DD298399A5 - Azabicyclo-chinolon-carbonsaeuren - Google Patents

Azabicyclo-chinolon-carbonsaeuren Download PDF

Info

Publication number: DD298399A5
Authority: DD; German Democratic Republic
Prior art keywords: azabicyclo; mmol; methyl; yield; compound
Prior art date: 1989-08-16

Application number

DD90343474A

Other languages

German (de)

English (en)

Inventor

Katherine E Brighty

Original Assignee

��@��Kk��

Priority date (The priority date 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 date listed.)

1989-08-16

Filing date

1990-08-15

Publication date

1992-02-20

1990-08-15 Application filed by ��@��Kk�� filed Critical ��@��Kk��

1992-02-20 Publication of DD298399A5 publication Critical patent/DD298399A5/de

Links

-1 quinolone carboxylic acids Chemical class 0.000 claims abstract description 208
230000000844 anti-bacterial effect Effects 0.000 claims abstract description 7
150000001875 compounds Chemical class 0.000 claims description 255
238000000034 method Methods 0.000 claims description 88
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 82
229910052739 hydrogen Inorganic materials 0.000 claims description 55
239000001257 hydrogen Substances 0.000 claims description 54
150000002431 hydrogen Chemical class 0.000 claims description 31
239000002253 acid Substances 0.000 claims description 29
125000001424 substituent group Chemical group 0.000 claims description 26
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
229910052799 carbon Inorganic materials 0.000 claims description 15
229910052757 nitrogen Inorganic materials 0.000 claims description 13
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
125000003277 amino group Chemical group 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 4
150000001768 cations Chemical class 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
229940002612 prodrug Drugs 0.000 claims description 4
239000000651 prodrug Substances 0.000 claims description 4
150000001413 amino acids Chemical class 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
239000003242 anti bacterial agent Substances 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
150000001721 carbon Chemical group 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
150000005054 naphthyridines Chemical class 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
229910052721 tungsten Inorganic materials 0.000 claims description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
229910052727 yttrium Inorganic materials 0.000 claims description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
ZMDQWHCTODNNLT-UHFFFAOYSA-N 2h-1,2-benzoxazine-3-carboxylic acid Chemical class C1=CC=C2ONC(C(=O)O)=CC2=C1 ZMDQWHCTODNNLT-UHFFFAOYSA-N 0.000 claims 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
125000001309 chloro group Chemical group Cl* 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical class N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 abstract description 4
239000003814 drug Substances 0.000 abstract description 2
229940079593 drug Drugs 0.000 abstract description 2
150000003840 hydrochlorides Chemical class 0.000 abstract 1
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 184
239000000047 product Substances 0.000 description 146
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 141
239000000243 solution Substances 0.000 description 136
238000005160 1H NMR spectroscopy Methods 0.000 description 129
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 97
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 90
239000007787 solid Substances 0.000 description 82
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
239000000203 mixture Substances 0.000 description 71
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 68
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
239000003921 oil Substances 0.000 description 57
239000002904 solvent Substances 0.000 description 54
239000011541 reaction mixture Substances 0.000 description 48
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 46
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 44
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 44
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
239000012074 organic phase Substances 0.000 description 41
239000003480 eluent Substances 0.000 description 39
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 38
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 37
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
125000004494 ethyl ester group Chemical group 0.000 description 36
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 33
238000002360 preparation method Methods 0.000 description 31
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 30
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
229910052938 sodium sulfate Inorganic materials 0.000 description 29
235000011152 sodium sulphate Nutrition 0.000 description 29
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 28
238000004440 column chromatography Methods 0.000 description 28
239000000706 filtrate Substances 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
239000012280 lithium aluminium hydride Substances 0.000 description 25
230000009467 reduction Effects 0.000 description 24
238000006722 reduction reaction Methods 0.000 description 24
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 23
238000010992 reflux Methods 0.000 description 23
