JP2007513151A - 新規化合物 - Google Patents
新規化合物 Download PDFInfo
- Publication number
- JP2007513151A JP2007513151A JP2006542530A JP2006542530A JP2007513151A JP 2007513151 A JP2007513151 A JP 2007513151A JP 2006542530 A JP2006542530 A JP 2006542530A JP 2006542530 A JP2006542530 A JP 2006542530A JP 2007513151 A JP2007513151 A JP 2007513151A
- Authority
- JP
- Japan
- Prior art keywords
- benzofuran
- chloro
- spiro
- formula
- oxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 78
- 238000000034 method Methods 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- -1 cyano, hydroxyl Chemical group 0.000 claims description 93
- 125000004122 cyclic group Chemical group 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- 239000012453 solvate Substances 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 17
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- 229910052717 sulfur Chemical group 0.000 claims description 14
- 239000011593 sulfur Chemical group 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Chemical group 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
- 208000006673 asthma Diseases 0.000 claims description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 8
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 4
- OKBKVQDQHCHNLG-NTISSMGPSA-N 8-[(2s)-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-2-hydroxypropoxy]-1h-quinazoline-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=CC=CC2=C1NC(=O)NC2=O OKBKVQDQHCHNLG-NTISSMGPSA-N 0.000 claims description 4
- FUANJWPWEJESIA-IBGZPJMESA-N 8-[(2s)-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-2-hydroxypropoxy]-1h-quinolin-2-one Chemical compound C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=CC=CC2=C1NC(=O)C=C2 FUANJWPWEJESIA-IBGZPJMESA-N 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- OXZQLFUZZGUKES-LMOVPXPDSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-(2,3,4-trichloronaphthalen-1-yl)oxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=C(Cl)C(Cl)=C(Cl)C2=CC=CC=C12 OXZQLFUZZGUKES-LMOVPXPDSA-N 0.000 claims description 3
- YKDYKFPGAQMMPA-LMOVPXPDSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-(2-iodo-6-methylpyridin-3-yl)oxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.IC1=NC(C)=CC=C1OC[C@@H](O)CN1CCC2(OC3=CC=C(Cl)C=C3C2)CC1 YKDYKFPGAQMMPA-LMOVPXPDSA-N 0.000 claims description 3
- RRGAOORIIMTRKY-LMOVPXPDSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-(6-methyl-2-nitropyridin-3-yl)oxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.[O-][N+](=O)C1=NC(C)=CC=C1OC[C@@H](O)CN1CCC2(OC3=CC=C(Cl)C=C3C2)CC1 RRGAOORIIMTRKY-LMOVPXPDSA-N 0.000 claims description 3
- CVGAXTRRJOEDEZ-SFHVURJKSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-[(2-methyl-1,3-benzothiazol-4-yl)oxy]propan-2-ol Chemical compound C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=C2N=C(C)SC2=CC=C1 CVGAXTRRJOEDEZ-SFHVURJKSA-N 0.000 claims description 3
- VTAMDRCWAHGLNN-IBGZPJMESA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-[(2-methyl-1-benzofuran-4-yl)oxy]propan-2-ol Chemical compound C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=C2C=C(C)OC2=CC=C1 VTAMDRCWAHGLNN-IBGZPJMESA-N 0.000 claims description 3
- DDVJHQJENQCNCW-FTBISJDPSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-[1-(1,3-dithiolan-2-yl)naphthalen-2-yl]oxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](O)CN1CCC2(OC3=CC=C(Cl)C=C3C2)CC1)OC1=CC=C2C=CC=CC2=C1C1SCCS1 DDVJHQJENQCNCW-FTBISJDPSA-N 0.000 claims description 3
- KVWARILUINGOKE-LMOVPXPDSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-[2-thiophen-2-yl-6-(trifluoromethyl)pyrimidin-4-yl]oxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](O)CN1CCC2(OC3=CC=C(Cl)C=C3C2)CC1)OC(N=1)=CC(C(F)(F)F)=NC=1C1=CC=CS1 KVWARILUINGOKE-LMOVPXPDSA-N 0.000 claims description 3
- KTURYBJWNQRREF-JIDHJSLPSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-[5-(cyclopropylmethyl)-6-methyl-2-pyridin-4-ylpyrimidin-4-yl]oxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=NC(C=2C=CN=CC=2)=NC(OC[C@@H](O)CN2CCC3(OC4=CC=C(Cl)C=C4C3)CC2)=C1CC1CC1 KTURYBJWNQRREF-JIDHJSLPSA-N 0.000 claims description 3
- OFRVVDAHFOCJEI-FYZYNONXSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-[7-(trifluoromethyl)quinolin-4-yl]oxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=CC=NC2=CC(C(F)(F)F)=CC=C12 OFRVVDAHFOCJEI-FYZYNONXSA-N 0.000 claims description 3
- BJTFWYBRHBYIQT-FERBBOLQSA-N (2s)-1-(6-bromoquinazolin-4-yl)oxy-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)propan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=NC=NC2=CC=C(Br)C=C12 BJTFWYBRHBYIQT-FERBBOLQSA-N 0.000 claims description 3
- XFXWAGHPHPQRHO-NTISSMGPSA-N (2s)-1-(6-chloropyridin-2-yl)oxy-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)propan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](O)CN1CCC2(OC3=CC=C(Cl)C=C3C2)CC1)OC1=CC=CC(Cl)=N1 XFXWAGHPHPQRHO-NTISSMGPSA-N 0.000 claims description 3
- WZHDJJWUENEWGM-INIZCTEOSA-N (2s)-1-[(2-amino-1,3-benzothiazol-4-yl)oxy]-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)propan-2-ol Chemical compound C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=C2N=C(N)SC2=CC=C1 WZHDJJWUENEWGM-INIZCTEOSA-N 0.000 claims description 3
- BSWWNZKLQDUCTA-BDQAORGHSA-N (2s)-1-[5-butyl-6-(methoxymethyl)-2-methylsulfanylpyrimidin-4-yl]oxy-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)propan-2-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCCCC1=C(COC)N=C(SC)N=C1OC[C@@H](O)CN1CCC2(OC3=CC=C(Cl)C=C3C2)CC1 BSWWNZKLQDUCTA-BDQAORGHSA-N 0.000 claims description 3
- FSFMFBFBDARFTK-FYZYNONXSA-N 1-[6-[(2s)-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-2-hydroxypropoxy]-4,7-dimethoxy-1-benzofuran-5-yl]ethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=C(OC)C(OC=C2)=C2C(OC)=C1C(C)=O FSFMFBFBDARFTK-FYZYNONXSA-N 0.000 claims description 3
- GCWKTPOJUPMUFO-KRWDZBQOSA-N 3-[(2s)-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-2-hydroxypropoxy]-n-methylpyridine-4-carboxamide Chemical compound CNC(=O)C1=CC=NC=C1OC[C@@H](O)CN1CCC2(OC3=CC=C(Cl)C=C3C2)CC1 GCWKTPOJUPMUFO-KRWDZBQOSA-N 0.000 claims description 3
- LUXDNYIVTMMDTA-KRWDZBQOSA-N 5-[(2s)-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-2-hydroxypropoxy]-4h-1,4-benzoxazin-3-one Chemical compound C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=CC=CC2=C1NC(=O)CO2 LUXDNYIVTMMDTA-KRWDZBQOSA-N 0.000 claims description 3
- SYOVYMUIPNLGAP-IBGZPJMESA-N 8-[(2s)-3-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-2-hydroxypropoxy]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=CC=CC2=C1NC(=O)CC2 SYOVYMUIPNLGAP-IBGZPJMESA-N 0.000 claims description 3
- 102000009410 Chemokine receptor Human genes 0.000 claims description 3
- 108050000299 Chemokine receptor Proteins 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- HVGRMDKFSZEPLL-BOXHHOBZSA-N (2s)-1-(5-chlorospiro[3h-1-benzofuran-2,4'-piperidine]-1'-yl)-3-naphthalen-1-yloxypropan-2-ol;2,2,2-trifluoroacetic acid Chemical class OC(=O)C(F)(F)F.C1C2=CC(Cl)=CC=C2OC1(CC1)CCN1C[C@H](O)COC1=CC=CC2=CC=CC=C12 HVGRMDKFSZEPLL-BOXHHOBZSA-N 0.000 claims description 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 239000007822 coupling agent Substances 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 230000009286 beneficial effect Effects 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 239000000203 mixture Substances 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 13
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 206010039083 rhinitis Diseases 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 7
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- BDYDBRINEAMBRZ-UHFFFAOYSA-N 5-chlorospiro[3h-1-benzofuran-2,4'-piperidine] Chemical compound C1C2=CC(Cl)=CC=C2OC21CCNCC2 BDYDBRINEAMBRZ-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 230000035605 chemotaxis Effects 0.000 description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| SE0303280A SE0303280D0 (sv) | 2003-12-05 | 2003-12-05 | Novel compounds |
| PCT/SE2004/001771 WO2005054249A1 (en) | 2003-12-05 | 2004-11-30 | Novel compounds |
Publications (2)
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| JP2007513151A true JP2007513151A (ja) | 2007-05-24 |
| JP2007513151A5 JP2007513151A5 (https=) | 2007-12-13 |
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| EP (1) | EP1699803A1 (https=) |
| JP (1) | JP2007513151A (https=) |
| CN (1) | CN1890248A (https=) |
| SE (1) | SE0303280D0 (https=) |
| WO (1) | WO2005054249A1 (https=) |
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| SE0303090D0 (sv) * | 2003-11-20 | 2003-11-20 | Astrazeneca Ab | Novel compounds |
| SE0303541D0 (sv) | 2003-12-22 | 2003-12-22 | Astrazeneca Ab | New compounds |
| BRPI0714463A2 (pt) * | 2006-07-19 | 2013-04-02 | Astrazeneca Ab | compostos de espiropiperidina tricÍclicos, sua sÍntese e seus usos como moduladores de atividade receptora de quimiocina |
| WO2008103126A1 (en) * | 2007-02-23 | 2008-08-28 | Astrazeneca Ab | Novel combination of compounds to be used in the treatment of airway diseases, especially chronic obstructive pulmonary disease (copd) and asthma |
| WO2009011654A1 (en) * | 2007-07-17 | 2009-01-22 | Astrazeneca Ab | Process for the preparation of cyclic spiropiperidines |
| WO2009011655A1 (en) * | 2007-07-17 | 2009-01-22 | Astrazeneca Ab | Splropiperidine compounds, a process of their preparation, pharmaceutical compositions containing them, and their use in the treatment of airway diseases, inflammatory diseases, copd or asthma |
| MX2011013437A (es) * | 2009-06-10 | 2012-02-21 | Sunovion Pharmaceuticals Inc | Antagonista y agonistas inversos de histamina h3 y metodos para el uso de los mismos. |
| EP2377850A1 (en) | 2010-03-30 | 2011-10-19 | Pharmeste S.r.l. | TRPV1 vanilloid receptor antagonists with a bicyclic portion |
| CN101919833B (zh) * | 2010-07-16 | 2012-01-11 | 暨南大学 | 一种芳香类化合物作为制备Caspase 3抑制剂的用途 |
| EP2565186A1 (en) | 2011-09-02 | 2013-03-06 | Hybrigenics S.A. | Selective and reversible inhibitors of ubiquitin specific protease 7 |
| CN102816116B (zh) * | 2012-07-09 | 2014-03-26 | 浙江工业大学 | 一种6-羟基-2（1h）-喹啉酮化合物的合成方法 |
| CN102816115B (zh) * | 2012-07-09 | 2014-03-26 | 浙江工业大学 | 一种羟基取代-3,4-二氢-2（1h）-喹啉酮类化合物的合成方法 |
| CN119431385A (zh) * | 2023-08-04 | 2025-02-14 | 中国科学院上海药物研究所 | 一种irak4降解剂及其药物组合物和药学上的应用 |
Citations (1)
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|---|---|---|---|---|
| WO2000071517A1 (en) * | 1999-05-24 | 2000-11-30 | Mitsubishi Pharma Corporation | Phenoxypropylamine compounds |
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| US4010201A (en) * | 1974-04-12 | 1977-03-01 | The Upjohn Company | Organic compounds |
| US4166120A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing benzoylpropyl-spiro[dihydrobenzofuran]piperidines and pyrrolidines |
| US4263317A (en) * | 1979-09-06 | 1981-04-21 | Hoechst-Roussel Pharmaceuticals, Inc. | Spiro[cyclohexane-1,1'(3'H)-isobenzofuran]s |
| WO1998025605A1 (en) * | 1996-12-13 | 1998-06-18 | Merck & Co., Inc. | Spiro-substituted azacycles as modulators of chemokine receptor activity |
| EP1003743A4 (en) * | 1997-01-21 | 2001-04-11 | Merck & Co Inc | 3,3-DISBSTITUED PIPERIDINE LIKE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY |
| US6288083B1 (en) * | 1998-09-04 | 2001-09-11 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
| AU2001243394A1 (en) * | 2000-03-02 | 2001-09-12 | Smith Kline Beecham Corporation | Compounds and methods |
| WO2002102387A1 (en) * | 2001-06-18 | 2002-12-27 | H. Lundbeck A/S | Treatment of neuropathic pain |
| SE0202133D0 (sv) * | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Novel compounds |
| US20070021498A1 (en) * | 2004-10-14 | 2007-01-25 | Nafizal Hossain | Novel tricyclic spiroderivatives as modulators of chemokine receptor activity |
-
2003
- 2003-12-05 SE SE0303280A patent/SE0303280D0/xx unknown
-
2004
- 2004-11-30 JP JP2006542530A patent/JP2007513151A/ja active Pending
- 2004-11-30 WO PCT/SE2004/001771 patent/WO2005054249A1/en not_active Ceased
- 2004-11-30 EP EP04800422A patent/EP1699803A1/en not_active Withdrawn
- 2004-11-30 US US10/581,171 patent/US20070123543A1/en not_active Abandoned
- 2004-11-30 CN CNA2004800368111A patent/CN1890248A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000071517A1 (en) * | 1999-05-24 | 2000-11-30 | Mitsubishi Pharma Corporation | Phenoxypropylamine compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1699803A1 (en) | 2006-09-13 |
| CN1890248A (zh) | 2007-01-03 |
| WO2005054249A1 (en) | 2005-06-16 |
| US20070123543A1 (en) | 2007-05-31 |
| SE0303280D0 (sv) | 2003-12-05 |
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