CA2359390A1 - Utilisation of 2-substituted 1,2-benzisothiazole derivatives and 3-substituted tetrahydropyridopyrimidinone derivatives for the prophylaxis and therapy of cerebral ischaemia - Google Patents
Utilisation of 2-substituted 1,2-benzisothiazole derivatives and 3-substituted tetrahydropyridopyrimidinone derivatives for the prophylaxis and therapy of cerebral ischaemia Download PDFInfo
- Publication number
- CA2359390A1 CA2359390A1 CA002359390A CA2359390A CA2359390A1 CA 2359390 A1 CA2359390 A1 CA 2359390A1 CA 002359390 A CA002359390 A CA 002359390A CA 2359390 A CA2359390 A CA 2359390A CA 2359390 A1 CA2359390 A1 CA 2359390A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- roro
- branched
- unbranched
- substituted
- 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.)
- Abandoned
Links
- 206010008120 Cerebral ischaemia Diseases 0.000 title claims abstract description 7
- 238000011321 prophylaxis Methods 0.000 title claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 7
- -1 2-substituted 1,2-benzisothiazole Chemical class 0.000 title description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 72
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 208000006011 Stroke Diseases 0.000 claims abstract description 4
- 150000007513 acids Chemical class 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 10
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 8
- 150000001923 cyclic compounds Chemical class 0.000 claims description 8
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 229910052786 argon Inorganic materials 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical group FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 claims description 4
- 201000006474 Brain Ischemia Diseases 0.000 claims description 4
- 206010008118 cerebral infarction Diseases 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- YBPWKEJCVLEMGU-UHFFFAOYSA-N 3-nitro-1h-pyrrole-2-carbonitrile Chemical compound [O-][N+](=O)C=1C=CNC=1C#N YBPWKEJCVLEMGU-UHFFFAOYSA-N 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- 239000000203 mixture Substances 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 14
- 239000007858 starting material Substances 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 11
- 101150041968 CDC13 gene Proteins 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000007795 chemical reaction product Substances 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 229910052721 tungsten Inorganic materials 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 101100149678 Caenorhabditis elegans snr-3 gene Proteins 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- FBPPFIPXMJEJCU-UHFFFAOYSA-N 1-(5,6,7,8-tetrahydronaphthalen-1-yl)piperazine Chemical compound C1CCCC2=C1C=CC=C2N1CCNCC1 FBPPFIPXMJEJCU-UHFFFAOYSA-N 0.000 description 3
- SSSBLYQLIOQJSB-UHFFFAOYSA-N 4-naphthalen-1-ylpiperidine Chemical compound C1CNCCC1C1=CC=CC2=CC=CC=C12 SSSBLYQLIOQJSB-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 229910052770 Uranium Inorganic materials 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
- VNICFCQJUVFULD-UHFFFAOYSA-N 1-(1-naphthalenyl)piperazine Chemical compound C1CNCCN1C1=CC=CC2=CC=CC=C12 VNICFCQJUVFULD-UHFFFAOYSA-N 0.000 description 2
- GJOBEWYDAQTKDU-UHFFFAOYSA-N 1-(2,3-dihydro-1h-inden-4-yl)piperazine Chemical compound C=12CCCC2=CC=CC=1N1CCNCC1 GJOBEWYDAQTKDU-UHFFFAOYSA-N 0.000 description 2
- HGYDREHWXXUUIS-UHFFFAOYSA-N 1-(naphthalen-1-ylmethyl)piperazine Chemical compound C=1C=CC2=CC=CC=C2C=1CN1CCNCC1 HGYDREHWXXUUIS-UHFFFAOYSA-N 0.000 description 2
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
- SCRBSGZBTHKAHU-UHFFFAOYSA-N 4-bromoisoquinoline Chemical compound C1=CC=C2C(Br)=CN=CC2=C1 SCRBSGZBTHKAHU-UHFFFAOYSA-N 0.000 description 2
- KARYKQNFDNURNN-UHFFFAOYSA-N 4-chloro-3,3-dimethyl-2h-1,2-benzothiazole 1,1-dioxide Chemical compound C1=CC(Cl)=C2C(C)(C)NS(=O)(=O)C2=C1 KARYKQNFDNURNN-UHFFFAOYSA-N 0.000 description 2
- NIBZKHUIJGTBOX-UHFFFAOYSA-N 4-piperazin-1-ylisoquinoline Chemical compound C1CNCCN1C1=CN=CC2=CC=CC=C12 NIBZKHUIJGTBOX-UHFFFAOYSA-N 0.000 description 2
- KLTHGJYCURVMAK-UHFFFAOYSA-N 4-piperazin-1-ylquinazoline Chemical compound C1CNCCN1C1=NC=NC2=CC=CC=C12 KLTHGJYCURVMAK-UHFFFAOYSA-N 0.000 description 2
- SODWJACROGQSMM-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalen-1-amine Chemical compound C1CCCC2=C1C=CC=C2N SODWJACROGQSMM-UHFFFAOYSA-N 0.000 description 2
- SPXJZGXITAWLIO-UHFFFAOYSA-N 6-benzyl-3-(2-chloroethyl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-one Chemical compound C1C=2C(=O)N(CCCl)C=NC=2CCN1CC1=CC=CC=C1 SPXJZGXITAWLIO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
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- 229960000583 acetic acid Drugs 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
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- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
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- 229940043279 diisopropylamine Drugs 0.000 description 2
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- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
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- 235000005074 zinc chloride Nutrition 0.000 description 2
- FHLXQXCQSUICIN-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrido[3,2-d]pyrimidine Chemical compound C1=CC=C2NCNCC2=N1 FHLXQXCQSUICIN-UHFFFAOYSA-N 0.000 description 1
- MUSOMUXTQGJZKD-UHFFFAOYSA-N 1-(2-chloroethyl)-4-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCN(CCCl)CC1 MUSOMUXTQGJZKD-UHFFFAOYSA-N 0.000 description 1
- MAIPOMCACBNHEI-UHFFFAOYSA-N 1-(2-chloroethyl)piperazine Chemical compound ClCCN1CCNCC1 MAIPOMCACBNHEI-UHFFFAOYSA-N 0.000 description 1
- OIZBMQFOSPOOIS-UHFFFAOYSA-N 1-(3-chloropropyl)-4-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCN(CCCCl)CC1 OIZBMQFOSPOOIS-UHFFFAOYSA-N 0.000 description 1
- QYHUWTWTZWQCJT-UHFFFAOYSA-N 1-(3-chloropropyl)-4-naphthalen-1-ylpiperazine Chemical compound C1CN(CCCCl)CCN1C1=CC=CC2=CC=CC=C12 QYHUWTWTZWQCJT-UHFFFAOYSA-N 0.000 description 1
- MLXIGMYNOXFJAH-UHFFFAOYSA-N 1-chloro-4-piperazin-1-ylphthalazine Chemical compound C12=CC=CC=C2C(Cl)=NN=C1N1CCNCC1 MLXIGMYNOXFJAH-UHFFFAOYSA-N 0.000 description 1
- PWMNWKMSCLDPAG-UHFFFAOYSA-N 1-naphthalen-1-ylazepane Chemical compound C1CCCCCN1C1=CC=CC2=CC=CC=C12 PWMNWKMSCLDPAG-UHFFFAOYSA-N 0.000 description 1
- DCPLVXOQIWQNDH-UHFFFAOYSA-N 1-naphthalen-1-yldiazepane Chemical compound C1CCCCNN1C1=CC=CC2=CC=CC=C12 DCPLVXOQIWQNDH-UHFFFAOYSA-N 0.000 description 1
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 1
- UQAWXKDXVXSCRD-UHFFFAOYSA-N 2-(2-chloroethyl)-3,3-diethyl-1,2-benzothiazole 1,1-dioxide Chemical compound C1=CC=C2C(CC)(CC)N(CCCl)S(=O)(=O)C2=C1 UQAWXKDXVXSCRD-UHFFFAOYSA-N 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19900544.3 | 1999-01-11 | ||
| DE19900544A DE19900544A1 (de) | 1999-01-11 | 1999-01-11 | Verwendung von Verbindungen der Formel I zur Prophylaxe und Therapie der zerebralen Ischämie |
| PCT/EP1999/010275 WO2000041697A1 (de) | 1999-01-11 | 1999-12-22 | Verwendung von 2-substituierten 1,2-benzisothiazol-derivaten und von 3-substituierten tetrahydropyridopyrimidinon-derivaten zur prophylaxe und therapie der zerebralen ischämie |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2359390A1 true CA2359390A1 (en) | 2000-07-20 |
Family
ID=7893835
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002359390A Abandoned CA2359390A1 (en) | 1999-01-11 | 1999-12-22 | Utilisation of 2-substituted 1,2-benzisothiazole derivatives and 3-substituted tetrahydropyridopyrimidinone derivatives for the prophylaxis and therapy of cerebral ischaemia |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1140099A1 (ja) |
| JP (1) | JP2002534467A (ja) |
| KR (1) | KR20010101440A (ja) |
| CN (1) | CN1333685A (ja) |
| AR (1) | AR029741A1 (ja) |
| AU (1) | AU2285100A (ja) |
| BG (1) | BG105688A (ja) |
| BR (1) | BR9916888A (ja) |
| CA (1) | CA2359390A1 (ja) |
| DE (1) | DE19900544A1 (ja) |
| HU (1) | HUP0200520A3 (ja) |
| IL (1) | IL144145A0 (ja) |
