ES2544488T3 - Derivados de (hetero)aril-ciclohexano - Google Patents
Derivados de (hetero)aril-ciclohexano Download PDFInfo
- Publication number
- ES2544488T3 ES2544488T3 ES09725704.2T ES09725704T ES2544488T3 ES 2544488 T3 ES2544488 T3 ES 2544488T3 ES 09725704 T ES09725704 T ES 09725704T ES 2544488 T3 ES2544488 T3 ES 2544488T3
- Authority
- ES
- Spain
- Prior art keywords
- nhc
- indole
- nhr0
- aliphatic
- methyl
- Prior art date
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- 125000005842 heteroatom Chemical group 0.000 title claims abstract description 31
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 118
- 239000000203 mixture Substances 0.000 claims abstract description 104
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 78
- 125000003118 aryl group Chemical group 0.000 claims abstract description 64
- 125000001424 substituent group Chemical group 0.000 claims abstract description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 21
- 229910006069 SO3H Inorganic materials 0.000 claims abstract description 18
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- 125000003367 polycyclic group Chemical group 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
- 238000006467 substitution reaction Methods 0.000 claims abstract description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000002723 alicyclic group Chemical group 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 3
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 239000011593 sulfur Substances 0.000 claims abstract description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 2
- -1 -SH Chemical group 0.000 claims description 135
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 28
- 239000003814 drug Substances 0.000 claims description 23
- 208000002193 Pain Diseases 0.000 claims description 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 230000036407 pain Effects 0.000 claims description 10
- LEUQQELOTXEJAG-UHFFFAOYSA-N 1-(3-fluorophenyl)-n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)-4-thiophen-2-ylcyclohexan-1-amine Chemical compound C1CC(N(C)C)(C=2C=C(F)C=CC=2)CCC1(C1=C(C2=CC=CC=C2N1)C)C1=CC=CS1 LEUQQELOTXEJAG-UHFFFAOYSA-N 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- YFXBMXXXKCCOIV-UHFFFAOYSA-N 1-butyl-4,4-bis(1,3-dimethylindol-2-yl)-n,n-dimethylcyclohexan-1-amine Chemical compound C1CC(CCCC)(N(C)C)CCC1(C=1N(C2=CC=CC=C2C=1C)C)C1=C(C)C2=CC=CC=C2N1C YFXBMXXXKCCOIV-UHFFFAOYSA-N 0.000 claims description 5
- KDQMUHLWMMPREV-UHFFFAOYSA-N 1-butyl-4,4-bis[3-[2-(3,4-dihydro-1h-isoquinolin-2-yl)ethyl]-1h-indol-2-yl]-n,n-dimethylcyclohexan-1-amine Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)CCN1CC2=CC=CC=C2CC1)C1=C(CCN2CC3=CC=CC=C3CC2)C2=CC=CC=C2N1 KDQMUHLWMMPREV-UHFFFAOYSA-N 0.000 claims description 5
- CLQBMEKBDZXMBN-UHFFFAOYSA-N 4-[3-(2-aminoethyl)-1h-indol-2-yl]-1-butyl-n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)cyclohexan-1-amine Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)CCN)C1=C(C)C2=CC=CC=C2N1 CLQBMEKBDZXMBN-UHFFFAOYSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 230000003444 anaesthetic effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- NOHFAXTYQMYOOD-UHFFFAOYSA-N 1-butyl-4-(1,3-dimethylindol-2-yl)-n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)cyclohexan-1-amine Chemical compound C1CC(CCCC)(N(C)C)CCC1(C=1N(C2=CC=CC=C2C=1C)C)C1=C(C)C2=CC=CC=C2N1 NOHFAXTYQMYOOD-UHFFFAOYSA-N 0.000 claims description 4
- WSCQZQRYQBQGLM-UHFFFAOYSA-N 1-butyl-n,n-dimethyl-4,4-bis(3-methyl-1h-indol-2-yl)cyclohexan-1-amine Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)C)C1=C(C)C2=CC=CC=C2N1 WSCQZQRYQBQGLM-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000004880 Polyuria Diseases 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 230000035619 diuresis Effects 0.000 claims description 4
- UIWRWOAJDRHUIH-UHFFFAOYSA-N 1-[2-[2-[4-butyl-4-(dimethylamino)-1-(3-methyl-1h-indol-2-yl)cyclohexyl]-1h-indol-3-yl]ethyl]-3-phenylurea Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)CCNC(=O)NC=1C=CC=CC=1)C1=C(C)C2=CC=CC=C2N1 UIWRWOAJDRHUIH-UHFFFAOYSA-N 0.000 claims description 3
- HIIRPBXAWXPDIH-UHFFFAOYSA-N 1-[2-[2-[4-butyl-4-(dimethylamino)-1-(5-fluoro-3-methyl-1h-indol-2-yl)cyclohexyl]-1h-indol-3-yl]ethyl]-3-phenylurea Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)CCNC(=O)NC=1C=CC=CC=1)C1=C(C)C2=CC(F)=CC=C2N1 HIIRPBXAWXPDIH-UHFFFAOYSA-N 0.000 claims description 3
- IPDAUJTVWRMFKT-UHFFFAOYSA-N 1-benzyl-n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)-4-thiophen-2-ylcyclohexan-1-amine Chemical compound C1CC(C2=C(C3=CC=CC=C3N2)C)(C=2SC=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 IPDAUJTVWRMFKT-UHFFFAOYSA-N 0.000 claims description 3
- IKMCGLBRZOQHPZ-UHFFFAOYSA-N 1-butyl-4,4-bis(5-fluoro-3-methyl-1h-indol-2-yl)-n,n-dimethylcyclohexan-1-amine Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC(F)=CC=C2N1)C)C1=C(C)C2=CC(F)=CC=C2N1 IKMCGLBRZOQHPZ-UHFFFAOYSA-N 0.000 claims description 3
- CDTIOGUIESQOJT-UHFFFAOYSA-N 1-phenyl-3-[2-(phenylcarbamoylamino)ethyl]urea Chemical compound C=1C=CC=CC=1NC(=O)NCCNC(=O)NC1=CC=CC=C1 CDTIOGUIESQOJT-UHFFFAOYSA-N 0.000 claims description 3
- CBISQFFYOFELJO-UHFFFAOYSA-N 2-[4-butyl-1-[3-(2-pyridin-4-ylethyl)-1h-indol-2-yl]-4-pyrrolidin-1-ylcyclohexyl]-3-(2-pyridin-4-ylethyl)-1h-indole Chemical compound C1CC(CCCC)(N2CCCC2)CCC1(C1=C(C2=CC=CC=C2N1)CCC=1C=CN=CC=1)C=1NC2=CC=CC=C2C=1CCC1=CC=NC=C1 CBISQFFYOFELJO-UHFFFAOYSA-N 0.000 claims description 3
- HUZILLSKENSLEU-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-yl)-n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)-1-phenylcyclohexan-1-amine Chemical compound C1CC(C=2C=C3OCOC3=CC=2)(C2=C(C3=CC=CC=C3N2)C)CCC1(N(C)C)C1=CC=CC=C1 HUZILLSKENSLEU-UHFFFAOYSA-N 0.000 claims description 3
- ZIQYOEDFEFSRQJ-UHFFFAOYSA-N 4-(3-methoxyphenyl)-n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)-1-phenylcyclohexan-1-amine Chemical compound COC1=CC=CC(C2(CCC(CC2)(N(C)C)C=2C=CC=CC=2)C2=C(C3=CC=CC=C3N2)C)=C1 ZIQYOEDFEFSRQJ-UHFFFAOYSA-N 0.000 claims description 3
- FIQQPFFLTHVIBR-UHFFFAOYSA-N 4-(4-methoxyphenyl)-n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)-1-phenylcyclohexan-1-amine Chemical compound C1=CC(OC)=CC=C1C1(C2=C(C3=CC=CC=C3N2)C)CCC(C=2C=CC=CC=2)(N(C)C)CC1 FIQQPFFLTHVIBR-UHFFFAOYSA-N 0.000 claims description 3
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 238000002483 medication Methods 0.000 claims description 3
- IVECIWLVOYDMRU-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O.COC(C)=O IVECIWLVOYDMRU-UHFFFAOYSA-N 0.000 claims description 3
- WTOAGNDKKZGSMX-UHFFFAOYSA-N n,n-dimethyl-1-phenyl-4-[3-(2-pyridin-4-ylethyl)-1h-indol-2-yl]-4-thiophen-2-ylcyclohexan-1-amine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1(C1=C(C2=CC=CC=C2N1)CCC=1C=CN=CC=1)C1=CC=CS1 WTOAGNDKKZGSMX-UHFFFAOYSA-N 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- IZWDLGKGBTTWEK-UHFFFAOYSA-N 2-[2-[2-[4-butyl-4-(dimethylamino)-1-(3-methyl-1h-indol-2-yl)cyclohexyl]-1h-indol-3-yl]ethyl]isoindole-1,3-dione Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)CCN1C(C2=CC=CC=C2C1=O)=O)C1=C(C)C2=CC=CC=C2N1 IZWDLGKGBTTWEK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010012735 Diarrhoea Diseases 0.000 claims description 2
- 208000030814 Eating disease Diseases 0.000 claims description 2
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- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000001953 Hypotension Diseases 0.000 claims description 2
- 206010021118 Hypotonia Diseases 0.000 claims description 2
- 208000020358 Learning disease Diseases 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000026251 Opioid-Related disease Diseases 0.000 claims description 2
- 208000003251 Pruritus Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000009205 Tinnitus Diseases 0.000 claims description 2
- 206010046543 Urinary incontinence Diseases 0.000 claims description 2
- 208000022531 anorexia Diseases 0.000 claims description 2
- 230000001773 anti-convulsant effect Effects 0.000 claims description 2
- 239000001961 anticonvulsive agent Substances 0.000 claims description 2
- 229960003965 antiepileptics Drugs 0.000 claims description 2
- 239000002249 anxiolytic agent Substances 0.000 claims description 2
- 230000000949 anxiolytic effect Effects 0.000 claims description 2
- 238000011260 co-administration Methods 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 235000014632 disordered eating Nutrition 0.000 claims description 2
- 239000006185 dispersion Substances 0.000 claims description 2
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- 230000036543 hypotension Effects 0.000 claims description 2
- 230000008991 intestinal motility Effects 0.000 claims description 2
- 201000003723 learning disability Diseases 0.000 claims description 2
- 230000003137 locomotive effect Effects 0.000 claims description 2
- WVEOSJLLKNIUFL-UHFFFAOYSA-N methyl propanoate Chemical compound CCC(=O)OC.CCC(=O)OC WVEOSJLLKNIUFL-UHFFFAOYSA-N 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 230000037023 motor activity Effects 0.000 claims description 2
- 230000036640 muscle relaxation Effects 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
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- 239000002858 neurotransmitter agent Substances 0.000 claims description 2
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- 239000000014 opioid analgesic Substances 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
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- 208000020401 Depressive disease Diseases 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 239
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 211
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 198
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 120
- 239000007787 solid Substances 0.000 description 73
- 235000019439 ethyl acetate Nutrition 0.000 description 67
- 239000000243 solution Substances 0.000 description 67
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 66
- 238000002844 melting Methods 0.000 description 44
- 230000008018 melting Effects 0.000 description 44
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
- 229910052938 sodium sulfate Inorganic materials 0.000 description 43
- 235000011152 sodium sulphate Nutrition 0.000 description 43
- 230000015572 biosynthetic process Effects 0.000 description 42
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 40
- 238000003786 synthesis reaction Methods 0.000 description 39
- 239000008346 aqueous phase Substances 0.000 description 38
- 238000000746 purification Methods 0.000 description 37
- 239000007832 Na2SO4 Substances 0.000 description 35
- 239000012074 organic phase Substances 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 34
- 239000000047 product Substances 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 29
- 239000012043 crude product Substances 0.000 description 29
- 238000004440 column chromatography Methods 0.000 description 27
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
- 239000012071 phase Substances 0.000 description 22
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical compound C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 22
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 21
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- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 20
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- 125000000217 alkyl group Chemical group 0.000 description 15
- 150000002576 ketones Chemical class 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 14
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
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- 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 10
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- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
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- 241001465754 Metazoa Species 0.000 description 6
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- 125000004093 cyano group Chemical group *C#N 0.000 description 6
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- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P1/12—Antidiarrhoeals
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Nutrition Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08005797 | 2008-03-27 | ||
| EP08005797 | 2008-03-27 | ||
| PCT/EP2009/002172 WO2009118163A1 (de) | 2008-03-27 | 2009-03-25 | (hetero-)aryl-cyclohexan-derivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2544488T3 true ES2544488T3 (es) | 2015-08-31 |
Family
ID=39671382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09725704.2T Active ES2544488T3 (es) | 2008-03-27 | 2009-03-25 | Derivados de (hetero)aril-ciclohexano |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7977370B2 (enExample) |
| EP (1) | EP2280941B1 (enExample) |
| JP (1) | JP5650637B2 (enExample) |
| CN (1) | CN102046597B (enExample) |
| AR (1) | AR071066A1 (enExample) |
| AU (1) | AU2009228637B2 (enExample) |
| CA (1) | CA2718209A1 (enExample) |
| CL (1) | CL2009000733A1 (enExample) |
| ES (1) | ES2544488T3 (enExample) |
| HU (1) | HUE026184T2 (enExample) |
| IL (1) | IL208137A (enExample) |
| MX (1) | MX2010010446A (enExample) |
| PE (1) | PE20091657A1 (enExample) |
| PL (1) | PL2280941T3 (enExample) |
| RU (1) | RU2502733C2 (enExample) |
| WO (1) | WO2009118163A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009118163A1 (de) | 2008-03-27 | 2009-10-01 | Grünenthal GmbH | (hetero-)aryl-cyclohexan-derivate |
| PL2271613T3 (pl) | 2008-03-27 | 2014-09-30 | Gruenenthal Gmbh | Hydroksymetylocykloheksyloaminy |
| AR071067A1 (es) | 2008-03-27 | 2010-05-26 | Gruenenthal Chemie | Ciclohexildiaminas sustituidas |
| PT2260042E (pt) | 2008-03-27 | 2011-12-06 | Gruenenthal Gmbh | Derivados de ciclo-hexano espirocíclicos substituídos |
| CA2719736C (en) | 2008-03-27 | 2016-02-09 | Gruenenthal Gmbh | Spiro(5.5)undecane derivatives |
| EP2502907B1 (de) | 2008-03-27 | 2018-08-29 | Grünenthal GmbH | Substituierte 4-Aminocyclohexan-Derivate |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4065573A (en) | 1976-06-03 | 1977-12-27 | The Upjohn Company | 4-Amino-4-phenylcyclohexanone ketal compositions and process of use |
| US4115589A (en) | 1977-05-17 | 1978-09-19 | The Upjohn Company | Compounds, compositions and method of use |
| US4366172A (en) | 1977-09-29 | 1982-12-28 | The Upjohn Company | 4-Amino-cyclohexanols, their pharmaceutical compositions and methods of use |
| US4239780A (en) * | 1979-10-11 | 1980-12-16 | The Upjohn Company | Phospholipase A2 inhibition |
| DE19830105C1 (de) * | 1998-07-06 | 2000-02-17 | Gruenenthal Gmbh | Acridinderivate |
| US6632836B1 (en) * | 1998-10-30 | 2003-10-14 | Merck & Co., Inc. | Carbocyclic potassium channel inhibitors |
| US6600015B2 (en) * | 2000-04-04 | 2003-07-29 | Hoffmann-La Roche Inc. | Selective linear peptides with melanocortin-4 receptor (MC4-R) agonist activity |
| GB0012240D0 (en) | 2000-05-19 | 2000-07-12 | Merck Sharp & Dohme | Therapeutic agents |
| RU2239642C1 (ru) * | 2000-08-30 | 2004-11-10 | Ф.Хоффманн-Ля Рош Аг | Селективные циклопептиды |
| DE10123163A1 (de) | 2001-05-09 | 2003-01-16 | Gruenenthal Gmbh | Substituierte Cyclohexan-1,4-diaminderivate |
| PE20030320A1 (es) * | 2001-07-17 | 2003-04-03 | Gruenenthal Chemie | Derivados sustituidos de 4-aminociclohexanol |
| DE10135636A1 (de) | 2001-07-17 | 2003-02-06 | Gruenenthal Gmbh | Substituierte 4-Aminocyclohexanole |
| IL159317A0 (en) | 2001-07-18 | 2004-06-01 | Dipiemme Dies And Plastic Mach | A corrugated/undulated sheet having protuberances in the grooves defined by the corrugations, process and apparatus |
| DE10213051B4 (de) | 2002-03-23 | 2013-03-07 | Grünenthal GmbH | Substituierte 4-Aminocyclohexanole |
| DE10252650A1 (de) | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Cyclohexyl-Harnstoff-Derivate |
| DE10252667A1 (de) | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE10252665A1 (de) | 2002-11-11 | 2004-06-03 | Grünenthal GmbH | 4-Aminomethyl-1-aryl-cyclohexylamin-Derivate |
| DE10252666A1 (de) | 2002-11-11 | 2004-08-05 | Grünenthal GmbH | N-Piperidyl-cyclohexan-Derivate |
| ES2279195T3 (es) | 2002-11-12 | 2007-08-16 | Grunenthal Gmbh | Derivados de 4-alquil/4-alquenil/4-alquenilmetil/-1-arilciclohexilamina. |
| WO2004043902A1 (de) | 2002-11-12 | 2004-05-27 | Grünenthal GmbH | 4-hydroxymethyl-1-aryl-cyclohexylamin-derivative |
| 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 |
| DE102004023508A1 (de) | 2004-05-10 | 2005-12-08 | Grünenthal GmbH | Säurederivate substituierter Cyclohexyl-1,4-diamine |
| DE102004023507A1 (de) | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Substituierte Cyclohexylessigsäure-Derivate |
| DE102004023635A1 (de) | 2004-05-10 | 2006-04-13 | Grünenthal GmbH | Heteroarylsubstituierte Cyclohexyl-1,4-diamin-Derivate |
| DE102004023632A1 (de) | 2004-05-10 | 2005-12-08 | Grünenthal GmbH | Substituierte Cyclohexylcarbonsäure-Derivate |
| DE102004023522A1 (de) | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Substituierte Cyclohexyl-1,4-diamin-Derivate |
| DE102004023501A1 (de) | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Oxosubstituierte Cyclohexyl-1,4-diamin-Derivate |
| DE102004023506A1 (de) | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Kettenverlängerte substituierte Cyclohexyl-1,4-diamin-Derivate |
| DE102004039382A1 (de) | 2004-08-13 | 2006-02-23 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE102005016460A1 (de) | 2005-04-11 | 2006-10-19 | Grünenthal GmbH | Spriocyclische Cyclohexanderivate zur Behandlung von Substanzabhängigkeit |
| DE102005061427A1 (de) | 2005-12-22 | 2007-06-28 | Grünenthal GmbH | Substituierte Oxadiazol-Derivate |
| DE102005061429A1 (de) | 2005-12-22 | 2007-06-28 | Grünenthal GmbH | Substituierte Oxazol-Derivate |
| DE102005061430A1 (de) | 2005-12-22 | 2007-07-05 | Grünenthal GmbH | Substituierte Imidazolin-Derivate |
| DE102005061428A1 (de) | 2005-12-22 | 2007-08-16 | Grünenthal GmbH | Substituierte Cyclohexylmethyl-Derivate |
| DE102006019597A1 (de) | 2006-04-27 | 2007-10-31 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| FR2902695B1 (fr) * | 2006-06-26 | 2009-11-20 | Packaging Partner | Etiquette d'information inviolable |
| DE102006033109A1 (de) * | 2006-07-18 | 2008-01-31 | Grünenthal GmbH | Substituierte Heteroaryl-Derivate |
| DE102006033114A1 (de) * | 2006-07-18 | 2008-01-24 | Grünenthal GmbH | Spirocyclische Azaindol-Derivate |
| CN101610761A (zh) * | 2006-12-22 | 2009-12-23 | 诺瓦提斯公司 | 作为ddp-iv抑制剂的1-氨基甲基-l-苯基-环己烷衍生物 |
| EP2179104A4 (en) | 2007-07-13 | 2012-01-18 | Tinnerman Palnut Engineered Products | SEAM CLAMP WITH HEAT LOCK |
| CA2719736C (en) | 2008-03-27 | 2016-02-09 | Gruenenthal Gmbh | Spiro(5.5)undecane derivatives |
| PL2271613T3 (pl) | 2008-03-27 | 2014-09-30 | Gruenenthal Gmbh | Hydroksymetylocykloheksyloaminy |
| EP2502907B1 (de) | 2008-03-27 | 2018-08-29 | Grünenthal GmbH | Substituierte 4-Aminocyclohexan-Derivate |
| AR071067A1 (es) | 2008-03-27 | 2010-05-26 | Gruenenthal Chemie | Ciclohexildiaminas sustituidas |
| WO2009118163A1 (de) | 2008-03-27 | 2009-10-01 | Grünenthal GmbH | (hetero-)aryl-cyclohexan-derivate |
| PT2260042E (pt) | 2008-03-27 | 2011-12-06 | Gruenenthal Gmbh | Derivados de ciclo-hexano espirocíclicos substituídos |
-
2009
- 2009-03-25 WO PCT/EP2009/002172 patent/WO2009118163A1/de not_active Ceased
- 2009-03-25 PL PL09725704T patent/PL2280941T3/pl unknown
- 2009-03-25 AR ARP090101056A patent/AR071066A1/es unknown
- 2009-03-25 CA CA2718209A patent/CA2718209A1/en not_active Abandoned
- 2009-03-25 ES ES09725704.2T patent/ES2544488T3/es active Active
- 2009-03-25 JP JP2011501139A patent/JP5650637B2/ja not_active Expired - Fee Related
- 2009-03-25 MX MX2010010446A patent/MX2010010446A/es active IP Right Grant
- 2009-03-25 US US12/410,692 patent/US7977370B2/en not_active Expired - Fee Related
- 2009-03-25 RU RU2010143451/04A patent/RU2502733C2/ru not_active IP Right Cessation
- 2009-03-25 EP EP20090725704 patent/EP2280941B1/de not_active Not-in-force
- 2009-03-25 CL CL2009000733A patent/CL2009000733A1/es unknown
- 2009-03-25 AU AU2009228637A patent/AU2009228637B2/en not_active Ceased
- 2009-03-25 CN CN2009801201880A patent/CN102046597B/zh not_active Expired - Fee Related
- 2009-03-25 PE PE2009000444A patent/PE20091657A1/es not_active Application Discontinuation
- 2009-03-25 HU HUE09725704A patent/HUE026184T2/en unknown
-
2010
- 2010-09-14 IL IL208137A patent/IL208137A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2502733C2 (ru) | 2013-12-27 |
| CN102046597B (zh) | 2013-09-11 |
| AU2009228637A1 (en) | 2009-10-01 |
| CN102046597A (zh) | 2011-05-04 |
| HK1153744A1 (zh) | 2012-04-05 |
| US7977370B2 (en) | 2011-07-12 |
| WO2009118163A1 (de) | 2009-10-01 |
| US20090247573A1 (en) | 2009-10-01 |
| AR071066A1 (es) | 2010-05-26 |
| PE20091657A1 (es) | 2009-11-07 |
| EP2280941A1 (de) | 2011-02-09 |
| JP5650637B2 (ja) | 2015-01-07 |
| CL2009000733A1 (es) | 2009-05-15 |
| IL208137A (en) | 2015-10-29 |
| IL208137A0 (en) | 2010-12-30 |
| EP2280941B1 (de) | 2015-05-06 |
| PL2280941T3 (pl) | 2015-10-30 |
| MX2010010446A (es) | 2010-11-05 |
| CA2718209A1 (en) | 2009-10-01 |
| RU2010143451A (ru) | 2012-05-10 |
| AU2009228637B2 (en) | 2013-12-19 |
| HUE026184T2 (en) | 2016-05-30 |
| JP2011515429A (ja) | 2011-05-19 |
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