JP2003501469A - 皮膚麻酔薬 - Google Patents
皮膚麻酔薬Info
- Publication number
- JP2003501469A JP2003501469A JP2001502843A JP2001502843A JP2003501469A JP 2003501469 A JP2003501469 A JP 2003501469A JP 2001502843 A JP2001502843 A JP 2001502843A JP 2001502843 A JP2001502843 A JP 2001502843A JP 2003501469 A JP2003501469 A JP 2003501469A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- hydrogen
- compound
- anesthesia
- 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.)
- Pending
Links
- 230000003444 anaesthetic effect Effects 0.000 title abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- -1 aminoindan compound Chemical class 0.000 claims abstract description 61
- 238000000034 method Methods 0.000 claims abstract description 40
- 239000000203 mixture Substances 0.000 claims abstract description 30
- 241000124008 Mammalia Species 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 34
- 206010002091 Anaesthesia Diseases 0.000 claims description 26
- 230000037005 anaesthesia Effects 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 238000002690 local anesthesia Methods 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 239000012458 free base Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 210000005036 nerve Anatomy 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 239000002585 base Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 230000036407 pain Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 150000003053 piperidines Chemical class 0.000 claims description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- FIULGFJIHJJXMT-UHFFFAOYSA-N [C]1[N]C=CC=C1 Chemical compound [C]1[N]C=CC=C1 FIULGFJIHJJXMT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 208000014617 hemorrhoid Diseases 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 208000007514 Herpes zoster Diseases 0.000 claims description 2
- 208000006877 Insect Bites and Stings Diseases 0.000 claims description 2
- 206010042496 Sunburn Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000006698 induction Effects 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 238000002691 topical anesthesia Methods 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 210000004877 mucosa Anatomy 0.000 claims 2
- 208000012266 Needlestick injury Diseases 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 230000008595 infiltration Effects 0.000 claims 1
- 238000001764 infiltration Methods 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 210000003800 pharynx Anatomy 0.000 claims 1
- 238000011477 surgical intervention Methods 0.000 claims 1
- 210000003437 trachea Anatomy 0.000 claims 1
- 239000003589 local anesthetic agent Substances 0.000 abstract description 12
- 239000000243 solution Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 20
- 239000002253 acid Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 230000009467 reduction Effects 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- 239000007858 starting material Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 150000002431 hydrogen Chemical group 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 230000000699 topical effect Effects 0.000 description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 7
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 238000005915 ammonolysis reaction Methods 0.000 description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 239000002674 ointment Substances 0.000 description 6
- 230000035515 penetration Effects 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000003381 stabilizer Substances 0.000 description 6
- 208000007101 Muscle Cramp Diseases 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- VEIWYFRREFUNRC-UHFFFAOYSA-N hydron;piperidine;chloride Chemical compound [Cl-].C1CC[NH2+]CC1 VEIWYFRREFUNRC-UHFFFAOYSA-N 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 4
- 238000000197 pyrolysis Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 4
- CPGUAMMBRXPVGH-UHFFFAOYSA-N 1-benzyl-2-(chloromethyl)piperidine Chemical compound ClCC1CCCCN1CC1=CC=CC=C1 CPGUAMMBRXPVGH-UHFFFAOYSA-N 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 3
- 229940092714 benzenesulfonic acid Drugs 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 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
- 239000013078 crystal Substances 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 210000004400 mucous membrane Anatomy 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- DBAFFPICNKYNAC-UHFFFAOYSA-N 1-benzyl-2-(2-chloroethyl)piperidine Chemical compound ClCCC1CCCCN1CC1=CC=CC=C1 DBAFFPICNKYNAC-UHFFFAOYSA-N 0.000 description 2
- FDSAEFDNXGQWPT-UHFFFAOYSA-N 1-butyl-2-(2-chloroethyl)piperidine Chemical compound CCCCN1CCCCC1CCCl FDSAEFDNXGQWPT-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- PTHDBHDZSMGHKF-UHFFFAOYSA-N 2-piperidin-2-ylethanol Chemical compound OCCC1CCCCN1 PTHDBHDZSMGHKF-UHFFFAOYSA-N 0.000 description 2
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-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
- 229910000497 Amalgam Inorganic materials 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
- 241000700198 Cavia Species 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- 229910021554 Chromium(II) chloride Inorganic materials 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000031361 Hiccup Diseases 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-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
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 108010046334 Urease Proteins 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 229910001297 Zn alloy Inorganic materials 0.000 description 2
- WDNIVTZNAPEMHF-UHFFFAOYSA-N acetic acid;chromium Chemical compound [Cr].CC(O)=O.CC(O)=O WDNIVTZNAPEMHF-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- UZEDIBTVIIJELN-UHFFFAOYSA-N chromium(2+) Chemical class [Cr+2] UZEDIBTVIIJELN-UHFFFAOYSA-N 0.000 description 2
- XBWRJSSJWDOUSJ-UHFFFAOYSA-L chromium(ii) chloride Chemical compound Cl[Cr]Cl XBWRJSSJWDOUSJ-UHFFFAOYSA-L 0.000 description 2
- 230000002057 chronotropic effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13835399P | 1999-06-10 | 1999-06-10 | |
| US60/138,353 | 1999-06-10 | ||
| US17926700P | 2000-01-31 | 2000-01-31 | |
| US60/179,267 | 2000-01-31 | ||
| PCT/US2000/015490 WO2000076510A1 (en) | 1999-06-10 | 2000-06-06 | Dermal anesthetic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003501469A true JP2003501469A (ja) | 2003-01-14 |
| JP2003501469A5 JP2003501469A5 (enExample) | 2006-01-05 |
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| JP2001502843A Pending JP2003501469A (ja) | 1999-06-10 | 2000-06-06 | 皮膚麻酔薬 |
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|---|---|
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| EP (1) | EP1185267B1 (enExample) |
| JP (1) | JP2003501469A (enExample) |
| CN (1) | CN1355700A (enExample) |
| AT (1) | ATE335482T1 (enExample) |
| AU (1) | AU777517B2 (enExample) |
| BR (1) | BR0011028A (enExample) |
| CA (1) | CA2376819C (enExample) |
| CY (1) | CY1105721T1 (enExample) |
| DE (1) | DE60029954T2 (enExample) |
| DK (1) | DK1185267T3 (enExample) |
| ES (1) | ES2267546T3 (enExample) |
| IL (2) | IL146190A0 (enExample) |
| MX (1) | MXPA01012632A (enExample) |
| NO (1) | NO323856B1 (enExample) |
| NZ (1) | NZ515143A (enExample) |
| PT (1) | PT1185267E (enExample) |
| WO (1) | WO2000076510A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1321139T3 (da) * | 2001-12-21 | 2007-01-02 | Chiesi Farma Spa | 2-indanylaminoderivater til behandling af kronisk, akut eller inflammatorisk smerte |
| RU2343145C2 (ru) | 2002-11-26 | 2009-01-10 | Маруиси Фармасьютикал Ко., Лтд. | Производные изоиндолина |
| WO2006037047A2 (en) * | 2004-09-27 | 2006-04-06 | Bridge Pharma, Inc. | The r-isomer of 2-{2-[n-(2-indanyl)-n-phenylamino]ethyl}piperidine and other dermal anesthetic agents |
| WO2006036936A2 (en) * | 2004-09-27 | 2006-04-06 | Bridge Pharma, Inc. | The s-isomer of 2-{2-[n-(2-indanyl)-n-phenylamino]ethyl}piperidine and other dermal anesthetic agents |
| US20090137628A1 (en) * | 2005-09-23 | 2009-05-28 | Bridge Pharma, Inc. | Formulations of Indanylamines and the Use Thereof as Local Anesthetics and as Medication for Chronic Pain |
| US20110218218A1 (en) * | 2005-09-23 | 2011-09-08 | Bridge Pharma, Inc. | Formulations Of Indanylamines And The Use Thereof As Local Anesthetics And As Medication For Chronic Pain |
| US7592458B2 (en) * | 2006-07-21 | 2009-09-22 | Wright George E | Dermal anesthetic compounds and pharmaceutical compositions for inducing local anesthesia and mitigating neuropathic pain |
| CN107661293A (zh) * | 2008-01-22 | 2018-02-06 | 得克萨斯大学体系董事会 | 用于局部麻醉和/或疼痛缓解的含有萃取溶剂的挥发性麻醉剂组合物 |
| KR102014203B1 (ko) * | 2011-02-18 | 2019-08-26 | 아사나 바이오사이언시스 엘엘씨 | 아미노인단 화합물 및 통증 치료에서 그것의 용도 |
| US8809372B2 (en) | 2011-09-30 | 2014-08-19 | Asana Biosciences, Llc | Pyridine derivatives |
| CA2853279C (en) | 2011-10-24 | 2021-03-23 | Endo Pharmaceuticals Inc. | Cyclohexylamines |
| US9044482B2 (en) | 2012-08-15 | 2015-06-02 | Asana Biosciences, Llc | Use of aminoindane compounds in treating overactive bladder and interstitial cystitis |
| US20170296484A1 (en) | 2015-11-23 | 2017-10-19 | Grace Therapeutics Llc | Topical Film-Forming Spray |
| EA202191506A1 (ru) | 2018-12-19 | 2021-10-08 | Нортик Холдингз Инк. | Терапевтическая композиция интраназального лидокаина |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE760018A (fr) * | 1969-12-19 | 1971-06-08 | Christiaens Sa A | Nouveau derives du 2-amino-indane, leur preparation et leur utilisation |
| US3923813A (en) | 1969-12-19 | 1975-12-02 | Christiaens Sa A | Derivatives of 2-aminoindanes |
| AR206505A1 (es) * | 1972-09-18 | 1976-07-30 | Christiaens Sa A | Procedimiento para obtener nuevos derivados de n-fenil-n-aminoalquil-2-aminoindano |
| ZA738419B (en) * | 1972-11-06 | 1974-09-25 | Christiaens Sa A | New derivatives of 2-aminoindane,the preparation and use thereof |
| GB1462036A (en) | 1973-02-05 | 1977-01-19 | Manuf Prod Pharma | Aminoindane derivatives |
| GB1468347A (en) * | 1973-03-02 | 1977-03-23 | Christiaens Sa A | Aminoindanes |
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2000
- 2000-06-06 CA CA002376819A patent/CA2376819C/en not_active Expired - Fee Related
- 2000-06-06 AU AU55963/00A patent/AU777517B2/en not_active Ceased
- 2000-06-06 WO PCT/US2000/015490 patent/WO2000076510A1/en not_active Ceased
- 2000-06-06 BR BR0011028-0A patent/BR0011028A/pt not_active Application Discontinuation
- 2000-06-06 PT PT00941227T patent/PT1185267E/pt unknown
- 2000-06-06 DE DE60029954T patent/DE60029954T2/de not_active Expired - Fee Related
- 2000-06-06 US US09/588,582 patent/US6413987B1/en not_active Expired - Fee Related
- 2000-06-06 DK DK00941227T patent/DK1185267T3/da active
- 2000-06-06 NZ NZ515143A patent/NZ515143A/en not_active IP Right Cessation
- 2000-06-06 CN CN00808753A patent/CN1355700A/zh active Pending
- 2000-06-06 AT AT00941227T patent/ATE335482T1/de not_active IP Right Cessation
- 2000-06-06 ES ES00941227T patent/ES2267546T3/es not_active Expired - Lifetime
- 2000-06-06 MX MXPA01012632A patent/MXPA01012632A/es active IP Right Grant
- 2000-06-06 EP EP00941227A patent/EP1185267B1/en not_active Expired - Lifetime
- 2000-06-06 IL IL14619000A patent/IL146190A0/xx unknown
- 2000-06-06 JP JP2001502843A patent/JP2003501469A/ja active Pending
-
2001
- 2001-10-25 IL IL146190A patent/IL146190A/en not_active IP Right Cessation
- 2001-12-10 NO NO20016037A patent/NO323856B1/no unknown
-
2006
- 2006-10-23 CY CY20061101516T patent/CY1105721T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL146190A0 (en) | 2002-07-25 |
| EP1185267A1 (en) | 2002-03-13 |
| WO2000076510A9 (en) | 2002-07-04 |
| DE60029954D1 (de) | 2006-09-21 |
| NO323856B1 (no) | 2007-07-16 |
| CA2376819C (en) | 2008-09-02 |
| BR0011028A (pt) | 2002-02-19 |
| NO20016037L (no) | 2002-02-11 |
| NZ515143A (en) | 2004-05-28 |
| US6413987B1 (en) | 2002-07-02 |
| WO2000076510A1 (en) | 2000-12-21 |
| AU777517B2 (en) | 2004-10-21 |
| NO20016037D0 (no) | 2001-12-10 |
| PT1185267E (pt) | 2006-12-29 |
| EP1185267A4 (en) | 2003-09-03 |
| DK1185267T3 (da) | 2006-12-11 |
| MXPA01012632A (es) | 2004-03-19 |
| ATE335482T1 (de) | 2006-09-15 |
| CN1355700A (zh) | 2002-06-26 |
| ES2267546T3 (es) | 2007-03-16 |
| DE60029954T2 (de) | 2007-03-08 |
| CY1105721T1 (el) | 2010-12-22 |
| EP1185267B1 (en) | 2006-08-09 |
| CA2376819A1 (en) | 2000-12-21 |
| IL146190A (en) | 2008-11-03 |
| AU5596300A (en) | 2001-01-02 |
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