Chemical compound *O/N=C1/C(C[N+])C*C1 0.000 description 2
- MALQYVMYKLHFQO-SOFGYWHQSA-P C/N=C1\C[NH2+]CC1C[NH3+] Chemical compound C/N=C1\C[NH2+]CC1C[NH3+] MALQYVMYKLHFQO-SOFGYWHQSA-P 0.000 description 2
- TVTQXRANZBERIW-CTFBAELQSA-N C/N=C1\CN(C2=C(F)C=C3C(=O)C(C(=O)O)=CN(C4CC4)C3=N2)C[C@@H]1CN Chemical compound C/N=C1\CN(C2=C(F)C=C3C(=O)C(C(=O)O)=CN(C4CC4)C3=N2)C[C@@H]1CN TVTQXRANZBERIW-CTFBAELQSA-N 0.000 description 1
- HTYDDEWDXJKJDA-VOTSOKGWSA-N C/N=C1\CN(P)CC1CNPP Chemical compound C/N=C1\CN(P)CC1CNPP HTYDDEWDXJKJDA-VOTSOKGWSA-N 0.000 description 1
- CYTICTZLZDVQEI-UHFFFAOYSA-N CC1=C(F)C=C2C(=O)C(C(=O)O)=CN(C3CC3)C2=N1 Chemical compound CC1=C(F)C=C2C(=O)C(C(=O)O)=CN(C3CC3)C2=N1 CYTICTZLZDVQEI-UHFFFAOYSA-N 0.000 description 1
- SALPZIQRKWJAAK-ZMLKLZOPSA-P CO/N=C1\CN(C(=O)OC(C)(C)C)CC1CNC(=O)OC(C)(C)C.CO/N=C1\C[NH2+]CC1C[NH3+] Chemical compound CO/N=C1\CN(C(=O)OC(C)(C)C)CC1CNC(=O)OC(C)(C)C.CO/N=C1\C[NH2+]CC1C[NH3+] SALPZIQRKWJAAK-ZMLKLZOPSA-P 0.000 description 1
- ZRCVYEYHRGVLOC-HYARGMPZSA-N CO/N=C1\CN(C2=C(F)C=C3C(=O)C(C(=O)O)=CN(C4CC4)C3=N2)CC1CN Chemical compound CO/N=C1\CN(C2=C(F)C=C3C(=O)C(C(=O)O)=CN(C4CC4)C3=N2)CC1CN ZRCVYEYHRGVLOC-HYARGMPZSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Definitions
- the present invention relates to novel compounds which are of use in the production of pharmaceutically active compounds, for example, quinolone carboxylic acid derivatives having antibacterial activity.
- EP 688772 discloses novel naphthyridine carboxylic acid derivatives having antibacterial activity, including anhydrous (R,S)7-(3-aminomethyl-4-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid of the formula:
- WO 98/42705 discloses (R,S)-7-(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate and hydrates thereof including the sesquihydrate.
- PCT/KR99/00099 discloses a process for the production of 4-aminomethyl-3-alkoxyiminopyrrolidines and salts thereof from aminomethylpyrrolidin-3-one and the corresponding alkoxylamine.
- Suitable salts of the 4-aminomethyl-3-alkoxyiminopyrrolidines are described as the hydrochloride, trifluoroacetate and sulfate salts.
- the present invention relates to novel 4-aminomethyl-3-alkoxyiminopyrrolidine salts which are of use in the synthesis of pharmaceutically active compounds.
- the compound of formula (I) is preferably 4-aminomethyl-3-methoxyiminopyrrolidinium dimethanesulfonate.
- Suitable protecting groups P 1 and P 2 include any suitable amino protecting groups which are removable by treatment with methanesulfonic acid.
- the preferred protecting group for both P 1 and P 2 is t-butoxycarbonyl.
- reaction of the compound of formula (II) and methanesulfonic acid is suitably carried out at a temperature between about 10° C. and about 50° C., more preferably at a temperature of 40-45° C.
- the amount of methanesulfonic acid used to effect the deprotection of the compound of formula (II) is suitably 2 to 4 equivalents.
