AU2002361493A1

AU2002361493A1 - New generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments

New generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments Download PDF

Info

Publication number: AU2002361493A1
Authority: AU; Australia
Prior art keywords: amino; oxo; dihydro; quinoline; fluoro
Prior art date: 2001-12-13
Legal status : Abandoned

Application number

AU2002361493A

Other languages

English (en)

Inventor

Yati Chugh

Noel J De Souza

Prasad K Deshpande

Mahesh V Patel

Milind C Shukla

Current Assignee

Wockhardt Ltd

Original Assignee

Wockhardt Ltd

Priority date

2001-12-13

Filing date

2002-12-12

Publication date

2003-06-23

2002-04-23 Priority claimed from US10/128,996 external-priority patent/US6964966B2/en

2002-12-12 Application filed by Wockhardt Ltd filed Critical Wockhardt Ltd

2003-06-23 Publication of AU2002361493A1 publication Critical patent/AU2002361493A1/en

Status Abandoned legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims description 350
-1 7-substituted piperidino-quinolone carboxylic acid Chemical class 0.000 title claims description 115
238000002360 preparation method Methods 0.000 title description 138
239000003814 drug Substances 0.000 title description 24
230000000845 anti-microbial effect Effects 0.000 title description 13
150000003839 salts Chemical class 0.000 claims description 461
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 318
150000001875 compounds Chemical class 0.000 claims description 232
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 207
238000000034 method Methods 0.000 claims description 156
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 122
229910052799 carbon Inorganic materials 0.000 claims description 83
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 76
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 76
125000000217 alkyl group Chemical group 0.000 claims description 69
125000001424 substituent group Chemical group 0.000 claims description 64
238000003756 stirring Methods 0.000 claims description 62
229910052739 hydrogen Inorganic materials 0.000 claims description 59
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 54
230000003287 optical effect Effects 0.000 claims description 50
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 48
239000002253 acid Substances 0.000 claims description 48
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 47
229940124307 fluoroquinolone Drugs 0.000 claims description 46
229910052757 nitrogen Inorganic materials 0.000 claims description 46
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 34
239000002585 base Substances 0.000 claims description 33
XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 claims description 32
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 description 32
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
150000001413 amino acids Chemical class 0.000 claims description 32
239000001257 hydrogen Substances 0.000 claims description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 31
239000003960 organic solvent Substances 0.000 claims description 31
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 31
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 30
150000002148 esters Chemical class 0.000 claims description 30
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 29
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
229940050410 gluconate Drugs 0.000 claims description 27
150000004677 hydrates Chemical class 0.000 claims description 27
239000002904 solvent Substances 0.000 claims description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 26
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 25
125000003710 aryl alkyl group Chemical group 0.000 claims description 25
125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
239000003054 catalyst Substances 0.000 claims description 24
OKZIUSOJQLYFSE-UHFFFAOYSA-N difluoroboron Chemical compound F[B]F OKZIUSOJQLYFSE-UHFFFAOYSA-N 0.000 claims description 24
208000015181 infectious disease Diseases 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 23
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 23
101100072644 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) INO2 gene Proteins 0.000 claims description 22
150000001412 amines Chemical class 0.000 claims description 22
239000013522 chelant Substances 0.000 claims description 22
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 20
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 18
229910052796 boron Inorganic materials 0.000 claims description 18
238000010438 heat treatment Methods 0.000 claims description 18
230000003301 hydrolyzing effect Effects 0.000 claims description 18
OBSJQTCTSCRURB-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N)C(C)(C)C1 OBSJQTCTSCRURB-UHFFFAOYSA-N 0.000 claims description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
125000000539 amino acid group Chemical group 0.000 claims description 17
HDHZKCZZHXUICO-UHFFFAOYSA-N 3,3-dimethylpiperidin-4-amine Chemical compound CC1(C)CNCCC1N HDHZKCZZHXUICO-UHFFFAOYSA-N 0.000 claims description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
125000001589 carboacyl group Chemical group 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
238000001704 evaporation Methods 0.000 claims description 15
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 14
239000000460 chlorine Substances 0.000 claims description 13
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 13
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 12
239000005695 Ammonium acetate Substances 0.000 claims description 12
229940043376 ammonium acetate Drugs 0.000 claims description 12
235000019257 ammonium acetate Nutrition 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
229910052760 oxygen Inorganic materials 0.000 claims description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 11
238000004737 colorimetric analysis Methods 0.000 claims description 11
238000000634 powder X-ray diffraction Methods 0.000 claims description 11
XJSUUJDMFDMIGK-UHFFFAOYSA-N 3,5-dimethylpiperidin-4-amine Chemical compound CC1CNCC(C)C1N XJSUUJDMFDMIGK-UHFFFAOYSA-N 0.000 claims description 10
125000003282 alkyl amino group Chemical group 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 10
230000000699 topical effect Effects 0.000 claims description 10
QCAHPSUNBOPUEE-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCC(N)C(C)(C)C1 QCAHPSUNBOPUEE-UHFFFAOYSA-N 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 9
150000001408 amides Chemical class 0.000 claims description 9
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
125000005842 heteroatom Chemical group 0.000 claims description 9
230000009885 systemic effect Effects 0.000 claims description 9
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 8
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 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
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
DFLLYSUNLAPOQH-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid;hydrochloride Chemical compound Cl.FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(C)=C1N1CCC(N)C(C)(C)C1 DFLLYSUNLAPOQH-UHFFFAOYSA-N 0.000 claims description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 7
RJCFLDDKHVMPDM-UHFFFAOYSA-N CS(=O)(=O)O.O=C1NC2=CC=CC=C2C=C1C(=O)O Chemical compound CS(=O)(=O)O.O=C1NC2=CC=CC=C2C=C1C(=O)O RJCFLDDKHVMPDM-UHFFFAOYSA-N 0.000 claims description 7
239000003513 alkali Substances 0.000 claims description 7
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 7
150000007522 mineralic acids Chemical class 0.000 claims description 7
WQXHWNIFQVJVSZ-UHFFFAOYSA-N n-ethyl-3,3-dimethylpiperidin-4-amine Chemical compound CCNC1CCNCC1(C)C WQXHWNIFQVJVSZ-UHFFFAOYSA-N 0.000 claims description 7
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 7
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 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
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
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 6
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 6
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-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
239000012453 solvate Substances 0.000 claims description 6
UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 6
XZUJMFOTXYKCTA-UHFFFAOYSA-N 1-benzyl-3-ethyl-3-methylpiperidin-4-amine Chemical class C1CC(N)C(CC)(C)CN1CC1=CC=CC=C1 XZUJMFOTXYKCTA-UHFFFAOYSA-N 0.000 claims description 5
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 5
KXBPUMSPCLLXRZ-UHFFFAOYSA-N 3,3-dimethylpiperidin-4-one Chemical compound CC1(C)CNCCC1=O KXBPUMSPCLLXRZ-UHFFFAOYSA-N 0.000 claims description 5
PMDJREADVMVMDY-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(C)=C1N1CCC(N)C(C)(C)C1 PMDJREADVMVMDY-UHFFFAOYSA-N 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
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 5
LVIDFINDEFXGRY-UHFFFAOYSA-N ethyl 4-amino-3-methylpiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(N)C(C)C1 LVIDFINDEFXGRY-UHFFFAOYSA-N 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 5
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 5
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
125000004434 sulfur atom Chemical group 0.000 claims description 5
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
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 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
NJNYBVVRUJTWSO-UHFFFAOYSA-N 3,3,5-trimethylpiperidin-4-one Chemical compound CC1CNCC(C)(C)C1=O NJNYBVVRUJTWSO-UHFFFAOYSA-N 0.000 claims description 4
BLYBATJMKNZTLN-UHFFFAOYSA-N 3,5-diethyl-3-methylpiperidin-4-amine Chemical compound CCC1CNCC(C)(CC)C1N BLYBATJMKNZTLN-UHFFFAOYSA-N 0.000 claims description 4
ILCINNUUWYAYNL-UHFFFAOYSA-N 5-amino-7-(4-amino-3,5-dimethylpiperidin-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)=C1N1CC(C)C(N)C(C)C1 ILCINNUUWYAYNL-UHFFFAOYSA-N 0.000 claims description 4
BLSDIPBMJIFTBY-UHFFFAOYSA-N 7-(4-amino-3,3-dimethylpiperidin-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)C(C)(C)C1 BLSDIPBMJIFTBY-UHFFFAOYSA-N 0.000 claims description 4
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 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-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
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 4
229910000085 borane Inorganic materials 0.000 claims description 4
150000001649 bromium compounds Chemical class 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
150000002431 hydrogen Chemical class 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
LTVSDBIRNKOKKA-UHFFFAOYSA-N n,n,3,3-tetramethylpiperidin-4-amine Chemical compound CN(C)C1CCNCC1(C)C LTVSDBIRNKOKKA-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
125000003107 substituted aryl group Chemical group 0.000 claims description 4
125000004169 (C1-C6) alkyl group Chemical group 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
LWLLCCNPSZZONV-UHFFFAOYSA-N 3,5-diethylpiperidin-4-amine Chemical compound CCC1CNCC(CC)C1N LWLLCCNPSZZONV-UHFFFAOYSA-N 0.000 claims description 3
YECOFTHXCMGRPR-UHFFFAOYSA-N 3-ethyl-3,5-dimethylpiperidin-4-amine Chemical compound CCC1(C)CNCC(C)C1N YECOFTHXCMGRPR-UHFFFAOYSA-N 0.000 claims description 3
SCEYNOTZAXPNIY-UHFFFAOYSA-N 3-ethyl-3-methylpiperidin-4-amine Chemical class CCC1(C)CNCCC1N SCEYNOTZAXPNIY-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 compound 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
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 compound 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 compound 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-BXKDBHETSA-N 5-amino-7-[(3r,4r)-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)=C1N1CC[C@@H](N)[C@H](C)C1 VWQAQWDYTJFQAE-BXKDBHETSA-N 0.000 claims description 3
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 3
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 3
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101100294102 Caenorhabditis elegans nhr-2 gene Proteins 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
125000005605 benzo group Chemical group 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
125000001246 bromo group Chemical group Br* 0.000 claims description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
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125000003147 glycosyl group Chemical group 0.000 claims description 3
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239000012312 sodium hydride Substances 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
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125000004385 trihaloalkyl group Chemical group 0.000 claims description 3
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