MX2009000670A - Derivados espirociclicos de azaindol. - Google Patents
Derivados espirociclicos de azaindol.Info
- Publication number
- MX2009000670A MX2009000670A MX2009000670A MX2009000670A MX2009000670A MX 2009000670 A MX2009000670 A MX 2009000670A MX 2009000670 A MX2009000670 A MX 2009000670A MX 2009000670 A MX2009000670 A MX 2009000670A MX 2009000670 A MX2009000670 A MX 2009000670A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- spiro
- mono
- polysubstituted
- unsubstituted
- Prior art date
Links
- 125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 abstract description 36
- 150000001875 compounds Chemical class 0.000 abstract description 30
- 239000003814 drug Substances 0.000 abstract description 20
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 271
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 250
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 203
- 239000000243 solution Substances 0.000 description 198
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 187
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 151
- 239000007787 solid Substances 0.000 description 142
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 135
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 129
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 112
- 239000000203 mixture Substances 0.000 description 112
- 239000012074 organic phase Substances 0.000 description 90
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 87
- 239000011541 reaction mixture Substances 0.000 description 77
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 75
- -1 unsaturated acyclic hydrocarbon radicals Chemical class 0.000 description 75
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 63
- 239000008346 aqueous phase Substances 0.000 description 62
- 239000002904 solvent Substances 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
- 238000001816 cooling Methods 0.000 description 54
- 235000019439 ethyl acetate Nutrition 0.000 description 53
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- 229910052739 hydrogen Inorganic materials 0.000 description 51
- 229960004132 diethyl ether Drugs 0.000 description 46
- 238000002360 preparation method Methods 0.000 description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- 229940093499 ethyl acetate Drugs 0.000 description 43
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 42
- 238000001914 filtration Methods 0.000 description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 40
- 238000002844 melting Methods 0.000 description 39
- 230000008018 melting Effects 0.000 description 39
- 239000003921 oil Substances 0.000 description 35
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 34
- 239000002274 desiccant Substances 0.000 description 31
- 125000003118 aryl group Chemical group 0.000 description 30
- 229920006395 saturated elastomer Polymers 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 125000001072 heteroaryl group Chemical group 0.000 description 27
- 235000019341 magnesium sulphate Nutrition 0.000 description 27
- 229910052938 sodium sulfate Inorganic materials 0.000 description 27
- 235000011152 sodium sulphate Nutrition 0.000 description 27
- 125000000217 alkyl group Chemical group 0.000 description 26
- 239000000284 extract Substances 0.000 description 26
- 150000002576 ketones Chemical class 0.000 description 26
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 25
- 239000011734 sodium Substances 0.000 description 25
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 21
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 21
- 208000002193 Pain Diseases 0.000 description 21
- 239000012071 phase Substances 0.000 description 21
- 239000013049 sediment Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- 239000012043 crude product Substances 0.000 description 18
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 17
- 230000003750 conditioning effect Effects 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000012300 argon atmosphere Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 230000036407 pain Effects 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- 101100386518 Caenorhabditis elegans dbl-1 gene Proteins 0.000 description 13
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 12
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 125000001544 thienyl group Chemical group 0.000 description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- WLMQVQNMEOPDKE-UHFFFAOYSA-N 2-ethylnonanenitrile Chemical compound CCCCCCCC(CC)C#N WLMQVQNMEOPDKE-UHFFFAOYSA-N 0.000 description 10
- DEOPEYZZVGZQFC-UHFFFAOYSA-N 4-(dimethylamino)-4-phenylcyclohexan-1-one Chemical compound C=1C=CC=CC=1C1(N(C)C)CCC(=O)CC1 DEOPEYZZVGZQFC-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 229910052731 fluorine Inorganic materials 0.000 description 10
- 229910052740 iodine Inorganic materials 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 9
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 229960001701 chloroform Drugs 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 235000017550 sodium carbonate Nutrition 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
- 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 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 8
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 125000002541 furyl group Chemical group 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 229940098779 methanesulfonic acid Drugs 0.000 description 7
- 108010020615 nociceptin receptor Proteins 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- KBSNWMBGOWOJDD-UHFFFAOYSA-N 4-(dimethylamino)-4-(3-fluorophenyl)cyclohexan-1-one Chemical compound C=1C=CC(F)=CC=1C1(N(C)C)CCC(=O)CC1 KBSNWMBGOWOJDD-UHFFFAOYSA-N 0.000 description 6
- ADDCVOVTPBVIOZ-UHFFFAOYSA-N 8-(dimethylamino)-1,4-dioxaspiro[4.5]decane-8-carbonitrile Chemical compound C1CC(N(C)C)(C#N)CCC21OCCO2 ADDCVOVTPBVIOZ-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 235000011054 acetic acid Nutrition 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 125000001041 indolyl group Chemical group 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 239000012047 saturated solution Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 125000001425 triazolyl group Chemical group 0.000 description 6
- MNELAFNGGZMCMI-UHFFFAOYSA-N 2-(1h-pyrrolo[2,3-b]pyridin-3-yl)ethanol Chemical compound C1=CC=C2C(CCO)=CNC2=N1 MNELAFNGGZMCMI-UHFFFAOYSA-N 0.000 description 5
- DPVUFUOYOCNVCZ-UHFFFAOYSA-N 4-butyl-4-(dimethylamino)cyclohexan-1-one Chemical compound CCCCC1(N(C)C)CCC(=O)CC1 DPVUFUOYOCNVCZ-UHFFFAOYSA-N 0.000 description 5
- 208000000094 Chronic Pain Diseases 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 229940005483 opioid analgesics Drugs 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- VTNCRPWLAMEALN-UHFFFAOYSA-N 2-(2-triethylsilyl-1h-pyrrolo[2,3-b]pyridin-3-yl)ethanol Chemical compound C1=CC=C2C(CCO)=C([Si](CC)(CC)CC)NC2=N1 VTNCRPWLAMEALN-UHFFFAOYSA-N 0.000 description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
- UUDNBWSHTUFGDQ-UHFFFAOYSA-N 3-iodopyridin-2-amine Chemical class NC1=NC=CC=C1I UUDNBWSHTUFGDQ-UHFFFAOYSA-N 0.000 description 4
- MWFVWRDGDVLNIJ-UHFFFAOYSA-N 4-(dimethylamino)-4-thiophen-2-ylcyclohexan-1-one Chemical compound C=1C=CSC=1C1(N(C)C)CCC(=O)CC1 MWFVWRDGDVLNIJ-UHFFFAOYSA-N 0.000 description 4
- OOHVPJGDPFGVNV-UHFFFAOYSA-N 4-(methylamino)-4-phenylcyclohexan-1-one Chemical compound C=1C=CC=CC=1C1(NC)CCC(=O)CC1 OOHVPJGDPFGVNV-UHFFFAOYSA-N 0.000 description 4
- NNVLJFCFBBPALU-UHFFFAOYSA-N 4-benzyl-4-morpholin-4-ylcyclohexan-1-one Chemical compound C1CC(=O)CCC1(N1CCOCC1)CC1=CC=CC=C1 NNVLJFCFBBPALU-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 230000036592 analgesia Effects 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000003373 pyrazinyl group Chemical group 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 229910052723 transition metal Inorganic materials 0.000 description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
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- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102006033114A DE102006033114A1 (de) | 2006-07-18 | 2006-07-18 | Spirocyclische Azaindol-Derivate |
| PCT/EP2007/006326 WO2008009416A1 (de) | 2006-07-18 | 2007-07-17 | Spirocyclische azaindol-derivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2009000670A true MX2009000670A (es) | 2009-01-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2009000670A MX2009000670A (es) | 2006-07-18 | 2007-07-17 | Derivados espirociclicos de azaindol. |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US8399503B2 (enExample) |
| EP (1) | EP2041142B1 (enExample) |
| JP (1) | JP5269784B2 (enExample) |
| KR (1) | KR101421034B1 (enExample) |
| CN (1) | CN101490055B (enExample) |
| AR (1) | AR062079A1 (enExample) |
| AU (1) | AU2007276414B2 (enExample) |
| BR (1) | BRPI0714650A2 (enExample) |
| CA (1) | CA2658379C (enExample) |
| CL (1) | CL2007001917A1 (enExample) |
| DE (1) | DE102006033114A1 (enExample) |
| ES (1) | ES2434114T3 (enExample) |
| IL (1) | IL196525A (enExample) |
| MX (1) | MX2009000670A (enExample) |
| NO (1) | NO342282B1 (enExample) |
| NZ (1) | NZ573688A (enExample) |
| PE (1) | PE20080277A1 (enExample) |
| PL (1) | PL2041142T3 (enExample) |
| RU (1) | RU2468028C2 (enExample) |
| WO (1) | WO2008009416A1 (enExample) |
| ZA (1) | ZA200901128B (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DE102005016460A1 (de) * | 2005-04-11 | 2006-10-19 | Grünenthal GmbH | Spriocyclische Cyclohexanderivate zur Behandlung von Substanzabhängigkeit |
| DE102006033114A1 (de) | 2006-07-18 | 2008-01-24 | Grünenthal GmbH | Spirocyclische Azaindol-Derivate |
| SI2271613T1 (sl) | 2008-03-27 | 2014-08-29 | Grunenthal Gmbh | Hidroksimetilcikloheksilamini |
| AR071066A1 (es) * | 2008-03-27 | 2010-05-26 | Gruenenthal Chemie | Derivados de (hetero) aril-ciclohexano |
| CA2719743A1 (en) | 2008-03-27 | 2009-10-01 | Gruenenthal Gmbh | Substituted cyclohexyldiamines |
| US8288430B2 (en) * | 2008-03-27 | 2012-10-16 | Grunenthal Gmbh | Spiro(5.5)undecane derivatives |
| RU2532545C2 (ru) | 2008-03-27 | 2014-11-10 | Грюненталь Гмбх | Замещенные производные 4-аминоциклогексана |
| TWI450899B (zh) * | 2008-03-27 | 2014-09-01 | 被取代之螺環環已烷衍生物 | |
| EP2575815A4 (en) | 2010-06-04 | 2013-12-25 | Albany Molecular Res Inc | GLYCIN TRANSPORTER 1 INHIBITORS, METHODS OF MAKING THE SAME, AND USES THEREOF |
| TWI582092B (zh) | 2010-07-28 | 2017-05-11 | 歌林達股份有限公司 | 順式－四氫－螺旋（環己烷－１,１’－吡啶［３,４－b］吲哚）－４－胺－衍生物 |
| AR084209A1 (es) | 2010-12-08 | 2013-05-02 | Gruenenthal Gmbh | Metodo para la sintesis de derivados de aminociclohexanona sustituidos |
| CA2942522A1 (en) * | 2014-03-12 | 2015-09-17 | The Trustees Of Columbia University In The City Of New York | 5,5-dioxo-11h-benzo[c][2,1]benzothiazepine derivatives and their use as mu-opioid receptor agonists |
| PL3169666T3 (pl) | 2014-07-15 | 2019-03-29 | Grünenthal GmbH | Podstawione pochodne azaspiro(4,5)dekanu |
| TW201607923A (zh) | 2014-07-15 | 2016-03-01 | 歌林達有限公司 | 被取代之氮螺環（４．５）癸烷衍生物 |
| WO2017049158A1 (en) | 2015-09-16 | 2017-03-23 | The Trustees Of Columbia University In The City Of New York | Carboxylic diarylthiazepineamines as mu-opioid receptor agonists |
| CN117447384B (zh) * | 2023-10-24 | 2024-12-27 | 四川大学 | 一种螺杂环芳基类化合物及其应用 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4065573A (en) | 1976-06-03 | 1977-12-27 | The Upjohn Company | 4-Amino-4-phenylcyclohexanone ketal compositions and process of use |
| JPH06502147A (ja) * | 1990-10-09 | 1994-03-10 | ニューロゲン コーポレイション | 或る種のシクロアルキルおよびアザシクロアルキルピロロピリミジン；新規な種類のｇａｂａ脳リセプタリガンド |
| WO2000038720A1 (en) * | 1998-12-24 | 2000-07-06 | Meiji Seika Kaisha, Ltd. | Remedies for pain |
| GB9918965D0 (en) * | 1999-08-11 | 1999-10-13 | Cerebrus Ltd | Chemical compounds xxi |
| EA005409B1 (ru) * | 2000-04-10 | 2005-02-24 | Пфайзер Продактс Инк. | Производные бензамидопиперидина в качестве антагонистов рецепторов вещества p |
| DE10123163A1 (de) | 2001-05-09 | 2003-01-16 | Gruenenthal Gmbh | Substituierte Cyclohexan-1,4-diaminderivate |
| RU2216737C1 (ru) * | 2002-03-19 | 2003-11-20 | Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова | Способ оценки течения хронического воспалительного процесса в бронхолегочной системе больного муковисцидозом |
| DE10252667A1 (de) * | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| EP1637521B1 (en) * | 2003-06-23 | 2013-06-19 | Ono Pharmaceutical Co., Ltd. | Novel tricyclic heterocycle compound |
| DE10360792A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE10360793A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE102004039382A1 (de) * | 2004-08-13 | 2006-02-23 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| CN101072771B (zh) * | 2004-10-07 | 2010-09-29 | 默沙东公司 | Cgrp受体拮抗剂 |
| EP1829874B1 (en) * | 2004-12-22 | 2014-02-12 | Ono Pharmaceutical Co., Ltd. | Tricyclic compound and use thereof |
| DE102005016460A1 (de) * | 2005-04-11 | 2006-10-19 | Grünenthal GmbH | Spriocyclische Cyclohexanderivate zur Behandlung von Substanzabhängigkeit |
| DE102006019597A1 (de) * | 2006-04-27 | 2007-10-31 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE102006033114A1 (de) | 2006-07-18 | 2008-01-24 | Grünenthal GmbH | Spirocyclische Azaindol-Derivate |
| DE102007009235A1 (de) * | 2007-02-22 | 2008-09-18 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE102007009319A1 (de) * | 2007-02-22 | 2008-08-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| TWI450899B (zh) * | 2008-03-27 | 2014-09-01 | 被取代之螺環環已烷衍生物 |
-
2006
- 2006-07-18 DE DE102006033114A patent/DE102006033114A1/de not_active Withdrawn
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2007
- 2007-06-29 CL CL200701917A patent/CL2007001917A1/es unknown
- 2007-07-16 PE PE2007000917A patent/PE20080277A1/es active IP Right Grant
- 2007-07-16 AR ARP070103151A patent/AR062079A1/es not_active Application Discontinuation
- 2007-07-17 CA CA2658379A patent/CA2658379C/en not_active Expired - Fee Related
- 2007-07-17 ES ES07786123T patent/ES2434114T3/es active Active
- 2007-07-17 EP EP07786123.5A patent/EP2041142B1/de active Active
- 2007-07-17 AU AU2007276414A patent/AU2007276414B2/en not_active Ceased
- 2007-07-17 BR BRPI0714650-7A patent/BRPI0714650A2/pt not_active Application Discontinuation
- 2007-07-17 CN CN2007800272998A patent/CN101490055B/zh not_active Expired - Fee Related
- 2007-07-17 KR KR1020097003277A patent/KR101421034B1/ko not_active Expired - Fee Related
- 2007-07-17 MX MX2009000670A patent/MX2009000670A/es active IP Right Grant
- 2007-07-17 JP JP2009519861A patent/JP5269784B2/ja not_active Expired - Fee Related
- 2007-07-17 WO PCT/EP2007/006326 patent/WO2008009416A1/de not_active Ceased
- 2007-07-17 PL PL07786123T patent/PL2041142T3/pl unknown
- 2007-07-17 NZ NZ573688A patent/NZ573688A/en not_active IP Right Cessation
- 2007-07-17 RU RU2009105399/04A patent/RU2468028C2/ru not_active IP Right Cessation
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2009
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- 2009-01-15 US US12/354,001 patent/US8399503B2/en not_active Expired - Fee Related
- 2009-01-19 NO NO20090294A patent/NO342282B1/no not_active IP Right Cessation
- 2009-02-17 ZA ZA2009/01128A patent/ZA200901128B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20090294L (no) | 2009-03-31 |
| EP2041142A1 (de) | 2009-04-01 |
| JP5269784B2 (ja) | 2013-08-21 |
| IL196525A0 (en) | 2009-11-18 |
| NZ573688A (en) | 2011-12-22 |
| KR20090035708A (ko) | 2009-04-10 |
| PL2041142T3 (pl) | 2014-01-31 |
| CN101490055A (zh) | 2009-07-22 |
| BRPI0714650A2 (pt) | 2013-04-02 |
| RU2009105399A (ru) | 2010-08-27 |
| US20090156593A1 (en) | 2009-06-18 |
| ES2434114T3 (es) | 2013-12-13 |
| HK1129676A1 (en) | 2009-12-04 |
| WO2008009416A1 (de) | 2008-01-24 |
| US8399503B2 (en) | 2013-03-19 |
| RU2468028C2 (ru) | 2012-11-27 |
| AU2007276414A1 (en) | 2008-01-24 |
| AR062079A1 (es) | 2008-10-15 |
| JP2009543825A (ja) | 2009-12-10 |
| CA2658379C (en) | 2014-05-06 |
| AU2007276414B2 (en) | 2012-05-31 |
| DE102006033114A1 (de) | 2008-01-24 |
| EP2041142B1 (de) | 2013-10-09 |
| IL196525A (en) | 2015-07-30 |
| NO342282B1 (no) | 2018-04-30 |
| KR101421034B1 (ko) | 2014-07-22 |
| ZA200901128B (en) | 2009-12-30 |
| PE20080277A1 (es) | 2008-04-11 |
| CN101490055B (zh) | 2013-10-16 |
| CL2007001917A1 (es) | 2008-03-14 |
| CA2658379A1 (en) | 2008-01-24 |
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