- 2.4 equivalents suitably used at a temperature of between 35° C. and 40° C.; or 3 equivalents, suitably used at ambient temperature. More preferably 2.5 equivalents used at a temperature of 40-45° C.
- the reaction is suitably carried out in a solvent, for example, an alcohol such as methanol, ethanol, isopropanol, or n-propanol, dichloromethane, acetonitrile, acetone, methyl iso-butyl ketone, DME, ThF, tert-butylmethyl ether, dioxane or ethyl acetate or a mixture of any of these.
- the solvent is preferably methanol.
- up to 10 equivalents by volume of solvent may be used, e.g. about 4 equivalents.
- the compounds of formula (II) may be prepared by the processes described in U.S. Pat. No. 5,633,262, EP 688772 and PCr/KR99/00099.
- the compounds of formula (I) are useful as an intermediates for preparing quinolone antibacterials particularly those described in U.S. Pat. No. 5,633,262 and EP 688772.
- the reaction of the compounds of formulae (I) and (IV) is preferably conducted in the presence of a base e.g. triethylamine.
- the reaction of the compounds of formulae (I) and (III) is preferably conducted in a solvent, e.g. acetonitrile, an aqueous solvent such as aqueous acetonitrile or an aqueous alcohol and more preferably water.
- a solvent e.g. acetonitrile, an aqueous solvent such as aqueous acetonitrile or an aqueous alcohol and more preferably water.
- water is used as solvent for this process the resulting compound of formula (III) is of superior quality to that obtained using other solvents. This leads to an improvement in the quality of the resulting drug substance as well as a process that may offer environmental advantages. Further details regarding the reaction of the compounds of formula (I) and (IV) can be found in U.S. Pat. No. 5,633,262 and EP 688772.
- the compound of formula (III) produced according to this aspect of the invention is preferably (R,S)-7(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate or a hydrate thereof, preferably the sesquihydrate, as disclosed in WO 98/42705.
- the methanesulfonate and hydrates thereof may be synthesised from the free acid as described in WO 98/42705 and WO 00/17199.
- the compounds of the invention have the advantage that they are stable, i.e. not hygroscopic. They can be isolated from the reaction in higher yield and purity than the corresponding dihydrochloride or free base.
- the dimesylate salts can be recrystallised if necessary, whereas the corresponding dihydrochloride or free base has not been successfully recrystallised.
- the dimesylate salts can be used to produce quinolone antibacterials of high purity and several advantages result from using this intermediate.
- the resulting drug substance is (R,S)-7-(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate or a hydrate thereof, it has improved colour and significantly lower levels of high molecular weight impurites compared to the drug substance produced using the corresponding dihydrochloride or free base as intermediate.
- Triethylamine (5.1 ml) was added to 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3 carboxylic acid (3.05 g) in water (25 ml) at 15-20° C. and the mixture stirred for 20 min 4-Aminomethyl-3-methoxyimino-pyrrolidinium dimethanesulfonate (3.86 g) was added, followed by water (5 ml), and the mixture stirred at 20-25° C. for 173 ⁇ 4 hours. The resulting product was filtered and the cake washed with water (30 ml) followed by ethanol (30 ml) and dried under vacuum at 50° C. to give the title compound as a white solid (4.23 g). (102% as is, 86% on assay). Characterising data were consistent with a standard sample of the title compound.
Abstract
Chemical intermediates which are of use in the production of quinolone carboxylic acid derivatives having antibacterial activity.
Description
- The present invention relates to novel compounds which are of use in the production of pharmaceutically active compounds, for example, quinolone carboxylic acid derivatives having antibacterial activity.
-
- WO 98/42705 discloses (R,S)-7-(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate and hydrates thereof including the sesquihydrate.
- PCT/KR99/00099 (published after the priority date of the present application) discloses a process for the production of 4-aminomethyl-3-alkoxyiminopyrrolidines and salts thereof from aminomethylpyrrolidin-3-one and the corresponding alkoxylamine. Suitable salts of the 4-aminomethyl-3-alkoxyiminopyrrolidines are described as the hydrochloride, trifluoroacetate and sulfate salts.
- The present invention relates to novel 4-aminomethyl-3-alkoxyiminopyrrolidine salts which are of use in the synthesis of pharmaceutically active compounds.
