MX2010011674A - 5-metil-1-(naftalen-2-il)-1h-pirazoles utiles como inhibidores de receptores sigma. - Google Patents
5-metil-1-(naftalen-2-il)-1h-pirazoles utiles como inhibidores de receptores sigma.Info
- Publication number
- MX2010011674A MX2010011674A MX2010011674A MX2010011674A MX2010011674A MX 2010011674 A MX2010011674 A MX 2010011674A MX 2010011674 A MX2010011674 A MX 2010011674A MX 2010011674 A MX2010011674 A MX 2010011674A MX 2010011674 A MX2010011674 A MX 2010011674A
- Authority
- MX
- Mexico
- Prior art keywords
- formula
- compound
- methyl
- pyrazol
- compounds
- Prior art date
Links
- 108010085082 sigma receptors Proteins 0.000 title claims abstract description 22
- 239000003112 inhibitor Substances 0.000 title description 7
- ZVHFNPCFAYIHHN-UHFFFAOYSA-N 5-methyl-1-naphthalen-2-ylpyrazole Chemical class 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 172
- 150000003839 salts Chemical class 0.000 claims abstract description 56
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 49
- 239000012453 solvate Substances 0.000 claims abstract description 38
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 35
- 239000000651 prodrug Substances 0.000 claims abstract description 33
- 229940002612 prodrug Drugs 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 31
- 238000002360 preparation method Methods 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 14
- 230000001404 mediated effect Effects 0.000 claims abstract description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 14
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 238000011321 prophylaxis Methods 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 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- -1 2- (2- (1- (6-methoxynaphthalen-2-yl) -5-methyl-1H-pyrazol-3-yloxy) ethylamino) ethanol 6- (3- (2- (2-hydroxyethylamino) ethoxy) -5-methyl-1H-pyrazol-1-yl) naphthalen-2-ol Chemical compound 0.000 claims description 44
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 208000002193 Pain Diseases 0.000 claims description 14
- 230000036407 pain Effects 0.000 claims description 14
- 208000004454 Hyperalgesia Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 206010053552 allodynia Diseases 0.000 claims description 7
- 208000035154 Hyperesthesia Diseases 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 208000004296 neuralgia Diseases 0.000 claims description 5
- 208000021722 neuropathic pain Diseases 0.000 claims description 5
- 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 4
- 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 description 4
- 206010065390 Inflammatory pain Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- NCKNDJKZGMKOOF-UHFFFAOYSA-N 4-[2-[1-(7-methoxynaphthalen-2-yl)-5-methylpyrazol-3-yl]oxyethyl]morpholine Chemical compound C=1C2=CC(OC)=CC=C2C=CC=1N(C(=C1)C)N=C1OCCN1CCOCC1 NCKNDJKZGMKOOF-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 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 description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 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 2
- 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 description 2
- 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 1
- UVBFOBAQOQZBHG-UHFFFAOYSA-N 4-[2-(5-methyl-1-naphthalen-2-ylpyrazol-3-yl)oxyethyl]-4-oxidomorpholin-4-ium Chemical compound N=1N(C=2C=C3C=CC=CC3=CC=2)C(C)=CC=1OCC[N+]1([O-])CCOCC1 UVBFOBAQOQZBHG-UHFFFAOYSA-N 0.000 claims 1
- MSZAXJGOIJGRAO-UHFFFAOYSA-N 4-[2-(5-methyl-1-naphthalen-2-ylpyrazol-3-yl)oxyethyl]morpholin-2-ol Chemical compound N=1N(C=2C=C3C=CC=CC3=CC=2)C(C)=CC=1OCCN1CCOC(O)C1 MSZAXJGOIJGRAO-UHFFFAOYSA-N 0.000 claims 1
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 239000000203 mixture Substances 0.000 description 31
- 239000007787 solid Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 229910052751 metal Inorganic materials 0.000 description 8
- 239000002184 metal Chemical class 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000001727 in vivo Methods 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
- 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
- 125000000217 alkyl group Chemical group 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- LYINKTVZUSKQEQ-UHFFFAOYSA-N furan-3-one Chemical compound O=C1COC=C1 LYINKTVZUSKQEQ-UHFFFAOYSA-N 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 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
- 101150041968 CDC13 gene Proteins 0.000 description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
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- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 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
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 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 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
- 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000004429 atom Chemical group 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
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- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 4
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
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- 239000000741 silica gel Substances 0.000 description 4
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- 229910052708 sodium Inorganic materials 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
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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 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 3
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- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 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
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 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
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 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
- 150000004965 peroxy acids Chemical class 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 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
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 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
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 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
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 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
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type 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)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08384005A EP2113501A1 (en) | 2008-04-25 | 2008-04-25 | 5-Methyl-1-(naphthalen-2-YL)-1H-Pyrazoles useful as sigma receptor inhibitors |
| PCT/EP2009/055065 WO2009130331A1 (en) | 2008-04-25 | 2009-04-27 | 5-methyl-1-(naphthalen-2-yl)-1h-pyrazoles useful as sigma receptor inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2010011674A true MX2010011674A (es) | 2010-11-25 |
Family
ID=39739580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2010011674A MX2010011674A (es) | 2008-04-25 | 2009-04-27 | 5-metil-1-(naftalen-2-il)-1h-pirazoles utiles como inhibidores de receptores sigma. |
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) |
Families Citing this family (19)
| 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 |
| HRP20161128T1 (hr) * | 2009-11-25 | 2016-11-18 | Laboratorios Del Dr. Esteve, S.A. | Hidrokloridna sol 4-[2-[[5-metil-1-(2-naftalenil)-1h-pirazol-3-il]oksi]etil]morfolina |
| 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 |
| 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 |
| 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 |
| PL2531177T3 (pl) * | 2010-02-04 | 2016-11-30 | Chlorowodorek 4-[2-[[5-metylo-1-(2-naftalenylo)-1h-pirazol-3-ilo]oksy]etylo]morfoliny i solwaty | |
| 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) |
| SG11201604480PA (en) | 2013-12-17 | 2016-07-28 | Esteve Labor Dr | SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) AND SIGMA RECEPTOR LIGANDS COMBINATIONS |
| JP6654633B2 (ja) | 2014-08-01 | 2020-02-26 | スマート ビリヤード ライティング エルエルシー | ビリヤードテーブル照明及びゲームプレイモニタ |
| MA41177A (fr) * | 2014-12-15 | 2017-10-24 | Esteve Labor Dr | Utilisation de ligands des récepteurs sigma dans l'arthrose |
| EP4475970A4 (en) | 2022-02-09 | 2025-05-14 | Martin, Blake Robert | Interactive led system for enhancing billiard gameplay |
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 |
| AU2005276590B2 (en) | 2004-08-27 | 2011-05-19 | Laboratorios Del Dr. Esteve, S.A. | Sigma receptor inhibitors |
| EP1634872A1 (en) * | 2004-08-27 | 2006-03-15 | Laboratorios Del Dr. Esteve, S.A. | Pyrazole derivatives as sigma receptor inhibitors |
| JP2009528315A (ja) | 2006-03-01 | 2009-08-06 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | シグマ受容体阻害剤としてのピラゾール誘導体 |
| EP1829875A1 (en) * | 2006-03-01 | 2007-09-05 | Laboratorios Del Dr. Esteve, S.A. | Pyrazole derivatives as sigma receptor inhibitors |
-
2008
- 2008-04-25 EP EP08384005A patent/EP2113501A1/en not_active Withdrawn
-
2009
- 2009-04-27 KR KR1020107026489A patent/KR20110006697A/ko not_active Withdrawn
- 2009-04-27 MX MX2010011674A patent/MX2010011674A/es unknown
- 2009-04-27 AU AU2009239906A patent/AU2009239906A1/en not_active Abandoned
- 2009-04-27 US US12/988,929 patent/US8492425B2/en not_active Expired - Fee Related
- 2009-04-27 EP EP09734847A patent/EP2285781A1/en 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 RU RU2010147918/04A patent/RU2010147918A/ru not_active Application Discontinuation
- 2009-04-27 CN CN200980122589XA patent/CN102066333A/zh active Pending
- 2009-04-27 CA CA2722256A patent/CA2722256A1/en not_active Abandoned
- 2009-04-27 WO PCT/EP2009/055065 patent/WO2009130331A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP2285781A1 (en) | 2011-02-23 |
| WO2009130331A1 (en) | 2009-10-29 |
| EP2113501A1 (en) | 2009-11-04 |
| RU2010147918A (ru) | 2012-05-27 |
| KR20110006697A (ko) | 2011-01-20 |
| JP2011518811A (ja) | 2011-06-30 |
| CN102066333A (zh) | 2011-05-18 |
| US8492425B2 (en) | 2013-07-23 |
| BRPI0910679A2 (pt) | 2015-09-29 |
| US20110118253A1 (en) | 2011-05-19 |
| AU2009239906A1 (en) | 2009-10-29 |
| CA2722256A1 (en) | 2009-10-29 |
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