238000000354 decomposition reaction Methods 0.000 description 22
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
150000003138 primary alcohols Chemical class 0.000 description 21
238000005481 NMR spectroscopy Methods 0.000 description 20
239000000908 ammonium hydroxide Substances 0.000 description 20
YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 description 20
238000001914 filtration Methods 0.000 description 20
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 20
238000003756 stirring Methods 0.000 description 20
150000005228 3‐azabicyclo[3.1.0]hexanes Chemical class 0.000 description 19
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
235000011114 ammonium hydroxide Nutrition 0.000 description 19
229940043379 ammonium hydroxide Drugs 0.000 description 19
150000001732 carboxylic acid derivatives Chemical class 0.000 description 19
229910052943 magnesium sulfate Inorganic materials 0.000 description 19
235000019341 magnesium sulphate Nutrition 0.000 description 19
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 18
125000001412 tetrahydropyranyl group Chemical group 0.000 description 17
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 16
230000002829 reductive effect Effects 0.000 description 16
239000002585 base Substances 0.000 description 15
239000012267 brine Substances 0.000 description 15
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 14
229910052763 palladium Inorganic materials 0.000 description 14
239000000725 suspension Substances 0.000 description 14
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 13
239000000463 material Substances 0.000 description 13
238000000746 purification Methods 0.000 description 13
SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 12
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
229940098779 methanesulfonic acid Drugs 0.000 description 11
238000001953 recrystallisation Methods 0.000 description 11
239000007858 starting material Substances 0.000 description 11
150000001412 amines Chemical class 0.000 description 10
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 10
MZFQJBMXUXJUHF-UHFFFAOYSA-N 4-azabicyclo[4.1.0]heptane Chemical class C1CNCC2CC21 MZFQJBMXUXJUHF-UHFFFAOYSA-N 0.000 description 9
WTCJJEJMYYASNT-UHFFFAOYSA-N 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1=CC=C(F)C=C1F WTCJJEJMYYASNT-UHFFFAOYSA-N 0.000 description 9
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 9
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
239000012230 colorless oil Substances 0.000 description 8
238000006352 cycloaddition reaction Methods 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
150000002576 ketones Chemical class 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
150000003335 secondary amines Chemical class 0.000 description 8
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
230000005595 deprotonation Effects 0.000 description 7
238000010537 deprotonation reaction Methods 0.000 description 7
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 7
238000005984 hydrogenation reaction Methods 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 7
150000002825 nitriles Chemical class 0.000 description 7
239000000843 powder Substances 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
230000002378 acidificating effect Effects 0.000 description 6
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
238000010626 work up procedure Methods 0.000 description 6
238000006969 Curtius rearrangement reaction Methods 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 5
239000012448 Lithium borohydride Substances 0.000 description 5
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
125000003047 N-acetyl group Chemical group 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
238000010640 amide synthesis reaction Methods 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
238000007327 hydrogenolysis reaction Methods 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 5
NMNMAKPMFYHCNM-UHFFFAOYSA-N oxan-2-yloxymethanol Chemical compound OCOC1CCCCO1 NMNMAKPMFYHCNM-UHFFFAOYSA-N 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
238000012546 transfer Methods 0.000 description 5
HGWUUOXXAIISDB-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2CC21 HGWUUOXXAIISDB-UHFFFAOYSA-N 0.000 description 4
OXNZWNNMJBOZQO-UHFFFAOYSA-N 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 OXNZWNNMJBOZQO-UHFFFAOYSA-N 0.000 description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 4
ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 4
ZMDGICHYDVYQDX-UHFFFAOYSA-N methylidenecarbamic acid Chemical compound OC(=O)N=C ZMDGICHYDVYQDX-UHFFFAOYSA-N 0.000 description 4
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238000002512 chemotherapy Methods 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
229960002173 citrulline Drugs 0.000 description 1
235000013477 citrulline Nutrition 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
RLWFMZKPPHHHCB-UHFFFAOYSA-N cyclopropane-1,2-dicarboxylate;hydron Chemical compound OC(=O)C1CC1C(O)=O RLWFMZKPPHHHCB-UHFFFAOYSA-N 0.000 description 1
YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
150000008049 diazo compounds Chemical class 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000000378 dietary effect Effects 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
125000004212 difluorophenyl group Chemical group 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical group CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
238000010931 ester hydrolysis Methods 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 1
UCHJWSNOVHXTKU-UHFFFAOYSA-N ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(F)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1=CC=C(F)C=C1F UCHJWSNOVHXTKU-UHFFFAOYSA-N 0.000 description 1
MSPOSRHJXMILNK-UHFFFAOYSA-N ethyl 1h-pyrazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=NN1 MSPOSRHJXMILNK-UHFFFAOYSA-N 0.000 description 1
SFFQYGDIFWFUAF-UHFFFAOYSA-N ethyl 3-benzyl-2,4-dioxo-3-azabicyclo[3.1.0]hexane-6-carboxylate Chemical compound CCOC(=O)C1C(C2=O)C1C(=O)N2CC1=CC=CC=C1 SFFQYGDIFWFUAF-UHFFFAOYSA-N 0.000 description 1
RTDJLOFWEDKRPR-UHFFFAOYSA-N ethyl 4-benzyl-5-oxo-4-azabicyclo[4.1.0]heptane-7-carboxylate Chemical compound O=C1C2C(C(=O)OCC)C2CCN1CC1=CC=CC=C1 RTDJLOFWEDKRPR-UHFFFAOYSA-N 0.000 description 1
YYZUSRORWSJGET-UHFFFAOYSA-N ethyl octanoate Chemical compound CCCCCCCC(=O)OCC YYZUSRORWSJGET-UHFFFAOYSA-N 0.000 description 1
NNQYFBSGBOKZKP-UHFFFAOYSA-N ethylidene(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC)C1=CC=CC=C1 NNQYFBSGBOKZKP-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
230000022244 formylation Effects 0.000 description 1
238000006170 formylation reaction Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000007306 functionalization reaction Methods 0.000 description 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
GZWIRHPWUOSRCO-UHFFFAOYSA-N heptanoic acid;hydrochloride Chemical compound Cl.CCCCCCC(O)=O GZWIRHPWUOSRCO-UHFFFAOYSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
XOPUORAQCYGJPT-UHFFFAOYSA-N methanesulfonic acid;hydrochloride Chemical class Cl.CS(O)(=O)=O XOPUORAQCYGJPT-UHFFFAOYSA-N 0.000 description 1
XMYQHJDBLRZMLW-UHFFFAOYSA-N methanolamine Chemical compound NCO XMYQHJDBLRZMLW-UHFFFAOYSA-N 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
GJKXAWWEZQIKST-UHFFFAOYSA-N methyl 2-(benzylamino)-3-(oxan-2-yloxy)propanoate Chemical compound C=1C=CC=CC=1CNC(C(=O)OC)COC1CCCCO1 GJKXAWWEZQIKST-UHFFFAOYSA-N 0.000 description 1
UAWVZBDVSNLPDT-UHFFFAOYSA-N methyl 2-(benzylamino)acetate Chemical compound COC(=O)CNCC1=CC=CC=C1 UAWVZBDVSNLPDT-UHFFFAOYSA-N 0.000 description 1
HIVDOHPKFIBYPZ-UHFFFAOYSA-N methyl 2-(benzylamino)propanoate Chemical compound COC(=O)C(C)NCC1=CC=CC=C1 HIVDOHPKFIBYPZ-UHFFFAOYSA-N 0.000 description 1
GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
125000004492 methyl ester group Chemical group 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
FSZLFPCAJQDDJU-UHFFFAOYSA-N n-(3-benzyl-3-azabicyclo[3.1.0]hexan-1-yl)acetamide Chemical compound C1C2(NC(=O)C)CC2CN1CC1=CC=CC=C1 FSZLFPCAJQDDJU-UHFFFAOYSA-N 0.000 description 1
IJTCVRCODZRTAE-UHFFFAOYSA-N n-[(3-benzyl-3-azabicyclo[3.1.0]hexan-1-yl)methyl]acetamide Chemical compound C1C2(CNC(=O)C)CC2CN1CC1=CC=CC=C1 IJTCVRCODZRTAE-UHFFFAOYSA-N 0.000 description 1
AILMJHHPMIRQHV-UHFFFAOYSA-N n-[(3-benzyl-3-azabicyclo[3.1.0]hexan-1-yl)methyl]ethanamine Chemical compound C1C2(CNCC)CC2CN1CC1=CC=CC=C1 AILMJHHPMIRQHV-UHFFFAOYSA-N 0.000 description 1
ROTSPSKRULUAJM-UHFFFAOYSA-N n-benzyl-2-(oxan-2-yloxymethyl)but-3-en-1-amine Chemical compound C1CCCOC1OCC(C=C)CNCC1=CC=CC=C1 ROTSPSKRULUAJM-UHFFFAOYSA-N 0.000 description 1
USEGQYNVYCNAPA-UHFFFAOYSA-N n-benzylbut-2-en-1-amine Chemical compound CC=CCNCC1=CC=CC=C1 USEGQYNVYCNAPA-UHFFFAOYSA-N 0.000 description 1
FILNVDDHDRXIEA-UHFFFAOYSA-N n-benzylpent-3-en-1-amine Chemical compound CC=CCCNCC1=CC=CC=C1 FILNVDDHDRXIEA-UHFFFAOYSA-N 0.000 description 1
BNYNJIKGRPHFAM-UHFFFAOYSA-N n-heptylidenehydroxylamine Chemical compound CCCCCCC=NO BNYNJIKGRPHFAM-UHFFFAOYSA-N 0.000 description 1
125000002560 nitrile group Chemical group 0.000 description 1
238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
239000012285 osmium tetroxide Substances 0.000 description 1
229910000489 osmium tetroxide Inorganic materials 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
238000006146 oximation reaction Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
ZHZCYWWNFQUZOR-UHFFFAOYSA-N pent-4-en-2-ol Chemical compound CC(O)CC=C ZHZCYWWNFQUZOR-UHFFFAOYSA-N 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920001184 polypeptide Chemical group 0.000 description 1
LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
239000002243 precursor Substances 0.000 description 1
108090000765 processed proteins & peptides Chemical group 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
238000009738 saturating Methods 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
239000001476 sodium potassium tartrate Substances 0.000 description 1
235000011006 sodium potassium tartrate Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
QHSPZGZEUDEIQM-AATRIKPKSA-N tert-butyl (e)-but-2-enoate Chemical compound C\C=C\C(=O)OC(C)(C)C QHSPZGZEUDEIQM-AATRIKPKSA-N 0.000 description 1
HJICHFZTBBOJTP-UHFFFAOYSA-N tert-butyl 1-amino-2-methyl-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1C(C2(CC2C1)N)C HJICHFZTBBOJTP-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
239000002023 wood Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
General Health & Medical Sciences (AREA)
Communicable Diseases (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Oncology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Quinoline Compounds (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