-
-
- wherein R is C1-4 alkyl or C1-4 haloalkyl.
- The compound of formula (I) is preferably 4-aminomethyl-3-methoxyiminopyrrolidinium dimethanesulfonate.
-
-
- wherein R is as defined for formula (I) and P1 and P2, which may be the same or different, are amino protecting groups, with methanesulfonic acid.
- Suitable protecting groups P1 and P2 include any suitable amino protecting groups which are removable by treatment with methanesulfonic acid. The preferred protecting group for both P1 and P2 is t-butoxycarbonyl.
- The reaction of the compound of formula (II) and methanesulfonic acid is suitably carried out at a temperature between about 10° C. and about 50° C., more preferably at a temperature of 40-45° C.
- The amount of methanesulfonic acid used to effect the deprotection of the compound of formula (II) is suitably 2 to 4 equivalents. For example, 2.4 equivalents, suitably used at a temperature of between 35° C. and 40° C.; or 3 equivalents, suitably used at ambient temperature. More preferably 2.5 equivalents used at a temperature of 40-45° C.
- The reaction is suitably carried out in a solvent, for example, an alcohol such as methanol, ethanol, isopropanol, or n-propanol, dichloromethane, acetonitrile, acetone, methyl iso-butyl ketone, DME, ThF, tert-butylmethyl ether, dioxane or ethyl acetate or a mixture of any of these. The solvent is preferably methanol. Suitably, up to 10 equivalents by volume of solvent may be used, e.g. about 4 equivalents.
- The compounds of formula (II) may be prepared by the processes described in U.S. Pat. No. 5,633,262, EP 688772 and PCr/KR99/00099.
- The compounds of formula (I) are useful as an intermediates for preparing quinolone antibacterials particularly those described in U.S. Pat. No. 5,633,262 and EP 688772. Thus according to a further aspect of the invention there is provided a process for the production of a compound of formula (III), or a pharmaceutically acceptable salt and/or hydrate thereof:
-
- wherein R is as defined for formula (I), which comprises reaction of a compound of formula (I), with a compound of formula (IV):
- wherein X is a leaving group, e.g. a halogen atom, preferably chlorine; and optionally forming a pharmaceutically acceptable salt and/or hydrate thereof.
- wherein R is as defined for formula (I), which comprises reaction of a compound of formula (I), with a compound of formula (IV):
- Other suitable leaving groups X will be apparent to those skilled in the art.
- The reaction of the compounds of formulae (I) and (IV) is preferably conducted in the presence of a base e.g. triethylamine. The reaction of the compounds of formulae (I) and (III) is preferably conducted in a solvent, e.g. acetonitrile, an aqueous solvent such as aqueous acetonitrile or an aqueous alcohol and more preferably water. When water is used as solvent for this process the resulting compound of formula (III) is of superior quality to that obtained using other solvents. This leads to an improvement in the quality of the resulting drug substance as well as a process that may offer environmental advantages. Further details regarding the reaction of the compounds of formula (I) and (IV) can be found in U.S. Pat. No. 5,633,262 and EP 688772. The compounds of formula (IV) may be synthesisied as described in U.S. Pat. No. 5,633,262 and EP 688772.
- The compound of formula (III) produced according to this aspect of the invention is preferably (R,S)-7(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate or a hydrate thereof, preferably the sesquihydrate, as disclosed in WO 98/42705. The methanesulfonate and hydrates thereof may be synthesised from the free acid as described in WO 98/42705 and WO 00/17199.
- The compounds of the invention have the advantage that they are stable, i.e. not hygroscopic. They can be isolated from the reaction in higher yield and purity than the corresponding dihydrochloride or free base. The dimesylate salts can be recrystallised if necessary, whereas the corresponding dihydrochloride or free base has not been successfully recrystallised. The dimesylate salts can be used to produce quinolone antibacterials of high purity and several advantages result from using this intermediate. For example, when the resulting drug substance is (R,S)-7-(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate or a hydrate thereof, it has improved colour and significantly lower levels of high molecular weight impurites compared to the drug substance produced using the corresponding dihydrochloride or free base as intermediate.
- All publications, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein as though fully set forth.
- The invention is illustrated by the following examples. However, it should be understood that the examples are intended to illustrate but not in any manner limit the scope of the invention.
-
- A solution of 1(N-t-butoxycarbonyl)-4-(t-butoxycarbonylaminomethyl) pyrrolidin-3-methoxime (100 g) in methanol (660 mL) at 15-20° C. under nitrogen was treated with methanesulfonic acid (56.4 mL) over 5 min keeping the temperature below 30° C. The solution was stirred at 20-25° C. for 16-20 hrs. During this time the product precipitated forming a thick suspension. The product was isolated by filtration, washed with methanol (165 ml) and dried under vacuo at 25° C. to give the title compound 84 g (86%).
- m.p. 189-193° C.;
- m/z: 144 (M+H)+;
- 1H NMR (400 MHz, d6-DMSO) δ: 9.27, (2H, brs), 7.95 (3H, brs), 4.01 (1H, d), 3.92 (1H, d), 3.87 (3H, s), 3.69 (1H, m), 3.26 (2H, m), 3.26 (2H, m), 3.15 (1H, m), 3.08 (1H, m), 2.39 (6H, s);
- Analysis: C, 28.64%, H, 6.25%, N, 12.46%; C8H21N3O7S2 requires C, 28.65%, H, 6.31%, N, 12.53%.
- Synthesis of 4-aminomethyl-3-methoxyiminopyrrolidinium Dimethanesulfonate
- A solution of 1-(N-t-butoxycarbonyl)-4-(t-butoxycarbonylaminomethyl) pyrrolidin-3-methoxime (100 g) in methanol (400 mL) at 20° C. under nitrogen was treated with methanesulfonic acid (47 mL, 70 g, 2.5 equiv) over 15 min keeping the temperature below 25° C. The solution was heated to 40-45° C. over 30 mins and maintained at this temperature for 4-5 hrs. During this time the product precipitated forming a thick suspension. The crude product was isolated by filtration under nitrogen and washed with methanol (200 mL). The crude product was suspended in methanol (4 volumes, approx. 360 mL) and heated to reflux for 1 hr. After cooling to 20° C. the suspension was stirred for 1 hour. The product was filtered, washed with methanol (2 volumes, approx. 180 ml) and dried under vacuum at 40° C. to give the title compound 73.8 g (78%). Characterising data were consistent with a standard sample of the title compound.
- Synthesis of (R,S)-7-(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic Acid
- Triethylamine (5.1 ml) was added to 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3 carboxylic acid (3.05 g) in water (25 ml) at 15-20° C. and the mixture stirred for 20 min 4-Aminomethyl-3-methoxyimino-pyrrolidinium dimethanesulfonate (3.86 g) was added, followed by water (5 ml), and the mixture stirred at 20-25° C. for 17¾ hours. The resulting product was filtered and the cake washed with water (30 ml) followed by ethanol (30 ml) and dried under vacuum at 50° C. to give the title compound as a white solid (4.23 g). (102% as is, 86% on assay). Characterising data were consistent with a standard sample of the title compound.
- Synthesis of (R,S)-7-(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic Acid Methanesulfonate
- A solution of methanesulfonic acid (0.33 g, 3.43 mmol) in dichloromethane (1 ml) was added to a suspension of (R,S)-7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (1.5 g at 89.9% purity, 3.46 mmol) in a mixture of dichloromethane (23.2 ml) and ethanol (2.7 ml) at 30° C. The mixture was stirred at 30° C. for 3 hours then cooled to 20° C. and filtered. The cake was washed with dichloromethane (20 ml) and dried at 50° C. under vacuum to give the title compound (1.71 g) (102% as is, 91% on assay). Characterising data were consistent with a standard sample of the title compound.
- Synthesis of (R,S)-7-(3-aminomethyl-4-syn-methoxyimino-pyrrolidin-1-yl)1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic Acid Methanesulfonate Sesquihydrate
- (R,S)-7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate (27.5 g at 91% purity, 51.4 mmol) was stirred in a mixture of isopropanol (150 ml) and water (75 ml) and heated until a clear solution was obtained (52° C.). The solution was cooled to 34° C. and seed crystals of (R,S)-7-(3-aminomethyl-4-syn-methoxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3 carboxylic acid methanesulfonate sesquihydrate added. The resulting suspension was allowed to cool to 25° C. over 1 hour and stirred for 18 hours. The slurry was cooled to 0-4° C., stirred for 2 hours, then filtered and the cake washed with isopropanol (30 ml). The product was sucked dry for 2 hours and then further dried at 50° C. under vacuum. The dried product was exposed to the atmosphere to give the sesquihydrate, 22.9 g (92%). Characterising data were consistent with a standard sample of the title compound.
Claims (2)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/935,357 US20050033064A1 (en) | 1999-09-03 | 2004-09-08 | Intermediates for the production of quinolone carboxylic acid derivatives |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9920919.9A GB9920919D0 (en) | 1999-09-03 | 1999-09-03 | Novel compound |
GB9920919.9 | 1999-09-03 | ||
US10/088,149 US6703512B1 (en) | 1999-09-03 | 2000-09-01 | Intermediates for the production of quinolone carboxylic acid derivatives |
US10/742,797 US6803467B2 (en) | 1999-09-03 | 2003-12-23 | Intermediates for the production of quinolone carboxylic acid derivatives |
US10/935,357 US20050033064A1 (en) | 1999-09-03 | 2004-09-08 | Intermediates for the production of quinolone carboxylic acid derivatives |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/742,797 Continuation US6803467B2 (en) | 1999-09-03 | 2003-12-23 | Intermediates for the production of quinolone carboxylic acid derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
US20050033064A1 true US20050033064A1 (en) | 2005-02-10 |
Family
ID=10860355
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/088,149 Expired - Lifetime US6703512B1 (en) | 1999-09-03 | 2000-09-01 | Intermediates for the production of quinolone carboxylic acid derivatives |
US10/742,797 Expired - Lifetime US6803467B2 (en) | 1999-09-03 | 2003-12-23 | Intermediates for the production of quinolone carboxylic acid derivatives |
US10/935,357 Abandoned US20050033064A1 (en) | 1999-09-03 | 2004-09-08 | Intermediates for the production of quinolone carboxylic acid derivatives |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/088,149 Expired - Lifetime US6703512B1 (en) | 1999-09-03 | 2000-09-01 | Intermediates for the production of quinolone carboxylic acid derivatives |
US10/742,797 Expired - Lifetime US6803467B2 (en) | 1999-09-03 | 2003-12-23 | Intermediates for the production of quinolone carboxylic acid derivatives |
Country Status (30)
Country | Link |
---|---|
US (3) | US6703512B1 (en) |
EP (1) | EP1212321B1 (en) |
JP (1) | JP4208463B2 (en) |
KR (1) | KR100705363B1 (en) |
CN (1) | CN1255402C (en) |
AR (1) | AR029452A1 (en) |
AT (1) | ATE270671T1 (en) |
AU (1) | AU773698B2 (en) |
BR (1) | BRPI0013750B8 (en) |
CA (1) | CA2383751C (en) |
CO (1) | CO5180620A1 (en) |
CZ (1) | CZ2002759A3 (en) |
DE (1) | DE60012028T2 (en) |