| MX (1) | MXPA01006966A (ja) |
| NO (1) | NO20013408L (ja) |
| PL (1) | PL348916A1 (ja) |
| SK (1) | SK9682001A3 (ja) |
| TR (1) | TR200102009T2 (ja) |
| WO (1) | WO2000041697A1 (ja) |
| ZA (1) | ZA200105473B (ja) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7618959B2 (en) | 2002-11-05 | 2009-11-17 | Smithklinebeecham Corp | Antibacterial agents |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7691879B2 (en) * | 2003-09-23 | 2010-04-06 | Merck Sharp & Dohme Corp. | Isoquinoline potassium channel inhibitors |
| CA2621164A1 (en) * | 2005-08-26 | 2007-03-01 | Shionogi & Co., Ltd. | Derivative having ppar agonistic activity |
| MX2010002890A (es) * | 2007-09-20 | 2010-07-02 | Cortex Pharma Inc | 1, 2, 3-triacin -4-onas sustituidas en la posicion 3 y 1, 3- pirimidinonas sustituidas en la posicion 3 para mejorar las respuestas sinapticas glutamatergicas. |
| MA41168A (fr) * | 2014-12-17 | 2017-10-24 | Acraf | Nouveaux composés antibactériens |
| CN108484594B (zh) * | 2018-02-09 | 2020-08-04 | 福建医科大学 | 一种烷氧基取代四氢吡啶并嘧啶类化合物或其可用盐及其制备方法与应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3620643A1 (de) * | 1985-06-22 | 1987-01-22 | Sandoz Ag | Thiazole, ihre herstellung und verwendung |
| DE3831888A1 (de) * | 1988-09-20 | 1990-03-29 | Troponwerke Gmbh & Co Kg | Arzneimittel zur behandlung von apoplexia cerebri |
| JP3036789B2 (ja) * | 1990-06-22 | 2000-04-24 | 三井化学株式会社 | 新規な複素環式化合物及び医薬組成物 |
| DE19746612A1 (de) * | 1997-10-22 | 1999-04-29 | Basf Ag | 2-Substituierte 1,2-Benzisothiazol-Derivate, ihre Herstellung und Verwendung |
| DE19747063A1 (de) * | 1997-10-24 | 1999-04-29 | Basf Ag | 3-substituierte Tetrahydropyridopyrimidinon-Derivate, ihre Herstellung und Verwendung |
-
1999
- 1999-01-11 DE DE19900544A patent/DE19900544A1/de not_active Withdrawn
- 1999-12-22 SK SK968-2001A patent/SK9682001A3/sk unknown
- 1999-12-22 AU AU22851/00A patent/AU2285100A/en not_active Abandoned
- 1999-12-22 TR TR2001/02009T patent/TR200102009T2/xx unknown
- 1999-12-22 CA CA002359390A patent/CA2359390A1/en not_active Abandoned
- 1999-12-22 HU HU0200520A patent/HUP0200520A3/hu unknown
- 1999-12-22 JP JP2000593308A patent/JP2002534467A/ja active Pending
- 1999-12-22 MX MXPA01006966A patent/MXPA01006966A/es unknown
- 1999-12-22 CN CN99815452A patent/CN1333685A/zh active Pending
- 1999-12-22 EP EP99966990A patent/EP1140099A1/de not_active Withdrawn
- 1999-12-22 BR BR9916888-0A patent/BR9916888A/pt not_active IP Right Cessation
- 1999-12-22 WO PCT/EP1999/010275 patent/WO2000041697A1/de not_active Application Discontinuation
- 1999-12-22 IL IL14414599A patent/IL144145A0/xx unknown
- 1999-12-22 PL PL99348916A patent/PL348916A1/xx not_active Application Discontinuation
- 1999-12-22 KR KR1020017008690A patent/KR20010101440A/ko not_active Application Discontinuation
-
2000
- 2000-01-06 AR ARP000100036A patent/AR029741A1/es unknown
-
2001
- 2001-07-03 ZA ZA200105473A patent/ZA200105473B/xx unknown
- 2001-07-10 NO NO20013408A patent/NO20013408L/no not_active Application Discontinuation
- 2001-07-10 BG BG105688A patent/BG105688A/xx unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7618959B2 (en) | 2002-11-05 | 2009-11-17 | Smithklinebeecham Corp | Antibacterial agents |
Also Published As
| Publication number | Publication date |
|---|---|
| BR9916888A (pt) | 2001-11-20 |
| DE19900544A1 (de) | 2000-07-13 |
| MXPA01006966A (es) | 2002-04-10 |
| WO2000041697A1 (de) | 2000-07-20 |
| BG105688A (en) | 2002-02-28 |
| NO20013408L (no) | 2001-08-21 |
| IL144145A0 (en) | 2002-05-23 |
| JP2002534467A (ja) | 2002-10-15 |
| AR029741A1 (es) | 2003-07-16 |
| NO20013408D0 (no) | 2001-07-10 |
| PL348916A1 (en) | 2002-06-17 |
| ZA200105473B (en) | 2002-10-03 |
| KR20010101440A (ko) | 2001-11-14 |
| SK9682001A3 (en) | 2002-03-05 |
| EP1140099A1 (de) | 2001-10-10 |
| HUP0200520A2 (hu) | 2002-07-29 |
| CN1333685A (zh) | 2002-01-30 |
| TR200102009T2 (tr) | 2002-01-21 |
| AU2285100A (en) | 2000-08-01 |
| HUP0200520A3 (en) | 2003-04-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |