NZ515143A - Aminoindane piperidine compounds as dermal anesthetic agents - Google Patents
Aminoindane piperidine compounds as dermal anesthetic agentsInfo
- Publication number
- NZ515143A NZ515143A NZ515143A NZ51514300A NZ515143A NZ 515143 A NZ515143 A NZ 515143A NZ 515143 A NZ515143 A NZ 515143A NZ 51514300 A NZ51514300 A NZ 51514300A NZ 515143 A NZ515143 A NZ 515143A
- Authority
- NZ
- New Zealand
- Prior art keywords
- formula
- group
- hydrogen
- compound
- anesthesia
- Prior art date
Links
- 230000002500 effect on skin Effects 0.000 title claims abstract description 29
- DEEUGGDCCPTQEN-UHFFFAOYSA-N C1CCNCC1.C1=CC=C2C(N)CCC2=C1 Chemical class C1CCNCC1.C1=CC=C2C(N)CCC2=C1 DEEUGGDCCPTQEN-UHFFFAOYSA-N 0.000 title abstract 2
- 239000003193 general anesthetic agent Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 239000000203 mixture Substances 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 28
- 239000003589 local anesthetic agent Substances 0.000 claims abstract description 11
- 241000124008 Mammalia Species 0.000 claims abstract description 3
- -1 alkoxy radical Chemical class 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 150000002431 hydrogen Chemical group 0.000 claims description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 206010002091 Anaesthesia Diseases 0.000 claims description 25
- 230000037005 anaesthesia Effects 0.000 claims description 25
- 150000003839 salts Chemical group 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 238000002690 local anesthesia Methods 0.000 claims description 18
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 14
- 210000005036 nerve Anatomy 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 150000003053 piperidines Chemical class 0.000 claims description 10
- 238000012360 testing method Methods 0.000 claims description 10
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 230000008595 infiltration Effects 0.000 claims description 9
- 238000001764 infiltration Methods 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 230000007062 hydrolysis Effects 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- FIULGFJIHJJXMT-UHFFFAOYSA-N [C]1[N]C=CC=C1 Chemical compound [C]1[N]C=CC=C1 FIULGFJIHJJXMT-UHFFFAOYSA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 238000002691 topical anesthesia Methods 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 230000003301 hydrolyzing effect Effects 0.000 claims description 6
- 230000001939 inductive effect Effects 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 208000014617 hemorrhoid Diseases 0.000 claims description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 210000004379 membrane Anatomy 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 210000004400 mucous membrane Anatomy 0.000 claims description 4
- 230000001131 transforming effect Effects 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 208000007514 Herpes zoster Diseases 0.000 claims description 2
- 208000031361 Hiccup Diseases 0.000 claims description 2
- 208000006877 Insect Bites and Stings Diseases 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 206010042496 Sunburn Diseases 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 238000001647 drug administration Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000006698 induction Effects 0.000 claims description 2
- 239000002504 physiological saline solution Substances 0.000 claims description 2
- 230000001988 toxicity Effects 0.000 claims description 2
- 231100000419 toxicity Toxicity 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 claims 2
- 208000007101 Muscle Cramp Diseases 0.000 claims 1
- 208000012266 Needlestick injury Diseases 0.000 claims 1
- 208000005392 Spasm Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 230000002057 chronotropic effect Effects 0.000 claims 1
- 230000001091 dromotropic effect Effects 0.000 claims 1
- 230000002526 effect on cardiovascular system Effects 0.000 claims 1
- 150000003840 hydrochlorides Chemical class 0.000 claims 1
- 230000000297 inotrophic effect Effects 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 210000000653 nervous system Anatomy 0.000 claims 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 claims 1
- 230000029058 respiratory gaseous exchange Effects 0.000 claims 1
- 230000026416 response to pain Effects 0.000 claims 1
- 210000002460 smooth muscle Anatomy 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 230000006641 stabilisation Effects 0.000 claims 1
- 238000011105 stabilization Methods 0.000 claims 1
- 238000011477 surgical intervention Methods 0.000 claims 1
- 238000005303 weighing Methods 0.000 claims 1
- 229960005015 local anesthetics Drugs 0.000 abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution 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 18
- 230000003444 anaesthetic effect Effects 0.000 description 17
- 239000012458 free base Substances 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 230000009467 reduction Effects 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- 239000007858 starting material Substances 0.000 description 14
- 230000000699 topical effect Effects 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 150000005829 chemical entities Chemical class 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 8
- 238000000197 pyrolysis Methods 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 238000010992 reflux Methods 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
- 238000000855 fermentation Methods 0.000 description 6
- 230000004151 fermentation Effects 0.000 description 6
- 239000002674 ointment Substances 0.000 description 6
- 230000036407 pain Effects 0.000 description 6
- 230000035515 penetration Effects 0.000 description 6
- 238000002360 preparation method Methods 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
- 125000003118 aryl group Chemical group 0.000 description 5
- 230000036461 convulsion Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000936 membranestabilizing effect Effects 0.000 description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-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
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 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
- 239000013078 crystal Substances 0.000 description 4
- 238000002474 experimental method Methods 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
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 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
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000036576 dermal application Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000002265 prevention Effects 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
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 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
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 2
- 229910000497 Amalgam Inorganic materials 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229910018954 NaNH2 Inorganic materials 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
- 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
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- 108010046334 Urease Proteins 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
- 150000001298 alcohols Chemical class 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
- 150000001412 amines Chemical class 0.000 description 2
- 229940035674 anesthetics Drugs 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
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- 230000004888 barrier function Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 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
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- 238000009835 boiling Methods 0.000 description 2
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- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
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- 239000010410 layer Substances 0.000 description 2
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- 230000007935 neutral effect Effects 0.000 description 2
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- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
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- 230000001737 promoting effect Effects 0.000 description 2
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- 238000002694 regional anesthesia Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 235000020712 soy bean extract Nutrition 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 229960002372 tetracaine Drugs 0.000 description 2
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
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Classifications
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13835399P | 1999-06-10 | 1999-06-10 | |
| US17926700P | 2000-01-31 | 2000-01-31 | |
| PCT/US2000/015490 WO2000076510A1 (en) | 1999-06-10 | 2000-06-06 | Dermal anesthetic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ515143A true NZ515143A (en) | 2004-05-28 |
Family
ID=26836123
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ515143A NZ515143A (en) | 1999-06-10 | 2000-06-06 | Aminoindane piperidine compounds as dermal anesthetic agents |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6413987B1 (OSRAM) |
| EP (1) | EP1185267B1 (OSRAM) |
| JP (1) | JP2003501469A (OSRAM) |
| CN (1) | CN1355700A (OSRAM) |
| AT (1) | ATE335482T1 (OSRAM) |
| AU (1) | AU777517B2 (OSRAM) |
| BR (1) | BR0011028A (OSRAM) |
| CA (1) | CA2376819C (OSRAM) |
| CY (1) | CY1105721T1 (OSRAM) |
| DE (1) | DE60029954T2 (OSRAM) |
| DK (1) | DK1185267T3 (OSRAM) |
| ES (1) | ES2267546T3 (OSRAM) |
| IL (2) | IL146190A0 (OSRAM) |
| MX (1) | MXPA01012632A (OSRAM) |
| NO (1) | NO323856B1 (OSRAM) |
| NZ (1) | NZ515143A (OSRAM) |
| PT (1) | PT1185267E (OSRAM) |
| WO (1) | WO2000076510A1 (OSRAM) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1321139T1 (sl) * | 2001-12-21 | 2007-02-28 | Chiesi Farma Spa | 2-indanilamino-derivati za zdravljenje kronicne, akutne ali vnetne bolecine |
| PL376890A1 (pl) * | 2002-11-26 | 2006-01-09 | Maruishi Pharmaceutical Co., Ltd. | Pochodne izoindoliny |
| 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 |
| US7718674B2 (en) | 2004-09-27 | 2010-05-18 | Bridge Pharma, Inc. | Methods of relieving neuropathic pain with the S-isomer of 2-{2[N-(2-indanyl)-N-phenylamino]ethyl}piperidine |
| 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 |
| CA2655809C (en) | 2006-07-21 | 2013-10-01 | Bridge Pharma, Inc. | Dermal anesthetic compounds |
| DK2244737T3 (da) * | 2008-01-22 | 2019-07-08 | Univ Texas | Flygtige anæstetiske sammensætninger omfattende ekstraktionsopløsningsmidler til regional anæstesi og/eller smertelindring |
| BR112013020874A2 (pt) * | 2011-02-18 | 2019-05-21 | Endo Pharmaceuticals Inc. | composto, regime, método para a preparação do referido composto, e, uso de um composto |
| US8809372B2 (en) | 2011-09-30 | 2014-08-19 | Asana Biosciences, Llc | Pyridine derivatives |
| US8685418B2 (en) | 2011-10-24 | 2014-04-01 | 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 |
| EA201891225A1 (ru) | 2015-11-23 | 2018-11-30 | Грейс Терапьютикс Ллк | Пленкообразующий спрей для местного применения |
| JP7656266B2 (ja) | 2018-12-19 | 2025-04-03 | グレイス セラピューティクス、インコーポレイテッド | 鼻腔内リドカインの治療用組成物 |
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 |
-
2000
- 2000-06-06 IL IL14619000A patent/IL146190A0/xx 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 ES ES00941227T patent/ES2267546T3/es not_active Expired - Lifetime
- 2000-06-06 EP EP00941227A patent/EP1185267B1/en not_active Expired - Lifetime
- 2000-06-06 DK DK00941227T patent/DK1185267T3/da active
- 2000-06-06 PT PT00941227T patent/PT1185267E/pt unknown
- 2000-06-06 AU AU55963/00A patent/AU777517B2/en not_active Ceased
- 2000-06-06 CN CN00808753A patent/CN1355700A/zh active Pending
- 2000-06-06 CA CA002376819A patent/CA2376819C/en not_active Expired - Fee Related
- 2000-06-06 AT AT00941227T patent/ATE335482T1/de not_active IP Right Cessation
- 2000-06-06 JP JP2001502843A patent/JP2003501469A/ja active Pending
- 2000-06-06 BR BR0011028-0A patent/BR0011028A/pt not_active Application Discontinuation
- 2000-06-06 MX MXPA01012632A patent/MXPA01012632A/es active IP Right Grant
- 2000-06-06 WO PCT/US2000/015490 patent/WO2000076510A1/en not_active Ceased
- 2000-06-06 NZ NZ515143A patent/NZ515143A/en not_active IP Right Cessation
-
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 |
|---|---|
| MXPA01012632A (es) | 2004-03-19 |
| US6413987B1 (en) | 2002-07-02 |
| CN1355700A (zh) | 2002-06-26 |
| CA2376819A1 (en) | 2000-12-21 |
| NO20016037D0 (no) | 2001-12-10 |
| CA2376819C (en) | 2008-09-02 |
| DK1185267T3 (da) | 2006-12-11 |
| EP1185267A4 (en) | 2003-09-03 |
| WO2000076510A9 (en) | 2002-07-04 |
| CY1105721T1 (el) | 2010-12-22 |
| JP2003501469A (ja) | 2003-01-14 |
| WO2000076510A1 (en) | 2000-12-21 |
| DE60029954T2 (de) | 2007-03-08 |
| DE60029954D1 (de) | 2006-09-21 |
| EP1185267A1 (en) | 2002-03-13 |
| BR0011028A (pt) | 2002-02-19 |
| EP1185267B1 (en) | 2006-08-09 |
| IL146190A0 (en) | 2002-07-25 |
| AU5596300A (en) | 2001-01-02 |
| ES2267546T3 (es) | 2007-03-16 |
| NO323856B1 (no) | 2007-07-16 |
| AU777517B2 (en) | 2004-10-21 |
| IL146190A (en) | 2008-11-03 |
| PT1185267E (pt) | 2006-12-29 |
| ATE335482T1 (de) | 2006-09-15 |
| NO20016037L (no) | 2002-02-11 |
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| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| LAPS | Patent lapsed |