KR20110006697A - 시그마 수용체 억제제로서 유용한 5-메틸-1-(나프탈렌-2-일)-1ｈ-피라졸 - Google Patents
시그마 수용체 억제제로서 유용한 5-메틸-1-(나프탈렌-2-일)-1ｈ-피라졸 Download PDFInfo
- Publication number
- KR20110006697A KR20110006697A KR1020107026489A KR20107026489A KR20110006697A KR 20110006697 A KR20110006697 A KR 20110006697A KR 1020107026489 A KR1020107026489 A KR 1020107026489A KR 20107026489 A KR20107026489 A KR 20107026489A KR 20110006697 A KR20110006697 A KR 20110006697A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- formula
- methyl
- pyrazol
- hydroxy
- 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.)
- Withdrawn
Links
- 108010085082 sigma receptors Proteins 0.000 title claims abstract description 21
- 239000003112 inhibitor Substances 0.000 title description 7
- ZVHFNPCFAYIHHN-UHFFFAOYSA-N 5-methyl-1-naphthalen-2-ylpyrazole Chemical compound CC1=CC=NN1C1=CC=C(C=CC=C2)C2=C1 ZVHFNPCFAYIHHN-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 181
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 31
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 230000001404 mediated effect Effects 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims abstract description 4
- -1 5-methyl-1-naphthalen-2-yl-1H-pyrazol-3-yloxy Chemical group 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 53
- 239000012453 solvate Substances 0.000 claims description 38
- 150000001204 N-oxides Chemical class 0.000 claims description 34
- 239000000651 prodrug Substances 0.000 claims description 31
- 229940002612 prodrug Drugs 0.000 claims description 31
- 208000002193 Pain Diseases 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 208000021722 neuropathic pain Diseases 0.000 claims description 7
- 208000004454 Hyperalgesia Diseases 0.000 claims description 5
- 208000035154 Hyperesthesia Diseases 0.000 claims description 5
- 206010065390 Inflammatory pain Diseases 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- XKKUADNMRCIGEQ-UHFFFAOYSA-N 4-[2-[1-(5-methoxynaphthalen-2-yl)-5-methylpyrazol-3-yl]oxyethyl]morpholine Chemical compound C=1C=C2C(OC)=CC=CC2=CC=1N(C(=C1)C)N=C1OCCN1CCOCC1 XKKUADNMRCIGEQ-UHFFFAOYSA-N 0.000 claims description 3
- RCRXAIHETYCNFA-UHFFFAOYSA-N 4-[2-[1-(6-methoxynaphthalen-2-yl)-5-methylpyrazol-3-yl]oxyethyl]morpholine Chemical compound C1=CC2=CC(OC)=CC=C2C=C1N(C(=C1)C)N=C1OCCN1CCOCC1 RCRXAIHETYCNFA-UHFFFAOYSA-N 0.000 claims description 3
- QLFRUKXPBASFEV-UHFFFAOYSA-N 2-[2-(5-methyl-1-naphthalen-2-ylpyrazol-3-yl)oxyethylamino]ethanol Chemical compound CC1=CC(OCCNCCO)=NN1C1=CC=C(C=CC=C2)C2=C1 QLFRUKXPBASFEV-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- DWWVZBAGMUBQFJ-UHFFFAOYSA-N 4-[2-[1-(5,6-dimethoxy-5,6-dihydronaphthalen-2-yl)-5-methylpyrazol-3-yl]oxyethyl]morpholine Chemical compound C=1C=C2C(OC)C(OC)C=CC2=CC=1N(C(=C1)C)N=C1OCCN1CCOCC1 DWWVZBAGMUBQFJ-UHFFFAOYSA-N 0.000 claims 1
- UAIDDVVABPDPPO-UHFFFAOYSA-N 6-[5-methyl-3-(2-morpholin-4-ylethoxy)pyrazol-1-yl]-1,2-dihydronaphthalene-1,2-diol Chemical compound N=1N(C=2C=C3C=CC(O)C(O)C3=CC=2)C(C)=CC=1OCCN1CCOCC1 UAIDDVVABPDPPO-UHFFFAOYSA-N 0.000 claims 1
- AKCTWXDZRPAVKI-UHFFFAOYSA-N 6-[5-methyl-3-(2-morpholin-4-ylethoxy)pyrazol-1-yl]naphthalen-1-ol Chemical compound N=1N(C=2C=C3C=CC=C(O)C3=CC=2)C(C)=CC=1OCCN1CCOCC1 AKCTWXDZRPAVKI-UHFFFAOYSA-N 0.000 claims 1
- AXSYOQVDCPXNII-UHFFFAOYSA-N 6-[5-methyl-3-(2-morpholin-4-ylethoxy)pyrazol-1-yl]naphthalen-2-ol Chemical compound N=1N(C=2C=C3C=CC(O)=CC3=CC=2)C(C)=CC=1OCCN1CCOCC1 AXSYOQVDCPXNII-UHFFFAOYSA-N 0.000 claims 1
- FGOYPSNOKLTECB-UHFFFAOYSA-N 7-[5-methyl-3-(2-morpholin-4-ylethoxy)pyrazol-1-yl]naphthalen-2-ol Chemical compound N=1N(C=2C=C3C=C(O)C=CC3=CC=2)C(C)=CC=1OCCN1CCOCC1 FGOYPSNOKLTECB-UHFFFAOYSA-N 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 230000002265 prevention Effects 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 239000000243 solution Substances 0.000 description 25
- 239000007787 solid Substances 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- LYINKTVZUSKQEQ-UHFFFAOYSA-N furan-3-one Chemical compound O=C1COC=C1 LYINKTVZUSKQEQ-UHFFFAOYSA-N 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Chemical class 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 150000004696 coordination complex Chemical group 0.000 description 4
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 4
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002287 radioligand Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- RJVUDVVFKFJYJX-UHFFFAOYSA-N 3-(2-chloroethoxy)-1-(6-methoxynaphthalen-2-yl)-5-methylpyrazole Chemical compound C1=CC2=CC(OC)=CC=C2C=C1N1N=C(OCCCl)C=C1C RJVUDVVFKFJYJX-UHFFFAOYSA-N 0.000 description 3
- UNGLBCFJUFFUSY-UHFFFAOYSA-N 5-methoxynaphthalen-2-amine Chemical compound NC1=CC=C2C(OC)=CC=CC2=C1 UNGLBCFJUFFUSY-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PLBVJJMEICHJAG-UHFFFAOYSA-N ClO.N1CCOCC1 Chemical compound ClO.N1CCOCC1 PLBVJJMEICHJAG-UHFFFAOYSA-N 0.000 description 3
- 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 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical class C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- VNICRWVQYFRWDK-UHFFFAOYSA-N naphthalen-2-ylhydrazine Chemical class C1=CC=CC2=CC(NN)=CC=C21 VNICRWVQYFRWDK-UHFFFAOYSA-N 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- OBEJJLTZNYBVFA-UHFFFAOYSA-N 2-(5-methoxynaphthalen-2-yl)-3-methyl-1h-pyrazol-5-one Chemical compound C=1C=C2C(OC)=CC=CC2=CC=1N1N=C(O)C=C1C OBEJJLTZNYBVFA-UHFFFAOYSA-N 0.000 description 2
- PYHYBOOPMDEKHY-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)-3-methyl-1h-pyrazol-5-one Chemical compound C1=CC2=CC(OC)=CC=C2C=C1N1N=C(O)C=C1C PYHYBOOPMDEKHY-UHFFFAOYSA-N 0.000 description 2
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 2
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- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- CYTJOCBQAVISLI-UHFFFAOYSA-N 5,6-dihydronaphthalen-2-ylhydrazine Chemical class C1CC=CC2=CC(NN)=CC=C21 CYTJOCBQAVISLI-UHFFFAOYSA-N 0.000 description 2
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- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 2
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- 230000002411 adverse Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
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- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- SYNLPOQKBSLESU-UHFFFAOYSA-N morpholin-2-ol Chemical compound OC1CNCCO1 SYNLPOQKBSLESU-UHFFFAOYSA-N 0.000 description 1
- UQMUIPXTUDIUJD-UHFFFAOYSA-N morpholin-3-ol Chemical compound OC1COCCN1 UQMUIPXTUDIUJD-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- ZLBUWBOZBAKWEA-UHFFFAOYSA-N naphthalen-2-ol;hydrochloride Chemical compound Cl.C1=CC=CC2=CC(O)=CC=C21 ZLBUWBOZBAKWEA-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 108010080097 sigma-1 receptor Proteins 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DDFYFBUWEBINLX-UHFFFAOYSA-M tetramethylammonium bromide Chemical compound [Br-].C[N+](C)(C)C DDFYFBUWEBINLX-UHFFFAOYSA-M 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08384005.8 | 2008-04-25 | ||
| EP08384005A EP2113501A1 (en) | 2008-04-25 | 2008-04-25 | 5-Methyl-1-(naphthalen-2-YL)-1H-Pyrazoles useful as sigma receptor inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20110006697A true KR20110006697A (ko) | 2011-01-20 |
Family
ID=39739580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020107026489A Withdrawn KR20110006697A (ko) | 2008-04-25 | 2009-04-27 | 시그마 수용체 억제제로서 유용한 5-메틸-1-(나프탈렌-2-일)-1ｈ-피라졸 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US8492425B2 (enExample) |
| EP (2) | EP2113501A1 (enExample) |
| JP (1) | JP2011518811A (enExample) |
| KR (1) | KR20110006697A (enExample) |
| CN (1) | CN102066333A (enExample) |
| AU (1) | AU2009239906A1 (enExample) |
| BR (1) | BRPI0910679A2 (enExample) |
| CA (1) | CA2722256A1 (enExample) |
| MX (1) | MX2010011674A (enExample) |
| RU (1) | RU2010147918A (enExample) |
| WO (1) | WO2009130331A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12268952B2 (en) | 2014-08-01 | 2025-04-08 | Smart Billiard Lighting LLC | Billiard table lighting |
| US12345406B2 (en) | 2022-02-09 | 2025-07-01 | Blake Martin | Interactive LED system for enhancing billiard gameplay |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2116539A1 (en) | 2008-04-25 | 2009-11-11 | Laboratorios Del. Dr. Esteve, S.A. | 1-aryl-3-aminoalkoxy-pyrazoles as sigma ligands enhancing analgesic effects of opioids and attenuating the dependency thereof |
| EP2361904A1 (en) * | 2010-02-04 | 2011-08-31 | Laboratorios Del. Dr. Esteve, S.A. | 4-[-2-[[5-methyl-1-(2-naphtalenyl)-1h-pyrazol-3-yl]oxy]ethyl]morpholine hydrochloride and crystalline forms thereof |
| CA2781744C (en) * | 2009-11-25 | 2017-11-07 | Laboratorios Del Dr. Esteve, S.A. | 4-[2-[[5-methyl-1-(2-naphtalenyl)-1h-pyrazol-3-yl]oxy]ethyl]morpholine salts |
| SG182628A1 (en) * | 2010-02-04 | 2012-08-30 | Esteve Labor Dr | 4-[-2-[[5-methyl-1-(2-naphtalenyl)-1h-pyrazol-3-yl]oxy]ethyl]morpholine hydrochloride polymorphs and solvates |
| EP2353591A1 (en) | 2010-02-04 | 2011-08-10 | Laboratorios Del. Dr. Esteve, S.A. | Sigma ligands for potentiating the analgesic effect of opioids and opiates in post-operative pain and attenuating the dependency thereof |
| EP2353598A1 (en) | 2010-02-04 | 2011-08-10 | Laboratorios Del. Dr. Esteve, S.A. | Sigma ligands for use in the prevention and/or treatment of postoperative pain |
| EP2388005A1 (en) | 2010-05-21 | 2011-11-23 | Laboratorios Del. Dr. Esteve, S.A. | Sigma ligands for the prevention and/or treatment of emesis induced by chemotherapy or radiotherapy |
| EP2395003A1 (en) | 2010-05-27 | 2011-12-14 | Laboratorios Del. Dr. Esteve, S.A. | Pyrazole compounds as sigma receptor inhibitors |
| EP2418192A1 (en) * | 2010-07-30 | 2012-02-15 | Esteve Química, S.A. | Intermediates for the preparation of 1-aryl-pyrazol-3-one compounds useful as sigma receptors inhibitors |
| EP2415471A1 (en) * | 2010-08-03 | 2012-02-08 | Laboratorios Del. Dr. Esteve, S.A. | Use of sigma ligands in opioid-induced hyperalgesia |
| EP2426111A1 (en) * | 2010-08-09 | 2012-03-07 | Laboratorios Del. Dr. Esteve, S.A. | 4-[-2-[[5-methyl-1-(2-naphtalenyl)-1h-pyrazol-3-yl]oxy]ethyl]morpholine hydrochloride amorphous solid forms |
| EP2460804A1 (en) * | 2010-12-03 | 2012-06-06 | Laboratorios Del Dr. Esteve, S.A. | 5-methyl-1-(naphthalen-2-yl)-1h-pyrazole derivatives and their use in potentiating the effect of opioid analgesics |
| EP2460519A1 (en) | 2010-12-03 | 2012-06-06 | Laboratorios Del. Dr. Esteve, S.A. | Use of sigma ligands in bone cancer pain |
| EP2524694A1 (en) * | 2011-05-19 | 2012-11-21 | Laboratorios Del. Dr. Esteve, S.A. | Use of sigma ligands in diabetes type-2 associated pain |
| EP2818166A1 (en) * | 2013-06-26 | 2014-12-31 | Laboratorios del Dr. Esteve S.A. | Use of sigma receptor ligands for the prevention and treatment of pain associated to interstitial cystitis/bladder pain syndrome (IC/BPS) |
| AU2014364647A1 (en) | 2013-12-17 | 2016-06-23 | Laboratorios Del Dr. Esteve, S.A. | Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) and Sigma receptor ligands combinations |
| MA41177A (fr) * | 2014-12-15 | 2017-10-24 | Esteve Labor Dr | Utilisation de ligands des récepteurs sigma dans l'arthrose |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9824310D0 (en) | 1998-11-05 | 1998-12-30 | Univ London | Activators of soluble guanylate cyclase |
| PL1781618T3 (pl) * | 2004-08-27 | 2013-03-29 | Esteve Labor Dr | Inhibitory receptora sigma |
| EP1634872A1 (en) * | 2004-08-27 | 2006-03-15 | Laboratorios Del Dr. Esteve, S.A. | Pyrazole derivatives as sigma receptor inhibitors |
| EP1829875A1 (en) * | 2006-03-01 | 2007-09-05 | Laboratorios Del Dr. Esteve, S.A. | Pyrazole derivatives as sigma receptor inhibitors |
| MX2008011016A (es) | 2006-03-01 | 2008-09-08 | Esteve Labor Dr | Inhibidores de receptor sigma. |
-
2008
- 2008-04-25 EP EP08384005A patent/EP2113501A1/en not_active Withdrawn
-
2009
- 2009-04-27 MX MX2010011674A patent/MX2010011674A/es unknown
- 2009-04-27 RU RU2010147918/04A patent/RU2010147918A/ru not_active Application Discontinuation
- 2009-04-27 US US12/988,929 patent/US8492425B2/en not_active Expired - Fee Related
- 2009-04-27 KR KR1020107026489A patent/KR20110006697A/ko not_active Withdrawn
- 2009-04-27 BR BRPI0910679A patent/BRPI0910679A2/pt not_active IP Right Cessation
- 2009-04-27 JP JP2011505534A patent/JP2011518811A/ja active Pending
- 2009-04-27 EP EP09734847A patent/EP2285781A1/en not_active Withdrawn
- 2009-04-27 CA CA2722256A patent/CA2722256A1/en not_active Abandoned
- 2009-04-27 WO PCT/EP2009/055065 patent/WO2009130331A1/en not_active Ceased
- 2009-04-27 CN CN200980122589XA patent/CN102066333A/zh active Pending
- 2009-04-27 AU AU2009239906A patent/AU2009239906A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12268952B2 (en) | 2014-08-01 | 2025-04-08 | Smart Billiard Lighting LLC | Billiard table lighting |
| US12345406B2 (en) | 2022-02-09 | 2025-07-01 | Blake Martin | Interactive LED system for enhancing billiard gameplay |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2722256A1 (en) | 2009-10-29 |
| EP2285781A1 (en) | 2011-02-23 |
| MX2010011674A (es) | 2010-11-25 |
| BRPI0910679A2 (pt) | 2015-09-29 |
| US8492425B2 (en) | 2013-07-23 |
| AU2009239906A1 (en) | 2009-10-29 |
| WO2009130331A1 (en) | 2009-10-29 |
| JP2011518811A (ja) | 2011-06-30 |
| RU2010147918A (ru) | 2012-05-27 |
| US20110118253A1 (en) | 2011-05-19 |
| CN102066333A (zh) | 2011-05-18 |
| EP2113501A1 (en) | 2009-11-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20101125 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |