BG64418B1 - Заместени 1,2,3,4,5,6-хексахидро-2,6-метано-3-бензазоцин- 10-оли, метод за тяхното получаване и приложението им като лекарствени средства - Google Patents
Заместени 1,2,3,4,5,6-хексахидро-2,6-метано-3-бензазоцин- 10-оли, метод за тяхното получаване и приложението им като лекарствени средства Download PDFInfo
- Publication number
- BG64418B1 BG64418B1 BG104232A BG10423200A BG64418B1 BG 64418 B1 BG64418 B1 BG 64418B1 BG 104232 A BG104232 A BG 104232A BG 10423200 A BG10423200 A BG 10423200A BG 64418 B1 BG64418 B1 BG 64418B1
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- methyl
- acid
- ethyl
- mean
- reaction
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- 238000000034 method Methods 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 239000002253 acid Substances 0.000 claims description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 59
- 150000001875 compounds Chemical class 0.000 claims description 55
- -1 hydroxy, methyl Chemical group 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 239000012074 organic phase Substances 0.000 claims description 21
- 239000000047 product Substances 0.000 claims description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
- 229910052794 bromium Inorganic materials 0.000 claims description 16
- 239000000460 chlorine Substances 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 239000011737 fluorine Substances 0.000 claims description 15
- 239000012442 inert solvent Substances 0.000 claims description 14
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 239000011707 mineral Substances 0.000 claims description 14
- 239000002585 base Substances 0.000 claims description 13
- NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 230000002378 acidificating effect Effects 0.000 claims description 10
- 150000007513 acids Chemical class 0.000 claims description 10
- 239000013543 active substance Substances 0.000 claims description 10
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 9
- 150000008282 halocarbons Chemical class 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 7
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- 206010021143 Hypoxia Diseases 0.000 claims description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 5
- 239000002798 polar solvent Substances 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 5
- 208000013016 Hypoglycemia Diseases 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 150000004292 cyclic ethers Chemical class 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 4
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
- 206010002660 Anoxia Diseases 0.000 claims description 3
- 241000976983 Anoxia Species 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 3
- 230000007953 anoxia Effects 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000003053 piperidines Chemical class 0.000 claims description 3
- 239000012429 reaction media Substances 0.000 claims description 3
- 239000011877 solvent mixture Substances 0.000 claims description 3
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 206010002091 Anaesthesia Diseases 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 208000020925 Bipolar disease Diseases 0.000 claims description 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010048962 Brain oedema Diseases 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 239000005046 Chlorosilane Substances 0.000 claims description 2
- 238000006845 Michael addition reaction Methods 0.000 claims description 2
- 238000006957 Michael reaction Methods 0.000 claims description 2
- 206010028923 Neonatal asphyxia Diseases 0.000 claims description 2
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 claims description 2
- 125000005396 acrylic acid ester group Chemical group 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 230000037005 anaesthesia Effects 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 208000006752 brain edema Diseases 0.000 claims description 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 claims description 2
- 150000005690 diesters Chemical class 0.000 claims description 2
- 238000007336 electrophilic substitution reaction Methods 0.000 claims description 2
- 230000001037 epileptic effect Effects 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 230000007954 hypoxia Effects 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 239000003978 infusion fluid Substances 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 238000002690 local anesthesia Methods 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 208000033300 perinatal asphyxia Diseases 0.000 claims description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 239000003195 sodium channel blocking agent Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 27
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 239000002262 Schiff base Substances 0.000 claims 1
- 150000004753 Schiff bases Chemical class 0.000 claims 1
- DDSZWBCJXDRQDU-UHFFFAOYSA-N [N].C1CCNCC1 Chemical group [N].C1CCNCC1 DDSZWBCJXDRQDU-UHFFFAOYSA-N 0.000 claims 1
- 208000029028 brain injury Diseases 0.000 claims 1
- 229910052802 copper Inorganic materials 0.000 claims 1
- 239000010949 copper Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 230000036407 pain Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 94
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 15
- 108010052164 Sodium Channels Proteins 0.000 description 12
- 102000018674 Sodium Channels Human genes 0.000 description 12
- 235000010755 mineral Nutrition 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 235000011114 ammonium hydroxide Nutrition 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- DWJKILXTMUGXOU-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC=C1CC#N DWJKILXTMUGXOU-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
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- 239000000126 substance Substances 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- OJVPARBSJMQOBF-UHFFFAOYSA-N ethyl 3-amino-4-(2-methoxyphenyl)-2-methylbutanoate Chemical compound CCOC(=O)C(C)C(N)CC1=CC=CC=C1OC OJVPARBSJMQOBF-UHFFFAOYSA-N 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
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- 239000013078 crystal Substances 0.000 description 4
- CVKUWYUHYHZFNV-UHFFFAOYSA-N diethyl 2-amino-3-[(2-methoxyphenyl)methyl]-2-methylhexanedioate Chemical compound CCOC(=O)CCC(C(C)(N)C(=O)OCC)CC1=CC=CC=C1OC CVKUWYUHYHZFNV-UHFFFAOYSA-N 0.000 description 4
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- IBWVEGFZPXRIDP-UHFFFAOYSA-N 2-[(2-methoxyphenyl)methyl]-3-methyl-4-methylidenepiperidine-1-carbaldehyde Chemical compound COC1=CC=CC=C1CC1N(C=O)CCC(=C)C1C IBWVEGFZPXRIDP-UHFFFAOYSA-N 0.000 description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
- ISNYUQWBWALXEY-UHFFFAOYSA-N Batrachotoxin Natural products C=1CC2(C3=CCC4C5(C)CCC(C4)(O)OC53C(O)C3)OCCN(C)CC32C=1C(C)OC(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
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- 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 description 3
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
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- 239000002775 capsule Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
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- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910001415 sodium ion Inorganic materials 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- ISNYUQWBWALXEY-OMIQOYQYSA-N tsg6xhx09r Chemical compound O([C@@H](C)C=1[C@@]23CN(C)CCO[C@]3(C3=CC[C@H]4[C@]5(C)CC[C@@](C4)(O)O[C@@]53[C@H](O)C2)CC=1)C(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-OMIQOYQYSA-N 0.000 description 3
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19740110A DE19740110A1 (de) | 1997-09-12 | 1997-09-12 | Substituierte 1,2,3,4,5,6-Hexahydro-2,6-methano-3-benzazocin-10-ole, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BG104232A BG104232A (en) | 2000-10-31 |
| BG64418B1 true BG64418B1 (bg) | 2005-01-31 |
Family
ID=7842134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG104232A Active BG64418B1 (bg) | 1997-09-12 | 2000-03-09 | Заместени 1,2,3,4,5,6-хексахидро-2,6-метано-3-бензазоцин- 10-оли, метод за тяхното получаване и приложението им като лекарствени средства |
Country Status (38)
| Country | Link |
|---|---|
| US (1) | US6455538B1 (xx) |
| EP (1) | EP1015433B1 (xx) |
| JP (1) | JP3827528B2 (xx) |
| KR (1) | KR100601008B1 (xx) |
| CN (1) | CN1166640C (xx) |
| AR (1) | AR017095A1 (xx) |
| AT (1) | ATE267811T1 (xx) |
| AU (1) | AU751036B2 (xx) |
| BG (1) | BG64418B1 (xx) |
| BR (1) | BR9812443A (xx) |
| CA (1) | CA2302347C (xx) |
| CO (1) | CO5011117A1 (xx) |
| CZ (1) | CZ296909B6 (xx) |
| DE (2) | DE19740110A1 (xx) |
| DK (1) | DK1015433T3 (xx) |
| EE (1) | EE04398B1 (xx) |
| ES (1) | ES2222612T3 (xx) |
| HR (1) | HRP980502B1 (xx) |
| HU (1) | HUP0004588A3 (xx) |
| ID (1) | ID24173A (xx) |
| IL (1) | IL134572A (xx) |
| MY (1) | MY120550A (xx) |
| NO (1) | NO315650B1 (xx) |
| NZ (1) | NZ503710A (xx) |
| PE (1) | PE122899A1 (xx) |
| PL (1) | PL198486B1 (xx) |
| PT (1) | PT1015433E (xx) |
| RS (1) | RS49888B (xx) |
| RU (1) | RU2218334C2 (xx) |
| SA (1) | SA98190765B1 (xx) |
| SK (1) | SK284670B6 (xx) |
| TR (1) | TR200000697T2 (xx) |
| TW (1) | TW505645B (xx) |
| UA (1) | UA61973C2 (xx) |
| UY (2) | UY25175A1 (xx) |
| WO (1) | WO1999014199A1 (xx) |
| YU (1) | YU12000A (xx) |
| ZA (1) | ZA988285B (xx) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19826365A1 (de) * | 1998-06-12 | 1999-12-16 | Gruenenthal Gmbh | Verwendung von Benzomorphanderivaten als Analgetikum |
| US6355652B1 (en) | 1999-11-27 | 2002-03-12 | Boehringer Ingelheim Pharma Kg | Substituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines and their use as pharmaceutical compositions |
| DE19957156A1 (de) * | 1999-11-27 | 2001-05-31 | Boehringer Ingelheim Pharma | Substituierte 1,2,3,4,5,6-Hexahydro-2,6-methano-3-benzazocine und ihre Verwendung als Arzneimittel |
| US6683089B2 (en) | 2002-02-02 | 2004-01-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | N-allyoxyethyl-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine-10-ols |
| DE10204276A1 (de) * | 2002-02-02 | 2003-08-07 | Boehringer Ingelheim Pharma | N-Allyloxyethyl-1,2,3,4,5,6-Hexahydro-2,6-methano-3-benzazocine und ihre Verwendung als Arzneimittel |
| US20040019075A1 (en) * | 2002-05-29 | 2004-01-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | New formulation for the parenteral application of crobenetine |
| DE10223783A1 (de) * | 2002-05-29 | 2003-12-11 | Boehringer Ingelheim Pharma | Neue Formulierung zur parenteralen Applikation eines Na-Kanal-Blockers |
| US6828311B2 (en) | 2002-05-29 | 2004-12-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Formulation for the parenteral application of a sodium channel blocker |
| US20030235576A1 (en) * | 2002-06-15 | 2003-12-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | New drug combinations for the treatment of ischaemic conditions |
| DE10226814A1 (de) * | 2002-06-15 | 2004-01-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Arzneimittelkombinationen zur Behandlung ischämischer Zustände |
| RS54522B1 (en) | 2005-12-22 | 2016-06-30 | Newron Pharmaceuticals S.P.A. | 2-Phenylethylamino Derivatives as Modulators of Calcium and (or Sodium) Channels |
| CN101687773B (zh) | 2007-06-15 | 2014-07-30 | 纽朗制药有限公司 | 取代的2-[2-(苯基)乙氨基]烷酰胺衍生物及其作为钠和/或钙通道调节剂的应用 |
| EA022973B1 (ru) | 2011-06-27 | 2016-03-31 | Ньюрон Фармасьютикалс С.П.А. | Фторированные арилалкиламинокарбоксамидные производные |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19528472A1 (de) * | 1995-08-03 | 1997-02-06 | Boehringer Ingelheim Kg | Neues Verfahren zur Herstellung von Norbenzomorphan einer Zwischenstufe bei Herstellung von pharmazeutisch wertvollen Benzomorphanderivaten, insbesondere von (-)-(1R,5S,S"R)-3'-Hydroxy-2-(2-methoxypropyl-)-5,9,9-trimethyl-6,7 benzomorphan |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| DE4121821A1 (de) * | 1991-07-02 | 1993-01-14 | Boehringer Ingelheim Kg | Neue benzomorphane und ihre verwendung als arzneimittel |
| US5607941A (en) * | 1992-06-26 | 1997-03-04 | Boehringer Ingelheim Kg | Useful for treating neurodegenerative diseases |
-
1997
- 1997-09-12 DE DE19740110A patent/DE19740110A1/de not_active Ceased
-
1998
- 1998-09-08 PE PE1998000847A patent/PE122899A1/es not_active Application Discontinuation
- 1998-09-09 DK DK98950009T patent/DK1015433T3/da active
- 1998-09-09 AT AT98950009T patent/ATE267811T1/de not_active IP Right Cessation
- 1998-09-09 CZ CZ20000894A patent/CZ296909B6/cs not_active IP Right Cessation
- 1998-09-09 EE EEP200000129A patent/EE04398B1/xx not_active IP Right Cessation
- 1998-09-09 JP JP2000511750A patent/JP3827528B2/ja not_active Expired - Fee Related
- 1998-09-09 SK SK334-2000A patent/SK284670B6/sk not_active IP Right Cessation
- 1998-09-09 PT PT98950009T patent/PT1015433E/pt unknown
- 1998-09-09 DE DE59811477T patent/DE59811477D1/de not_active Expired - Fee Related
- 1998-09-09 CA CA002302347A patent/CA2302347C/en not_active Expired - Fee Related
- 1998-09-09 PL PL339061A patent/PL198486B1/pl not_active IP Right Cessation
- 1998-09-09 RS YUP-120/00A patent/RS49888B/sr unknown
- 1998-09-09 ES ES98950009T patent/ES2222612T3/es not_active Expired - Lifetime
- 1998-09-09 HU HU0004588A patent/HUP0004588A3/hu unknown
- 1998-09-09 ID IDW20000461A patent/ID24173A/id unknown
- 1998-09-09 IL IL13457298A patent/IL134572A/xx not_active IP Right Cessation
- 1998-09-09 RU RU2000109358/04A patent/RU2218334C2/ru not_active IP Right Cessation
- 1998-09-09 TR TR2000/00697T patent/TR200000697T2/xx unknown
- 1998-09-09 UY UY25175A patent/UY25175A1/es not_active IP Right Cessation
- 1998-09-09 NZ NZ503710A patent/NZ503710A/xx unknown
- 1998-09-09 CN CNB988090155A patent/CN1166640C/zh not_active Expired - Fee Related
- 1998-09-09 BR BR9812443-9A patent/BR9812443A/pt not_active Application Discontinuation
- 1998-09-09 WO PCT/EP1998/005734 patent/WO1999014199A1/de active IP Right Grant
- 1998-09-09 AU AU96242/98A patent/AU751036B2/en not_active Ceased
- 1998-09-09 KR KR1020007002562A patent/KR100601008B1/ko not_active IP Right Cessation
- 1998-09-09 UA UA2000042088A patent/UA61973C2/uk unknown
- 1998-09-09 EP EP98950009A patent/EP1015433B1/de not_active Expired - Lifetime
- 1998-09-10 ZA ZA988285A patent/ZA988285B/xx unknown
- 1998-09-10 TW TW087115042A patent/TW505645B/zh active
- 1998-09-10 CO CO98052134A patent/CO5011117A1/es unknown
- 1998-09-10 MY MYPI98004142A patent/MY120550A/en unknown
- 1998-09-11 AR ARP980104530A patent/AR017095A1/es active Pending
- 1998-09-11 HR HR980502A patent/HRP980502B1/xx not_active IP Right Cessation
- 1998-11-16 SA SA98190765A patent/SA98190765B1/ar unknown
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1999
- 1999-03-22 UY UY25439A patent/UY25439A1/es not_active IP Right Cessation
-
2000
- 2000-03-02 YU YU12000A patent/YU12000A/sh unknown
- 2000-03-09 BG BG104232A patent/BG64418B1/bg active Active
- 2000-03-10 US US09/523,473 patent/US6455538B1/en not_active Expired - Lifetime
- 2000-03-10 NO NO20001288A patent/NO315650B1/no not_active IP Right Cessation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19528472A1 (de) * | 1995-08-03 | 1997-02-06 | Boehringer Ingelheim Kg | Neues Verfahren zur Herstellung von Norbenzomorphan einer Zwischenstufe bei Herstellung von pharmazeutisch wertvollen Benzomorphanderivaten, insbesondere von (-)-(1R,5S,S"R)-3'-Hydroxy-2-(2-methoxypropyl-)-5,9,9-trimethyl-6,7 benzomorphan |
| WO1997006146A1 (de) * | 1995-08-03 | 1997-02-20 | Boehringer Ingelheim Kg | Neues verfahren zur herstellung von norbenzomorphan einer zwischenstufe bei herstellung von pharmazeutisch wertvollen benzomorphanderivaten, insbesondere von (-)-(1r,5s,2'r)-3'-hydroxy-2-(2-methoxypropyl)-5,9,9-trimethyl-6,7-benzomorphan |
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