DD90343474A 1989-08-16 1990-08-15 Azabicyclo-chinolon-carbonsaeuren DD298399A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PCT/US1989/003489 WO1991002526A1 (fr)	1989-08-16	1989-08-16	Acides azabicyclo quinolone carboxyliques

Publications (1)

Publication Number	Publication Date
DD298399A5 true DD298399A5 (de)	1992-02-20

Family

ID=22215165

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD90343474A DD298399A5 (de)	1989-08-16	1990-08-15	Azabicyclo-chinolon-carbonsaeuren

Country Status (30)

Country	Link
EP (1)	EP0413455B1 (fr)
JP (2)	JPH072734B2 (fr)
KR (1)	KR930004844B1 (fr)
CN (1)	CN1025192C (fr)
AT (1)	ATE124040T1 (fr)
AU (1)	AU623801B2 (fr)
BA (1)	BA98299A (fr)
CA (2)	CA2127561C (fr)
CY (2)	CY1969A (fr)
CZ (1)	CZ281127B6 (fr)
DD (1)	DD298399A5 (fr)
DE (3)	DE19875050I2 (fr)
DK (1)	DK0413455T3 (fr)
EG (1)	EG19251A (fr)
ES (1)	ES2074131T4 (fr)
FI (2)	FI108228B (fr)
GR (1)	GR3017072T3 (fr)
HK (1)	HK1000207A1 (fr)
HU (2)	HU219403B (fr)
IE (1)	IE66202B1 (fr)
IL (1)	IL95331A (fr)
LU (2)	LU90310I2 (fr)
NL (2)	NL980032I2 (fr)
NO (1)	NO300214B1 (fr)
NZ (1)	NZ234920A (fr)
PL (1)	PL166381B1 (fr)
PT (1)	PT94998B (fr)
RU (1)	RU2049777C1 (fr)
WO (1)	WO1991002526A1 (fr)
ZA (1)	ZA906450B (fr)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0449445A3 (en) *	1990-03-27	1993-08-25	Pfizer Inc.	Preparation of beta-ketoesters useful in preparing quinolone antibiotics
FR2675144B1 (fr) *	1991-04-10	1995-06-16	Bouchara Sa	Nouvelles quinolones difluorees - leur procede de preparation et les compositions pharmaceutiques en renfermant.
CA2111463C (fr) *	1991-06-19	1997-08-26	Bingwei V. Yang	Agents antibacteriens azaspiro quinolone
US5256791A (en) *	1992-03-02	1993-10-26	Pfizer Inc.	Preparation of intermediates in the synthesis of quinoline antibiotics
EG20543A (en) *	1992-10-30	1999-07-31	Procter & Gamble	Process for preparing of novel antimicrobial -5- (n-heterosubstituted amino) quinolones
US5527910A (en) *	1992-12-30	1996-06-18	Cheil Foods & Chemicals, Inc.	Pyridone carboxylic acid compounds and their uses for treating infectious diseases caused by bacteria
US5591766A (en) *	1993-12-03	1997-01-07	Cheil Foods & Chemicals, Inc.	Solid oral formulations of pyridone carboxylic acids
PT812838E (pt) *	1994-02-04	2002-10-31	Dainippon Pharmaceutical Co	Derivado de acido piridonacarboxilico substituido com o grupo amino biciclico seu ester seu sal e amina biciclica como seu intermediario
PT807630E (pt) *	1995-02-02	2003-08-29	Daiichi Seiyaku Co	Compostos heterociclicos
JPH08213881A (ja) *	1995-02-02	1996-08-20	Fujitsu Ltd	周波数制御回路
WO1996024593A1 (fr) *	1995-02-07	1996-08-15	Daiichi Pharmaceutical Co., Ltd.	Derives spiro heterocycliques
DE69503066T2 (de) *	1995-06-06	1998-10-15	Pfizer Inc., New York, N.Y.	KRISTALLFORM VON WASSERFREIEN 7-((1a,5a,6a)-6-AMINO-3-AZABICYCLO (3.1.0.) HEX-3-YL)-6-FLUORO-1-(2,4-DIFLUOROPHENYL)-1,4-DIHYDRO-4-OXO-1,8-NAPHTHYRIDIN-CARBONSÄURE METHANESULFONSÄURE SALZ
DE69622715T2 (de) *	1995-06-15	2002-11-14	Pfizer Inc., New York	Verfahren zur herstellung von derivaten der ein peptid enthaltenden azabizylo-naphtyridin-carbonsäure
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1989
- 1989-08-16 PL PL90286484A patent/PL166381B1/pl unknown
- 1989-08-16 HU HU9200460A patent/HU219403B/hu not_active IP Right Cessation
- 1989-08-16 RU SU5011662/04A patent/RU2049777C1/ru not_active IP Right Cessation
- 1989-08-16 WO PCT/US1989/003489 patent/WO1991002526A1/fr not_active Ceased
- 1989-08-16 IE IE295090A patent/IE66202B1/en not_active IP Right Cessation
1990
- 1990-07-30 AT AT90308331T patent/ATE124040T1/de active
- 1990-07-30 ES ES90308331T patent/ES2074131T4/es not_active Expired - Lifetime
- 1990-07-30 DE DE19875050C patent/DE19875050I2/de active Active
- 1990-07-30 EP EP90308331A patent/EP0413455B1/fr not_active Expired - Lifetime
- 1990-07-30 DK DK90308331.9T patent/DK0413455T3/da active
- 1990-07-30 DE DE69020262T patent/DE69020262T2/de not_active Expired - Fee Related
- 1990-07-30 DE DE19875052C patent/DE19875052I2/de active Active
- 1990-08-09 IL IL9533190A patent/IL95331A/en not_active IP Right Cessation
- 1990-08-14 KR KR1019900012528A patent/KR930004844B1/ko not_active Expired - Fee Related
- 1990-08-14 PT PT94998A patent/PT94998B/pt not_active IP Right Cessation
- 1990-08-14 EG EG48390A patent/EG19251A/xx active
- 1990-08-14 CA CA002127561A patent/CA2127561C/fr not_active Expired - Lifetime
- 1990-08-14 CA CA002023217A patent/CA2023217C/fr not_active Expired - Lifetime
- 1990-08-15 CN CN90106794A patent/CN1025192C/zh not_active Expired - Fee Related
- 1990-08-15 AU AU61042/90A patent/AU623801B2/en not_active Expired
- 1990-08-15 NZ NZ234920A patent/NZ234920A/en unknown
- 1990-08-15 ZA ZA906450A patent/ZA906450B/xx unknown
- 1990-08-15 DD DD90343474A patent/DD298399A5/de unknown
- 1990-08-16 JP JP2216461A patent/JPH072734B2/ja not_active Expired - Fee Related
- 1990-08-16 CZ CS904027A patent/CZ281127B6/cs not_active IP Right Cessation
1992
- 1992-02-14 NO NO920599A patent/NO300214B1/no not_active IP Right Cessation
- 1992-02-14 FI FI920632A patent/FI108228B/fi active Protection Beyond IP Right Term
1994
- 1994-07-08 JP JP6157008A patent/JPH0819099B2/ja not_active Expired - Fee Related
1995
- 1995-06-22 HU HU95P/P00380P patent/HU211681A9/hu unknown
- 1995-08-09 GR GR950402200T patent/GR3017072T3/el unknown
1996
- 1996-11-11 FI FI964520A patent/FI103879B/fi active
1997
- 1997-09-05 CY CY196997A patent/CY1969A/xx unknown
- 1997-09-12 HK HK97101767A patent/HK1000207A1/en not_active IP Right Cessation
1998
- 1998-03-30 BA BA980299A patent/BA98299A/bs unknown
- 1998-11-04 LU LU90310C patent/LU90310I2/fr unknown
- 1998-11-04 LU LU90311C patent/LU90311I2/fr unknown
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Also Published As

Publication number	Publication date
FI964520A0 (fi)	1996-11-11
DE19875052I2 (de)	2009-05-28
HU211681A9 (en)	1995-12-28
CY99010I2 (en)	2010-07-28
HU219403B (hu)	2001-04-28
FI920632A0 (fi)	1992-02-14
NO920599L (no)	1992-04-14
PT94998B (pt)	1997-05-28
KR910004572A (ko)	1991-03-28
NO920599D0 (no)	1992-02-14
KR930004844B1 (ko)	1993-06-09
NL980033I2 (nl)	1999-05-03
EP0413455A2 (fr)	1991-02-20
LU90311I2 (fr)	1999-01-25
FI103879B1 (fi)	1999-10-15
BA98299A (bs)	2001-09-14
EP0413455A3 (en)	1991-10-09
PL286484A1 (en)	1991-05-20
DE69020262D1 (de)	1995-07-27
DE19875050I2 (de)	2009-05-28
ZA906450B (en)	1992-03-25
CA2127561C (fr)	1998-07-28
FI964520L (fi)	1996-11-11
WO1991002526A1 (fr)	1991-03-07
IL95331A (en)	1995-07-31
AU623801B2 (en)	1992-05-21
FI108228B (fi)	2001-12-14
PL166381B1 (pl)	1995-05-31
EP0413455B1 (fr)	1995-06-21
HK1000207A1 (en)	1998-02-06
AU6104290A (en)	1991-02-21
NL980032I2 (nl)	1999-05-03
CN1025192C (zh)	1994-06-29
NZ234920A (en)	1992-06-25
JPH0386875A (ja)	1991-04-11
CN1049501A (zh)	1991-02-27
NL980033I1 (nl)	1999-02-01
IE66202B1 (en)	1995-12-13
JPH072734B2 (ja)	1995-01-18
CZ402790A3 (en)	1996-04-17
IE902950A1 (en)	1991-02-27
CZ281127B6 (cs)	1996-06-12
CA2023217A1 (fr)	1991-02-17
ATE124040T1 (de)	1995-07-15
NO300214B1 (no)	1997-04-28
NL980032I1 (nl)	1999-02-01
ES2074131T3 (es)	1995-09-01
CA2127561A1 (fr)	1991-02-17
ES2074131T4 (es)	1996-05-01
JPH07149758A (ja)	1995-06-13
LU90310I2 (fr)	1999-01-25
GR3017072T3 (en)	1995-11-30
RU2049777C1 (ru)	1995-12-10
CY1969A (en)	1997-09-05
EG19251A (en)	1994-09-29
DE69020262T2 (de)	1995-10-26
PT94998A (pt)	1991-04-18
CA2023217C (fr)	1996-12-10
DK0413455T3 (da)	1995-08-14
JPH0819099B2 (ja)	1996-02-28
IL95331A0 (en)	1991-06-30
FI103879B (fi)	1999-10-15

Legal Events

Date	Code	Title	Description
2004-04-28	IF04	In force in the year 2004	Expiry date: 20100816

Publication	Publication Date	Title
DE69020262T2 (de)	1995-10-26	Azabicyclo-Chinolin-Carbonsäuren.
US5164402A (en)	1992-11-17	Azabicyclo quinolone and naphthyridinone carboxylic acids
RU2167873C2 (ru)	2001-05-27	Производные пиридонкарбоновой кислоты или их соли и антибактериальное средство
DE68910441T2 (de)	1994-03-03	Spiro-Verbindungen.
HK1000207B (en)	1998-02-06	Azabicyclo quinolone carboxylic acids
DE69724140T2 (de)	2004-06-03	Pyridoncarbonsäurederivate oder ihre salze und diese als aktive bestandteile enthaltende medikamente
HK1003000B (en)	1998-09-30	Spiro compounds
US5286723A (en)	1994-02-15	Spiro compound
JPH09221424A (ja)	1997-08-26	抗腫瘍剤
JPH06239857A (ja)	1994-08-30	二環性環状アミン誘導体
JP2817907B2 (ja)	1998-10-30	抗菌剤製造用の中間体
WO1998002431A1 (fr)	1998-01-22	DERIVES D'AMINOCYCLOPROPANE cis-SUBSTITUES
US5391763A (en)	1995-02-21	3-aza-bicyclo[3.1.0]hexanes which are intermediates for anti-bacterial azabicyclo quinolone carboxylic acids
JP2807277B2 (ja)	1998-10-08	スピロ化合物
US5266569A (en)	1993-11-30	Azatricyclo carboxylic acids useful as anti-bacterial agents
KR940010411B1 (ko)	1994-10-22	아자비시클로 퀴놀론 카르복실산을 함유하는 제약 조성물
JPWO1996023775A1 (ja)	1998-02-24	新規ピリドンカルボン酸誘導体又はその塩並びに該物質を有効成分とする抗菌剤
JP2004115530A (ja)	2004-04-15	新規ピリドンカルボン酸誘導体又はその塩並びに該物質を有効成分とする抗菌剤