JP2005511743A - 新世代の三重標的化したキラルな広域スペクトラム抗菌性の７位置換ピペリジノ−キノロンカルボン酸誘導体、その調製方法、組成物、および医薬としての使用 - Google Patents

Info

Publication number

JP2005511743A

JP2005511743A JP2003551131A JP2003551131A JP2005511743A JP 2005511743 A JP2005511743 A JP 2005511743A JP 2003551131 A JP2003551131 A JP 2003551131A JP 2003551131 A JP2003551131 A JP 2003551131A JP 2005511743 A JP2005511743 A JP 2005511743A

Authority

JP

Japan

Prior art keywords

amino

dihydro

oxo

quinoline

fluoro

Prior art date

2001-12-13

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• -1 7-substituted piperidino-quinolone carboxylic acid Chemical class 0.000 title claims abstract description 320
• 239000000203 mixture Substances 0.000 title claims abstract description 275
• 238000000034 method Methods 0.000 title claims abstract description 206
• 238000002360 preparation method Methods 0.000 title claims description 144
• 230000000844 anti-bacterial effect Effects 0.000 title abstract description 27
• 150000003839 salts Chemical class 0.000 claims abstract description 459
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 83
• 230000003287 optical effect Effects 0.000 claims abstract description 45
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 31
• 150000004677 hydrates Chemical class 0.000 claims abstract description 27
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 315
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 207
• 150000001875 compounds Chemical class 0.000 claims description 204
• 239000002253 acid Chemical group 0.000 claims description 130
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 102
• 229910052799 carbon Inorganic materials 0.000 claims description 99
• 239000005973 Carvone Substances 0.000 claims description 97
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 78
• 229910052739 hydrogen Inorganic materials 0.000 claims description 65
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 62
• 238000003756 stirring Methods 0.000 claims description 55
• 125000001424 substituent group Chemical group 0.000 claims description 55
• 125000000217 alkyl group Chemical group 0.000 claims description 53
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 45
• 229940124307 fluoroquinolone Drugs 0.000 claims description 45
• 229910052757 nitrogen Inorganic materials 0.000 claims description 45
• 239000003960 organic solvent Substances 0.000 claims description 35
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 35
• 239000001257 hydrogen Substances 0.000 claims description 33
• 150000001413 amino acids Chemical class 0.000 claims description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 30
• 150000002148 esters Chemical class 0.000 claims description 30
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 29
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
• 239000002904 solvent Substances 0.000 claims description 28
• 238000000113 differential scanning calorimetry Methods 0.000 claims description 26
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 25
• 239000003054 catalyst Substances 0.000 claims description 24
• FHWXHXRRCMIUIK-UHFFFAOYSA-N n,3,3-trimethylpiperidin-4-amine Chemical compound CNC1CCNCC1(C)C FHWXHXRRCMIUIK-UHFFFAOYSA-N 0.000 claims description 24
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 22
• 125000000539 amino acid group Chemical group 0.000 claims description 22
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
• 238000011282 treatment Methods 0.000 claims description 22
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 21
• 239000013522 chelant Substances 0.000 claims description 20
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims description 19
• 150000001412 amines Chemical class 0.000 claims description 19
• 238000004458 analytical method Methods 0.000 claims description 19
• 208000015181 infectious disease Diseases 0.000 claims description 19
• 239000000843 powder Substances 0.000 claims description 19
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
• 229940050410 gluconate Drugs 0.000 claims description 17
• 230000008569 process Effects 0.000 claims description 17
• XJSUUJDMFDMIGK-UHFFFAOYSA-N 3,5-dimethylpiperidin-4-amine Chemical compound CC1CNCC(C)C1N XJSUUJDMFDMIGK-UHFFFAOYSA-N 0.000 claims description 16
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 16
• 229910052796 boron Inorganic materials 0.000 claims description 16
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 16
• HDHZKCZZHXUICO-UHFFFAOYSA-N 3,3-dimethylpiperidin-4-amine Chemical compound CC1(C)CNCCC1N HDHZKCZZHXUICO-UHFFFAOYSA-N 0.000 claims description 15
• SHTUTXIOXCCHBW-UHFFFAOYSA-N ethyl 4-amino-3,5-dimethylpiperidine-1-carboxylate Chemical compound CCOC(=O)N1CC(C)C(N)C(C)C1 SHTUTXIOXCCHBW-UHFFFAOYSA-N 0.000 claims description 15
• YPSXMDISEKEGKH-UHFFFAOYSA-N n,3,5-trimethylpiperidin-4-amine Chemical compound CNC1C(C)CNCC1C YPSXMDISEKEGKH-UHFFFAOYSA-N 0.000 claims description 14
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 13
• 125000001589 carboacyl group Chemical group 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 13
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 12
• MGGWXOOXFIXMCF-UHFFFAOYSA-N benzyl 4-amino-3,3-dimethylpiperidine-1-carboxylate Chemical compound C1CC(N)C(C)(C)CN1C(=O)OCC1=CC=CC=C1 MGGWXOOXFIXMCF-UHFFFAOYSA-N 0.000 claims description 12
• 229910052731 fluorine Inorganic materials 0.000 claims description 11
• SSCLELDZYWNJJT-QLJPJBMISA-N 1-cyclopropyl-6-fluoro-7-[(3r,4r)-4-hydroxy-3-methylpiperidin-1-yl]-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1C[C@@H](O)[C@H](C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1C SSCLELDZYWNJJT-QLJPJBMISA-N 0.000 claims description 10
• 238000002441 X-ray diffraction Methods 0.000 claims description 10
• 125000003282 alkyl amino group Chemical group 0.000 claims description 10
• 150000001408 amides Chemical class 0.000 claims description 10
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 9
• 230000009885 systemic effect Effects 0.000 claims description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
• SOWSVRBSHHQLAB-UHFFFAOYSA-N 5-amino-7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C(N)C(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(C)=C1N1CCC(N)C(C)(C)C1 SOWSVRBSHHQLAB-UHFFFAOYSA-N 0.000 claims description 8
• 238000010438 heat treatment Methods 0.000 claims description 8
• PZQUEAMFJFUJGG-UHFFFAOYSA-N n-cyclopropyl-3,5-dimethylpiperidin-4-amine Chemical compound CC1CNCC(C)C1NC1CC1 PZQUEAMFJFUJGG-UHFFFAOYSA-N 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• WPBQEWYKGUXFAT-UHFFFAOYSA-N 1-cyclopropyl-7-[3,3-dimethyl-4-(phenylmethoxycarbonylamino)piperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N(CC1(C)C)CCC1NC(=O)OCC1=CC=CC=C1 WPBQEWYKGUXFAT-UHFFFAOYSA-N 0.000 claims description 7
• FKQVCNIEJCPZQT-MEBBXXQBSA-N 7-[(3r,4r)-4-amino-3-methylpiperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CC[C@@H](N)[C@H](C)C1 FKQVCNIEJCPZQT-MEBBXXQBSA-N 0.000 claims description 7
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 7
• 239000005695 Ammonium acetate Substances 0.000 claims description 7
• 229940043376 ammonium acetate Drugs 0.000 claims description 7
• 235000019257 ammonium acetate Nutrition 0.000 claims description 7
• YWGPBLOOAKHZQF-UHFFFAOYSA-N benzyl n-(3,3-dimethylpiperidin-4-yl)carbamate Chemical compound CC1(C)CNCCC1NC(=O)OCC1=CC=CC=C1 YWGPBLOOAKHZQF-UHFFFAOYSA-N 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 230000003301 hydrolyzing effect Effects 0.000 claims description 7
• NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 claims description 7
• 150000007522 mineralic acids Chemical class 0.000 claims description 7
• PAIUOUOHLLEEEP-UHFFFAOYSA-N n,3-dimethylpiperidin-4-amine Chemical compound CNC1CCNCC1C PAIUOUOHLLEEEP-UHFFFAOYSA-N 0.000 claims description 7
• QDZDQKRSBWFIAK-UHFFFAOYSA-N n-ethyl-3,5-dimethylpiperidin-4-amine Chemical compound CCNC1C(C)CNCC1C QDZDQKRSBWFIAK-UHFFFAOYSA-N 0.000 claims description 7
• ZSWUAMLORPBSTM-UHFFFAOYSA-N 1-benzyl-3,3-dimethylpiperidin-4-amine Chemical compound C1CC(N)C(C)(C)CN1CC1=CC=CC=C1 ZSWUAMLORPBSTM-UHFFFAOYSA-N 0.000 claims description 6
• ILNJBIQQAIIMEY-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CN=C21 ILNJBIQQAIIMEY-UHFFFAOYSA-N 0.000 claims description 6
• DWHXCQMDSVTVCU-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1,8-diethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2CC)=O)=C2C(CC)=C1N1CCC(N)C(C)(C)C1 DWHXCQMDSVTVCU-UHFFFAOYSA-N 0.000 claims description 6
• BDSBSELVBOBYOQ-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-(2,4-difluorophenyl)-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C=3C(=CC(F)=CC=3)F)=O)=C2C(C)=C1N1CCC(N)C(C)(C)C1 BDSBSELVBOBYOQ-UHFFFAOYSA-N 0.000 claims description 6
• MZJYKRXJUVVRLL-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-(2,4-difluorophenyl)-8-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C=3C(=CC(F)=CC=3)F)=O)=C2C(CC)=C1N1CCC(N)C(C)(C)C1 MZJYKRXJUVVRLL-UHFFFAOYSA-N 0.000 claims description 6
• AALWVRXNONLKQH-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-ethyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCC(N)C(C)(C)C1 AALWVRXNONLKQH-UHFFFAOYSA-N 0.000 claims description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 6
• AXIBJJFOGYUHHJ-UHFFFAOYSA-N n-ethyl-3-methylpiperidin-4-amine Chemical compound CCNC1CCNCC1C AXIBJJFOGYUHHJ-UHFFFAOYSA-N 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
• DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 claims description 6
• 239000012453 solvate Substances 0.000 claims description 6
• UPXRTDGIBOVLGV-UHFFFAOYSA-N tert-butyl n-(3,3-dimethylpiperidin-4-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1(C)C UPXRTDGIBOVLGV-UHFFFAOYSA-N 0.000 claims description 6
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 5
• XZUJMFOTXYKCTA-UHFFFAOYSA-N 1-benzyl-3-ethyl-3-methylpiperidin-4-amine Chemical compound C1CC(N)C(CC)(C)CN1CC1=CC=CC=C1 XZUJMFOTXYKCTA-UHFFFAOYSA-N 0.000 claims description 5
• BXENYJFWTOWMLO-UHFFFAOYSA-N 1-benzyl-3-ethyl-n,3-dimethylpiperidin-4-amine Chemical compound C1CC(NC)C(CC)(C)CN1CC1=CC=CC=C1 BXENYJFWTOWMLO-UHFFFAOYSA-N 0.000 claims description 5
• GGHNGUZZIFQUHK-UHFFFAOYSA-N 1-cyclopropyl-7-[3,5-dimethyl-4-(methylamino)piperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)C(NC)C(C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC GGHNGUZZIFQUHK-UHFFFAOYSA-N 0.000 claims description 5
• SAMHFFGNBBJKBM-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(dimethylamino)-3-methylpiperidin-1-yl]-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1CC(N(C)C)C(C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1C SAMHFFGNBBJKBM-UHFFFAOYSA-N 0.000 claims description 5
• SCEYNOTZAXPNIY-UHFFFAOYSA-N 3-ethyl-3-methylpiperidin-4-amine Chemical compound CCC1(C)CNCCC1N SCEYNOTZAXPNIY-UHFFFAOYSA-N 0.000 claims description 5
• NOTIVFRUVAGKJJ-UHFFFAOYSA-N 3-ethyl-n,3-dimethylpiperidin-4-amine Chemical compound CCC1(C)CNCCC1NC NOTIVFRUVAGKJJ-UHFFFAOYSA-N 0.000 claims description 5
• ZOHCCEOISYCJEH-UHFFFAOYSA-N 3-ethyl-n,n,3-trimethylpiperidin-4-amine Chemical compound CCC1(C)CNCCC1N(C)C ZOHCCEOISYCJEH-UHFFFAOYSA-N 0.000 claims description 5
• PMBHAWNZPPNADR-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N)C(C)(C)C1 PMBHAWNZPPNADR-UHFFFAOYSA-N 0.000 claims description 5
• WFVBVDCOWIUOBX-UHFFFAOYSA-N 7-(4-amino-3,5-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CC(C)C(N)C(C)C1 WFVBVDCOWIUOBX-UHFFFAOYSA-N 0.000 claims description 5
• CGOYMYAGVNRAGM-XGAJLMLQSA-N 7-[(3r,4r)-4-amino-3-methylpiperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.C1C[C@@H](N)[C@H](C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1C CGOYMYAGVNRAGM-XGAJLMLQSA-N 0.000 claims description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 5
• 125000004442 acylamino group Chemical group 0.000 claims description 5
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 5
• XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 5
• LTVSDBIRNKOKKA-UHFFFAOYSA-N n,n,3,3-tetramethylpiperidin-4-amine Chemical compound CN(C)C1CCNCC1(C)C LTVSDBIRNKOKKA-UHFFFAOYSA-N 0.000 claims description 5
• GLXSANUPYLXYBF-UHFFFAOYSA-N n-cyclopropyl-3,3-dimethylpiperidin-4-amine Chemical compound CC1(C)CNCCC1NC1CC1 GLXSANUPYLXYBF-UHFFFAOYSA-N 0.000 claims description 5
• SMIRTKHVMVGXDQ-UHFFFAOYSA-N n-cyclopropyl-3-ethyl-3-methylpiperidin-4-amine Chemical compound CCC1(C)CNCCC1NC1CC1 SMIRTKHVMVGXDQ-UHFFFAOYSA-N 0.000 claims description 5
• CAZWZOFUXCIGSR-UHFFFAOYSA-N n-cyclopropyl-3-methylpiperidin-4-amine Chemical compound CC1CNCCC1NC1CC1 CAZWZOFUXCIGSR-UHFFFAOYSA-N 0.000 claims description 5
• WQXHWNIFQVJVSZ-UHFFFAOYSA-N n-ethyl-3,3-dimethylpiperidin-4-amine Chemical compound CCNC1CCNCC1(C)C WQXHWNIFQVJVSZ-UHFFFAOYSA-N 0.000 claims description 5
• 125000004434 sulfur atom Chemical group 0.000 claims description 5
• HAUKUCGBYWFHFC-GDBMZVCRSA-N tert-butyl n-[(3r,4r)-1-benzyl-3-methylpiperidin-4-yl]carbamate Chemical compound C1C[C@@H](NC(=O)OC(C)(C)C)[C@H](C)CN1CC1=CC=CC=C1 HAUKUCGBYWFHFC-GDBMZVCRSA-N 0.000 claims description 5
• LHSNRJGZDUFKQT-BDAKNGLRSA-N tert-butyl n-[(3r,4s)-3-methylpiperidin-4-yl]carbamate Chemical compound C[C@@H]1CNCC[C@@H]1NC(=O)OC(C)(C)C LHSNRJGZDUFKQT-BDAKNGLRSA-N 0.000 claims description 5
• BIRRFYKJOVTPGR-BDJLRTHQSA-N 1,8-diethyl-6-fluoro-7-[(3r,4r)-4-hydroxy-3-methylpiperidin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2CC)=O)=C2C(CC)=C1N1CC[C@@H](O)[C@H](C)C1 BIRRFYKJOVTPGR-BDJLRTHQSA-N 0.000 claims description 4
• BRCVXCLSBOTCIT-NSPYISDASA-N 1-(2,4-difluorophenyl)-6-fluoro-7-[(3r,4r)-4-hydroxy-3-methylpiperidin-1-yl]-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1C[C@@H](O)[C@H](C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C=3C(=CC(F)=CC=3)F)C2=C1C BRCVXCLSBOTCIT-NSPYISDASA-N 0.000 claims description 4
• SKJVBTKTRDJINY-MPBGBICISA-N 1-(2,4-difluorophenyl)-8-ethyl-6-fluoro-7-[(3r,4r)-4-hydroxy-3-methylpiperidin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C=3C(=CC(F)=CC=3)F)=O)=C2C(CC)=C1N1CC[C@@H](O)[C@H](C)C1 SKJVBTKTRDJINY-MPBGBICISA-N 0.000 claims description 4
• HERVTRCHMAOCNM-UHFFFAOYSA-N 1-benzyl-3,3-diethylpiperidin-4-amine Chemical compound C1CC(N)C(CC)(CC)CN1CC1=CC=CC=C1 HERVTRCHMAOCNM-UHFFFAOYSA-N 0.000 claims description 4
• GYHFWENUVFMIBE-UHFFFAOYSA-N 1-benzyl-3,5-diethyl-3-methylpiperidin-4-amine Chemical compound C1C(C)(CC)C(N)C(CC)CN1CC1=CC=CC=C1 GYHFWENUVFMIBE-UHFFFAOYSA-N 0.000 claims description 4
• TYLFZMBNLFRBNH-UHFFFAOYSA-N 1-benzyl-3,5-diethylpiperidin-4-amine Chemical compound C1C(CC)C(N)C(CC)CN1CC1=CC=CC=C1 TYLFZMBNLFRBNH-UHFFFAOYSA-N 0.000 claims description 4
• HYERCZPARKEXQI-UHFFFAOYSA-N 1-benzyl-3-ethyl-3,5-dimethylpiperidin-4-amine Chemical compound C1C(C)C(N)C(CC)(C)CN1CC1=CC=CC=C1 HYERCZPARKEXQI-UHFFFAOYSA-N 0.000 claims description 4
• SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 claims description 4
• LMRFKZLZAKKLQL-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(cyclopropylamino)-3,5-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N(CC1C)CC(C)C1NC1CC1 LMRFKZLZAKKLQL-UHFFFAOYSA-N 0.000 claims description 4
• VXJKPXJWIQCESI-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(ethylamino)-3,5-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)C(NCC)C(C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC VXJKPXJWIQCESI-UHFFFAOYSA-N 0.000 claims description 4
• CKIYQWIJAIZFGL-PIGZYNQJSA-N 1-cyclopropyl-8-ethyl-6-fluoro-7-[(3r,4r)-4-hydroxy-3-methylpiperidin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(CC)=C1N1CC[C@@H](O)[C@H](C)C1 CKIYQWIJAIZFGL-PIGZYNQJSA-N 0.000 claims description 4
• SVZYXCYFQWYNKL-MEBBXXQBSA-N 1-ethyl-6-fluoro-7-[(3r,4r)-4-hydroxy-3-methylpiperidin-1-yl]-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CC[C@@H](O)[C@H](C)C1 SVZYXCYFQWYNKL-MEBBXXQBSA-N 0.000 claims description 4
• VHMOQXXAZJHHNR-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(ethylamino)-3,5-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical class C1C(C)C(NCC)C(C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC VHMOQXXAZJHHNR-UHFFFAOYSA-N 0.000 claims description 4
• QNNHERLTFGYZFS-BDJLRTHQSA-N 7-[(3r,4r)-4-amino-3-methylpiperidin-1-yl]-1,8-diethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2CC)=O)=C2C(CC)=C1N1CC[C@@H](N)[C@H](C)C1 QNNHERLTFGYZFS-BDJLRTHQSA-N 0.000 claims description 4
• QHCUWXGKRRWDPY-CWTRNNRKSA-N 7-[(3r,4r)-4-amino-3-methylpiperidin-1-yl]-1-(2,4-difluorophenyl)-8-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C=3C(=CC(F)=CC=3)F)=O)=C2C(CC)=C1N1CC[C@@H](N)[C@H](C)C1 QHCUWXGKRRWDPY-CWTRNNRKSA-N 0.000 claims description 4
• NDOZWLIOAXKRQZ-MEBBXXQBSA-N 7-[(3r,4r)-4-amino-3-methylpiperidin-1-yl]-1-ethyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound CC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CC[C@@H](N)[C@H](C)C1 NDOZWLIOAXKRQZ-MEBBXXQBSA-N 0.000 claims description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
• KSXRRCOGLFVKJR-SJKOYZFVSA-N C1(CC1)N1C=C(C(C2=CC(=C(C(=C12)C)N1C[C@H]([C@@H](CC1)O)CC)F)=O)C(=O)O Chemical compound C1(CC1)N1C=C(C(C2=CC(=C(C(=C12)C)N1C[C@H]([C@@H](CC1)O)CC)F)=O)C(=O)O KSXRRCOGLFVKJR-SJKOYZFVSA-N 0.000 claims description 4
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 claims description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
• 150000001350 alkyl halides Chemical class 0.000 claims description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 claims description 4
• FHWVQKMCUWPKKK-UHFFFAOYSA-N ethyl 1-benzyl-3-methyl-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)(C)CN1CC1=CC=CC=C1 FHWVQKMCUWPKKK-UHFFFAOYSA-N 0.000 claims description 4
• ZVUOQTOUYBSARS-UHFFFAOYSA-N ethyl 4-(dimethylamino)-3-methylpiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(N(C)C)C(C)C1 ZVUOQTOUYBSARS-UHFFFAOYSA-N 0.000 claims description 4
• SKSJFDIIYVNVPZ-UHFFFAOYSA-N ethyl n-(3,3-dimethylpiperidin-4-yl)carbamate Chemical compound CCOC(=O)NC1CCNCC1(C)C SKSJFDIIYVNVPZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000003147 glycosyl group Chemical group 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• JCIHJQGIECMFCJ-UHFFFAOYSA-N n,n,3,5-tetramethylpiperidin-4-amine Chemical compound CC1CNCC(C)C1N(C)C JCIHJQGIECMFCJ-UHFFFAOYSA-N 0.000 claims description 4
• TWXWNGCNYWNMJR-UHFFFAOYSA-N n-(1-benzyl-3,3-dimethylpiperidin-4-yl)acetamide Chemical compound C1C(C)(C)C(NC(=O)C)CCN1CC1=CC=CC=C1 TWXWNGCNYWNMJR-UHFFFAOYSA-N 0.000 claims description 4
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 claims description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
• 229910000104 sodium hydride Inorganic materials 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• WJBJAZZZQBXWOQ-UHFFFAOYSA-N tert-butyl 3,3-dimethyl-4-(phenylmethoxycarbonylamino)piperidine-1-carboxylate Chemical compound CC1(C)CN(C(=O)OC(C)(C)C)CCC1NC(=O)OCC1=CC=CC=C1 WJBJAZZZQBXWOQ-UHFFFAOYSA-N 0.000 claims description 4
• MNJCZOJFFXXZKR-UHFFFAOYSA-N tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)C(C)(C)C1 MNJCZOJFFXXZKR-UHFFFAOYSA-N 0.000 claims description 4
• LHSNRJGZDUFKQT-RKDXNWHRSA-N tert-butyl n-[(3r,4r)-3-methylpiperidin-4-yl]carbamate Chemical compound C[C@@H]1CNCC[C@H]1NC(=O)OC(C)(C)C LHSNRJGZDUFKQT-RKDXNWHRSA-N 0.000 claims description 4
• BOZBHPFGGMLULS-UHFFFAOYSA-N 1-benzyl-n-cyclopropyl-3-ethyl-3-methylpiperidin-4-amine Chemical compound C1CC(NC2CC2)C(CC)(C)CN1CC1=CC=CC=C1 BOZBHPFGGMLULS-UHFFFAOYSA-N 0.000 claims description 3
• YPVAUCAFVGWRRD-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-8-methoxy-7-[3-methyl-4-(methylamino)piperidin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)C(NC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC YPVAUCAFVGWRRD-UHFFFAOYSA-N 0.000 claims description 3
• RCELUFUGKXQHNV-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-8-methyl-7-[3-methyl-4-(methylamino)piperidin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)C(NC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1C RCELUFUGKXQHNV-UHFFFAOYSA-N 0.000 claims description 3
• WCTJNDAOIPAZTB-UHFFFAOYSA-N 1-cyclopropyl-7-[3,3-dimethyl-4-(methylamino)piperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)(C)C(NC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC WCTJNDAOIPAZTB-UHFFFAOYSA-N 0.000 claims description 3
• OCYUILSKZFPISR-UHFFFAOYSA-N 1-cyclopropyl-7-[3-ethyl-3-methyl-4-(methylamino)piperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1CC(NC)C(CC)(C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC OCYUILSKZFPISR-UHFFFAOYSA-N 0.000 claims description 3
• QNKUVSSRZPXKCZ-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(cyclopropylamino)-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N(CC1C)CCC1NC1CC1 QNKUVSSRZPXKCZ-UHFFFAOYSA-N 0.000 claims description 3
• SIKQBMFDHCUFCC-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(dimethylamino)-3,3-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N(C)C)C(C)(C)C1 SIKQBMFDHCUFCC-UHFFFAOYSA-N 0.000 claims description 3
• IJRQQTNFYUXWKB-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(dimethylamino)-3-ethyl-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1CC(N(C)C)C(CC)(C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC IJRQQTNFYUXWKB-UHFFFAOYSA-N 0.000 claims description 3
• MZSAPVYMQQRDSY-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(dimethylamino)-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N(C)C)C(C)C1 MZSAPVYMQQRDSY-UHFFFAOYSA-N 0.000 claims description 3
• ZREHPVQMLCZWPW-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(ethoxycarbonylamino)-3,3-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)(C)C(NC(=O)OCC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC ZREHPVQMLCZWPW-UHFFFAOYSA-N 0.000 claims description 3
• QMJALDCTLKTBCC-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(ethylamino)-3,3-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)(C)C(NCC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC QMJALDCTLKTBCC-UHFFFAOYSA-N 0.000 claims description 3
• KYWNBWYZJSFADV-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(ethylamino)-3,3-dimethylpiperidin-1-yl]-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)(C)C(NCC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1C KYWNBWYZJSFADV-UHFFFAOYSA-N 0.000 claims description 3
• AJZGLHJVIGMIIQ-UHFFFAOYSA-N 1-cyclopropyl-7-[4-(ethylamino)-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)C(NCC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC AJZGLHJVIGMIIQ-UHFFFAOYSA-N 0.000 claims description 3
• JPIIHMKDXDQRGO-UHFFFAOYSA-N 3,3-diethylpiperidin-4-amine Chemical compound CCC1(CC)CNCCC1N JPIIHMKDXDQRGO-UHFFFAOYSA-N 0.000 claims description 3
• BLYBATJMKNZTLN-UHFFFAOYSA-N 3,5-diethyl-3-methylpiperidin-4-amine Chemical compound CCC1CNCC(C)(CC)C1N BLYBATJMKNZTLN-UHFFFAOYSA-N 0.000 claims description 3
• LWLLCCNPSZZONV-UHFFFAOYSA-N 3,5-diethylpiperidin-4-amine Chemical compound CCC1CNCC(CC)C1N LWLLCCNPSZZONV-UHFFFAOYSA-N 0.000 claims description 3
• JSYULFBQUYEKLN-UHFFFAOYSA-N 3-ethyl-n-methylpiperidin-4-amine Chemical compound CCC1CNCCC1NC JSYULFBQUYEKLN-UHFFFAOYSA-N 0.000 claims description 3
• FBFQGEJRJSQFPO-UHFFFAOYSA-N 5-amino-1-cyclopropyl-6-fluoro-8-methoxy-7-[3-methyl-4-(methylamino)piperidin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)C(NC)CCN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC FBFQGEJRJSQFPO-UHFFFAOYSA-N 0.000 claims description 3
• CVPCTGBYMZBRGT-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[3-ethyl-3-methyl-4-(methylamino)piperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1CC(NC)C(CC)(C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC CVPCTGBYMZBRGT-UHFFFAOYSA-N 0.000 claims description 3
• RPKSLXMVKIDARG-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(cyclopropylamino)-3,5-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical class FC1=C(N)C(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N(CC1C)CC(C)C1NC1CC1 RPKSLXMVKIDARG-UHFFFAOYSA-N 0.000 claims description 3
• MJXXTQYRNULOLG-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(cyclopropylamino)-3-ethyl-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound CCC1(C)CN(C=2C(=C3C(C(C(C(O)=O)=CN3C3CC3)=O)=C(N)C=2F)OC)CCC1NC1CC1 MJXXTQYRNULOLG-UHFFFAOYSA-N 0.000 claims description 3
• QCOVJFDRMPJLMR-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(dimethylamino)-3,3-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical class FC1=C(N)C(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N(C)C)C(C)(C)C1 QCOVJFDRMPJLMR-UHFFFAOYSA-N 0.000 claims description 3
• SBKCWRWBCQUJIR-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(dimethylamino)-3-ethyl-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical class C1CC(N(C)C)C(CC)(C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC SBKCWRWBCQUJIR-UHFFFAOYSA-N 0.000 claims description 3
• ODDBWDOIFIWNOL-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(dimethylamino)-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C(N)C(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N(C)C)C(C)C1 ODDBWDOIFIWNOL-UHFFFAOYSA-N 0.000 claims description 3
• WQSQBIWKXFBZDI-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(ethylamino)-3,3-dimethylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical class C1C(C)(C)C(NCC)CCN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC WQSQBIWKXFBZDI-UHFFFAOYSA-N 0.000 claims description 3
• PFDYGIFPWFBRNX-UHFFFAOYSA-N 5-amino-1-cyclopropyl-7-[4-(ethylamino)-3-methylpiperidin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1C(C)C(NCC)CCN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC PFDYGIFPWFBRNX-UHFFFAOYSA-N 0.000 claims description 3
• FLKXLIKUHDDZJV-UHFFFAOYSA-N 5-amino-7-(4-amino-3,3,5-trimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical class FC1=C(N)C(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CC(C)C(N)C(C)(C)C1 FLKXLIKUHDDZJV-UHFFFAOYSA-N 0.000 claims description 3
• CRHWGUGMZHKRHJ-UHFFFAOYSA-N 5-amino-7-(4-amino-3-ethyl-3-methylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical class C1CC(N)C(CC)(C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC CRHWGUGMZHKRHJ-UHFFFAOYSA-N 0.000 claims description 3
• VWQAQWDYTJFQAE-UHFFFAOYSA-N 5-amino-7-(4-amino-3-methylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=C(N)C(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N)C(C)C1 VWQAQWDYTJFQAE-UHFFFAOYSA-N 0.000 claims description 3
• CWIBZDKDJUMICC-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(C)=C1N1CCC(N)C(C)(C)C1 CWIBZDKDJUMICC-UHFFFAOYSA-N 0.000 claims description 3
• XKGJZCWVWCHZDO-UHFFFAOYSA-N 7-(4-amino-3-ethyl-3-methylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1CC(N)C(CC)(C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC XKGJZCWVWCHZDO-UHFFFAOYSA-N 0.000 claims description 3
• FKQVCNIEJCPZQT-UHFFFAOYSA-N 7-(4-amino-3-methylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N)C(C)C1 FKQVCNIEJCPZQT-UHFFFAOYSA-N 0.000 claims description 3
• ULXGWVFYSUWFIR-UHFFFAOYSA-N 7-(4-aminopiperidin-1-yl)-1-cyclopropyl-8-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(CC)=C1N1CCC(N)CC1 ULXGWVFYSUWFIR-UHFFFAOYSA-N 0.000 claims description 3
• BCVAMDPUKLPDNZ-ADLMAVQZSA-N 7-[(3r,4r)-4-amino-3-methylpiperidin-1-yl]-1-(2,4-difluorophenyl)-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1C[C@@H](N)[C@H](C)CN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C=3C(=CC(F)=CC=3)F)C2=C1C BCVAMDPUKLPDNZ-ADLMAVQZSA-N 0.000 claims description 3
• CJLPMNQSZBWSQD-KZULUSFZSA-N C1(CC1)N1C=C(C(C2=CC(=C(C(=C12)CC)N1C[C@H]([C@@H](CC1)O)CC)F)=O)C(=O)O Chemical compound C1(CC1)N1C=C(C(C2=CC(=C(C(=C12)CC)N1C[C@H]([C@@H](CC1)O)CC)F)=O)C(=O)O CJLPMNQSZBWSQD-KZULUSFZSA-N 0.000 claims description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 3
• IDONWUALARWGFR-UHFFFAOYSA-N benzyl 3,3-dimethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]piperidine-1-carboxylate Chemical compound C1C(C)(C)C(NC(=O)OC(C)(C)C)CCN1C(=O)OCC1=CC=CC=C1 IDONWUALARWGFR-UHFFFAOYSA-N 0.000 claims description 3
• QHCSLEQTUOGKAJ-UHFFFAOYSA-N benzyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate Chemical compound C1CC(=O)C(C)(C)CN1C(=O)OCC1=CC=CC=C1 QHCSLEQTUOGKAJ-UHFFFAOYSA-N 0.000 claims description 3
• 229910000085 borane Inorganic materials 0.000 claims description 3
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
• CJXIYPTVYDXXDI-UHFFFAOYSA-N ethyl 3,5-dimethyl-4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CC(C)C(=O)C(C)C1 CJXIYPTVYDXXDI-UHFFFAOYSA-N 0.000 claims description 3
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• HBWVHKLBIDCOHJ-UHFFFAOYSA-N ethyl 4-(ethylamino)-3-methylpiperidine-1-carboxylate Chemical compound CCNC1CCN(C(=O)OCC)CC1C HBWVHKLBIDCOHJ-UHFFFAOYSA-N 0.000 claims description 3
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• 239000001301 oxygen Substances 0.000 claims description 3
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
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