KR20060054370A - 퀴놀린 유도체 및 치료에 있어서의 그의 용도 - Google Patents
퀴놀린 유도체 및 치료에 있어서의 그의 용도 Download PDFInfo
- Publication number
- KR20060054370A KR20060054370A KR1020067001966A KR20067001966A KR20060054370A KR 20060054370 A KR20060054370 A KR 20060054370A KR 1020067001966 A KR1020067001966 A KR 1020067001966A KR 20067001966 A KR20067001966 A KR 20067001966A KR 20060054370 A KR20060054370 A KR 20060054370A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- chloro
- compound
- group
- quinolinyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000002560 therapeutic procedure Methods 0.000 title description 4
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title description 2
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 208
- 238000000034 method Methods 0.000 claims abstract description 54
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 201
- -1 —COOR 13 Chemical group 0.000 claims description 127
- 125000001424 substituent group Chemical group 0.000 claims description 95
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 70
- 229910052736 halogen Inorganic materials 0.000 claims description 65
- 150000002367 halogens Chemical group 0.000 claims description 65
- 239000001257 hydrogen Substances 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- 229910052757 nitrogen Inorganic materials 0.000 claims description 55
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 42
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 229910052717 sulfur Chemical group 0.000 claims description 29
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 239000012453 solvate Substances 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000004122 cyclic group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
- 239000001301 oxygen Chemical group 0.000 claims description 23
- 239000011593 sulfur Chemical group 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 15
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- QIPHOMBDWJEGDN-HNNXBMFYSA-N n-[2-[(3s)-3-aminopyrrolidin-1-yl]-6-chloroquinolin-5-yl]-3-(2-chlorophenyl)propanamide Chemical compound C1[C@@H](N)CCN1C1=CC=C(C(NC(=O)CCC=2C(=CC=CC=2)Cl)=C(Cl)C=C2)C2=N1 QIPHOMBDWJEGDN-HNNXBMFYSA-N 0.000 claims description 6
- 201000008482 osteoarthritis Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- KUAGIPCPUKVKDX-QUCCMNQESA-N (3r)-n-[6-chloro-2-[(3s)-3-(3-hydroxypropylamino)pyrrolidin-1-yl]quinolin-5-yl]-3-phenylbutanamide Chemical compound C([C@@H](C)C=1C=CC=CC=1)C(=O)NC(C1=CC=2)=C(Cl)C=CC1=NC=2N1CC[C@H](NCCCO)C1 KUAGIPCPUKVKDX-QUCCMNQESA-N 0.000 claims description 5
- UFXQGZOKXNJGEG-GOSISDBHSA-N (3r)-n-[6-chloro-2-[3-(3-hydroxypropylamino)propyl]quinolin-5-yl]-3-phenylbutanamide Chemical compound C1([C@@H](CC(=O)NC=2C3=CC=C(CCCNCCCO)N=C3C=CC=2Cl)C)=CC=CC=C1 UFXQGZOKXNJGEG-GOSISDBHSA-N 0.000 claims description 5
- KCWSDKICODBYRE-UHFFFAOYSA-N 1-[6-chloro-5-(2-phenylethylcarbamoyl)quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(C(=O)NCCC=2C=CC=CC=2)=C(Cl)C=C2)C2=N1 KCWSDKICODBYRE-UHFFFAOYSA-N 0.000 claims description 5
- GSAGYAQILPUYNV-UHFFFAOYSA-N 1-[6-chloro-5-[2-(2,6-dichlorophenyl)ethylcarbamoyl]quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(C(=O)NCCC=2C(=CC=CC=2Cl)Cl)=C(Cl)C=C2)C2=N1 GSAGYAQILPUYNV-UHFFFAOYSA-N 0.000 claims description 5
- CRJDINJRUVRMOC-UHFFFAOYSA-N 1-[6-chloro-5-[2-(2-chlorophenyl)ethylcarbamoyl]quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(C(=O)NCCC=2C(=CC=CC=2)Cl)=C(Cl)C=C2)C2=N1 CRJDINJRUVRMOC-UHFFFAOYSA-N 0.000 claims description 5
- WNYZCFCQFZXZHF-UHFFFAOYSA-N 1-[6-chloro-5-[2-(2-fluorophenyl)ethylcarbamoyl]quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(C(=O)NCCC=2C(=CC=CC=2)F)=C(Cl)C=C2)C2=N1 WNYZCFCQFZXZHF-UHFFFAOYSA-N 0.000 claims description 5
- YWQHIVPXCXZJRT-UHFFFAOYSA-N 1-[6-chloro-5-[2-(2-methylphenyl)ethylcarbamoyl]quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound CC1=CC=CC=C1CCNC(=O)C1=C(Cl)C=CC2=NC(N3CCC(CC3)C(O)=O)=CC=C12 YWQHIVPXCXZJRT-UHFFFAOYSA-N 0.000 claims description 5
- PPDLJZBXSGMJNN-UHFFFAOYSA-N 1-[6-chloro-5-[2-(4-chlorophenyl)ethylcarbamoyl]quinolin-2-yl]piperidine-4-carboxylic acid Chemical class C1CC(C(=O)O)CCN1C1=CC=C(C(C(=O)NCCC=2C=CC(Cl)=CC=2)=C(Cl)C=C2)C2=N1 PPDLJZBXSGMJNN-UHFFFAOYSA-N 0.000 claims description 5
- SNZIFZIIBGBVAZ-UHFFFAOYSA-N 1-[6-chloro-5-[3-(2-chlorophenyl)propanoylamino]quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(NC(=O)CCC=2C(=CC=CC=2)Cl)=C(Cl)C=C2)C2=N1 SNZIFZIIBGBVAZ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- JLSUJDXRJOLXMV-UHFFFAOYSA-N n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-3-(2-methoxyphenyl)propanamide Chemical compound COC1=CC=CC=C1CCC(=O)NC1=C(Cl)C=CC2=NC(N3CCNCC3)=CC=C12 JLSUJDXRJOLXMV-UHFFFAOYSA-N 0.000 claims description 5
- UAVOXGQJGZBOBO-KRWDZBQOSA-N n-[6-chloro-2-[(3s)-3-(2-hydroxyethylamino)pyrrolidin-1-yl]quinolin-5-yl]-3-(2-chlorophenyl)propanamide Chemical compound C1[C@@H](NCCO)CCN1C1=CC=C(C(NC(=O)CCC=2C(=CC=CC=2)Cl)=C(Cl)C=C2)C2=N1 UAVOXGQJGZBOBO-KRWDZBQOSA-N 0.000 claims description 5
- QLWVEYMPLVEDGZ-MRXNPFEDSA-N (3r)-n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-3-phenylbutanamide Chemical compound C([C@@H](C)C=1C=CC=CC=1)C(=O)NC(C1=CC=2)=C(Cl)C=CC1=NC=2N1CCNCC1 QLWVEYMPLVEDGZ-MRXNPFEDSA-N 0.000 claims description 4
- QBBJXWLPTPKFRD-WBVHZDCISA-N (3r)-n-[2-[(3s)-3-aminopyrrolidin-1-yl]-6-chloroquinolin-5-yl]-3-phenylbutanamide Chemical compound C([C@@H](C)C=1C=CC=CC=1)C(=O)NC(C1=CC=2)=C(Cl)C=CC1=NC=2N1CC[C@H](N)C1 QBBJXWLPTPKFRD-WBVHZDCISA-N 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 4
- NCJPBVDUTKJDMQ-UHFFFAOYSA-N 1-[6-chloro-5-(2,2-diphenylethylcarbamoyl)quinolin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C(C(=O)NCC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C(Cl)C=C2)C2=N1 NCJPBVDUTKJDMQ-UHFFFAOYSA-N 0.000 claims description 4
- QPJLXQIFYVOTGJ-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-2-methyl-n-quinolin-5-ylpropanamide Chemical compound C=1C=CC2=NC=CC=C2C=1NC(=O)C(C)CC1=CC=C(Cl)C(Cl)=C1 QPJLXQIFYVOTGJ-UHFFFAOYSA-N 0.000 claims description 4
- PXFQSPCEISBBTQ-UHFFFAOYSA-N 6-chloro-2-methyl-n-(2-phenylethyl)quinoline-5-carboxamide Chemical compound ClC=1C=CC2=NC(C)=CC=C2C=1C(=O)NCCC1=CC=CC=C1 PXFQSPCEISBBTQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 claims description 4
- FWEPRJAGHDPQGK-UHFFFAOYSA-N n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-3-phenylpropanamide Chemical compound ClC1=CC=C2N=C(N3CCNCC3)C=CC2=C1NC(=O)CCC1=CC=CC=C1 FWEPRJAGHDPQGK-UHFFFAOYSA-N 0.000 claims description 4
- 230000000414 obstructive effect Effects 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 208000023504 respiratory system disease Diseases 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
- VHWQUGFTNYMILN-HNNXBMFYSA-N 2-[(3s)-3-aminopyrrolidin-1-yl]-6-chloro-n-[2-(2-chlorophenyl)ethyl]quinoline-5-carboxamide Chemical compound C1[C@@H](N)CCN1C1=CC=C(C(C(=O)NCCC=2C(=CC=CC=2)Cl)=C(Cl)C=C2)C2=N1 VHWQUGFTNYMILN-HNNXBMFYSA-N 0.000 claims description 3
- NJPLQPPNWLAIMV-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)propanamide Chemical compound ClC1=CC=CC=C1CCC(=O)NC1=C(Cl)C=CC2=NC(N3CCNCC3)=CC=C12 NJPLQPPNWLAIMV-UHFFFAOYSA-N 0.000 claims description 3
- PBIWLVXNUJLCQW-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)propanamide Chemical compound C1=CC(Cl)=CC=C1CCC(=O)NC1=C(Cl)C=CC2=NC(N3CCNCC3)=CC=C12 PBIWLVXNUJLCQW-UHFFFAOYSA-N 0.000 claims description 3
- FKNRDGLGAVYQNE-ZDUSSCGKSA-N 6-chloro-2-methyl-n-[(2r)-2-phenylpropyl]quinoline-5-carboxamide Chemical compound C1([C@H](CNC(=O)C=2C3=CC=C(C)N=C3C=CC=2Cl)C)=CC=CC=C1 FKNRDGLGAVYQNE-ZDUSSCGKSA-N 0.000 claims description 3
- FKNRDGLGAVYQNE-CYBMUJFWSA-N 6-chloro-2-methyl-n-[(2s)-2-phenylpropyl]quinoline-5-carboxamide Chemical compound C1([C@@H](CNC(=O)C=2C3=CC=C(C)N=C3C=CC=2Cl)C)=CC=CC=C1 FKNRDGLGAVYQNE-CYBMUJFWSA-N 0.000 claims description 3
- IPHOLPIMAJTCJX-UHFFFAOYSA-N 6-chloro-n-[2-(2-chlorophenyl)ethyl]-2-[4-(5-oxo-1h-1,2,4-triazol-4-yl)piperidin-1-yl]quinoline-5-carboxamide Chemical compound ClC1=CC=CC=C1CCNC(=O)C1=C(Cl)C=CC2=NC(N3CCC(CC3)N3C(NN=C3)=O)=CC=C12 IPHOLPIMAJTCJX-UHFFFAOYSA-N 0.000 claims description 3
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 3
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- ZOZCOBFRWRSKQM-UHFFFAOYSA-N n-(6-chloro-2-piperazin-1-ylquinolin-5-yl)-3-(2,4-dichlorophenyl)propanamide Chemical compound ClC1=CC(Cl)=CC=C1CCC(=O)NC1=C(Cl)C=CC2=NC(N3CCNCC3)=CC=C12 ZOZCOBFRWRSKQM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 2
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229940126062 Compound A Drugs 0.000 claims 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 239000007787 solid Substances 0.000 description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 238000000746 purification Methods 0.000 description 42
- 239000003480 eluent Substances 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- 229910004298 SiO 2 Inorganic materials 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 24
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 23
- 239000000460 chlorine Substances 0.000 description 23
- 229910052801 chlorine Inorganic materials 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 17
- 229910052794 bromium Inorganic materials 0.000 description 17
- 239000003112 inhibitor Substances 0.000 description 17
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 16
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
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Classifications
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- 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
- C07D215/38—Nitrogen atoms
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- 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
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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| SE0302139-1 | 2003-07-28 |
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| KR20060054370A true KR20060054370A (ko) | 2006-05-22 |
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| EP (1) | EP1651610A1 (enExample) |
| JP (1) | JP2007500187A (enExample) |
| KR (1) | KR20060054370A (enExample) |
| CN (1) | CN1829694A (enExample) |
| AU (1) | AU2004259615A1 (enExample) |
| BR (1) | BRPI0413094A (enExample) |
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| IS (1) | IS8329A (enExample) |
| MX (1) | MXPA06000882A (enExample) |
| RU (1) | RU2006102127A (enExample) |
| SE (1) | SE0302139D0 (enExample) |
| WO (1) | WO2005009968A1 (enExample) |
| ZA (1) | ZA200600820B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190129083A (ko) * | 2017-03-13 | 2019-11-19 | 라퀄리아 파마 인코포레이티드 | P2x7 수용체 길항제로서 테트라히드로퀴놀린 유도체 |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0312609D0 (en) | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
| WO2006110516A1 (en) * | 2005-04-11 | 2006-10-19 | Abbott Laboratories | Acylhydrazide p2x7 antagonists and uses thereof |
| CA2645556C (en) | 2006-03-16 | 2016-05-24 | Renovis, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| WO2007109160A2 (en) | 2006-03-16 | 2007-09-27 | Renovis, Inc. | Bicycloheteroaryl compounds as p2x7 modulators and uses thereof |
| US20080058309A1 (en) * | 2006-07-27 | 2008-03-06 | Astrazeneca Ab | Novel Compounds 171 |
| KR20090122396A (ko) * | 2007-03-22 | 2009-11-27 | 아스트라제네카 아베 | 염증성 질환 치료용 퀴놀린 유도체 |
| US8106073B2 (en) | 2007-11-30 | 2012-01-31 | Astrazeneca Ab | Quinoline derivatives 057 |
| ES2357682T3 (es) | 2008-03-25 | 2011-04-28 | Affectis Pharmaceuticals Ag | Antagonistas de p2x7r novedosos y su utilización. |
| CN102395562A (zh) | 2009-04-14 | 2012-03-28 | 阿费克蒂斯制药股份公司 | 新的p2x7r拮抗剂及其用途 |
| ME02421B (me) * | 2009-12-17 | 2016-09-20 | Merck Sharp & Dohme | Pozitivni alosterni modulatori m1 receptora na bazi hinolin amida |
| EP2386541A1 (en) | 2010-05-14 | 2011-11-16 | Affectis Pharmaceuticals AG | Novel methods for the preparation of P2X7R antagonists |
| WO2012110190A1 (en) | 2011-02-17 | 2012-08-23 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2012163456A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2012163792A1 (en) | 2011-05-27 | 2012-12-06 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| WO2013014587A1 (en) | 2011-07-22 | 2013-01-31 | Actelion Pharmaceuticals Ltd | Heterocyclic amide derivatives as p2x7 receptor antagonists |
| TWI576347B (zh) | 2012-01-20 | 2017-04-01 | 艾克泰聯製藥有限公司 | 作為p2x受體拮抗劑之雜環醯胺衍生物 |
| PL2931717T3 (pl) | 2012-12-12 | 2017-05-31 | Actelion Pharmaceuticals Ltd. | Pochodne indolokarboksyamidu jako antagoniści receptora p2x7 |
| CN104854087B (zh) | 2012-12-18 | 2017-03-22 | 埃科特莱茵药品有限公司 | 作为p2x7受体拮抗剂的吲哚羧酰胺衍生物 |
| WO2014115078A1 (en) | 2013-01-22 | 2014-07-31 | Actelion Pharmaceuticals Ltd | Heterocyclic amide derivatives as p2x7 receptor antagonists |
| CN104918617B (zh) | 2013-01-22 | 2017-05-10 | 埃科特莱茵药品有限公司 | 作为p2x7受体拮抗剂的杂环酰胺衍生物 |
| EP3152192A1 (en) * | 2014-06-05 | 2017-04-12 | Merck Patent GmbH | Novel quinoline derivatives and their use in neurodegenerative diseases |
| CN111777638B (zh) * | 2020-05-22 | 2023-05-09 | 瀚海新拓(杭州)生物医药有限公司 | 喹啉类化合物、其制备方法、药物组合物和用途 |
| CN114989082B (zh) * | 2022-06-30 | 2024-06-21 | 华东理工大学 | 基于i价铜化物和三取代膦协同催化的羟氯喹的高效制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3471491A (en) * | 1967-08-28 | 1969-10-07 | Squibb & Sons Inc | Adamantyl-s-triazines |
| US3464998A (en) * | 1968-03-04 | 1969-09-02 | Searle & Co | Adamantyl esters and amides of pyridinecarboxylic acids |
| US4751292A (en) * | 1985-07-02 | 1988-06-14 | The Plant Cell Research Institute, Inc. | Adamantyl purines |
| ES2099206T3 (es) * | 1991-02-21 | 1997-05-16 | Sankyo Co | Derivados de benceno que favorecen la produccion del factor de crecimiento de los nervios humanos. |
| SK282721B6 (sk) * | 1994-05-27 | 2002-11-06 | Smithkline Beecham S.P.A. | Nepeptidové NK3 antagonistické látky, spôsob ich výroby, farmaceutické prostriedky s ich obsahom a ich použitie |
| AR004735A1 (es) * | 1995-11-24 | 1999-03-10 | Smithkline Beecham Spa | Quinoleina 4-amido sustituida, un procedimiento para su preparacion, una composicion farmaceutica que los contiene y el uso de los mismos para lapreparacion de un medicamento. |
| EP0952832B1 (en) * | 1996-05-20 | 2008-08-27 | Darwin Discovery Limited | Quinoline carboxamides as tnf inhibitors and as pde-iv inhibitors |
| GB0013737D0 (en) * | 2000-06-07 | 2000-07-26 | Astrazeneca Ab | Novel compounds |
| JP4523273B2 (ja) * | 2001-07-02 | 2010-08-11 | ナームローゼ・フエンノートチヤツプ・オルガノン | テトラヒドロキノリン誘導体 |
| SE0103836D0 (sv) * | 2001-11-16 | 2001-11-16 | Astrazeneca Ab | Novel compounds |
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2004
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- 2004-07-21 MX MXPA06000882A patent/MXPA06000882A/es not_active Application Discontinuation
- 2004-07-21 US US10/566,320 patent/US20080058293A1/en not_active Abandoned
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- 2004-07-21 KR KR1020067001966A patent/KR20060054370A/ko not_active Withdrawn
- 2004-07-21 AU AU2004259615A patent/AU2004259615A1/en not_active Abandoned
- 2004-07-21 WO PCT/SE2004/001144 patent/WO2005009968A1/en not_active Ceased
- 2004-07-21 EP EP04749180A patent/EP1651610A1/en not_active Withdrawn
- 2004-07-21 BR BRPI0413094-4A patent/BRPI0413094A/pt not_active Application Discontinuation
- 2004-07-21 JP JP2006521802A patent/JP2007500187A/ja not_active Withdrawn
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2005
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2006
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- 2006-01-27 ZA ZA200600820A patent/ZA200600820B/en unknown
- 2006-02-24 IS IS8329A patent/IS8329A/is unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190129083A (ko) * | 2017-03-13 | 2019-11-19 | 라퀄리아 파마 인코포레이티드 | P2x7 수용체 길항제로서 테트라히드로퀴놀린 유도체 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1651610A1 (en) | 2006-05-03 |
| BRPI0413094A (pt) | 2006-10-03 |
| MXPA06000882A (es) | 2006-03-30 |
| ZA200600820B (en) | 2007-04-25 |
| US20080058293A1 (en) | 2008-03-06 |
| JP2007500187A (ja) | 2007-01-11 |
| CN1829694A (zh) | 2006-09-06 |
| AU2004259615A1 (en) | 2005-02-03 |
| RU2006102127A (ru) | 2006-08-27 |
| CO5640110A2 (es) | 2006-05-31 |
| SE0302139D0 (sv) | 2003-07-28 |
| IS8329A (is) | 2006-02-24 |
| IL172826A0 (en) | 2006-06-11 |
| WO2005009968A1 (en) | 2005-02-03 |
| CA2532154A1 (en) | 2005-02-03 |
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