CA1332238C - 4h-1-benzopyran-4-one derivatives, a process for their preparation and their use as medicaments - Google Patents
4h-1-benzopyran-4-one derivatives, a process for their preparation and their use as medicamentsInfo
- Publication number
- CA1332238C CA1332238C CA000534430A CA534430A CA1332238C CA 1332238 C CA1332238 C CA 1332238C CA 000534430 A CA000534430 A CA 000534430A CA 534430 A CA534430 A CA 534430A CA 1332238 C CA1332238 C CA 1332238C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- formula
- compound
- hydroxy
- hydrogen
- 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.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 title claims description 3
- 150000004777 chromones Chemical class 0.000 title abstract description 5
- -1 C3-C6-alkynyl Chemical group 0.000 claims abstract description 29
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 28
- 150000002367 halogens Chemical class 0.000 claims abstract description 28
- 239000001257 hydrogen Substances 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
- 239000002253 acid Substances 0.000 claims abstract description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 18
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims abstract description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 4
- 239000000730 antalgic agent Substances 0.000 claims abstract 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract 2
- 239000000043 antiallergic agent Substances 0.000 claims abstract 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims abstract 2
- 239000003018 immunosuppressive agent Substances 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 85
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 230000003287 optical effect Effects 0.000 claims description 5
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 150000001805 chlorine compounds Chemical class 0.000 claims description 3
- 230000002519 immonomodulatory effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000005594 diketone group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 229920002866 paraformaldehyde Polymers 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000005490 tosylate group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims 1
- 150000008046 alkali metal hydrides Chemical class 0.000 claims 1
- 125000005907 alkyl ester group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000802 nitrating effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 8
- 125000003118 aryl group Chemical group 0.000 abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 7
- 230000000202 analgesic effect Effects 0.000 abstract description 2
- 125000003435 aroyl group Chemical group 0.000 abstract description 2
- 125000004104 aryloxy group Chemical group 0.000 abstract description 2
- 230000001506 immunosuppresive effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 235000013350 formula milk Nutrition 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- 229910001868 water Inorganic materials 0.000 description 26
- 238000002844 melting Methods 0.000 description 23
- 230000008018 melting Effects 0.000 description 23
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 22
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 22
- 239000000203 mixture Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 229960001701 chloroform Drugs 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 206010030113 Oedema Diseases 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000002026 chloroform extract Substances 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 210000002683 foot Anatomy 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 208000000104 Arthus reaction Diseases 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- 229910017974 NH40H Inorganic materials 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- YONLFQNRGZXBBF-KBPBESRZSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-KBPBESRZSA-N 0.000 description 2
- MGNNDUKLPNLAFW-NWDGAFQWSA-N (3s,4r)-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-ol Chemical compound COC1=CC(OC)=CC(OC)=C1[C@@H]1[C@H](O)CN(C)CC1 MGNNDUKLPNLAFW-NWDGAFQWSA-N 0.000 description 2
- MGNNDUKLPNLAFW-VXGBXAGGSA-N (3s,4s)-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-ol Chemical compound COC1=CC(OC)=CC(OC)=C1[C@H]1[C@H](O)CN(C)CC1 MGNNDUKLPNLAFW-VXGBXAGGSA-N 0.000 description 2
- CRUILBNAQILVHZ-UHFFFAOYSA-N 1,2,3-trimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1OC CRUILBNAQILVHZ-UHFFFAOYSA-N 0.000 description 2
- LKUDPHPHKOZXCD-UHFFFAOYSA-N 1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1 LKUDPHPHKOZXCD-UHFFFAOYSA-N 0.000 description 2
- VSYLKOXFYGLIPZ-UHFFFAOYSA-N 2,3-dimethoxychromen-4-one Chemical class C1=CC=C2C(=O)C(OC)=C(OC)OC2=C1 VSYLKOXFYGLIPZ-UHFFFAOYSA-N 0.000 description 2
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003892 tartrate salts Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
- HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 1
- VWRZNLHDQXFHDR-UHFFFAOYSA-N 1-methyl-4-(2,4,6-trimethoxyphenyl)-3,6-dihydro-2h-pyridine Chemical compound COC1=CC(OC)=CC(OC)=C1C1=CCN(C)CC1 VWRZNLHDQXFHDR-UHFFFAOYSA-N 0.000 description 1
- RFAWITYVAHWPNN-UHFFFAOYSA-N 1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-one Chemical compound COC1=CC(OC)=CC(OC)=C1C1C(=O)CN(C)CC1 RFAWITYVAHWPNN-UHFFFAOYSA-N 0.000 description 1
- GGYVTHJIUNGKFZ-UHFFFAOYSA-N 1-methylpiperidin-2-one Chemical compound CN1CCCCC1=O GGYVTHJIUNGKFZ-UHFFFAOYSA-N 0.000 description 1
- 239000005631 2,4-Dichlorophenoxyacetic acid Substances 0.000 description 1
- CILPHQCEVYJUDN-VWYCJHECSA-N 2-[(1s,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl]oxyacetic acid Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1OCC(O)=O CILPHQCEVYJUDN-VWYCJHECSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- DFZIJAGHWXOSDA-UHFFFAOYSA-N 2-methoxychromen-4-one Chemical compound C1=CC=C2OC(OC)=CC(=O)C2=C1 DFZIJAGHWXOSDA-UHFFFAOYSA-N 0.000 description 1
- 229910015845 BBr3 Inorganic materials 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical group C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 101100336279 Caenorhabditis elegans icl-1 gene Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 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 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- ZVTQWXCKQTUVPY-UHFFFAOYSA-N chloromethylcyclopropane Chemical compound ClCC1CC1 ZVTQWXCKQTUVPY-UHFFFAOYSA-N 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000012067 demethylated product Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940035429 isobutyl alcohol Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HMQAYHWQXVJMHR-UHFFFAOYSA-N methylsulfinylmethane 1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-one Chemical compound CS(=O)C.CN1CC(C(CC1)C1=C(C=C(C=C1OC)OC)OC)=O HMQAYHWQXVJMHR-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- HVFSJXUIRWUHRG-UHFFFAOYSA-N oic acid Natural products C1CC2C3CC=C4CC(OC5C(C(O)C(O)C(CO)O5)O)CC(O)C4(C)C3CCC2(C)C1C(C)C(O)CC(C)=C(C)C(=O)OC1OC(COC(C)=O)C(O)C(O)C1OC(C(C1O)O)OC(COC(C)=O)C1OC1OC(CO)C(O)C(O)C1O HVFSJXUIRWUHRG-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 101150081985 scrib gene Proteins 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 229940030010 trimethoxybenzene Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3612337.4 | 1986-04-11 | ||
| DE19863612337 DE3612337A1 (de) | 1986-04-11 | 1986-04-11 | 4h-1-benzopyran-4-on-derivate, ein verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1332238C true CA1332238C (en) | 1994-10-04 |
Family
ID=6298535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000534430A Expired - Lifetime CA1332238C (en) | 1986-04-11 | 1987-04-10 | 4h-1-benzopyran-4-one derivatives, a process for their preparation and their use as medicaments |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4900727A (en:Method) |
| EP (1) | EP0241003B1 (en:Method) |
| JP (1) | JPH0686446B2 (en:Method) |
| KR (1) | KR950009861B1 (en:Method) |
| AT (2) | ATE95519T1 (en:Method) |
| AU (1) | AU602891B2 (en:Method) |
| CA (1) | CA1332238C (en:Method) |
| DE (2) | DE3612337A1 (en:Method) |
| DK (1) | DK169760B1 (en:Method) |
| ES (1) | ES2060582T3 (en:Method) |
| IE (1) | IE62244B1 (en:Method) |
| IL (1) | IL82149A (en:Method) |
| IN (1) | IN164232B (en:Method) |
| PT (1) | PT84654B (en:Method) |
| ZA (1) | ZA872555B (en:Method) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5284856A (en) * | 1988-10-28 | 1994-02-08 | Hoechst Aktiengesellschaft | Oncogene-encoded kinases inhibition using 4-H-1-benzopyran-4-one derivatives |
| DE3836676A1 (de) * | 1988-10-28 | 1990-05-03 | Hoechst Ag | Die verwendung von 4h-1-benzopyran-4-on-derivaten, neue 4h-1-benzopyran-4-on-derivate und diese enthaltende arzneimittel |
| US5278174A (en) * | 1990-06-04 | 1994-01-11 | Scios Nova, Inc. | Sigma binding site agents |
| EP0508347A1 (en) * | 1991-04-10 | 1992-10-14 | Hoechst Aktiengesellschaft | 5,7-Dihydroxy-2-methyl-8-[4-(3-hydroxy-1-(1-propyl)) piperidinyl]-4H-1-benzopyran-4-one, its preparation and its use |
| GB9604709D0 (en) * | 1996-03-05 | 1996-05-01 | Imperial College | A compound |
| US6476011B1 (en) | 1991-08-28 | 2002-11-05 | Sterix Limited | Methods for introducing an estrogenic compound |
| US6903084B2 (en) | 1991-08-28 | 2005-06-07 | Sterix Limited | Steroid sulphatase inhibitors |
| US6011024A (en) | 1991-08-28 | 2000-01-04 | Imperial College Of Science Technology & Medicine | Steroid sulphatase inhibitors |
| SK280617B6 (sk) * | 1992-01-16 | 2000-05-16 | Hoechst Aktiengesellschaft | Arylcykloalkylové deriváty, spôsob ich prípravy, f |
| US5733920A (en) * | 1995-10-31 | 1998-03-31 | Mitotix, Inc. | Inhibitors of cyclin dependent kinases |
| US6506792B1 (en) | 1997-03-04 | 2003-01-14 | Sterix Limited | Compounds that inhibit oestrone sulphatase and/or aromatase and methods for making and using |
| US20060241173A1 (en) * | 1996-02-16 | 2006-10-26 | Sterix Ltd. | Compound |
| US6087366A (en) * | 1996-03-07 | 2000-07-11 | The Trustees Of Columbia University In The City Of New York | Use of flavopiridol or a pharmaceutically acceptable salt thereof for inhibiting cell damage or cell death |
| US5849733A (en) * | 1996-05-10 | 1998-12-15 | Bristol-Myers Squibb Co. | 2-thio or 2-oxo flavopiridol analogs |
| US5908934A (en) * | 1996-09-26 | 1999-06-01 | Bristol-Myers Squibb Company | Process for the preparation of chiral ketone intermediates useful for the preparation of flavopiridol and analogs |
| DE19802449A1 (de) * | 1998-01-23 | 1999-07-29 | Hoechst Marion Roussel De Gmbh | Verfahren zur Herstellung von (-)cis-3-Hydroxy-1-methyl-4-(2,4,6-trimethoxypyhenyl)-piperidin |
| GB9807779D0 (en) * | 1998-04-09 | 1998-06-10 | Ciba Geigy Ag | Organic compounds |
| US6399633B1 (en) * | 1999-02-01 | 2002-06-04 | Aventis Pharmaceuticals Inc. | Use of 4-H-1-benzopryan-4-one derivatives as inhibitors of smooth muscle cell proliferation |
| DE19959546A1 (de) * | 1999-12-09 | 2001-06-21 | Rhone Poulenc Rorer Gmbh | Pharmazeutische Zubereitung zur Behandlung von Tumorerkrankungen |
| US7335650B2 (en) | 2000-01-14 | 2008-02-26 | Sterix Limited | Composition |
| US6821990B2 (en) * | 2000-01-18 | 2004-11-23 | Aventis Pharma Deutschland Gmbh | Ethanol solvate of (-)-cis-2-(2-chlorophenyl)-5, 7-dihydroxy-8 [4R-(3S-hydroxy-1-M ethyl) piperidinyl]-4H-1-benzopyran-4-one |
| US6576647B2 (en) | 2000-01-18 | 2003-06-10 | Aventis Pharmaceuticals Inc. | Pseudopolymorph of (—)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8[4R-(3S-hydroxy -1-methyl)piperidinyl]-4H-1-benzopyran-4-one |
| HUP0204126A3 (en) * | 2000-01-18 | 2006-02-28 | Aventis Pharma Inc | Pseudopolymorph of (-)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8[4r-(3s-hydroxy-1-methyl)piperidinyl]-4h-1-benzopyran-4-one, process for their preparation and pharmaceutical compositions containing them |
| JP2003520798A (ja) * | 2000-01-18 | 2003-07-08 | アベンテイス・フアーマシユーチカルズ・インコーポレーテツド | （−）−シス−２−（２−クロロフェニル）−５，７−ジヒドロキシ−８［４ｒ−（３ｓ−ヒドロキシ−１−メチル）ピペリジニル］−４ｈ−１−ベンゾピラン−４−オンのエタノール溶媒化合物 |
| FR2805538B1 (fr) * | 2000-02-29 | 2006-08-04 | Hoechst Marion Roussel Inc | Nouveaux derives de flavones, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation |
| KR100423899B1 (ko) | 2000-05-10 | 2004-03-24 | 주식회사 엘지생명과학 | 세포 증식 억제제로 유용한 1,1-디옥소이소티아졸리딘을갖는 인다졸 |
| CN100381437C (zh) | 2002-04-17 | 2008-04-16 | 赛特凯恩蒂克公司 | 化合物、组合物和方法 |
| US7271193B2 (en) * | 2002-07-08 | 2007-09-18 | Nicholas Piramal India, Ltd. | Inhibitors of cyclin-dependent kinases and their use |
| US7884127B2 (en) * | 2002-07-08 | 2011-02-08 | Pirimal Life Sciences Ltd. | Inhibitors of cyclin dependent kinases and their use |
| US7915301B2 (en) | 2002-07-08 | 2011-03-29 | Piramal Life Science Limited | Inhibitors of cyclin dependent kinases and their use |
| EP1539727B1 (en) * | 2002-07-17 | 2009-02-18 | Cytokinetics, Inc. | Compounds, compositions, and methods for treating cellular proliferative diseases |
| JP2005539062A (ja) * | 2002-09-13 | 2005-12-22 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
| WO2005042697A2 (en) * | 2003-10-06 | 2005-05-12 | Cytokinetics, Inc. | Compounds, compositions and methods |
| MXPA06006651A (es) * | 2003-12-09 | 2006-08-11 | Gov Health & Human Serv | Metodos para suprimir una respuesta inmune o un tratamiento para un trastorno proliferativo. |
| WO2005058341A2 (en) * | 2003-12-11 | 2005-06-30 | Theravance, Inc. | Compositions for use in the treatment of mutant receptor tyrosine kinase driven cellular proliferative diseases |
| ES2552338T3 (es) | 2005-01-21 | 2015-11-27 | Astex Therapeutics Limited | Compuestos farmacéuticos |
| WO2007148158A1 (en) | 2006-06-21 | 2007-12-27 | Piramal Life Sciences Limited | Enantiomerically pure flavone derivatives for the treatment of poliferative disorders and processes for their preparation |
| WO2008044041A1 (en) | 2006-10-12 | 2008-04-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| JP5528807B2 (ja) | 2006-10-12 | 2014-06-25 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
| TWI461194B (zh) | 2009-05-05 | 2014-11-21 | Piramal Entpr Ltd | 吡咯啶取代黃酮作為輻射致敏劑 |
| EP2538941A1 (en) | 2010-02-26 | 2013-01-02 | Piramal Enterprises Limited | Pyrrolidine substituted flavones for the treatment of inflammatory disorders |
| WO2011159726A2 (en) | 2010-06-14 | 2011-12-22 | The Scripps Research Institute | Reprogramming of cells to a new fate |
| TW201300105A (zh) | 2011-05-31 | 2013-01-01 | Piramal Life Sciences Ltd | 治療頭頸鱗狀細胞癌之相乘藥物組合物 |
| CA2909280C (en) | 2013-04-10 | 2021-03-30 | Council Of Scientific & Industrial Research | Chromone alkaloid dysoline for the treatment of cancer and inflammatory disorders |
| EP2986605B1 (en) | 2013-04-17 | 2017-11-15 | Council of Scientific and Industrial Research | Rohitukine analogs as cyclin-dependent kinase inhibitors and a process for the preparation thereof |
| TWI680760B (zh) | 2013-07-12 | 2020-01-01 | 印度商皮拉馬爾企業有限公司 | 治療黑色素瘤的藥物組合 |
| US20170306046A1 (en) | 2014-11-12 | 2017-10-26 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| EP3611506B1 (en) | 2015-04-20 | 2021-11-17 | Sumitomo Dainippon Pharma Oncology, Inc. | Predicting response to alvocidib by mitochondrial profiling |
| AU2016264212B2 (en) | 2015-05-18 | 2020-10-22 | Sumitomo Pharma Oncology, Inc. | Alvocidib prodrugs having increased bioavailability |
| RU2759963C2 (ru) | 2015-08-03 | 2021-11-19 | Сумитомо Даиниппон Фарма Онколоджи, Инк. | Комбинированные терапии для лечения рака |
| IL302822A (en) | 2015-11-12 | 2023-07-01 | Seagen Inc | Glycan-interacting compounds and methods of use |
| US11401330B2 (en) | 2016-11-17 | 2022-08-02 | Seagen Inc. | Glycan-interacting compounds and methods of use |
| WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
| KR20190099260A (ko) | 2016-12-19 | 2019-08-26 | 톨레로 파마수티컬스, 인크. | 프로파일링 펩티드 및 감도 프로파일링을 위한 방법 |
| AU2018226824A1 (en) | 2017-03-03 | 2019-09-19 | Seagen Inc. | Glycan-interacting compounds and methods of use |
| US11497756B2 (en) | 2017-09-12 | 2022-11-15 | Sumitomo Pharma Oncology, Inc. | Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib |
| KR20210099066A (ko) | 2018-12-04 | 2021-08-11 | 스미토모 다이니폰 파마 온콜로지, 인크. | 암의 치료를 위한 작용제로서 사용하기 위한 cdk9 억제제 및 그의 다형체 |
| US11793802B2 (en) | 2019-03-20 | 2023-10-24 | Sumitomo Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (AML) with venetoclax failure |
| WO2020213714A1 (ja) * | 2019-04-18 | 2020-10-22 | 大日本住友製薬株式会社 | シス－（－）－フロシノピペリドールの製造方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1223690A (en) * | 1967-10-17 | 1971-03-03 | Fisons Pharmaceuticals Ltd | Substituted chromon-2-carboxylic acids |
| DE2731566A1 (de) * | 1977-07-13 | 1979-02-01 | Bayer Ag | Verfahren zur herstellung von neuen chromon-derivaten, sowie ihre verwendung als pflanzenschutzmittel |
| GB2101115A (en) * | 1980-10-23 | 1983-01-12 | Pfizer Ltd | Thromboxane synthetase inhibitors |
| DE3311005A1 (de) * | 1983-03-25 | 1984-09-27 | Bayer Ag, 5090 Leverkusen | Chromon- und thiochromonsubstituierte 1,4-dihydropyridinderivate, mehrere verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln |
| DE3329186A1 (de) * | 1983-08-12 | 1985-02-21 | Hoechst Ag, 6230 Frankfurt | Chromonalkaloid, verfahren zu seiner isolierung aus dysoxylum binectariferum, und seine verwendung als arzneimittel |
| DE3445852A1 (de) * | 1984-12-15 | 1986-06-19 | Bayer Ag, 5090 Leverkusen | Dihydropyridin-carbonsaeureamide, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln |
-
1985
- 1985-10-31 IN IN300/BOM/85A patent/IN164232B/en unknown
-
1986
- 1986-04-11 DE DE19863612337 patent/DE3612337A1/de not_active Withdrawn
-
1987
- 1987-04-08 EP EP87105180A patent/EP0241003B1/de not_active Expired - Lifetime
- 1987-04-08 ES ES87105180T patent/ES2060582T3/es not_active Expired - Lifetime
- 1987-04-08 AT AT87105180T patent/ATE95519T1/de not_active IP Right Cessation
- 1987-04-08 DE DE87105180T patent/DE3787661D1/de not_active Expired - Lifetime
- 1987-04-09 ZA ZA872555A patent/ZA872555B/xx unknown
- 1987-04-09 IL IL8214987A patent/IL82149A/en not_active IP Right Cessation
- 1987-04-10 KR KR87003427A patent/KR950009861B1/ko not_active Expired - Lifetime
- 1987-04-10 CA CA000534430A patent/CA1332238C/en not_active Expired - Lifetime
- 1987-04-10 DK DK185287A patent/DK169760B1/da not_active IP Right Cessation
- 1987-04-10 IE IE94187A patent/IE62244B1/en not_active IP Right Cessation
- 1987-04-10 AU AU71397/87A patent/AU602891B2/en not_active Expired
- 1987-04-10 PT PT84654A patent/PT84654B/pt unknown
- 1987-04-10 JP JP62087252A patent/JPH0686446B2/ja not_active Expired - Lifetime
- 1987-10-08 AT AT0260587A patent/AT389875B/de active
-
1989
- 1989-01-26 US US07/302,084 patent/US4900727A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| IL82149A0 (en) | 1987-10-30 |
| DK185287A (da) | 1987-10-12 |
| DE3787661D1 (de) | 1993-11-11 |
| IL82149A (en) | 1994-01-25 |
| PT84654A (de) | 1987-05-01 |
| EP0241003B1 (de) | 1993-10-06 |
| PT84654B (pt) | 1989-12-29 |
| HK1006021A1 (en) | 1999-02-05 |
| JPH0686446B2 (ja) | 1994-11-02 |
| ZA872555B (en) | 1987-11-25 |
| AU602891B2 (en) | 1990-11-01 |
| DE3612337A1 (de) | 1987-10-15 |
| KR870010045A (ko) | 1987-11-30 |
| KR950009861B1 (en) | 1995-08-29 |
| US4900727A (en) | 1990-02-13 |
| JPS62242680A (ja) | 1987-10-23 |
| IE870941L (en) | 1987-10-11 |
| ATE95519T1 (de) | 1993-10-15 |
| IE62244B1 (en) | 1995-01-11 |
| DK185287D0 (da) | 1987-04-10 |
| AT389875B (de) | 1990-02-12 |
| IN164232B (en:Method) | 1989-02-04 |
| DK169760B1 (da) | 1995-02-20 |
| ES2060582T3 (es) | 1994-12-01 |
| ATA260587A (de) | 1989-07-15 |
| EP0241003A3 (en) | 1988-10-12 |
| EP0241003A2 (de) | 1987-10-14 |
| AU7139787A (en) | 1987-10-15 |
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