NO910187L - Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser. - Google Patents
Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser.Info
- Publication number
- NO910187L NO910187L NO91910187A NO910187A NO910187L NO 910187 L NO910187 L NO 910187L NO 91910187 A NO91910187 A NO 91910187A NO 910187 A NO910187 A NO 910187A NO 910187 L NO910187 L NO 910187L
- Authority
- NO
- Norway
- Prior art keywords
- indol
- ethylamine
- oxadiazol
- dimethyl
- ylmethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 61
- 238000002360 preparation method Methods 0.000 title claims description 23
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical class OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 title 1
- 239000000556 agonist Substances 0.000 claims abstract description 10
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 290
- 150000001875 compounds Chemical class 0.000 claims description 104
- 150000003839 salts Chemical class 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 150000002430 hydrocarbons Chemical class 0.000 claims description 20
- 239000004215 Carbon black (E152) Substances 0.000 claims description 18
- 229930195733 hydrocarbon Natural products 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 239000005864 Sulphur Substances 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 150000001450 anions Chemical class 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 238000010561 standard procedure Methods 0.000 claims description 7
- 239000002243 precursor Substances 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 4
- LUPGHCUZARGGAG-UHFFFAOYSA-N 5-[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]-1,2,4-oxadiazol-3-amine Chemical compound C1CN(C)CCC1C1=CNC2=CC=C(C=3ON=C(N)N=3)C=C12 LUPGHCUZARGGAG-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 238000007126 N-alkylation reaction Methods 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- CQXMPRCDEFWGEN-UHFFFAOYSA-N n-[4-[[5-[[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]methyl]phenyl]methanesulfonamide Chemical compound C1CN(C)CCC1C(C1=C2)=CNC1=CC=C2CC1=NC(CC=2C=CC(NS(C)(=O)=O)=CC=2)=NO1 CQXMPRCDEFWGEN-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- SFVYCZXNJHFLNP-UHFFFAOYSA-N 5-[[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-amine Chemical compound C1CN(C)CCC1C(C1=C2)=CNC1=CC=C2CC1=NC(N)=NO1 SFVYCZXNJHFLNP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 3
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- MPSSFKDXUNOCMC-UHFFFAOYSA-N 1-[4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]phenyl]-n-methylmethanesulfonamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1C1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 MPSSFKDXUNOCMC-UHFFFAOYSA-N 0.000 claims description 2
- VOQRRSFSAOOBOA-UHFFFAOYSA-N 1-[4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]piperazin-1-yl]ethanone Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1N1CCN(C(C)=O)CC1 VOQRRSFSAOOBOA-UHFFFAOYSA-N 0.000 claims description 2
- IMBUWDPVLHNYMC-UHFFFAOYSA-N 1-tert-butyl-3-[2-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]ethyl]urea Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC1=NC(CCNC(=O)NC(C)(C)C)=NO1 IMBUWDPVLHNYMC-UHFFFAOYSA-N 0.000 claims description 2
- PGGBQIXTFVYDAU-UHFFFAOYSA-N 2-[5-(3-benzyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C(ON=1)=NC=1CC1=CC=CC=C1 PGGBQIXTFVYDAU-UHFFFAOYSA-N 0.000 claims description 2
- LSUAPUGYEULDQN-UHFFFAOYSA-N 2-[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1C1CC1 LSUAPUGYEULDQN-UHFFFAOYSA-N 0.000 claims description 2
- RGZGVSMFNKBYQY-UHFFFAOYSA-N 2-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]ethanamine Chemical compound CCC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 RGZGVSMFNKBYQY-UHFFFAOYSA-N 0.000 claims description 2
- FDPKHZFSVDEEFR-UHFFFAOYSA-N 2-[5-(3-phenyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1C1=CC=CC=C1 FDPKHZFSVDEEFR-UHFFFAOYSA-N 0.000 claims description 2
- PKBMHXUBNRYPMY-UHFFFAOYSA-N 2-[5-(5-benzyl-1,2,4-oxadiazol-3-yl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(N=1)=NOC=1CC1=CC=CC=C1 PKBMHXUBNRYPMY-UHFFFAOYSA-N 0.000 claims description 2
- CXOIDKMODXFHCK-UHFFFAOYSA-N 2-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-1h-indol-3-yl]ethanamine Chemical compound O1C(C)=NC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 CXOIDKMODXFHCK-UHFFFAOYSA-N 0.000 claims description 2
- NAWLGGCQEZUAJT-UHFFFAOYSA-N 2-[5-[(3-benzyl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1CC1=CC=CC=C1 NAWLGGCQEZUAJT-UHFFFAOYSA-N 0.000 claims description 2
- NHIRYTRRCNWYFT-UHFFFAOYSA-N 2-[5-[(3-benzyl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(ON=1)=NC=1CC1=CC=CC=C1 NHIRYTRRCNWYFT-UHFFFAOYSA-N 0.000 claims description 2
- PHNPQGKBBZNFFK-UHFFFAOYSA-N 2-[5-[(3-naphthalen-1-yl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=CC=C2C(C=3N=C(ON=3)CC3=CC=C4NC=C(C4=C3)CCN)=CC=CC2=C1 PHNPQGKBBZNFFK-UHFFFAOYSA-N 0.000 claims description 2
- DUCJXOYLGYOOQB-UHFFFAOYSA-N 2-[5-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(ON=1)=NC=1C1=CC=CC=C1 DUCJXOYLGYOOQB-UHFFFAOYSA-N 0.000 claims description 2
- LCMKXAZDWQVTEJ-UHFFFAOYSA-N 2-[5-[(5-benzyl-1,2,4-oxadiazol-3-yl)methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(N=1)=NOC=1CC1=CC=CC=C1 LCMKXAZDWQVTEJ-UHFFFAOYSA-N 0.000 claims description 2
- IEJZWIUEFHBSOU-UHFFFAOYSA-N 2-[5-[(5-benzyl-1,2,4-oxadiazol-3-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(N=1)=NOC=1CC1=CC=CC=C1 IEJZWIUEFHBSOU-UHFFFAOYSA-N 0.000 claims description 2
- FEBZQFFWELBCOG-UHFFFAOYSA-N 2-[5-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound O1C(C)=NC(CC=2C=C3C(CCN)=CNC3=CC=2)=N1 FEBZQFFWELBCOG-UHFFFAOYSA-N 0.000 claims description 2
- KYUWHJMADOFUBT-UHFFFAOYSA-N 2-[5-[2-(3-benzyl-1,2,4-oxadiazol-5-yl)ethyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CCC(ON=1)=NC=1CC1=CC=CC=C1 KYUWHJMADOFUBT-UHFFFAOYSA-N 0.000 claims description 2
- SCFZGOGBRPRNPV-UHFFFAOYSA-N 2-[5-[2-(3-benzyl-1,2,4-oxadiazol-5-yl)ethyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CCC(ON=1)=NC=1CC1=CC=CC=C1 SCFZGOGBRPRNPV-UHFFFAOYSA-N 0.000 claims description 2
- WBZVRZYJUXWCRS-UHFFFAOYSA-N 2-[5-[2-[3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]ethyl]-1h-indol-3-yl]ethanamine Chemical compound C1=CC(OC)=CC=C1CC1=NOC(CCC=2C=C3C(CCN)=CNC3=CC=2)=N1 WBZVRZYJUXWCRS-UHFFFAOYSA-N 0.000 claims description 2
- OVCUAXXAZOYIFP-UHFFFAOYSA-N 2-[5-[3-(2-phenylethyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1CCC1=CC=CC=C1 OVCUAXXAZOYIFP-UHFFFAOYSA-N 0.000 claims description 2
- JTBDYCCVUAQYMO-UHFFFAOYSA-N 2-[5-[3-(3-benzyl-1,2,4-oxadiazol-5-yl)propyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CCCC(ON=1)=NC=1CC1=CC=CC=C1 JTBDYCCVUAQYMO-UHFFFAOYSA-N 0.000 claims description 2
- HSJQSSUOMJZTMK-UHFFFAOYSA-N 2-[5-[3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)propyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CCCC(ON=1)=NC=1C1CC1 HSJQSSUOMJZTMK-UHFFFAOYSA-N 0.000 claims description 2
- FZVHHUSZLLUIQC-UHFFFAOYSA-N 2-[5-[3-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]-1h-indol-3-yl]ethanamine Chemical compound CC1=NOC(CCCC=2C=C3C(CCN)=CNC3=CC=2)=N1 FZVHHUSZLLUIQC-UHFFFAOYSA-N 0.000 claims description 2
- NJDHGOXGGNXAKI-UHFFFAOYSA-N 2-[5-[3-(3-phenylpropyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1CCCC1=CC=CC=C1 NJDHGOXGGNXAKI-UHFFFAOYSA-N 0.000 claims description 2
- NPFRJMBPAZUERU-UHFFFAOYSA-N 2-[5-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C1=NC(CN)=NO1 NPFRJMBPAZUERU-UHFFFAOYSA-N 0.000 claims description 2
- ZBVQOYFWQDPVBU-UHFFFAOYSA-N 2-[5-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound COCC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 ZBVQOYFWQDPVBU-UHFFFAOYSA-N 0.000 claims description 2
- YSBPVPHNOKZUKE-UHFFFAOYSA-N 2-[5-[3-[(2-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound COC1=CC=CC=C1CC1=NOC(C=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 YSBPVPHNOKZUKE-UHFFFAOYSA-N 0.000 claims description 2
- TWZLBEKNARALNH-UHFFFAOYSA-N 2-[5-[3-[(2-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound COC1=CC=CC=C1CC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 TWZLBEKNARALNH-UHFFFAOYSA-N 0.000 claims description 2
- XYSVDZDGDYOEQP-UHFFFAOYSA-N 2-[5-[3-[(3-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound COC1=CC=CC(CC=2N=C(ON=2)C=2C=C3C(CCN)=CNC3=CC=2)=C1 XYSVDZDGDYOEQP-UHFFFAOYSA-N 0.000 claims description 2
- LJFAPKDDNIXRTD-UHFFFAOYSA-N 2-[5-[3-[(4-methylsulfonylphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 LJFAPKDDNIXRTD-UHFFFAOYSA-N 0.000 claims description 2
- NISBLVDKMALBFA-UHFFFAOYSA-N 2-[5-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]ethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C1=NC(CCN)=NO1 NISBLVDKMALBFA-UHFFFAOYSA-N 0.000 claims description 2
- MVCDNIJSCRIQST-UHFFFAOYSA-N 2-[5-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]ethylurea Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C1=NC(CCNC(N)=O)=NO1 MVCDNIJSCRIQST-UHFFFAOYSA-N 0.000 claims description 2
- RJQWPRYMOKNGFR-UHFFFAOYSA-N 2-[5-[3-[[4-(trifluoromethyl)phenyl]methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1CC1=CC=C(C(F)(F)F)C=C1 RJQWPRYMOKNGFR-UHFFFAOYSA-N 0.000 claims description 2
- AWKHPNLMHRTDEQ-UHFFFAOYSA-N 2-[5-[[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC1=NC(CN)=NO1 AWKHPNLMHRTDEQ-UHFFFAOYSA-N 0.000 claims description 2
- NROOPDGYHXQHJT-UHFFFAOYSA-N 2-[5-[[3-[(2-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]ethanamine Chemical compound COC1=CC=CC=C1CC1=NOC(CC=2C=C3C(CCN)=CNC3=CC=2)=N1 NROOPDGYHXQHJT-UHFFFAOYSA-N 0.000 claims description 2
- JCZWGZKYZYBIIG-UHFFFAOYSA-N 2-[5-[[3-[(6-methoxypyridin-3-yl)methyl]-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=NC(OC)=CC=C1CC1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 JCZWGZKYZYBIIG-UHFFFAOYSA-N 0.000 claims description 2
- KFICIUZZUVCGKV-UHFFFAOYSA-N 2-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]acetamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC1=NC(CC(N)=O)=NO1 KFICIUZZUVCGKV-UHFFFAOYSA-N 0.000 claims description 2
- QPFQAMAECLOAMI-UHFFFAOYSA-N 2-[5-[[3-[4-(benzenesulfonyl)piperazin-1-yl]-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1N(CC1)CCN1S(=O)(=O)C1=CC=CC=C1 QPFQAMAECLOAMI-UHFFFAOYSA-N 0.000 claims description 2
- PRTCSIDNPRTJHA-UHFFFAOYSA-N 4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 PRTCSIDNPRTJHA-UHFFFAOYSA-N 0.000 claims description 2
- SEQRRDDBAQJBTP-UHFFFAOYSA-N 4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]-n-methylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCN1C1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 SEQRRDDBAQJBTP-UHFFFAOYSA-N 0.000 claims description 2
- PXRPVIKQMBGGBX-UHFFFAOYSA-N 4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]benzamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1C1=CC=C(C(N)=O)C=C1 PXRPVIKQMBGGBX-UHFFFAOYSA-N 0.000 claims description 2
- KPULPRRFVSBRHP-UHFFFAOYSA-N 4-[[5-[3-(2-aminoethyl)-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]methyl]-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1CC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 KPULPRRFVSBRHP-UHFFFAOYSA-N 0.000 claims description 2
- HUZDZSZTHSEWGI-UHFFFAOYSA-N 4-[[5-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]methyl]-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1CC1=NOC(C=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 HUZDZSZTHSEWGI-UHFFFAOYSA-N 0.000 claims description 2
- JUIAOPBIMMONAG-UHFFFAOYSA-N 4-[[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]methyl]-n-methylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1CC1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 JUIAOPBIMMONAG-UHFFFAOYSA-N 0.000 claims description 2
- RZROEUJADIXUOQ-UHFFFAOYSA-N 4-[[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]methyl]benzamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1CC1=CC=C(C(N)=O)C=C1 RZROEUJADIXUOQ-UHFFFAOYSA-N 0.000 claims description 2
- QMDXYKSJNYUFML-UHFFFAOYSA-N 5-[2-[3-(2-aminoethyl)-1h-indol-5-yl]ethyl]-n,n-dimethyl-1,2,4-oxadiazol-3-amine Chemical compound CN(C)C1=NOC(CCC=2C=C3C(CCN)=CNC3=CC=2)=N1 QMDXYKSJNYUFML-UHFFFAOYSA-N 0.000 claims description 2
- CVSXIEGQYNXATH-UHFFFAOYSA-N 5-[2-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]ethyl]-1,2,4-oxadiazol-3-amine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CCC1=NC(N)=NO1 CVSXIEGQYNXATH-UHFFFAOYSA-N 0.000 claims description 2
- AZPGZTOVCHWLMC-UHFFFAOYSA-N 5-[3-(2-aminoethyl)-1h-indol-5-yl]-1,2,4-oxadiazol-3-amine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C1=NC(N)=NO1 AZPGZTOVCHWLMC-UHFFFAOYSA-N 0.000 claims description 2
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- 150000003511 tertiary amides Chemical class 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000004867 thiadiazoles Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB909001018A GB9001018D0 (en) | 1990-01-17 | 1990-01-17 | Therapeutic agents |
GB909008587A GB9008587D0 (en) | 1990-04-17 | 1990-04-17 | Therapeutic agents |
Publications (2)
Publication Number | Publication Date |
---|---|
NO910187D0 NO910187D0 (no) | 1991-01-16 |
NO910187L true NO910187L (no) | 1991-07-18 |
Family
ID=26296509
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO91910187A NO910187L (no) | 1990-01-17 | 1991-01-16 | Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser. |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP0438230B1 (fi) |
JP (1) | JPH06100558A (fi) |
KR (1) | KR910014373A (fi) |
CN (1) | CN1053429A (fi) |
AT (1) | ATE152110T1 (fi) |
AU (1) | AU6944091A (fi) |
CA (1) | CA2034189A1 (fi) |
CS (1) | CS8691A2 (fi) |
DE (1) | DE69125731T2 (fi) |
FI (1) | FI910228A (fi) |
HU (1) | HU910128D0 (fi) |
IE (1) | IE910139A1 (fi) |
IL (1) | IL96891A0 (fi) |
NO (1) | NO910187L (fi) |
PT (1) | PT96477A (fi) |
Families Citing this family (70)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0619805T3 (da) * | 1991-11-25 | 2000-06-05 | Pfizer | 5-(Hetero-eller carbocyclylamino)-indolderivater, deres fremstilling og anvendelse som 5-HT1-agonister |
US5409941A (en) * | 1992-02-03 | 1995-04-25 | Pfizer Inc. | 5-heteroyl indole derivatives |
US5233050A (en) * | 1992-02-07 | 1993-08-03 | Merck & Co., Inc. | Antimigraine alkyl indole |
TW288010B (fi) * | 1992-03-05 | 1996-10-11 | Pfizer | |
GB9207396D0 (en) * | 1992-04-03 | 1992-05-13 | Merck Sharp & Dohme | Therapeutic agents |
US6380233B1 (en) | 1992-04-07 | 2002-04-30 | Pfizer Inc | Indole derivatives as 5-HT1 agonists |
RU2101283C1 (ru) | 1992-04-07 | 1998-01-10 | Пфайзер Инк. | Производные индола или их фармацевтически приемлемые соли |
ATE148465T1 (de) * | 1992-04-10 | 1997-02-15 | Pfizer | Acylaminoindolderivate als 5-ht1 agonisten |
GB9207930D0 (en) * | 1992-04-10 | 1992-05-27 | Pfizer Ltd | Indoles |
GB9208161D0 (en) * | 1992-04-14 | 1992-05-27 | Pfizer Ltd | Indoles |
GB9208463D0 (en) * | 1992-04-16 | 1992-06-03 | Merck Sharp & Dohme | Therapeutic agents |
GB9211277D0 (en) | 1992-05-28 | 1992-07-15 | Glaxo Group Inc | Pharmaceutical compositions |
TW251284B (fi) * | 1992-11-02 | 1995-07-11 | Pfizer | |
GB9226537D0 (en) * | 1992-12-21 | 1993-02-17 | Smithkline Beecham Plc | Compounds |
ES2070087B1 (es) * | 1993-08-13 | 1996-02-16 | Pfizer | Derivados de indol |
JP2860603B2 (ja) * | 1993-08-31 | 1999-02-24 | ファイザー・インク. | 5−アリールインドール誘導体 |
JPH10501212A (ja) * | 1994-05-19 | 1998-02-03 | メルク シヤープ エンド ドーム リミテツド | 5−ht▲下1d▼−アルファ作働薬としてのインドール−3−イルアルキルのピペラジン、ピペリジンおよびテトラヒドロピリジン誘導体 |
GB9410031D0 (en) * | 1994-05-19 | 1994-07-06 | Merck Sharp & Dohme | Therapeutic agents |
US5552402A (en) * | 1994-05-19 | 1996-09-03 | Merck, Sharp & Dohme Ltd. | Five-membered heteroaromatic compounds as 5-HT receptor agonists |
WO1995032965A1 (fr) * | 1994-06-01 | 1995-12-07 | Yamanouchi Pharmaceutical Co. Ltd. | Derive de l'oxadiazole et composition medicinale a base de ce dernier |
US5597826A (en) | 1994-09-14 | 1997-01-28 | Pfizer Inc. | Compositions containing sertraline and a 5-HT1D receptor agonist or antagonist |
US5521196A (en) * | 1994-10-05 | 1996-05-28 | Eli Lilly And Company | 5-HT1F agonists for the treatment of migraine |
GB9423460D0 (en) * | 1994-11-21 | 1995-01-11 | Merck Sharp & Dohme | Therapeutic agents |
US5521197A (en) * | 1994-12-01 | 1996-05-28 | Eli Lilly And Company | 3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists |
GB9501865D0 (en) * | 1995-01-31 | 1995-03-22 | Merck Sharp & Dohme | Therapeutic agents |
CZ288897A3 (cs) * | 1995-03-20 | 1998-02-18 | Eli Lilly And Company | V poloze 5-substituovaný 3-(1,2,3,6-tetrahydropyridin-4-yl)indol a 3-(piperidin-4-yl)indol a farmaceutický prostředek, který je obsahuje |
US5942536A (en) * | 1995-10-10 | 1999-08-24 | Eli Lilly And Company | N- 2-substituted-3-(2-aminoethyl)-1H-indol-5-YL!-Amides: new 5-HT1F agonists |
WO1997016446A1 (en) * | 1995-11-02 | 1997-05-09 | Merck Sharp & Dohme Limited | Bicyclic heteroaryl-alkylene-(homo)piperazinones and thione analogues thereof, their preparation and their use as selective agonists of 5-ht1-like receptors |
GB9523250D0 (en) * | 1995-11-14 | 1996-01-17 | Merck Sharp & Dohme | Therapeutic agents |
GB9523583D0 (en) * | 1995-11-17 | 1996-01-17 | Merck Sharp & Dohme | Therapeutic agents |
US5998438A (en) * | 1996-11-26 | 1999-12-07 | Allelix Biopharmaceuticals, Inc. | 5-cyclo indole compounds |
US7189753B1 (en) | 1997-11-06 | 2007-03-13 | Cady Roger K | Preemptive prophylaxis of migraine |
AU4831899A (en) | 1998-06-30 | 2000-01-17 | Eli Lilly And Company | 5-HT1F agonists |
US5994352A (en) * | 1998-11-13 | 1999-11-30 | Pfizer Inc. | 5-arylindole derivatives |
US6645990B2 (en) | 2000-08-15 | 2003-11-11 | Amgen Inc. | Thiazolyl urea compounds and methods of uses |
US7390813B1 (en) | 2001-12-21 | 2008-06-24 | Xenon Pharmaceuticals Inc. | Pyridylpiperazines and aminonicotinamides and their use as therapeutic agents |
US6974818B2 (en) * | 2002-03-01 | 2005-12-13 | Euro-Celtique S.A. | 1,2,5-thiadiazol-3-YL-piperazine therapeutic agents useful for treating pain |
WO2003099206A2 (en) | 2002-05-21 | 2003-12-04 | Bristol-Myers Squibb Company | Indole compounds useful as impdh inhibitors |
CA2490254C (en) | 2002-06-21 | 2011-11-01 | Suven Life Sciences Limited | Novel tetracyclic arylsulfonyl indoles having serotonin receptor affinity useful as therapeutic agents, process for their preparation and pharmaceutical compositions containing them |
DK1537113T5 (da) | 2002-06-21 | 2011-01-10 | Suven Life Sciences Ltd | Arylalkylindoler med serotoninreceptoraffinitet anvendelige som terapeutiske midler, fremgangsmåde til fremstilling heraf og farmaceutiske sammensætninger indeholdende disse |
AR040847A1 (es) | 2002-08-09 | 2005-04-20 | Astrazeneca Ab | 1,2,4-oxadiazoles como moduladores de receptores de glutamato metabotropicos, para el tratamiento de desordenes neurologicos y psiquiatricos |
AU2003264018A1 (en) | 2002-08-09 | 2004-02-25 | Astrazeneca Ab | Compounds having an activity at metabotropic glutamate receptors |
AR041508A1 (es) * | 2002-08-09 | 2005-05-18 | Astra Ab | Compuestos con actividad en los receptores de glutamato metabotropicos |
BRPI0315958B8 (pt) | 2002-11-28 | 2021-05-25 | Suven Life Sciences Ltd | composto, composição farmacêutica, processo para a preparação de um composto, novos intermediários e uso do composto |
NZ572186A (en) | 2002-11-28 | 2010-02-26 | Suven Life Sciences Ltd | N-arylsulfonyl-3-substituted indoles having serotonin receptor affinity, process for their preparation and pharmaceutical composition containing them |
PT1581538E (pt) | 2002-12-18 | 2007-05-31 | Suven Life Sciences Ltd | Indolos tetracíclicos substituidos na posição 3 que possuem afinidade pelo receptor de serotonina. |
ES2375134T3 (es) | 2003-07-30 | 2012-02-27 | Xenon Pharmaceuticals Inc. | Derivados de piperazina y su uso como agentes terapéuticos. |
US20070135485A1 (en) * | 2003-10-22 | 2007-06-14 | Gillig James R | Novel mch receptor antagonists |
WO2005077373A2 (en) * | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
WO2005077368A2 (en) * | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
WO2006034341A2 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives for inhibiting human stearoyl-coa-desaturase |
TW200626138A (en) | 2004-09-20 | 2006-08-01 | Xenon Pharmaceuticals Inc | Heterocyclic derivatives and their use as therapeutic agents |
MX2007003318A (es) | 2004-09-20 | 2007-05-18 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como agentes terapeuticos. |
CA2580857A1 (en) | 2004-09-20 | 2006-09-28 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
WO2006034441A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
WO2006034440A2 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
JP5094398B2 (ja) | 2004-09-20 | 2012-12-12 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | 複素環式誘導体およびステアロイル−CoAデサチュラーゼのメディエータとしてのそれらの使用 |
KR20130136010A (ko) | 2005-04-13 | 2013-12-11 | 네우렉슨 인코포레이티드 | Nos 저해 활성을 갖는 치환된 인돌 화합물 |
AU2006343359A1 (en) | 2005-06-03 | 2007-11-15 | Xenon Pharmaceuticals Inc. | Aminothiazole derivatives as human stearoyl-coa desaturase inhibitors |
JP5350219B2 (ja) | 2006-04-13 | 2013-11-27 | ニューラクソン,インコーポレーテッド | Nos阻害活性を有する1,5および3,6−置換インドール化合物 |
MX2009002019A (es) | 2006-08-24 | 2009-03-09 | Novartis Ag | Derivados de 2-(pirazin-2-il)-tiazol y 2-(1h-pirazol-3-il)-tiazol asi como compuestos relacionados como inhibidores de la estearoil-coa-desaturasa (scd) para el tratamiento de trastornos metabolicos, cardiovasculares, y otros. |
NZ586082A (en) | 2007-11-16 | 2013-03-28 | Neuraxon Inc | Indole compounds and methods for treating visceral pain |
AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
WO2011133920A1 (en) | 2010-04-23 | 2011-10-27 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
US8759380B2 (en) | 2011-04-22 | 2014-06-24 | Cytokinetics, Inc. | Certain heterocycles, compositions thereof, and methods for their use |
JP2018507235A (ja) * | 2015-03-04 | 2018-03-15 | メディベイション テクノロジーズ エルエルシー | ステロール調節エレメント結合タンパク質(srebp)阻害剤 |
US10183015B2 (en) | 2015-03-04 | 2019-01-22 | Medivation Technologies Llc | Heterocyclic compounds and methods of use |
EP3592739A1 (en) | 2017-03-07 | 2020-01-15 | H. Hoffnabb-La Roche Ag | Oxadiazole transient receptor potential channel inhibitors |
US10710994B2 (en) | 2018-03-19 | 2020-07-14 | Genentech, Inc. | Oxadiazole transient receptor potential channel inhibitors |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4833153A (en) * | 1985-11-08 | 1989-05-23 | Glaxo Group Limited | Indole derivatives |
GB8724912D0 (en) * | 1987-10-23 | 1987-11-25 | Wellcome Found | Indole derivatives |
NZ227841A (en) * | 1988-02-12 | 1991-08-27 | Merck Sharp & Dohme | Heterocyclic compounds with at least two non-condensed five membered rings and pharmaceutical compositions |
-
1991
- 1991-01-07 IL IL96891A patent/IL96891A0/xx unknown
- 1991-01-10 AT AT91300180T patent/ATE152110T1/de not_active IP Right Cessation
- 1991-01-10 DE DE69125731T patent/DE69125731T2/de not_active Expired - Fee Related
- 1991-01-10 EP EP91300180A patent/EP0438230B1/en not_active Expired - Lifetime
- 1991-01-15 PT PT96477A patent/PT96477A/pt not_active Application Discontinuation
- 1991-01-15 CA CA002034189A patent/CA2034189A1/en not_active Abandoned
- 1991-01-16 CS CS9186A patent/CS8691A2/cs unknown
- 1991-01-16 AU AU69440/91A patent/AU6944091A/en not_active Abandoned
- 1991-01-16 IE IE013991A patent/IE910139A1/en unknown
- 1991-01-16 NO NO91910187A patent/NO910187L/no unknown
- 1991-01-16 HU HU91128A patent/HU910128D0/hu unknown
- 1991-01-16 FI FI910228A patent/FI910228A/fi unknown
- 1991-01-16 KR KR1019910000593A patent/KR910014373A/ko not_active Application Discontinuation
- 1991-01-17 CN CN91100380A patent/CN1053429A/zh active Pending
- 1991-01-17 JP JP3216736A patent/JPH06100558A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
IE910139A1 (en) | 1991-07-17 |
HU910128D0 (en) | 1991-08-28 |
PT96477A (pt) | 1991-10-15 |
CN1053429A (zh) | 1991-07-31 |
ATE152110T1 (de) | 1997-05-15 |
EP0438230A3 (en) | 1992-02-12 |
DE69125731D1 (de) | 1997-05-28 |
CA2034189A1 (en) | 1991-07-18 |
FI910228A0 (fi) | 1991-01-16 |
IL96891A0 (en) | 1992-03-29 |
DE69125731T2 (de) | 1997-11-27 |
KR910014373A (ko) | 1991-08-31 |
EP0438230A2 (en) | 1991-07-24 |
AU6944091A (en) | 1991-07-25 |
EP0438230B1 (en) | 1997-04-23 |
FI910228A (fi) | 1991-07-18 |
CS8691A2 (en) | 1991-09-15 |
JPH06100558A (ja) | 1994-04-12 |
NO910187D0 (no) | 1991-01-16 |
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