JPS61277668A - Antibacterial compound, manufacture and medicine - Google Patents
Antibacterial compound, manufacture and medicineInfo
- Publication number
- JPS61277668A JPS61277668A JP61107539A JP10753986A JPS61277668A JP S61277668 A JPS61277668 A JP S61277668A JP 61107539 A JP61107539 A JP 61107539A JP 10753986 A JP10753986 A JP 10753986A JP S61277668 A JPS61277668 A JP S61277668A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- mathematical
- general formula
- chemical
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims description 25
- 239000003814 drug Substances 0.000 title description 8
- 230000000844 anti-bacterial effect Effects 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000003242 anti bacterial agent Substances 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- -1 8-ethyl-5,8-dihydro-5-oxo-2- (4-styryl-1-piperazinyl)-pyrido[2,3 -d] pyrimidine-6-carboxylic acid Chemical compound 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 8
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 229960001180 norfloxacin Drugs 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229940100595 phenylacetaldehyde Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 229960001699 ofloxacin Drugs 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical class N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 description 2
- 229960001732 pipemidic acid Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RQXXCWHCUOJQGR-UHFFFAOYSA-N 1,1-dichlorohexane Chemical compound CCCCCC(Cl)Cl RQXXCWHCUOJQGR-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 125000000637 arginyl group Chemical class N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- IDYZIJYBMGIQMJ-UHFFFAOYSA-N enoxacin Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 IDYZIJYBMGIQMJ-UHFFFAOYSA-N 0.000 description 1
- 229960002549 enoxacin Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical class C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 description 1
- 229960000210 nalidixic acid Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- YPOXGDJGKBXRFP-UHFFFAOYSA-N pyrimidine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は一般式（Ｉ）：
（式中、Ｒは０１〜Ｃ４のアルキル基または０３〜Ｃ８
のシクロアルキル基、Ｒ′およびＲｎは同じかまたは異
なり、水素原子、ハロゲン原子、メチル基、トリフルオ
ロメチル基またはメトキシ基、ＸおよびＹは同じかまた
は異なり、チッ素原子、ンＣ−Ｈ基または′；Ｃ−Ｆ基
をあられす）であられされる化合物または薬理学的に許
容しうるその塩基イず加塩、その製法および有効成分と
してそれを含有してなる抗菌剤に関する。Detailed Description of the Invention [Industrial Application Field] The present invention relates to the general formula (I): (wherein R is a 01-C4 alkyl group or a 03-C8
cycloalkyl group, R' and Rn are the same or different, hydrogen atom, halogen atom, methyl group, trifluoromethyl group or methoxy group, X and Y are the same or different, nitrogen atom, C-H group The present invention relates to a compound having a C-F group or a pharmacologically acceptable base salt thereof, a method for producing the same, and an antibacterial agent containing the compound as an active ingredient.
［従来の技術および発明が解決しようとする問題点］
一般式（■）：
（式中、Ｒ，ＸおよびＹは前記と同じ）であられされる
化合物は知られており、該化合物のいくつかは、とくに
尿感染の治療のために抗菌剤としてすでに広く用いられ
ている。[Prior art and problems to be solved by the invention] Compounds represented by the general formula (■): (wherein R, X and Y are the same as above) are known, and some of these compounds is already widely used as an antibacterial agent, especially for the treatment of urinary infections.
たとえばベルギー特許第８７０．９１７号明細書に記載
されている１−エチル−６−フルオロ−１，４−ジヒド
ロ−４−オキソ−（１−ピペラジニル）−キノリン−３
−カルボン酸すなわちノルフロキサシン（Ｎｏｒｆ’１
ｏｘａｅＩｎ） （一般式（Ｉｔ）においてＲがエチ
ル基、ＹがンＣ−Ｈ基、Ｘが′；ｃ−ｐ基）は広い作用
スペクトル、およびピペミド酸（一般式［１）において
Ｒがエチル基、ＸおよびＹがチッ素原子）よりも高いす
ぐれた抗菌作用を示す。このピペミド酸は、ナリジクス
酸とともにキノリン系抗菌剤の前駆体とみなされてよい
。For example, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-(1-piperazinyl)-quinoline-3 as described in Belgian Patent No. 870.917.
-carboxylic acid i.e. norfloxacin (Norf'1
oxaeIn) (in the general formula (It), R is an ethyl group, Y is a C-H group, and , X and Y are nitrogen atoms). This pipemidic acid, along with nalidixic acid, may be considered a precursor of quinoline antibacterial agents.
ノルフロキサシンのあと、６位にフッ素原子を有するこ
とで特徴づけられるノルフロキサシンの系列の他の誘導
体が合成されている。これらのうちではシプロフロキサ
シン
（Ｃｙｐｒｏｆｌｏｘａｃｔｎ） （一般式（Ｉ［）
においてＲがシクロプロピル基、ＹがンＣ−Ｈ基、Ｘが
一〇−Ｐ基）、ベフロキサシン（Ｐｅｆ’１ｏｘａｃｌ
ｎ） （ノルフロキサシンの同族体、ピペラジン環がメ
チル化されている）、オフロキサシン（Ｏｆｌｏｘａｃ
ｉｎ）およびエノキサシン（Ｅｎｏｘａｃｌｎ）が最も
有望な化合物であるように思われる。After norfloxacin, other derivatives of the norfloxacin series have been synthesized, which are characterized by having a fluorine atom in the 6-position. Among these, ciprofloxacin (Cyprofloxactn) (general formula (I[)
, R is a cyclopropyl group, Y is a C-H group, X is a 10-P group), befloxacin (Pef'1oxacl
n) (homolog of norfloxacin, the piperazine ring is methylated), ofloxacin (ofloxacin)
in) and enoxacin (Enoxacln) appear to be the most promising compounds.
［問題点を解決するための手段］
いまや驚くべきことに本発明の一般式ｍであられされる
化合物が、適当な製剤形で用いられて治療に重要な薬理
学的特質を有することが見出された。その抗菌作用およ
び広い作用スペクトルはとくに有利である。[Means for Solving the Problems] It has now surprisingly been found that the compounds of the present invention having the general formula m have therapeutically important pharmacological properties when used in suitable formulations. It was done. Its antibacterial action and broad spectrum of action are particularly advantageous.
本発明の一般式（１）であられされる化合物のうち、と
くに好ましいのはＲがエチル基またはシクロプロピル基
、ＸがンＣ−Ｆ基、Ｙがチッ素原子、ンＣ−Ｕ基または
ンＣ−Ｐ基であるものである。Among the compounds represented by the general formula (1) of the present invention, particularly preferred are R for ethyl group or cyclopropyl group, X for C-F group, and Y for nitrogen atom, C-U group or N It is a C-P group.
１？″およびＲ／／はともに水素原子であってもよいし
、または一方が水素原子で他方が２，３も［７くは４−
位での塩素原子、臭素原子もしくはヨウ素原子；メチル
基、トリフルオロメチル基もしくはメトキシ基であって
もよく、フェニル環上でたとえば２，４位；３，４位；
３，５位；２，６位において同じかまたは異なっていて
よい基で両方置換されているものを含む。1? '' and R// may both be hydrogen atoms, or one may be a hydrogen atom and the other may be 2,3 [7 or 4-
a chlorine atom, a bromine atom or an iodine atom at a position; it may be a methyl group, a trifluoromethyl group or a methoxy group, for example on the phenyl ring at the 2, 4 position; the 3, 4 position;
3 and 5 positions; including those substituted with the same or different groups at the 2 and 6 positions.
本発明の一般式（１）の化合物は適当な有機もしくは無
機塩基と塩を形成してよい。そのような塩の例はナトリ
ウム塩、カリウム塩、カルシウム塩、マグネシウム塩、
アンモニウム塩、トリエチルアミン塩へ トロメタモル
（ｔｒｏｍｅｔａｍｏｌ）塩、ウロトロピン塩、リジン
塩、アルギニン塩、′プロ力イン塩、モルホリン塩など
である。The compounds of general formula (1) of the present invention may form salts with suitable organic or inorganic bases. Examples of such salts are sodium salts, potassium salts, calcium salts, magnesium salts,
Ammonium salt, triethylamine salt, trometamol salt, urotropin salt, lysine salt, arginine salt, 'propylene salt, morpholine salt, etc.
本発明の一般式（Ｉ）の化合物は、前記一般式（Ｉ）の
化合物を一般式（ＩＩＩ） 。The compound of general formula (I) of the present invention is the compound of general formula (I) described above.
（式中、Ｒ゛およびＲ／／は前記と同じ）であられされ
るフェニルアセトアルデヒドと反応させることによって
製造される。。(wherein R' and R// are the same as above) by reacting with phenylacetaldehyde. .
反応は触媒量の硫酸、塩酸、ｐ−トルエンスルホン酸な
どを用い、酸触媒によって行なわれる。The reaction is carried out with an acid catalyst using a catalytic amount of sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, or the like.
反応溶媒はベンゼン、トルエンもしくはキシレンなどの
無水芳香族炭化水素；塩化メチレンもしくはクロロホル
ムなどの無水ハロゲン化炭化水素；テトラヒドロフラン
もしくはエチルエーテルなどのエーテル類；ヘキサン、
ジクロヘキサン、石油エーテルなどの脂肪族炭化水素な
どから選ばれてよい。無水芳香族炭化水素、とりわけベ
ンゼンおよびトルエンが最も好ましい。Reaction solvents include anhydrous aromatic hydrocarbons such as benzene, toluene or xylene; anhydrous halogenated hydrocarbons such as methylene chloride or chloroform; ethers such as tetrahydrofuran or ethyl ether; hexane,
It may be selected from aliphatic hydrocarbons such as dichlorohexane and petroleum ether. Most preferred are anhydrous aromatic hydrocarbons, especially benzene and toluene.
反応は通常、溶媒の還流温度において適当な変換収率を
うるために必要な時間のあいだ行なわれる。The reaction is normally carried out at the reflux temperature of the solvent for the time necessary to obtain a suitable conversion yield.
本発明の一般式（１）の化合物は酸のかたちでえられ、
たとえばン濾過などの通常の方法で回収される。The compound of general formula (1) of the present invention is obtained in the form of an acid,
It is recovered by conventional methods such as filtration.
対応する塩はアルカリ金属もしくはアルカリ土類金属の
炭酸塩、炭酸水素塩もしくは水酸化物、または叙上のア
ミンと反応させることによってえられてよい。The corresponding salts may be obtained by reaction with alkali metal or alkaline earth metal carbonates, bicarbonates or hydroxides, or with the above-mentioned amines.
塩の形成は水または他の適当な溶媒中で行なわれてよい
。Salt formation may be carried out in water or other suitable solvent.
［実施例］
つぎに本発明を実施例を用いてさらに詳しく説明するが
、本発明はもとよりこれらに限られるものではない。[Example] Next, the present invention will be explained in more detail using Examples, but the present invention is not limited to these.
実施例１
ニーエチル−１，４−ジヒドロ−４−オキソ−７−（１
−ピペラジニル）−キノリン−３−カルボン酸（ノルフ
ロキサシン） ５．６８ｇ （１，７７Ｘ １０’モル
）、２−（２−クロロフェニル）アセトアルデヒド２．
７４ｇ（１，７７ｘ ｆＯ’モル）および触媒量の１）
−トルエンスルホン酸を無水トルエン１５０ｍ１中で反
応させた。Example 1 Niethyl-1,4-dihydro-4-oxo-7-(1
-piperazinyl)-quinoline-3-carboxylic acid (norfloxacin) 5.68g (1,77X 10'mol), 2-(2-chlorophenyl)acetaldehyde2.
74 g (1,77x fO'mol) and a catalytic amount of 1)
-Toluenesulfonic acid was reacted in 150 ml of anhydrous toluene.
混合物を還流し、攪拌化に２４時間反応させた。The mixture was refluxed and reacted for 24 hours with stirring.
冷却後、沈澱した固体をン濾過し、乾燥し、メタノール
で温時洗浄した。つぎのような性質を有するｌ−エチル
−６−フルオロ−１，４−ジヒドロ−４−オキソ−７−
（４−（２−（２−クロロフェニル）−エテノ−ｌ−イ
ル）−１−ピペラジニル）−３−キノリンカルボン酸（
化合物１ ） ８．９ ｇをえた。After cooling, the precipitated solid was filtered, dried and washed hot with methanol. l-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- having the following properties
(4-(2-(2-chlorophenyl)-etheno-l-yl)-1-piperazinyl)-3-quinolinecarboxylic acid (
Compound 1) 8.9 g was obtained.
融点：２２４〜２３０℃
元素分析値： Ｃ２４Ｈ２３ＦＮ３ ０３ Ｃ１（分
子量４５５．９０）として
計算値（Ｘ） ：Ｃ８３，２２）１５．０８ Ｎ９
．２１実測値（％） ：Ｃ８２，９７Ｈ５，１２Ｎ９
．０８ＩＲスペクトル（ヌジョール）（ｃｍ−１）：１
５８０、 １８２０ 、１７１Ｇ
ＮＭＲスペクトル（ＤＭＳＯ，ＴＭＳ、δ）：１．４２
（ｔ 、３Ｈ，−ＣＨ５） 、３．１０〜３．８
２（ｍ 、８Ｈ，−ＣＨ２−Ｎ、Ｃ００ＩＩ） 、
４４Ｏ〜４．８２（ａ＋ 、 ２Ｈ，Ｃ１１２）
、５．３４〜５．７８ （ｍ 、ＩＨ。Melting point: 224-230°C Elemental analysis value: Calculated value (X) as C24H23FN3 03 C1 (molecular weight 455.90): C83,22) 15.08 N9
．． 21 Actual value (%): C82, 97H5, 12N9
．． 08IR spectrum (nujol) (cm-1): 1
580, 1820, 171G NMR spectrum (DMSO, TMS, δ): 1.42
(t, 3H, -CH5), 3.10-3.8
2(m, 8H, -CH2-N, C00II),
44O~4.82 (a+, 2H, C112)
, 5.34-5.78 (m, IH.
−ＣＨ−） 、８．７６〜７．６０ （ｍ 、ＯＨ，−
ＣＨ−１芳香環、８位のＨ） 、７．６０〜８．００
（ｍ 、 ＩＨ。-CH-), 8.76-7.60 (m, OH,-
CH-1 aromatic ring, H at position 8), 7.60-8.00
(m, IH.
５位のＨ） 、８．８４（ｓ 、 ＬＨ，２位のＨ）実
施例２
実施例１と同様にしてフェニルアセトアルデヒド１．８
８ｇ （１，５７ｘｌＯ−２モル）をノルフロキサシン
５ ｇ （１，５７Ｘ ｔｏ−２モル）と反応させて、
つぎのような性質を有するｌ−エチル−６−フルオロ−
１，４−ジヒドロ−４−オキソ−Ｒ−（４−スチリル−
１−ピペラジニル）−３−キノリンカルボン酸（化合物
２）５．５ｒをえた。H at position 5), 8.84 (s, LH, H at position 2) Example 2 Phenylacetaldehyde 1.8 in the same manner as in Example 1
8 g (1,57×lO−2 mol) was reacted with 5 g (1,57× to−2 mol) of norfloxacin,
l-ethyl-6-fluoro- having the following properties
1,4-dihydro-4-oxo-R-(4-styryl-
5.5 r of 1-piperazinyl)-3-quinolinecarboxylic acid (compound 2) was obtained.
融点＝１７８〜１９０℃（分解）
元素分析値： Ｃ２４Ｔｏ４ＰＮ３０３（分子量４２
１．４５）として
計算値（％） ：Ｃ６８，３９Ｈ５゜７４ Ｎｔａ
、ｒａｒ実測値（％） ： Ｃ８ｇ、２３ Ｈ５，
７０Ｎ９．７３ｒＲスペクトル（ヌジョール） （ｃ
ｍ−１）：ＩＢ００〜１８２０．１７２５
ＮＭＲスペクトル（ＤＭＳＯ，ＴＭＳ、δ）：１．４２
（ｔ 、 ３Ｈ，−ＣＨ５） 、２．７０〜３．８５
（ａ 、 ９ＨＳＣＯＯＨ，−ＣＨ２−Ｎ） 、４．３
０〜４．８２（ｆｆｌ 、２Ｈ％ −Ｃ）１２） 、５
．２３〜５．７０ Ｃｍ 、 ＩＨ。Melting point = 178-190℃ (decomposition) Elemental analysis value: C24To4PN303 (molecular weight 42
Calculated value (%) as 1.45): C68,39H5゜74 Nta
, rar actual value (%): C8g, 23 H5,
70N9.73rR spectrum (Nujol) (c
m-1): IB00-1820.1725 NMR spectrum (DMSO, TMS, δ): 1.42
(t, 3H, -CH5), 2.70-3.85
(a, 9HSCOOH,-CH2-N), 4.3
0 to 4.82 (ffl, 2H% -C)12), 5
．． 23-5.70 Cm, IH.
−ＣＨ−） 、６．７５〜７．８８ （ｍ 、 ７Ｈ，
８位のＨ１芳香環のＨ、−Ｃ）ｉ−） 、７．７０〜１
１．１０’（ｓ 。-CH-), 6.75-7.88 (m, 7H,
H of H1 aromatic ring at position 8, -C)i-), 7.70-1
1.10'(s.
１８１５位のＨ） 、８．９５ （ｓ 、 ＬＨ，２位
のＨ）
同様にして、それぞれに対応する置換されたフェニルア
セトアルデヒドおよび一般式（Ｉ［）の酸から出発して
つぎの化合物をえた。H at position 1815), 8.95 (s, LH, H at position 2) Similarly, the following compounds were obtained starting from the corresponding substituted phenylacetaldehyde and the acid of general formula (I[). .
■−ジシクロプロピル−６−フルオロ１．４−ジヒドロ
−４−オキソ−７−（４−（２−（２，４−ジフルオロ
フェニル）エテンー１−イル）−１−ピペラジニル）−
３−キノリンカルボン酸
ｌ−エチル−６，８−ジフルオロ−１，４−ジヒドロ−
４−オキソ−７−（４−（２−（４−メトキシフェニル
）エテシー１−イル）−１−ピペラジニル）−３−キノ
リンカルボン酸
■−エチルー６−フルオロー１．４−ジヒドロ−４−オ
キソ−７−（４−（２−（（３−１−リフルオロメチル
フェニル）エテノ−１−イル）−１−ピペラジニル）−
３−キノリンカルボン酸
１−エチル−６−フルオロ−１，４−ジヒドロ−４−オ
キソ−７−（４−（２−（（３，５−ジメトキシフェニ
ル）エテノ−１−イル）−１−ピペラジニル）−１，８
−ナフチリジン−３−カルボン酸
■−エチルー６−フルオロー１．４−ジヒドロ−４−オ
キソ−７−（４−（２−（（２−フルオロ−４−メチル
フェニル）エテノ−１−イル）−１−ピペラジニル）−
１，８−ナフチリジン−３−カルボン酸
実施例３
実施例１．２と同様にしてフェニルアセトアルデヒド１
．９８ｇ （１，６４Ｘ １Ｇ−２モル）およびピペミ
ド酸５ ｇ （１，６４Ｘ１０−２モル）を反応させて
、つぎのような性質を有する８−エチル−５，８−ジヒ
ドロ−５−オキソ−２−（４−スチリル−１−ピペラジ
ニル）−ピリド［２，３−ｄｌ ピリミジン−６−カ
ルボン酸（化合物３）５．５ｇをえた（収率：８３％）
。-Dicyclopropyl-6-fluoro1,4-dihydro-4-oxo-7-(4-(2-(2,4-difluorophenyl)ethen-1-yl)-1-piperazinyl)-
l-ethyl-6,8-difluoro-1,4-dihydro-3-quinolinecarboxylate
4-Oxo-7-(4-(2-(4-methoxyphenyl)ethyl-1-yl)-1-piperazinyl)-3-quinolinecarboxylic acid ■-Ethyl-6-fluoro-1,4-dihydro-4-oxo- 7-(4-(2-((3-1-lifluoromethylphenyl)etheno-1-yl)-1-piperazinyl)-
1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(2-((3,5-dimethoxyphenyl)ethen-1-yl)-1-piperazinyl 3-quinolinecarboxylate) )-1,8
-Naphthyridine-3-carboxylic acid -ethyl-6-fluoro1,4-dihydro-4-oxo-7-(4-(2-((2-fluoro-4-methylphenyl)ethen-1-yl)-1 -piperazinyl)-
1,8-Naphthyridine-3-carboxylic acid Example 3 Phenylacetaldehyde 1 was prepared in the same manner as in Example 1.2.
．． 98 g (1,64X 1G-2 mol) and 5 g (1,64X 10-2 mol) of pipemidic acid are reacted to give 8-ethyl-5,8-dihydro-5-oxo-2 having the following properties -(4-styryl-1-piperazinyl)-pyrido[2,3-dl 5.5 g of pyrimidine-6-carboxylic acid (compound 3) was obtained (yield: 83%)
.
融点二１９８〜２００℃
ＩＲスペクトル（ヌジョール） （０１１１−１）
：１７２０．１６２５．１６０Ｏ
ＮＭＩ？スペクトル（ＤＭＳＯｌＴＭＳ、δ）；１．３
５ （ｔ 、 ３１Ｌ −ＣＨａ） 、２．７３〜３．
５３（＋ａ 、 ４Ｈ，−Ｃ）（２−Ｎ） 、３．ＢＯ
〜４．８８ （ｍ 。Melting point 2 198-200℃ IR spectrum (Nujol) (0111-1)
:1720.1625.160O NMI? Spectrum (DMSOTMS, δ); 1.3
5 (t, 31L-CHa), 2.73-3.
53 (+a, 4H, -C) (2-N), 3. B.O.
~4.88 (m.
７１Ｌ−ＣＨ２−ド１、Ｃ０ＯＨ，−ＣＨ２−）、５．
２０〜５．５６（ＩＩＩ 、 ｉｌｌ −Ｃ１１−）
、６．７０〜７．８０ （ｍ 、 ６Ｈ。71L-CH2-do1,C0OH,-CH2-),5.
20-5.56 (III, ill-C11-)
, 6.70-7.80 (m, 6H.
芳香環、−ＣＩＩ＝Ｃ） 、８．９３ （ｓ 、 ＬＨ
，５位のＩＩ ） 、９．１６ （ｓ 、 ＩＨ，２位
のＨ）ダラム陽性菌およびダラム陰性菌に対する最少阻
止濃度を測定することによって、ノルフロキサシンと比
較して化合物１〜３の抗菌作用を評価した。供試化合物
のジメチルスルホキシド（ＤＭＳＯ）中のスカラー希釈
液（ｓｃａｌａｒ ｄｉｌｕｔｉｏｎｓ）をムエラーー
ヒントン（Ｍｕｅｌ Ｉｅｒ−旧ｎｔｏｎ）寒天平板に
最終濃度が０．１〜１００μｇ ／ ｍｌになるように
接種した。細菌のブロス培養を前もって接種したプレー
トを３５℃で４８時間インキュベートした。病院から分
離された菌株とともに種々の国内および国際寄託機関か
らの菌株を用いた。えられた結果を第１表に示す。Aromatic ring, -CII=C), 8.93 (s, LH
, II at position 5), 9.16 (s, IH, H at position 2) The antibacterial activity of compounds 1 to 3 was evaluated in comparison with norfloxacin by measuring the minimum inhibitory concentration against Durham-positive and Durham-negative bacteria. evaluated. Scalar dilutions of test compounds in dimethyl sulfoxide (DMSO) were inoculated onto Muel Ier-Hinton agar plates to a final concentration of 0.1-100 μg/ml. Plates preinoculated with bacterial broth cultures were incubated at 35°C for 48 hours. Strains isolated from hospitals as well as strains from various national and international depositories were used. The results obtained are shown in Table 1.
［以下余白］
本発明はまた、一般式（Ｊ）の化合物またはその塩の抗
菌剤としての治療学的な用途に関連するすべての工業的
側面に関する。[Margins below] The present invention also relates to all industrial aspects related to the therapeutic use of compounds of general formula (J) or salts thereof as antibacterial agents.
したがって本発明の主要な面は、従来の賦形剤とともに
有効成分として治療学的に有効な量の一般°式（１）の
化合物またはその塩を含有し、経口、非経口または局所
投与のための医薬からなる。Accordingly, a key aspect of the invention is to contain a therapeutically effective amount of a compound of general formula (1) or a salt thereof as an active ingredient together with conventional excipients for oral, parenteral or topical administration. It consists of medicines.
本発明の経口投与のだめの医薬は、カプセル剤、錠剤、
糖衣錠、顆粒剤、シロップ剤および水剤からなる。本発
明の非経口投与のための医薬は、滅菌注射液からなる。The orally administered drug of the present invention includes capsules, tablets,
Consists of sugar-coated tablets, granules, syrups and solutions. The medicament according to the invention for parenteral administration consists of a sterile injection solution.
本発明の局所投与のための医薬は、クリーム剤、オーバ
ル剤（ｏｖｕｌｅｓ）、洗浄剤（ｖａｓｈｉｎｇｓ）、
ローション剤などからなる。The medicaments for topical administration of the present invention include creams, ovules, washes,
Consists of lotions, etc.
本発明の医薬はまた、結合剤、保存剤、安定化剤、着香
剤などのような従来の賦形剤も含む。The medicaments of the invention also include conventional excipients such as binders, preservatives, stabilizers, flavoring agents and the like.
さらに詳しくは、カプセル剤、錠剤、糖衣錠および顆粒
剤は、乳糖、リン酸カルシウム、マンニトール、デンプ
ン、カオリンなどの賦形剤、トラガントゴム、ゼラチン
、トウモロコシデンプンなどの結合剤、ステアリン酸マ
グネシウム、ステアリン酸カルシウム、タルクなどの滑
沢剤、アルギン酸、トウモロコシデンプンなどの分散剤
（ｄｉｓｇｒｅｇａｔｉｎｇ ａｇＢｎｔｓ） 、天然
もしくは合成の甘味剤、着香剤および着色剤を含んでい
てよい。More specifically, capsules, tablets, dragees and granules are prepared using excipients such as lactose, calcium phosphate, mannitol, starch, kaolin, binders such as gum tragacanth, gelatin, corn starch, magnesium stearate, calcium stearate, talc, etc. lubricants, dispersing agents such as alginic acid, corn starch, natural or synthetic sweetening agents, flavoring agents, and coloring agents.
経口投与のためのシロップ剤および水剤は、水もしくは
水性キャリヤーに溶解した有効成分に加えてショ糖など
の甘味剤、パラオキシ安息香酸メチル、バラオキシ安息
香酸プロピルのような保存剤、着色剤および着香剤を含
んでいてよい。Syrups and solutions for oral administration contain, in addition to the active ingredient dissolved in water or an aqueous carrier, a sweetening agent such as sucrose, preservatives such as methyl parahydroxybenzoate, propyl paraoxybenzoate, coloring agents and dyes. May contain fragrance.
局所投与用調合物は、中性脂肪族塩基または水溶性もし
くは自己乳化性の賦形剤とともに調合される。Formulations for topical administration are formulated with neutral aliphatic bases or water-soluble or self-emulsifying excipients.
製剤学の分野の当業者にはよく知られているように、叙
上の賦形剤に加えて、もしくは叙上の賦形剤のかわりに
いくつかの他の物質を用いてもよい。本明細書中ではと
くに明示していなぃが、これらのすべての調合物も本発
明の範囲に含まれることは理解されるべきである。A number of other materials may be used in addition to or in place of the excipients listed, as is well known to those skilled in the art of pharmaceutical sciences. Although not specifically mentioned herein, it should be understood that all of these formulations are within the scope of the present invention.
本発明の医薬の経口投与のためには、１日あたりの投与
量は患者の年齢、体重および健康状態に依存して１００
〜２０００ ｌｌ１ｇであってよく、ばあいによって２
〜４回に分けて投与される。それゆえ、１回服用量は５
０〜５００ｍｇの有効成分を含んでいる。For oral administration of the medicament of the invention, the daily dosage depends on the age, weight and state of health of the patient.
~2000 ll1g, depending on the case 2
~ Administered in 4 divided doses. Therefore, the single dose is 5
Contains 0-500 mg of active ingredient.
本発明の医薬のヒトに対する１日あたりの有効投与量は
１〜３０ｍｇ／ｋｇ体重である。The effective daily dose for humans of the medicament of the present invention is 1 to 30 mg/kg body weight.
Claims (1)
〜Ｃ＿６のシクロアルキル基、Ｒ′およびＲ″は同じか
または異なり、水素原子、ハロゲン原子メチル基、トリ
フルオロメチル基またはメトキシ基、ＸおよびＹは同じ
かまたは異なり、チッ素原子、▲数式、化学式、表等が
あります▼基または▲数式、化学式、表等があります▼
基をあらわす）であらわされる化合物または薬理学的に
許容しうるその塩基付加塩。 ２ 一般式（ I ）においてＹが▲数式、化学式、表等
があります▼基、Ｘが▲数式、化学式、表等があります
▼基、Ｒがエチル基である特許請求の範囲第１項記載の
化合物または薬理学的に許容しうるその塩基付加塩。 ３ 一般式（ I ）においてＹが▲数式、化学式、表等
があります▼基、Ｘが▲数式、化学式、表等があります
▼基、Ｒがシクロプロピル基である特許請求の範囲第１
項記載の化合物または薬理学的に許容しうるその塩基付
加塩。 ４ 一般式（ I ）においてＸとＹの両方がチッ素原子
であり、Ｒがエチル基である特許請求の範囲第１項記載
の化合物または薬理学的に許容しうるその塩基付加塩。 ５ 一般式（ I ）においてＸが▲数式、化学式、表等
があります▼基、Ｙがチッ素原子、Ｒがエチル基である
特許請求の範囲第１項記載の化合物または薬理学的に許
容しうるその塩基付加塩。 ６ 一般式（ I ）においてＸとＹの両方が▲数式、化
学式、表等があります▼基であり、Ｒがエチル基である
特許請求の範囲第１項記載の化合物または薬理学的に許
容しうるその塩基付加塩。 ７ １−エチル−６−フルオロ−１，４−ジヒドロ−４
−オキソ−７−（４−（２−（２−クロロフェニル）−
エテン−１−イル）−１−ピペラジニル）−３−キノリ
ンカルボン酸である特許請求の範囲第１項記載の化合物
または薬理学的に許容しうるその塩基付加塩。 ８ １−エチル−６−フルオロ−１，４−ジヒドロ−４
−オキソ−７−（４−スチリル−１−ピペラジニル）−
３−キノリンカルボン酸である特許請求の範囲第１項記
載の化合物または薬理学的に許容しうるその塩基付加塩
。 ９ ８−エチル−５，８−ジヒドロ−５−オキソ−２−
（４−スチリル−１−ピペラジニル）−ピリド［２，３
−ｄ］ピリミジン−６−カルボン酸である特許請求の範
囲第１項記載の化合物または薬理学的に許容しうるその
塩基付加塩。 １０ 一般式（II）： ▲数式、化学式、表等があります▼（II） （式中、ＲはＣ＿１〜Ｃ＿４のアルキル基またはＣ＿３
〜Ｃ＿６のシクロアルキル基、ＸおよびＹは同じかまた
は異なり、チッ素原子、▲数式、化学式、表等がありま
す▼基または▲数式、化学式、表等があります▼基をあ
らわす）であらわされる化合物を一般式（III）： ▲数式、化学式、表等があります▼（III） （式中、Ｒ′およびＲ″は同じかまたは異なり、水素原
子、ハロゲン原子、メチル基、トリフルオロメチル基ま
たはメトキシ基をあらわす）であらわされるフェニルア
セトアルデヒドと反応させることからなる一般式（ I
）：▲数式、化学式、表等があります▼（ I ） （式中、Ｒ、Ｒ′、Ｒ″、ＸおよびＹは前記と同じ）で
あらわされる化合物の製法。 １１ 反応が触媒量の酸の存在下において還流温度でト
ルエン中で行なわれる特許請求の範囲第１０項記載の製
法。 １２ 薬理学的に許容しうる賦形剤とともに有効成分と
して一般式（ I ）： ▲数式、化学式、表等があります▼（ I ） （式中、ＲはＣ＿１〜Ｃ＿４のアルキル基またはＣ＿３
〜Ｃ＿６のシクロアルキル基、Ｒ′およびＲ″は同じか
または異なり、水素原子、ハロゲン原子、メチル基、ト
リフルオロメチル基またはメトキシ基、ＸおよびＹは同
じかまたは異なり、チッ素原子、▲数式、化学式、表等
があります▼基または▲数式、化学式、表等があります
▼基をあらわす）であらわされる化合物または薬理学的
に許容しうるその塩基付加塩を含有してなる抗菌剤。[Claims] 1 General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R is an alkyl group of C_1 to C_4 or C_3
-C_6 cycloalkyl group, R' and R'' are the same or different, hydrogen atom, halogen atom methyl group, trifluoromethyl group or methoxy group, X and Y are the same or different, nitrogen atom, ▲ formula, There are chemical formulas, tables, etc. ▼ Groups or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼
or a pharmacologically acceptable base addition salt thereof. 2 In the general formula (I), Y is a ▲ mathematical formula, chemical formula, table, etc. ▼ group, X is a ▲ mathematical formula, chemical formula, table, etc. ▼ group, and R is an ethyl group. compound or a pharmacologically acceptable base addition salt thereof. 3 In the general formula (I), Y is a ▲ mathematical formula, chemical formula, table, etc. ▼ group, X is a ▲ mathematical formula, chemical formula, table, etc. ▼ group, and R is a cyclopropyl group. Claim 1
A compound or a pharmacologically acceptable base addition salt thereof. 4. The compound according to claim 1, or a pharmacologically acceptable base addition salt thereof, wherein in the general formula (I), both X and Y are nitrogen atoms, and R is an ethyl group. 5. In the general formula (I), X is a ▲ mathematical formula, chemical formula, table, etc. ▼ group, Y is a nitrogen atom, and R is an ethyl group; Uruso base addition salt. 6. In the general formula (I), both X and Y are ▲groups with mathematical formulas, chemical formulas, tables, etc.▼, and R is an ethyl group, or a compound according to claim 1, or a pharmacologically acceptable compound. Uruso base addition salt. 7 1-ethyl-6-fluoro-1,4-dihydro-4
-oxo-7-(4-(2-(2-chlorophenyl)-
2. The compound according to claim 1, which is (ethen-1-yl)-1-piperazinyl)-3-quinolinecarboxylic acid or a pharmacologically acceptable base addition salt thereof. 8 1-ethyl-6-fluoro-1,4-dihydro-4
-oxo-7-(4-styryl-1-piperazinyl)-
A compound according to claim 1 which is 3-quinolinecarboxylic acid or a pharmacologically acceptable base addition salt thereof. 9 8-ethyl-5,8-dihydro-5-oxo-2-
(4-styryl-1-piperazinyl)-pyrido[2,3
-d] pyrimidine-6-carboxylic acid, or a pharmacologically acceptable base addition salt thereof. 10 General formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R is an alkyl group of C_1 to C_4 or C_3
~C_6 cycloalkyl group, X and Y are the same or different, a nitrogen atom, a ▲ mathematical formula, chemical formula, table, etc. ▼ group, or ▲ a numerical formula, chemical formula, table, etc. ▼ group) General formula (III): ▲Mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R' and R'' are the same or different, and represent a hydrogen atom, a halogen atom, a methyl group, a trifluoromethyl group, or a methoxy The general formula ( I
): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( I ) (In the formula, R, R', R'', X and Y are the same as above). The process according to claim 10, which is carried out in toluene at reflux temperature in the presence of general formula (I) as an active ingredient together with pharmacologically acceptable excipients: ▲ Numerical formula, chemical formula, table, etc. ▼(I) (wherein, R is a C_1 to C_4 alkyl group or C_3
~C_6 cycloalkyl group, R' and R'' are the same or different, hydrogen atom, halogen atom, methyl group, trifluoromethyl group or methoxy group, X and Y are the same or different, nitrogen atom, ▲ formula An antibacterial agent containing a compound represented by a ▼ group, or a ▼ group, or a pharmacologically acceptable base addition salt thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT20653/85A IT1200470B (en) | 1985-05-10 | 1985-05-10 | ANTIBACTERIAL ACTIVITY COMPOUNDS, THEIR PREPARATION AND RELATED PHARMACEUTICAL COMPOSITIONS |
| IT20653A/85 | 1985-05-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS61277668A true JPS61277668A (en) | 1986-12-08 |
Family
ID=11170084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61107539A Pending JPS61277668A (en) | 1985-05-10 | 1986-05-09 | Antibacterial compound, manufacture and medicine |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS61277668A (en) |
| DE (1) | DE3615303A1 (en) |
| ES (1) | ES8707188A1 (en) |
| FR (1) | FR2583418A1 (en) |
| GB (1) | GB2174704A (en) |
| IT (1) | IT1200470B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8625325D0 (en) * | 1986-10-22 | 1986-11-26 | Glaxo Group Ltd | Chemical compounds |
| US5262417A (en) * | 1988-12-06 | 1993-11-16 | The Upjohn Company | Antibacterial quinolone compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59157068A (en) * | 1983-02-25 | 1984-09-06 | バイエル・アクチエンゲゼルシヤフト | Quinolonecarboxylic acids |
| JPS59170070A (en) * | 1983-03-12 | 1984-09-26 | バイエル・アクチエンゲゼルシヤフト | Bactericide |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5624671B2 (en) * | 1973-07-05 | 1981-06-08 | ||
| JPS5824438B2 (en) * | 1974-02-12 | 1983-05-20 | 大日本製薬株式会社 | 2-(1-piperazinyl) pyrido (2,3-D) pyrimidine |
| DE2903850A1 (en) * | 1979-02-01 | 1980-08-07 | Bayer Ag | 2-AMINO-8-CYCLOPROPYL-5-OXO-5,8- DIHYDRO-PYRIDO CORNER CLAMP ON 2,3-D CORNER CLAMP FOR -PYRIMIDINE-6-CARNONIC ACIDS, METHOD FOR THE PRODUCTION AND USE THEREOF |
| DE3033157A1 (en) * | 1980-09-03 | 1982-04-01 | Bayer Ag, 5090 Leverkusen | 7-AMINO-1-CYCLOPROPYL-4-OXO-1,4-DIHYDRO-NAPHTHYRIDINE-3-CARBONIC ACIDS, METHOD FOR THE PRODUCTION THEREOF AND THE ANTIBACTERIAL AGENTS CONTAINING THEM |
| NZ208470A (en) * | 1983-07-18 | 1988-06-30 | Abbott Lab | 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives and antibacterial compositions containing such |
-
1985
- 1985-05-10 IT IT20653/85A patent/IT1200470B/en active
-
1986
- 1986-05-06 DE DE19863615303 patent/DE3615303A1/en not_active Ceased
- 1986-05-06 GB GB08610985A patent/GB2174704A/en not_active Withdrawn
- 1986-05-09 JP JP61107539A patent/JPS61277668A/en active Pending
- 1986-05-09 ES ES555246A patent/ES8707188A1/en not_active Expired
- 1986-05-09 FR FR8606710A patent/FR2583418A1/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59157068A (en) * | 1983-02-25 | 1984-09-06 | バイエル・アクチエンゲゼルシヤフト | Quinolonecarboxylic acids |
| JPS59170070A (en) * | 1983-03-12 | 1984-09-26 | バイエル・アクチエンゲゼルシヤフト | Bactericide |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2583418A1 (en) | 1986-12-19 |
| GB8610985D0 (en) | 1986-06-11 |
| IT8520653A0 (en) | 1985-05-10 |
| DE3615303A1 (en) | 1986-11-13 |
| IT1200470B (en) | 1989-01-18 |
| ES555246A0 (en) | 1987-07-16 |
| ES8707188A1 (en) | 1987-07-16 |
| GB2174704A (en) | 1986-11-12 |
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