IE43450B1 - New 6,7-benzomorphans, methods for their preparation and new intermediates - Google Patents
New 6,7-benzomorphans, methods for their preparation and new intermediatesInfo
- Publication number
- IE43450B1 IE43450B1 IE334/76A IE33476A IE43450B1 IE 43450 B1 IE43450 B1 IE 43450B1 IE 334/76 A IE334/76 A IE 334/76A IE 33476 A IE33476 A IE 33476A IE 43450 B1 IE43450 B1 IE 43450B1
- Authority
- IE
- Ireland
- Prior art keywords
- compound
- group
- benzomorphan
- hydroxy
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 50
- 239000000543 intermediate Substances 0.000 title abstract description 5
- 238000002360 preparation method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 127
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 8
- 230000003287 optical effect Effects 0.000 claims abstract description 6
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims abstract description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 4
- 125000000262 haloalkenyl group Chemical group 0.000 claims abstract description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 4
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 4
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 3
- 125000000304 alkynyl group Chemical group 0.000 claims abstract 2
- -1 tetrahydrofurfuryl Chemical group 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000002168 alkylating agent Substances 0.000 claims description 12
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 10
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 claims description 7
- AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 claims description 7
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 230000020176 deacylation Effects 0.000 claims description 3
- 238000005947 deacylation reaction Methods 0.000 claims description 3
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 claims description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- 229940051805 benzomorphan derivative analgesics Drugs 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 2
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 claims 2
- RZPFVRFSYMUDJO-UHFFFAOYSA-N 2h-naphthalen-1-one Chemical class C1=CC=C2C(=O)CC=CC2=C1 RZPFVRFSYMUDJO-UHFFFAOYSA-N 0.000 claims 1
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 1
- 125000006193 alkinyl group Chemical group 0.000 claims 1
- 239000007858 starting material Substances 0.000 abstract description 8
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 abstract description 2
- JRZGPXSSNPTNMA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-1-amine Chemical class C1=CC=C2C(N)CCCC2=C1 JRZGPXSSNPTNMA-UHFFFAOYSA-N 0.000 abstract 1
- 230000000202 analgesic effect Effects 0.000 abstract 1
- 239000003085 diluting agent Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 59
- 239000000243 solution Substances 0.000 description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 46
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 41
- 239000000155 melt Substances 0.000 description 39
- 239000000047 product Chemical group 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 20
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- 238000000354 decomposition reaction Methods 0.000 description 17
- NSLKFRGZLUIUKO-QWRGUYRKSA-N 6,7-benzomorphan Chemical class C1C2=CC=CC=C2[C@H]2CCN[C@@H]1C2 NSLKFRGZLUIUKO-QWRGUYRKSA-N 0.000 description 15
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 229940100198 alkylating agent Drugs 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 238000001953 recrystallisation Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 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 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical group OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229940093499 ethyl acetate Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- RRWASFFSKLPJMJ-ACMTZBLWSA-N (1S,9R)-10-azatricyclo[7.3.1.02,7]trideca-2,4,6-triene hydrochloride Chemical compound Cl.C1C2=CC=CC=C2[C@H]2CCN[C@@H]1C2 RRWASFFSKLPJMJ-ACMTZBLWSA-N 0.000 description 2
- LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- FOUKSGMTCVZXSB-UHFFFAOYSA-N methyl 4-(4-methoxyphenyl)-2,2-dimethyl-3-[(4-methylphenyl)sulfonylamino]butanoate Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)NC(C(C)(C)C(=O)OC)CC1=CC=C(OC)C=C1 FOUKSGMTCVZXSB-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- MWVHERVYWUIZAL-UHFFFAOYSA-N n-(6-methoxy-3,3-dimethyl-4-oxo-1,2-dihydronaphthalen-2-yl)-n,4-dimethylbenzenesulfonamide Chemical compound CC1(C)C(=O)C2=CC(OC)=CC=C2CC1N(C)S(=O)(=O)C1=CC=C(C)C=C1 MWVHERVYWUIZAL-UHFFFAOYSA-N 0.000 description 2
- KFGMJNPYOWPFJA-UHFFFAOYSA-N n-[4-(2-hydroxyethyl)-6-methoxy-3,3-dimethyl-2,4-dihydro-1h-naphthalen-2-yl]-n,4-dimethylbenzenesulfonamide Chemical compound CC1(C)C(CCO)C2=CC(OC)=CC=C2CC1N(C)S(=O)(=O)C1=CC=C(C)C=C1 KFGMJNPYOWPFJA-UHFFFAOYSA-N 0.000 description 2
- STSVYSHBLLDOCU-UHFFFAOYSA-N n-[4-(2-hydroxyethylidene)-6-methoxy-3,3-dimethyl-1,2-dihydronaphthalen-2-yl]-n,4-dimethylbenzenesulfonamide Chemical compound CC1(C)C(=CCO)C2=CC(OC)=CC=C2CC1N(C)S(=O)(=O)C1=CC=C(C)C=C1 STSVYSHBLLDOCU-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- AVMHMVJVHYGDOO-NSCUHMNNSA-N (e)-1-bromobut-2-ene Chemical compound C\C=C\CBr AVMHMVJVHYGDOO-NSCUHMNNSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- IPHFEAMSIOVYCA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene;hydrochloride Chemical compound Cl.C1=CC=C2CCCCC2=C1 IPHFEAMSIOVYCA-UHFFFAOYSA-N 0.000 description 1
- PZCCSJYFXQXAST-UHFFFAOYSA-N 1-(chloromethyl)cyclohexene Chemical compound ClCC1=CCCCC1 PZCCSJYFXQXAST-UHFFFAOYSA-N 0.000 description 1
- FALCMQXTWHPRIH-UHFFFAOYSA-N 2,3-dichloroprop-1-ene Chemical compound ClCC(Cl)=C FALCMQXTWHPRIH-UHFFFAOYSA-N 0.000 description 1
- VOHILFSOWRNVJJ-UHFFFAOYSA-N 2-(bromomethyl)oxolane Chemical compound BrCC1CCCO1 VOHILFSOWRNVJJ-UHFFFAOYSA-N 0.000 description 1
- ZLOSALLYJOFVIY-UHFFFAOYSA-N 2-chloroethylidenecyclohexane Chemical compound ClCC=C1CCCCC1 ZLOSALLYJOFVIY-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- AJKDUJRRWLQXHM-UHFFFAOYSA-N 3-bromocyclohexene Chemical compound BrC1CCCC=C1 AJKDUJRRWLQXHM-UHFFFAOYSA-N 0.000 description 1
- LOSZZUXZGRZMPO-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2,2-dimethyl-3-[methyl-(4-methylphenyl)sulfonylamino]butanoic acid Chemical compound C1=CC(OC)=CC=C1CC(C(C)(C)C(O)=O)N(C)S(=O)(=O)C1=CC=C(C)C=C1 LOSZZUXZGRZMPO-UHFFFAOYSA-N 0.000 description 1
- RQUJTAKZUOLREL-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2,2-dimethyl-3-[methyl-(4-methylphenyl)sulfonylamino]butanoyl chloride Chemical compound C1=CC(OC)=CC=C1CC(C(C)(C)C(Cl)=O)N(C)S(=O)(=O)C1=CC=C(C)C=C1 RQUJTAKZUOLREL-UHFFFAOYSA-N 0.000 description 1
- GQORAUKAWPYEBJ-UHFFFAOYSA-N C(=C)C1(CCCC2CC=CC=C12)O Chemical compound C(=C)C1(CCCC2CC=CC=C12)O GQORAUKAWPYEBJ-UHFFFAOYSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 241001522306 Serinus serinus Species 0.000 description 1
- 241000534944 Thia Species 0.000 description 1
- ACIAHEMYLLBZOI-ZZXKWVIFSA-N Unsaturated alcohol Chemical compound CC\C(CO)=C/C ACIAHEMYLLBZOI-ZZXKWVIFSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001339 alkali metal compounds Chemical class 0.000 description 1
- 238000007075 allylic rearrangement reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- ARNWQMJQALNBBV-UHFFFAOYSA-N lithium carbide Chemical compound [Li+].[Li+].[C-]#[C-] ARNWQMJQALNBBV-UHFFFAOYSA-N 0.000 description 1
- WMWSRIHFAVOHSW-UHFFFAOYSA-N lithium;ethane-1,2-diamine;ethyne Chemical compound [Li+].[C-]#C.NCCN WMWSRIHFAVOHSW-UHFFFAOYSA-N 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- KFAQETCQBMUQHT-UHFFFAOYSA-N methyl 3-amino-4-(4-methoxyphenyl)-2,2-dimethylbutanoate Chemical compound COC(=O)C(C)(C)C(N)CC1=CC=C(OC)C=C1 KFAQETCQBMUQHT-UHFFFAOYSA-N 0.000 description 1
- RMSNWMAHXBWAEI-UHFFFAOYSA-N methyl 4-(4-methoxyphenyl)-2,2-dimethyl-3-[methyl-(4-methylphenyl)sulfonylamino]butanoate Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(C)C(C(C)(C)C(=O)OC)CC1=CC=C(OC)C=C1 RMSNWMAHXBWAEI-UHFFFAOYSA-N 0.000 description 1
- ZPAPCUKKKOSLPZ-UHFFFAOYSA-N morphan Chemical compound C1CNC2CCCC1C2 ZPAPCUKKKOSLPZ-UHFFFAOYSA-N 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- DZBZDIXMFWPPTP-UHFFFAOYSA-N n-(4-ethenyl-4-hydroxy-6-methoxy-3,3-dimethyl-1,2-dihydronaphthalen-2-yl)-n,4-dimethylbenzenesulfonamide Chemical compound CC1(C)C(O)(C=C)C2=CC(OC)=CC=C2CC1N(C)S(=O)(=O)C1=CC=C(C)C=C1 DZBZDIXMFWPPTP-UHFFFAOYSA-N 0.000 description 1
- 239000004084 narcotic analgesic agent Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 1
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/26—Benzomorphans
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- One-Way And Automatic Clutches, And Combinations Of Different Clutches (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7891/75A GB1513961A (en) | 1975-02-25 | 1975-02-25 | 6,7-benzomorphans method for their preparation and intermediates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE43450L IE43450L (en) | 1976-08-25 |
| IE43450B1 true IE43450B1 (en) | 1981-02-25 |
Family
ID=9841801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE334/76A IE43450B1 (en) | 1975-02-25 | 1976-02-20 | New 6,7-benzomorphans, methods for their preparation and new intermediates |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US4128548A (en, 2012) |
| JP (2) | JPS51111550A (en, 2012) |
| AT (1) | AT360663B (en, 2012) |
| AU (1) | AU505939B2 (en, 2012) |
| BE (1) | BE838708A (en, 2012) |
| CA (1) | CA1080704A (en, 2012) |
| CH (2) | CH621115A5 (en, 2012) |
| DE (1) | DE2606267A1 (en, 2012) |
| DK (1) | DK76176A (en, 2012) |
| ES (1) | ES445494A1 (en, 2012) |
| FR (1) | FR2302092A1 (en, 2012) |
| GB (1) | GB1513961A (en, 2012) |
| HU (1) | HU173571B (en, 2012) |
| IE (1) | IE43450B1 (en, 2012) |
| IL (1) | IL48990A (en, 2012) |
| IT (1) | IT1057250B (en, 2012) |
| LU (1) | LU74431A1 (en, 2012) |
| NL (1) | NL7601924A (en, 2012) |
| PH (1) | PH12974A (en, 2012) |
| SE (1) | SE7602235L (en, 2012) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5381778A (en) * | 1976-12-27 | 1978-07-19 | Toshiharu Nakao | Cloth loop forming apparatus in steaming apparatus |
| NL7804509A (nl) * | 1978-04-26 | 1979-10-30 | Acf Chemiefarma Nv | Nieuwe 6,7-benzomorfanderivaten en zuuradditiezouten daarvan. |
| DE2828039A1 (de) * | 1978-06-26 | 1980-01-10 | Boehringer Sohn Ingelheim | 2-(2-alkoxyethyl)-2'-hydroxy-6,7-benzomorphane deren saeureadditionssalze diese enthaltende arzneimittel und verfahren zu deren herstellung |
| US4208523A (en) * | 1978-11-30 | 1980-06-17 | Sterling Drug Inc. | 11-Lower-alkyl-, 11-phenyl-lower-alkyl- and 11-cyclo-lower-alkyl-lower-alkyl-hexahydro-2,6-methano-3-benzazocines |
| NL7907800A (nl) | 1979-10-23 | 1981-04-27 | Acf Chemiefarma Nv | Nieuwe 6,7-benzomorfanderivaten en zuuradditiezouten daarvan, farmaceutische preparaten die een dergelijke verbinding bevatten, alsmede werkwijze voor het bereiden van deze verbindingen en de farmaceutische preparaten. |
| US5490436A (en) * | 1994-03-17 | 1996-02-13 | At&T Corp. | Liquid-chamber apparatus for active, dynamic balancing of rotating machinery |
| US7501433B2 (en) * | 2002-05-17 | 2009-03-10 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| WO2003097608A2 (en) | 2002-05-17 | 2003-11-27 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US7923454B2 (en) * | 2002-05-17 | 2011-04-12 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US8017622B2 (en) * | 2003-05-16 | 2011-09-13 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| TW200911796A (en) * | 2007-07-26 | 2009-03-16 | Vitae Pharmaceuticals Inc | Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| AR069207A1 (es) * | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| EP2220048B1 (en) * | 2007-11-16 | 2017-01-25 | Boehringer Ingelheim International GmbH | Aryl- and heteroarylcarbonyl derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use |
| CA2708303A1 (en) | 2007-12-11 | 2009-06-18 | Vitae Pharmaceuticals, Inc. | Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 |
| TW200934490A (en) * | 2008-01-07 | 2009-08-16 | Vitae Pharmaceuticals Inc | Lactam inhibitors of 11 &abgr;-hydroxysteroid dehydrogenase 1 |
| ATE531696T1 (de) * | 2008-02-12 | 2011-11-15 | Boehringer Ingelheim Int | Harnstoff-derivate von benzomorphanen, entsprechende gerüste, medikamente mit solchen verbindungen und ihre verwendung |
| CL2009001059A1 (es) | 2008-05-01 | 2010-11-12 | Boehringer Ingelheim Int | Compuestos derivados de 1,3-oxazin-2-ona-3,6 sustituidos, inhibidores de la actividad de la 11-beta-hidroxiesteroide deshidrogenasa i; composicion farmaceutica que los comprende; utiles en el tratamiento de enfermedades tales como diabetes mellitus, entre otras. |
| JP5711115B2 (ja) | 2008-05-13 | 2015-04-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンゾモルファン及び関連骨格のアリサイクリックカルボン酸誘導体、そのような化合物を含有する医薬及びその使用 |
| ES2432150T3 (es) | 2008-07-25 | 2013-12-02 | Boehringer Ingelheim International Gmbh | Inhibidores cíclicos de la 11 beta-hidroxiesteroide deshidrogenasa 1 |
| US8846668B2 (en) | 2008-07-25 | 2014-09-30 | Vitae Pharmaceuticals, Inc. | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| US8680093B2 (en) | 2009-04-30 | 2014-03-25 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2010139673A1 (en) | 2009-06-02 | 2010-12-09 | Boehringer Ingelheim International Gmbh | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2011011123A1 (en) | 2009-06-11 | 2011-01-27 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 based on the 1,3 -oxazinan- 2 -one structure |
| JP5456555B2 (ja) * | 2010-04-23 | 2014-04-02 | 株式会社マキタ | 電動工具 |
| WO2011159760A1 (en) | 2010-06-16 | 2011-12-22 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| WO2011161128A1 (en) | 2010-06-25 | 2011-12-29 | Boehringer Ingelheim International Gmbh | Azaspirohexanones as inhibitors of 11-beta-hsd1 for the treatment of metabolic disorders |
| MX2013004699A (es) | 2010-11-02 | 2013-05-22 | Boehringer Ingelheim Int | Combinaciones farmaceuticas para el tratamiento de trastornos metabolicos. |
| JP2014524438A (ja) | 2011-08-17 | 2014-09-22 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | インデノピリジン誘導体 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3138603A (en) * | 1958-10-31 | 1964-06-23 | Everette L May | New benzomorphans (methanobenzazocines) and preparation thereof |
| US3372165A (en) * | 1960-12-01 | 1968-03-05 | Sterling Drug Inc | 1, 2, 3, 4, 5, 6-hexahydro-8-hydroxy-2, 6-methano-3-benzazocine derivatives |
| NL156047B (nl) * | 1969-06-04 | 1978-03-15 | Acf Chemiefarma Nv | Werkwijze voor de bereiding van farmaceutische preparaten met analgetische en/of morfine-antagonistische werking, gevormde preparaten, alsmede werkwijze voor de bereiding van daartoe geschikte nieuwe 6,7-benzomorfanen. |
| IE34235B1 (en) * | 1969-06-04 | 1975-03-19 | Acf Chemiefarma Nv | 6,7-benzomorphans and their preparation |
| US3969468A (en) * | 1972-10-31 | 1976-07-13 | Kyowa Hakko Kogyo Co., Ltd. | 2-Amino-1,2,3,4-tetrahydronaphthalene derivatives |
| US4010164A (en) * | 1973-03-28 | 1977-03-01 | Boehringer Ingelheim Gmbh | N-(furyl-methyl)-2-hydroxy-5,9,9-trimethyl-benzomorphans and salts thereof |
| SU510999A3 (ru) * | 1973-10-27 | 1976-04-15 | К.Х.Берингер Зон, (Фирма) | Способ получени (метоксиметил-фурилметил)6,7-бензоморфанов илиморфинанов |
| US4087532A (en) * | 1974-03-09 | 1978-05-02 | Boehringer Ingelheim Gmbh | Analgesically useful 2-tetrahydrofurfuryl-5-lower alkyl-2-oxy-6,7-benzomorphans and salts thereof |
| US4032529A (en) * | 1974-09-20 | 1977-06-28 | Sterling Drug Inc. | Aminomethanobenzazocine intermediates |
-
1975
- 1975-02-25 GB GB7891/75A patent/GB1513961A/en not_active Expired
-
1976
- 1976-02-05 AU AU10856/76A patent/AU505939B2/en not_active Expired
- 1976-02-09 IL IL48990A patent/IL48990A/xx unknown
- 1976-02-17 DE DE19762606267 patent/DE2606267A1/de not_active Withdrawn
- 1976-02-17 US US05/658,739 patent/US4128548A/en not_active Expired - Lifetime
- 1976-02-19 BE BE164433A patent/BE838708A/xx unknown
- 1976-02-20 IE IE334/76A patent/IE43450B1/en unknown
- 1976-02-23 PH PH18131A patent/PH12974A/en unknown
- 1976-02-23 JP JP1875676A patent/JPS51111550A/ja active Pending
- 1976-02-24 IT IT67415/76A patent/IT1057250B/it active
- 1976-02-24 SE SE7602235A patent/SE7602235L/xx not_active Application Discontinuation
- 1976-02-24 ES ES445494A patent/ES445494A1/es not_active Expired
- 1976-02-24 DK DK76176*#A patent/DK76176A/da unknown
- 1976-02-24 FR FR7605083A patent/FR2302092A1/fr active Granted
- 1976-02-25 AT AT137276A patent/AT360663B/de not_active IP Right Cessation
- 1976-02-25 HU HU76CE1075A patent/HU173571B/hu unknown
- 1976-02-25 CH CH234376A patent/CH621115A5/de not_active IP Right Cessation
- 1976-02-25 JP JP51019022A patent/JPS51118767A/ja active Pending
- 1976-02-25 LU LU74431A patent/LU74431A1/xx unknown
- 1976-02-25 CA CA246,540A patent/CA1080704A/en not_active Expired
- 1976-02-25 NL NL7601924A patent/NL7601924A/xx not_active Application Discontinuation
-
1978
- 1978-07-28 US US05/928,862 patent/US4268673A/en not_active Expired - Lifetime
-
1979
- 1979-11-20 CH CH1036579A patent/CH623572A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU505939B2 (en) | 1979-12-06 |
| PH12974A (en) | 1979-10-24 |
| US4128548A (en) | 1978-12-05 |
| CH623572A5 (en, 2012) | 1981-06-15 |
| LU74431A1 (en, 2012) | 1976-08-13 |
| IE43450L (en) | 1976-08-25 |
| FR2302092B1 (en, 2012) | 1978-11-10 |
| DE2606267A1 (de) | 1976-09-30 |
| DK76176A (da) | 1976-08-26 |
| NL7601924A (nl) | 1976-08-27 |
| JPS51111550A (en) | 1976-10-01 |
| IL48990A (en) | 1980-01-31 |
| CH621115A5 (en, 2012) | 1981-01-15 |
| US4268673A (en) | 1981-05-19 |
| AT360663B (de) | 1981-01-26 |
| BE838708A (fr) | 1976-08-19 |
| HU173571B (hu) | 1979-06-28 |
| ES445494A1 (es) | 1977-11-01 |
| AU1085676A (en) | 1977-08-11 |
| IT1057250B (it) | 1982-03-10 |
| JPS51118767A (en) | 1976-10-18 |
| ATA137276A (de) | 1980-06-15 |
| CA1080704A (en) | 1980-07-01 |
| GB1513961A (en) | 1978-06-14 |
| SE7602235L (sv) | 1976-08-26 |
| FR2302092A1 (fr) | 1976-09-24 |
| IL48990A0 (en) | 1976-04-30 |
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