JPS5817457B2 - チカンアミジンカゴウブツノ セイゾウホウホウ - Google Patents
チカンアミジンカゴウブツノ セイゾウホウホウInfo
- Publication number
- JPS5817457B2 JPS5817457B2 JP50118188A JP11818875A JPS5817457B2 JP S5817457 B2 JPS5817457 B2 JP S5817457B2 JP 50118188 A JP50118188 A JP 50118188A JP 11818875 A JP11818875 A JP 11818875A JP S5817457 B2 JPS5817457 B2 JP S5817457B2
- Authority
- JP
- Japan
- Prior art keywords
- salt
- product
- hydrochloride
- reaction
- naphthaleneacetamidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000003839 salts Chemical class 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 14
- 150000001409 amidines Chemical class 0.000 claims description 11
- OQRMWUNUKVUHQO-UHFFFAOYSA-N 2-naphthalen-1-ylacetonitrile Chemical compound C1=CC=C2C(CC#N)=CC=CC2=C1 OQRMWUNUKVUHQO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000000047 product Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000000376 reactant Substances 0.000 description 12
- -1 amidine compounds Chemical class 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000012458 free base Substances 0.000 description 8
- 150000003973 alkyl amines Chemical class 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000012429 reaction media Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 150000001450 anions Chemical class 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- 125000005210 alkyl ammonium group Chemical group 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 2
- LPCWDVLDJVZIHA-UHFFFAOYSA-N 2-naphthalen-2-ylacetonitrile Chemical compound C1=CC=CC2=CC(CC#N)=CC=C21 LPCWDVLDJVZIHA-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 2
- 229960003147 reserpine Drugs 0.000 description 2
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- FPJKHRYOOKUFHF-UHFFFAOYSA-N 2-naphthalen-2-ylethanimidamide;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(CC(=N)N)=CC=C21 FPJKHRYOOKUFHF-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010002869 Anxiety symptoms Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- LXTQGYPVTFADHK-UHFFFAOYSA-N Cl.C1=C(C=CC2=CC=CC=C12)CC(O)=N Chemical compound Cl.C1=C(C=CC2=CC=CC=C12)CC(O)=N LXTQGYPVTFADHK-UHFFFAOYSA-N 0.000 description 1
- FYDXHIHBSUSLDH-UHFFFAOYSA-N Cl.CNC(CC1=CC2=C(C=CC(=C2C=C1)Cl)Cl)=NC Chemical compound Cl.CNC(CC1=CC2=C(C=CC(=C2C=C1)Cl)Cl)=NC FYDXHIHBSUSLDH-UHFFFAOYSA-N 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 235000008694 Humulus lupulus Nutrition 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 125000000320 amidine group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical class C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- VJKYNWPQVZHJAR-UHFFFAOYSA-H hexasodium trisulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O VJKYNWPQVZHJAR-UHFFFAOYSA-H 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- PIPZGJSEDRMUAW-VJDCAHTMSA-N hydron;methyl (1s,15r,18s,19r,20s)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate;chloride Chemical compound Cl.C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 PIPZGJSEDRMUAW-VJDCAHTMSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910001412 inorganic anion Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000009191 jumping Effects 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- PVLNOYVXDQKAAH-UHFFFAOYSA-N n,n'-dimethyl-2-(3-methylnaphthalen-2-yl)ethanimidamide;hydrochloride Chemical compound Cl.C1=CC=C2C=C(C)C(CC(/NC)=N/C)=CC2=C1 PVLNOYVXDQKAAH-UHFFFAOYSA-N 0.000 description 1
- WEDBCIMSKMMRAG-UHFFFAOYSA-N n,n'-dimethyl-2-naphthalen-2-ylethanimidamide;hydrochloride Chemical compound [Cl-].C1=CC=CC2=CC(CC([NH2+]C)=NC)=CC=C21 WEDBCIMSKMMRAG-UHFFFAOYSA-N 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 150000003864 primary ammonium salts Chemical class 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- DGCPSAFMAXHHDM-UHFFFAOYSA-N sulfuric acid;hydrofluoride Chemical compound F.OS(O)(=O)=O DGCPSAFMAXHHDM-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 229960000317 yohimbine Drugs 0.000 description 1
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1
- 229960000949 yohimbine hydrochloride Drugs 0.000 description 1
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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US510956A US3903163A (en) | 1974-10-02 | 1974-10-02 | N,N-Disubstituted naphthaleneacetamidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5159844A JPS5159844A (en) | 1976-05-25 |
| JPS5817457B2 true JPS5817457B2 (ja) | 1983-04-07 |
Family
ID=24032883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50118188A Expired JPS5817457B2 (ja) | 1974-10-02 | 1975-09-30 | チカンアミジンカゴウブツノ セイゾウホウホウ |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US3903163A (en, 2012) |
| JP (1) | JPS5817457B2 (en, 2012) |
| AR (1) | AR211104A1 (en, 2012) |
| BE (1) | BE834079A (en, 2012) |
| CA (1) | CA1055960A (en, 2012) |
| CH (1) | CH615153A5 (en, 2012) |
| DE (1) | DE2542791C2 (en, 2012) |
| DK (2) | DK154643C (en, 2012) |
| ES (1) | ES456605A1 (en, 2012) |
| FR (1) | FR2286644A1 (en, 2012) |
| GB (1) | GB1463945A (en, 2012) |
| IE (1) | IE42754B1 (en, 2012) |
| LU (1) | LU73484A1 (en, 2012) |
| NL (1) | NL184000C (en, 2012) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1121792B (it) * | 1978-07-03 | 1986-04-23 | Dow Chemical Co | Un processo per preparare 2-naftalenetanimidamidi n,n'-di-sostituite e intermedi usati in questo processo |
| CA2188680A1 (en) * | 1994-05-07 | 1996-01-25 | James Edwin Macdonald | Bicyclic amidine derivatives as inhibitors of nitric oxide synthetase |
| US6025355A (en) | 1997-05-19 | 2000-02-15 | Cambridge Neuroscience, Inc. | Pharmaceutically active compounds and methods of use |
| US6242198B1 (en) | 1996-07-25 | 2001-06-05 | Cambridge Neuroscience, Inc. | Methods of treatment of eye trauma and disorders |
| US6756389B2 (en) * | 1996-08-09 | 2004-06-29 | Cambridge Neuroscience, Inc. | Pharmaceutically active compounds and methods of use |
-
1974
- 1974-10-02 US US510956A patent/US3903163A/en not_active Expired - Lifetime
-
1975
- 1975-09-24 NL NLAANVRAGE7511245,A patent/NL184000C/xx not_active IP Right Cessation
- 1975-09-25 DE DE2542791A patent/DE2542791C2/de not_active Expired
- 1975-09-25 DK DK430475A patent/DK154643C/da not_active IP Right Cessation
- 1975-09-25 CA CA236,376A patent/CA1055960A/en not_active Expired
- 1975-09-26 FR FR7529528A patent/FR2286644A1/fr active Granted
- 1975-09-26 GB GB3959975A patent/GB1463945A/en not_active Expired
- 1975-09-29 AR AR260600A patent/AR211104A1/es active
- 1975-09-30 IE IE2140/75A patent/IE42754B1/en not_active IP Right Cessation
- 1975-09-30 LU LU73484A patent/LU73484A1/xx unknown
- 1975-09-30 JP JP50118188A patent/JPS5817457B2/ja not_active Expired
- 1975-10-01 BE BE160595A patent/BE834079A/xx not_active IP Right Cessation
- 1975-10-02 CH CH1281275A patent/CH615153A5/de not_active IP Right Cessation
-
1977
- 1977-03-07 ES ES456605A patent/ES456605A1/es not_active Expired
-
1988
- 1988-05-26 DK DK289188A patent/DK159266C/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NL184000C (nl) | 1989-03-16 |
| DK289188D0 (da) | 1988-05-26 |
| BE834079A (fr) | 1976-04-01 |
| CA1055960A (en) | 1979-06-05 |
| IE42754L (en) | 1976-04-02 |
| DK289188A (da) | 1988-05-26 |
| IE42754B1 (en) | 1980-10-08 |
| AR211104A1 (es) | 1977-10-31 |
| NL7511245A (nl) | 1976-04-06 |
| AU8518775A (en) | 1977-03-31 |
| DK154643B (da) | 1988-12-05 |
| GB1463945A (en) | 1977-02-09 |
| DK154643C (da) | 1989-05-08 |
| DE2542791C2 (de) | 1984-11-08 |
| CH615153A5 (en, 2012) | 1980-01-15 |
| DK159266C (da) | 1991-03-11 |
| FR2286644B1 (en, 2012) | 1980-05-16 |
| FR2286644A1 (fr) | 1976-04-30 |
| JPS5159844A (en) | 1976-05-25 |
| ES456605A1 (es) | 1978-01-16 |
| DK159266B (da) | 1990-09-24 |
| LU73484A1 (en, 2012) | 1977-05-11 |
| DK430475A (da) | 1976-04-03 |
| DE2542791A1 (de) | 1976-04-15 |
| NL184000B (nl) | 1988-10-17 |
| US3903163A (en) | 1975-09-02 |
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