HU176479B - Process for preparing new n-/methoxymethyl-furyl-methyl/-6,7-benzomorphans and -morphians further acid addition snlts thereof - Google Patents
Process for preparing new n-/methoxymethyl-furyl-methyl/-6,7-benzomorphans and -morphians further acid addition snlts thereof Download PDFInfo
- Publication number
- HU176479B HU176479B HU74BO1521A HUBO001521A HU176479B HU 176479 B HU176479 B HU 176479B HU 74BO1521 A HU74BO1521 A HU 74BO1521A HU BO001521 A HUBO001521 A HU BO001521A HU 176479 B HU176479 B HU 176479B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- methyl
- methoxymethyl
- hydrogen
- compound
- Prior art date
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- 239000002253 acid Substances 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- -1 1,4-butylene Chemical group 0.000 claims description 76
- 238000000034 method Methods 0.000 claims description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 50
- 230000008569 process Effects 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 230000002829 reductive effect Effects 0.000 claims description 17
- 239000004480 active ingredient Substances 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 4
- 229910052987 metal hydride Inorganic materials 0.000 claims description 4
- 150000004681 metal hydrides Chemical class 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000003810 morphinanes Chemical class 0.000 claims description 3
- 239000011877 solvent mixture Substances 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 230000015556 catabolic process Effects 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 238000006731 degradation reaction Methods 0.000 claims description 2
- 238000011161 development Methods 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 230000001035 methylating effect Effects 0.000 claims description 2
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical compound C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 claims description 2
- 239000012038 nucleophile Substances 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims description 2
- 229910052623 talc Inorganic materials 0.000 claims description 2
- 125000005208 trialkylammonium group Chemical group 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 3
- 239000012153 distilled water Substances 0.000 claims 2
- 239000011780 sodium chloride Substances 0.000 claims 2
- 239000002511 suppository base Substances 0.000 claims 2
- 238000007126 N-alkylation reaction Methods 0.000 claims 1
- 230000006179 O-acylation Effects 0.000 claims 1
- 150000003868 ammonium compounds Chemical class 0.000 claims 1
- 239000003708 ampul Substances 0.000 claims 1
- 150000001450 anions Chemical class 0.000 claims 1
- 238000007257 deesterification reaction Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000002516 radical scavenger Substances 0.000 claims 1
- 239000000730 antalgic agent Substances 0.000 abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 229940035676 analgesics Drugs 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 75
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
- 239000000243 solution Substances 0.000 description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 230000009467 reduction Effects 0.000 description 25
- 239000012280 lithium aluminium hydride Substances 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- 239000002585 base Substances 0.000 description 23
- 238000002844 melting Methods 0.000 description 22
- 230000008018 melting Effects 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 239000007795 chemical reaction product Substances 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- SGCRYWIPJCJOGF-UHFFFAOYSA-N 3-(methoxymethyl)furan-2-carbonyl chloride Chemical class COCC=1C=COC=1C(Cl)=O SGCRYWIPJCJOGF-UHFFFAOYSA-N 0.000 description 10
- 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 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- XPZAGMPKJYYADL-UHFFFAOYSA-N 3-(chloromethyl)-2-(methoxymethyl)furan Chemical compound COCC=1OC=CC=1CCl XPZAGMPKJYYADL-UHFFFAOYSA-N 0.000 description 7
- 239000002026 chloroform extract Substances 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- XUCHPONFCMIULD-UHFFFAOYSA-N 2-(methoxymethyl)furan-3-carbonyl chloride Chemical compound COCC=1OC=CC=1C(Cl)=O XUCHPONFCMIULD-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 5
- 125000005521 carbonamide group Chemical group 0.000 description 5
- 239000008298 dragée Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229960005181 morphine Drugs 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 2
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 125000004970 halomethyl group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000005956 quaternization reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- HADKRTWCOYPCPH-UHFFFAOYSA-M trimethylphenylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C1=CC=CC=C1 HADKRTWCOYPCPH-UHFFFAOYSA-M 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- UVROAJFELBNMRA-UHFFFAOYSA-N (1-chloro-2-phenylethyl)benzene Chemical compound C=1C=CC=CC=1C(Cl)CC1=CC=CC=C1 UVROAJFELBNMRA-UHFFFAOYSA-N 0.000 description 1
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- 235000005985 organic acids Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
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- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732354002 DE2354002A1 (de) | 1973-10-27 | 1973-10-27 | Neue n-(methoxymethyl-furylmethyl)6,7-benzomorphane und -morphinane, deren saeureadditionssalze, ihre verwendung als arzneimittel und verfahren zu deren herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU176479B true HU176479B (en) | 1981-03-28 |
Family
ID=5896658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU74BO1521A HU176479B (en) | 1973-10-27 | 1974-10-25 | Process for preparing new n-/methoxymethyl-furyl-methyl/-6,7-benzomorphans and -morphians further acid addition snlts thereof |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US3981874A (en, 2012) |
| JP (1) | JPS5738590B2 (en, 2012) |
| AT (6) | AT335634B (en, 2012) |
| BE (1) | BE821505A (en, 2012) |
| BG (3) | BG27901A3 (en, 2012) |
| CA (1) | CA1056377A (en, 2012) |
| CH (6) | CH609340A5 (en, 2012) |
| CS (3) | CS171195B2 (en, 2012) |
| DD (1) | DD115909A5 (en, 2012) |
| DE (1) | DE2354002A1 (en, 2012) |
| DK (1) | DK138325C (en, 2012) |
| ES (6) | ES431054A1 (en, 2012) |
| FI (1) | FI62079C (en, 2012) |
| FR (1) | FR2248838B1 (en, 2012) |
| GB (1) | GB1482552A (en, 2012) |
| HU (1) | HU176479B (en, 2012) |
| IE (1) | IE41528B1 (en, 2012) |
| IL (1) | IL45938A (en, 2012) |
| NL (1) | NL7413980A (en, 2012) |
| NO (1) | NO140859C (en, 2012) |
| PH (1) | PH11894A (en, 2012) |
| PL (3) | PL92053B1 (en, 2012) |
| RO (5) | RO65656A (en, 2012) |
| SE (1) | SE422791B (en, 2012) |
| SU (6) | SU510999A3 (en, 2012) |
| YU (5) | YU36949B (en, 2012) |
| ZA (1) | ZA746790B (en, 2012) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1513961A (en) * | 1975-02-25 | 1978-06-14 | Acf Chemiefarma Nv | 6,7-benzomorphans method for their preparation and intermediates |
| 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 |
| TW200911796A (en) | 2007-07-26 | 2009-03-16 | Vitae Pharmaceuticals Inc | Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 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 |
| WO2009094169A1 (en) | 2008-01-24 | 2009-07-30 | Vitae Pharmaceuticals, Inc. | Cyclic carbazate and semicarbazide inhibitors of 11beta-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 |
| EP2254872A2 (en) | 2008-02-15 | 2010-12-01 | Vitae Pharmaceuticals, Inc. | Cycloalkyl lactame derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| CA2723034A1 (en) | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| 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. |
| US8569292B2 (en) | 2008-05-01 | 2013-10-29 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| 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 |
| 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 |
| AR078887A1 (es) | 2009-11-06 | 2011-12-07 | Boehringer Ingelheim Int | Derivados arilo y heteroarilcarbonilo de hexahidroindenopiridina y octahidrobenzoquinolina y composiciones farmaceuticas que los contienen. |
| 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 |
| TWI537258B (zh) | 2010-11-05 | 2016-06-11 | 百靈佳殷格翰國際股份有限公司 | 六氫茚并吡啶及八氫苯并喹啉之芳基－及雜環芳基羰基衍生物 |
| 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 (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3632591A (en) * | 1968-07-19 | 1972-01-04 | Sterling Drug Inc | 1 2 3 4 5 6 - hexahydro-3-(cycloaliphatic or cycloaliphatic 11-dimethyl-2 alkyl)-66-methano-3-benzazocines |
| US3833595A (en) * | 1968-12-26 | 1974-09-03 | Sumitomo Chemical Co | 2-aroylalkyl benzomorphans |
| CS166803B2 (en, 2012) * | 1971-02-08 | 1976-03-29 | Boehringer Sohn Ingelheim |
-
1973
- 1973-10-25 SU SU2069684A patent/SU510999A3/ru active
- 1973-10-25 SU SU2069691A patent/SU511005A3/ru active
- 1973-10-27 DE DE19732354002 patent/DE2354002A1/de not_active Withdrawn
-
1974
- 1974-01-25 RO RO7480315A patent/RO65656A/ro unknown
- 1974-10-02 CS CS6768A patent/CS171195B2/cs unknown
- 1974-10-02 CS CS6769A patent/CS171196B2/cs unknown
- 1974-10-02 CS CS6767A patent/CS171194B2/cs unknown
- 1974-10-15 US US05/514,474 patent/US3981874A/en not_active Expired - Lifetime
- 1974-10-16 ES ES431054A patent/ES431054A1/es not_active Expired
- 1974-10-16 AT AT829074A patent/AT335634B/de not_active IP Right Cessation
- 1974-10-16 ES ES431059A patent/ES431059A1/es not_active Expired
- 1974-10-16 AT AT828574A patent/AT335631B/de not_active IP Right Cessation
- 1974-10-16 ES ES431057A patent/ES431057A1/es not_active Expired
- 1974-10-16 ES ES431055A patent/ES431055A1/es not_active Expired
- 1974-10-16 AT AT828674A patent/AT335632B/de not_active IP Right Cessation
- 1974-10-16 ES ES431056A patent/ES431056A1/es not_active Expired
- 1974-10-16 AT AT828874A patent/AT335076B/de active
- 1974-10-16 AT AT828974A patent/AT336202B/de not_active IP Right Cessation
- 1974-10-16 AT AT828774A patent/AT335633B/de not_active IP Right Cessation
- 1974-10-16 ES ES431058A patent/ES431058A1/es not_active Expired
- 1974-10-24 PH PH16448A patent/PH11894A/en unknown
- 1974-10-24 CH CH1426574A patent/CH609340A5/xx not_active IP Right Cessation
- 1974-10-24 YU YU2854/74A patent/YU36949B/xx unknown
- 1974-10-24 YU YU02852/74A patent/YU36519B/xx unknown
- 1974-10-24 CH CH1426374A patent/CH609047A5/xx not_active IP Right Cessation
- 1974-10-24 YU YU2851/74A patent/YU36951B/xx unknown
- 1974-10-24 YU YU2856/74A patent/YU36950B/xx unknown
- 1974-10-24 CH CH1426274A patent/CH609046A5/xx not_active IP Right Cessation
- 1974-10-24 YU YU2853/74A patent/YU36952B/xx unknown
- 1974-10-24 CH CH1426474A patent/CH609048A5/xx not_active IP Right Cessation
- 1974-10-25 BG BG028036A patent/BG27901A3/xx unknown
- 1974-10-25 CA CA212,340A patent/CA1056377A/en not_active Expired
- 1974-10-25 DD DD181929A patent/DD115909A5/xx unknown
- 1974-10-25 JP JP12261074A patent/JPS5738590B2/ja not_active Expired
- 1974-10-25 CH CH1436974A patent/CH609685A5/xx not_active IP Right Cessation
- 1974-10-25 FI FI3141/74A patent/FI62079C/fi active
- 1974-10-25 GB GB46323/74A patent/GB1482552A/en not_active Expired
- 1974-10-25 BG BG028037A patent/BG27902A3/xx unknown
- 1974-10-25 BG BG028038A patent/BG27903A3/xx unknown
- 1974-10-25 NO NO743845A patent/NO140859C/no unknown
- 1974-10-25 SU SU2070657A patent/SU508193A3/ru active
- 1974-10-25 SU SU2069689A patent/SU508192A3/ru active
- 1974-10-25 FR FR7435890A patent/FR2248838B1/fr not_active Expired
- 1974-10-25 SU SU7402069685A patent/SU578870A3/ru active
- 1974-10-25 ZA ZA00746790A patent/ZA746790B/xx unknown
- 1974-10-25 RO RO7480318A patent/RO65659A/ro unknown
- 1974-10-25 DK DK559874A patent/DK138325C/da not_active IP Right Cessation
- 1974-10-25 CH CH1437074A patent/CH609686A5/xx not_active IP Right Cessation
- 1974-10-25 BE BE149902A patent/BE821505A/xx not_active IP Right Cessation
- 1974-10-25 RO RO7480317A patent/RO65658A/ro unknown
- 1974-10-25 RO RO7480314A patent/RO65655A/ro unknown
- 1974-10-25 SE SE7413485A patent/SE422791B/xx unknown
- 1974-10-25 SU SU2070713A patent/SU512707A3/ru active
- 1974-10-25 IE IE2206/74A patent/IE41528B1/en unknown
- 1974-10-25 NL NL7413980A patent/NL7413980A/xx unknown
- 1974-10-25 RO RO7480316A patent/RO65657A/ro unknown
- 1974-10-25 HU HU74BO1521A patent/HU176479B/hu unknown
- 1974-10-25 IL IL45938A patent/IL45938A/en unknown
- 1974-10-26 PL PL1974175142A patent/PL92053B1/pl unknown
- 1974-10-26 PL PL1974175144A patent/PL92086B1/pl unknown
- 1974-10-26 PL PL1974175143A patent/PL92052B1/pl unknown
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