DK (1) | DK1212321T3 (en) |
ES (1) | ES2223570T3 (en) |
GB (1) | GB9920919D0 (en) |
HK (1) | HK1046908B (en) |
HU (1) | HU229391B1 (en) |
IL (2) | IL148441A0 (en) |
MX (1) | MXPA02002356A (en) |
MY (1) | MY126789A (en) |
NO (1) | NO322501B1 (en) |
NZ (1) | NZ517601A (en) |
PL (1) | PL206491B1 (en) |
PT (1) | PT1212321E (en) |
SI (1) | SI1212321T1 (en) |
TR (1) | TR200200548T2 (en) |
TW (1) | TWI264435B (en) |
WO (1) | WO2001017961A2 (en) |
ZA (1) | ZA200201779B (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2281817C (en) * | 1999-06-29 | 2008-07-29 | Smithkline Beecham Corporation | Methods of use of fluoroquinolone compounds against maxillary sinus pathogenic bacteria |
GB9920917D0 (en) | 1999-09-03 | 1999-11-10 | Sb Pharmco Inc | Novel process |
GB9920919D0 (en) | 1999-09-03 | 1999-11-10 | Sb Pharmco Inc | Novel compound |
US7199242B2 (en) | 2001-08-02 | 2007-04-03 | Lg Life Sciences Limited | Processes for the production of amino-protected derivatives of 4-aminomethylene-pyrrolidin-3-one and/or 4-aminomethylene-pyrrolidin-3-alkoxyimino derivatives and/or gemifloxacin or a salt thereof |
KR100517638B1 (en) | 2002-04-08 | 2005-09-28 | 주식회사 엘지생명과학 | New process for preparing acid salts of Gemifloxacin |
ATE310773T1 (en) * | 2002-07-17 | 2005-12-15 | Ciba Sc Holding Ag | OXIDATION PROCESS FOR PRODUCING QUINACRIDONE PIGMENTS |
KR100653334B1 (en) * | 2003-03-07 | 2006-12-04 | 주식회사 엘지생명과학 | New process for preparing 4-aminomethyl-3-alkoxyiminopyrrolidine methanesulphonate |
US8822934B2 (en) * | 2006-11-03 | 2014-09-02 | Accuray Incorporated | Collimator changer |
CN104693088B (en) * | 2013-12-06 | 2018-01-05 | 常州市勇毅生物药业有限公司 | A kind of preparation method of gemifloxacin side chain |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5633262A (en) * | 1994-06-16 | 1997-05-27 | Lg Chemical Ltd. | Quinoline carboxylic acid derivatives having 7-(4-amino-methyl-3-oxime) pyrrolidine substituent and processes for preparing thereof |
US5776944A (en) * | 1994-06-16 | 1998-07-07 | Lg Chemical Ltd. | 7-(4-aminomethyl-3-methyloxyiminopyrroplidin-1-yl)-1-cyclopropyl-6-flu oro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and the process for the preparation thereof |
US6307059B1 (en) * | 1998-03-04 | 2001-10-23 | Lg Chemical, Ltd | Process for preparing a protected 4-aminomethyl-pyrrolidi-3-one |
US6703512B1 (en) * | 1999-09-03 | 2004-03-09 | Sb Pharmco Puerto Rico Inc. Of The United States Corporation Company | Intermediates for the production of quinolone carboxylic acid derivatives |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57134482A (en) | 1981-02-13 | 1982-08-19 | Dainippon Pharmaceut Co Ltd | 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8- naphthyridine-3-carboxylic acid-3/2 hydrate and its preparation |
IN162769B (en) | 1984-11-13 | 1988-07-09 | Kyorin Seiyaku Kk | |
NZ222047A (en) | 1986-10-08 | 1991-01-29 | Bristol Myers Co | Quinoline - or naphthyridine - carboxylic acid anti-bacterial agents |
JPH01100165A (en) | 1987-10-13 | 1989-04-18 | Shionogi & Co Ltd | Oxime or hydroxylamine derivative based antimicrobial agent |
US4920120A (en) | 1988-01-25 | 1990-04-24 | Warner-Lambert Company | Antibacterial agents |
JPH0356479A (en) | 1989-07-24 | 1991-03-12 | Takeshi Yokota | P-toluenesulfonate of water-soluble quinolone derivative |
IE66202B1 (en) | 1989-08-16 | 1995-12-13 | Pfizer | Azabicyclo quinolone carboxylic acids |
US5137892A (en) | 1990-12-12 | 1992-08-11 | Abbott Laboratories | Quinoline, naphthyridine and pyridobenzoxazine derivatives |
US5276041A (en) | 1991-11-08 | 1994-01-04 | Kaken Pharmaceutical Co., Ltd. | Oxime derivatives |
JPH0673056A (en) | 1992-08-26 | 1994-03-15 | Kaken Pharmaceut Co Ltd | Quinolinecarboxylic acid derivative and salt thereof |
JP3449658B2 (en) | 1994-12-21 | 2003-09-22 | 杏林製薬株式会社 | 8-Alkoxyquinolonecarboxylic acid hydrate excellent in stability and method for producing the same |
ES2117426T3 (en) | 1995-06-06 | 1998-08-01 | Pfizer | CRYSTALLINE FORM OF ANHYDRAUS SALT COMPOSED OF ACIDS 7 - ((1A, 5A, 6A) -6-AMINO-3-AZABICICLO (3.1.0.) HEX-3-IL) -6-FLUORO-1- (2, 4-DIFLUOROFENIL) -1,4-DIHIDRO-4-OXO-1,8-NAFTIRIDINA-3-CARBOXILICO AND METANOSULFONICO. |
KR100291882B1 (en) | 1995-08-11 | 2001-10-26 | 디. 제이. 우드, 스피겔 알렌 제이 | (1S, 2S) -1- (4-hydroxyphenyl) -2- (4-hydroxy-4-phenylpiperidin-1-yl) -1-propanolmethanesulfonate trihydrate |
UA49880C2 (en) | 1996-03-29 | 2002-10-15 | Смітклайн Бічам Корпорейшн | ERPOSARTANE dihydrate, PHARMACEUTICAL COMPOSITION, process for SOLID DOSE production, method to block angiotensin II receptors |
MA24500A1 (en) * | 1997-03-21 | 1998-10-01 | Lg Life Sciences Ltd | CARBOXYLIC ACID SALT DERIVATIVE FROM NAPHTHYRIDINE. |
DE69911203T2 (en) | 1998-05-29 | 2004-07-15 | Pharmacia & Upjohn Co., Kalamazoo | 3 - [(1'-N-methylamino) ethyl-N-benzyl] pyrrolidine-MONOMETHANESULFONAT |
GB9820405D0 (en) | 1998-09-18 | 1998-11-11 | Smithkline Beecham Plc | Process |
PT1223935E (en) | 1999-06-29 | 2008-04-03 | Lg Life Sciences Ltd | Use of gemifloxacin compounds against bacteria |
EP1401440A4 (en) | 1999-09-01 | 2006-07-05 | Lg Life Sciences Ltd | Methods of use of fluoroquinolone compounds against bacteria |
GB9920917D0 (en) * | 1999-09-03 | 1999-11-10 | Sb Pharmco Inc | Novel process |
WO2001021176A1 (en) | 1999-09-22 | 2001-03-29 | Smithkline Beecham Corporation | Methods of use of fluoroquinolone compounds against bacteria |
KR20010091379A (en) | 2000-03-15 | 2001-10-23 | 성재갑 | Novel process for the preparation of quinoline carboxylic acid derivatives having 7-(4-aminomethyl-3-oxime)pyrrolidine substituent |
KR20020018560A (en) | 2000-09-01 | 2002-03-08 | 성재갑 | Novel process for preparing 3-aminomethyl-4-Z-methoxyiminopyrrolidine |
-
1999
- 1999-09-03 GB GBGB9920919.9A patent/GB9920919D0/en not_active Ceased
-
2000
- 2000-09-01 CA CA2383751A patent/CA2383751C/en not_active Expired - Lifetime
- 2000-09-01 JP JP2001521708A patent/JP4208463B2/en not_active Expired - Fee Related
- 2000-09-01 MX MXPA02002356A patent/MXPA02002356A/en active IP Right Grant
- 2000-09-01 BR BRPI0013750A patent/BRPI0013750B8/en not_active IP Right Cessation
- 2000-09-01 KR KR1020027002876A patent/KR100705363B1/en active IP Right Grant
- 2000-09-01 US US10/088,149 patent/US6703512B1/en not_active Expired - Lifetime
- 2000-09-01 AR ARP000104596A patent/AR029452A1/en active IP Right Grant
- 2000-09-01 CO CO00065923A patent/CO5180620A1/en active IP Right Grant
- 2000-09-01 NZ NZ517601A patent/NZ517601A/en not_active IP Right Cessation
- 2000-09-01 CN CNB008123292A patent/CN1255402C/en not_active Expired - Lifetime
- 2000-09-01 CZ CZ2002759A patent/CZ2002759A3/en unknown
- 2000-09-01 AU AU68573/00A patent/AU773698B2/en not_active Ceased
- 2000-09-01 EP EP00956706A patent/EP1212321B1/en not_active Expired - Lifetime
- 2000-09-01 TR TR2002/00548T patent/TR200200548T2/en unknown
- 2000-09-01 ES ES00956706T patent/ES2223570T3/en not_active Expired - Lifetime
- 2000-09-01 DE DE60012028T patent/DE60012028T2/en not_active Expired - Lifetime
- 2000-09-01 IL IL14844100A patent/IL148441A0/en active IP Right Grant
- 2000-09-01 WO PCT/GB2000/003358 patent/WO2001017961A2/en active IP Right Grant
- 2000-09-01 MY MYPI20004053 patent/MY126789A/en unknown
- 2000-09-01 SI SI200030481T patent/SI1212321T1/en unknown
- 2000-09-01 DK DK00956706T patent/DK1212321T3/en active
- 2000-09-01 PT PT00956706T patent/PT1212321E/en unknown
- 2000-09-01 HU HU0202733A patent/HU229391B1/en not_active IP Right Cessation
- 2000-09-01 AT AT00956706T patent/ATE270671T1/en active
- 2000-09-01 PL PL354725A patent/PL206491B1/en not_active IP Right Cessation
- 2000-09-29 TW TW089120154A patent/TWI264435B/en not_active IP Right Cessation
-
2002
- 2002-02-28 IL IL148441A patent/IL148441A/en unknown
- 2002-03-01 NO NO20021043A patent/NO322501B1/en not_active IP Right Cessation
- 2002-03-04 ZA ZA200201779A patent/ZA200201779B/en unknown
- 2002-11-21 HK HK02108460.2A patent/HK1046908B/en not_active IP Right Cessation
-
2003
- 2003-12-23 US US10/742,797 patent/US6803467B2/en not_active Expired - Lifetime
-
2004
- 2004-09-08 US US10/935,357 patent/US20050033064A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5633262A (en) * | 1994-06-16 | 1997-05-27 | Lg Chemical Ltd. | Quinoline carboxylic acid derivatives having 7-(4-amino-methyl-3-oxime) pyrrolidine substituent and processes for preparing thereof |
US5776944A (en) * | 1994-06-16 | 1998-07-07 | Lg Chemical Ltd. | 7-(4-aminomethyl-3-methyloxyiminopyrroplidin-1-yl)-1-cyclopropyl-6-flu oro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and the process for the preparation thereof |
US5869670A (en) * | 1994-06-16 | 1999-02-09 | Lg Chemical Ltd. | 7-(4-aminomethyl-3-methyloxyiminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and the process for the preparation thereof |
US5962468A (en) * | 1994-06-16 | 1999-10-05 | Lg Chemical Ltd. | 7-(4-aminomethyl-3-methyloxyiminopyrrolidin-1-yl)-1- cyclopropyl-6-fluoro-4-oxo-1, 4-dihydro-1, 8-naphthyridine-3-carboxylic acid and the process for the preparation thereof |
US6307059B1 (en) * | 1998-03-04 | 2001-10-23 | Lg Chemical, Ltd | Process for preparing a protected 4-aminomethyl-pyrrolidi-3-one |
US6703512B1 (en) * | 1999-09-03 | 2004-03-09 | Sb Pharmco Puerto Rico Inc. Of The United States Corporation Company | Intermediates for the production of quinolone carboxylic acid derivatives |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7115744B2 (en) | Method for producing 8-methoxy-quinolinecarboxylic acids | |
US6703512B1 (en) | Intermediates for the production of quinolone carboxylic acid derivatives | |
US7232907B2 (en) | Process for production of naphthyridine-3-carboxylic acid derivatives | |
IL299949A (en) | Process for preparing aminofuranes | |
Barrett et al. | Alkylation of 1-(N-(Hydroxymethyl)-N-methylamino)-4-quinolones. An Improved Preparation of Intermediates for Novel Potent Tricyclic Quinolone Antibacterial Agents. | |
US20020062026A1 (en) | Method for preparing N-methyleneglycinates | |
WO2011016016A9 (en) | Processes for the preparation of vardenafil | |
WO1994002487A1 (en) | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |