MX2010010446A - Derivados de (hetero)arilo ciclohexano. - Google Patents
Derivados de (hetero)arilo ciclohexano.Info
- Publication number
- MX2010010446A MX2010010446A MX2010010446A MX2010010446A MX2010010446A MX 2010010446 A MX2010010446 A MX 2010010446A MX 2010010446 A MX2010010446 A MX 2010010446A MX 2010010446 A MX2010010446 A MX 2010010446A MX 2010010446 A MX2010010446 A MX 2010010446A
- Authority
- MX
- Mexico
- Prior art keywords
- indol
- nhc
- aliphatic
- methyl
- dimethyl
- Prior art date
Links
- -1 aryl cyclohexane derivatives Chemical class 0.000 title claims description 95
- 150000001875 compounds Chemical class 0.000 claims abstract description 165
- 239000000203 mixture Substances 0.000 claims abstract description 64
- 238000004519 manufacturing process Methods 0.000 claims abstract description 53
- 239000003814 drug Substances 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 19
- 229940079593 drug Drugs 0.000 claims abstract description 17
- 125000001931 aliphatic group Chemical group 0.000 claims description 138
- 125000003118 aryl group Chemical group 0.000 claims description 72
- 229910052757 nitrogen Inorganic materials 0.000 claims description 62
- 125000001424 substituent group Chemical group 0.000 claims description 50
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 49
- 125000001246 bromo group Chemical group Br* 0.000 claims description 39
- 125000005842 heteroatom Chemical group 0.000 claims description 34
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 229920006395 saturated elastomer Polymers 0.000 claims description 30
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 208000002193 Pain Diseases 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 238000006467 substitution reaction Methods 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 108020001612 μ-opioid receptors Proteins 0.000 claims description 13
- 229910006069 SO3H Inorganic materials 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- 102000051367 mu Opioid Receptors Human genes 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
- 229940005483 opioid analgesics Drugs 0.000 claims description 10
- 102000005962 receptors Human genes 0.000 claims description 10
- 108020003175 receptors Proteins 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- SDTNARWMABOGPN-UHFFFAOYSA-N N1=CC=C(C=C1)CCC1=C(NC2=CC=CC=C12)C1(CCCCC1)N Chemical compound N1=CC=C(C=C1)CCC1=C(NC2=CC=CC=C12)C1(CCCCC1)N SDTNARWMABOGPN-UHFFFAOYSA-N 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- YKEWDKRXVHSLCC-UHFFFAOYSA-N 1-(5-fluoro-3-methyl-1H-indol-2-yl)-N,N-dimethylcyclohexan-1-amine Chemical compound FC=1C=C2C(=C(NC2=CC=1)C1(CCCCC1)N(C)C)C YKEWDKRXVHSLCC-UHFFFAOYSA-N 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 5
- 230000003444 anaesthetic effect Effects 0.000 claims description 5
- IYESVYAQQBUTRX-UHFFFAOYSA-N n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)-1-phenyl-4-thiophen-2-ylcyclohexan-1-amine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1(C1=C(C2=CC=CC=C2N1)C)C1=CC=CS1 IYESVYAQQBUTRX-UHFFFAOYSA-N 0.000 claims description 5
- 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 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 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
- 239000012453 solvate Substances 0.000 claims description 4
- 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
- 206010012335 Dependence Diseases 0.000 claims description 3
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 claims description 3
- DBIAXUQJDZDFDY-UHFFFAOYSA-N n,n-dimethyl-4-(3-methyl-1h-indol-2-yl)-1,4-diphenylcyclohexan-1-amine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1(C1=C(C2=CC=CC=C2N1)C)C1=CC=CC=C1 DBIAXUQJDZDFDY-UHFFFAOYSA-N 0.000 claims description 3
- 125000003367 polycyclic group Chemical group 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 125000006655 (C3-C8) heteroaryl group Chemical group 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- 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 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000032841 Bulimia Diseases 0.000 claims description 2
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
- MZIWEDIFUMWYAE-UHFFFAOYSA-N C(CC)(=O)OC=1NC2=CC=CC=C2C1OC(CC)=O Chemical compound C(CC)(=O)OC=1NC2=CC=CC=C2C1OC(CC)=O MZIWEDIFUMWYAE-UHFFFAOYSA-N 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims description 2
- 206010012735 Diarrhoea Diseases 0.000 claims description 2
- 208000030814 Eating disease Diseases 0.000 claims description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000001953 Hypotension Diseases 0.000 claims description 2
- 208000019695 Migraine 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
- 125000002723 alicyclic group Chemical group 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
- 230000036506 anxiety Effects 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
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 230000036543 hypotension Effects 0.000 claims description 2
- 230000008991 intestinal motility Effects 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- 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 2
- DDGIBQURIZDQMM-UHFFFAOYSA-N n,n-dimethyl-4,4-bis(3-methyl-1h-indol-2-yl)-1-phenylcyclohexan-1-amine Chemical compound C1CC(C2=C(C3=CC=CC=C3N2)C)(C2=C(C3=CC=CC=C3N2)C)CCC1(N(C)C)C1=CC=CC=C1 DDGIBQURIZDQMM-UHFFFAOYSA-N 0.000 claims description 2
- BIUVCUNDWHNGFO-UHFFFAOYSA-N n-[2-[2-[4-butyl-4-(dimethylamino)-1-(3-methyl-1h-indol-2-yl)cyclohexyl]-1h-indol-3-yl]ethyl]cyclopentanesulfonamide Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)CCNS(=O)(=O)C1CCCC1)C1=C(C)C2=CC=CC=C2N1 BIUVCUNDWHNGFO-UHFFFAOYSA-N 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 239000002858 neurotransmitter agent Substances 0.000 claims description 2
- 230000001777 nootropic effect Effects 0.000 claims description 2
- 239000000014 opioid analgesic Substances 0.000 claims description 2
- 230000012495 positive regulation of renal sodium excretion Effects 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 231100000886 tinnitus Toxicity 0.000 claims description 2
- LKTYBGSDBHRPMR-UHFFFAOYSA-N 1-butyl-n,n-dimethyl-4,4-bis[3-(2-pyridin-4-ylethyl)-1h-indol-2-yl]cyclohexan-1-amine Chemical compound C1CC(CCCC)(N(C)C)CCC1(C1=C(C2=CC=CC=C2N1)CCC=1C=CN=CC=1)C1=C(CCC=2C=CN=CC=2)C2=CC=CC=C2N1 LKTYBGSDBHRPMR-UHFFFAOYSA-N 0.000 claims 1
- 239000002131 composite material Substances 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- DHUZMLVWDUJDMC-UHFFFAOYSA-N n,n,4-trimethyl-4-(3-methyl-1h-indol-2-yl)-1-phenylcyclohexan-1-amine Chemical compound C1CC(C)(C2=C(C3=CC=CC=C3N2)C)CCC1(N(C)C)C1=CC=CC=C1 DHUZMLVWDUJDMC-UHFFFAOYSA-N 0.000 claims 1
- IPOCNSUALLUPCK-UHFFFAOYSA-N n,n-dimethyl-4,4-bis[3-(2-pyridin-4-ylethyl)-1h-indol-2-yl]-1-thiophen-2-ylcyclohexan-1-amine Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCC1(C1=C(C2=CC=CC=C2N1)CCC=1C=CN=CC=1)C=1NC2=CC=CC=C2C=1CCC1=CC=NC=C1 IPOCNSUALLUPCK-UHFFFAOYSA-N 0.000 claims 1
- 239000002664 nootropic agent Substances 0.000 claims 1
- 229930195734 saturated hydrocarbon Natural products 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 abstract description 10
- 102000003840 Opioid Receptors Human genes 0.000 abstract description 6
- 108090000137 Opioid Receptors Proteins 0.000 abstract 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 abstract description 5
- 239000002585 base Substances 0.000 abstract description 4
- 150000007524 organic acids Chemical class 0.000 abstract description 4
- 108010020615 nociceptin receptor Proteins 0.000 abstract description 3
- 235000005985 organic acids Nutrition 0.000 abstract description 2
- 150000004677 hydrates Chemical class 0.000 abstract 2
- 229940127597 CGRP antagonist Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 233
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 231
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 186
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 120
- 235000019439 ethyl acetate Nutrition 0.000 description 78
- 239000000243 solution Substances 0.000 description 76
- 239000007787 solid Substances 0.000 description 71
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 45
- 238000002844 melting Methods 0.000 description 43
- 230000008018 melting Effects 0.000 description 43
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 40
- 239000008346 aqueous phase Substances 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 38
- 238000011161 development Methods 0.000 description 36
- 239000012074 organic phase Substances 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000003786 synthesis reaction Methods 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 101150041968 CDC13 gene Proteins 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 239000012043 crude product Substances 0.000 description 28
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 26
- 229910052938 sodium sulfate Inorganic materials 0.000 description 26
- 235000011152 sodium sulphate Nutrition 0.000 description 26
- 239000012071 phase Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 22
- 239000003921 oil Substances 0.000 description 22
- 238000000926 separation method Methods 0.000 description 21
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 20
- 239000000284 extract Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 239000007832 Na2SO4 Substances 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
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- 239000011734 sodium Substances 0.000 description 16
- 239000002244 precipitate Substances 0.000 description 15
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 14
- 150000002576 ketones Chemical class 0.000 description 14
- 238000001816 cooling Methods 0.000 description 13
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- 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 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- 238000009835 boiling Methods 0.000 description 9
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- 125000000524 functional group Chemical group 0.000 description 9
- 125000001041 indolyl group Chemical group 0.000 description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 8
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- 230000027455 binding Effects 0.000 description 7
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000006073 displacement reaction Methods 0.000 description 6
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- 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
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 230000009471 action Effects 0.000 description 5
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- 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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- 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
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- 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
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- 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)
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- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
|---|---|
| MX2010010446A true MX2010010446A (es) | 2010-11-05 |
Family
ID=39671382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2010010446A MX2010010446A (es) | 2008-03-27 | 2009-03-25 | Derivados de (hetero)arilo 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) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7977370B2 (en) | 2008-03-27 | 2011-07-12 | Gruenenthal Gmbh | (Hetero)aryl cyclohexane derivatives |
| US8288430B2 (en) | 2008-03-27 | 2012-10-16 | Grunenthal Gmbh | Spiro(5.5)undecane derivatives |
| US8288406B2 (en) | 2008-03-27 | 2012-10-16 | Gruenenthal Gmbh | Hydroxymethylcyclohexylamines |
| US8293758B2 (en) | 2008-03-27 | 2012-10-23 | Grunenthal Gmbh | Substituted spirocyclic cyclohexane derivatives |
| US8357705B2 (en) | 2008-03-27 | 2013-01-22 | Gruenenthal Gmbh | Substituted cyclohexyldiamines |
| US8835689B2 (en) | 2008-03-27 | 2014-09-16 | Grünenthal GmbH | Substituted 4-aminocyclohexane derivatives |
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
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7977370B2 (en) | 2008-03-27 | 2011-07-12 | Gruenenthal Gmbh | (Hetero)aryl cyclohexane derivatives |
| US8288430B2 (en) | 2008-03-27 | 2012-10-16 | Grunenthal Gmbh | Spiro(5.5)undecane derivatives |
| US8288406B2 (en) | 2008-03-27 | 2012-10-16 | Gruenenthal Gmbh | Hydroxymethylcyclohexylamines |
| US8293758B2 (en) | 2008-03-27 | 2012-10-23 | Grunenthal Gmbh | Substituted spirocyclic cyclohexane derivatives |
| US8357705B2 (en) | 2008-03-27 | 2013-01-22 | Gruenenthal Gmbh | Substituted cyclohexyldiamines |
| US8835689B2 (en) | 2008-03-27 | 2014-09-16 | Grünenthal GmbH | Substituted 4-aminocyclohexane derivatives |
| US9403767B2 (en) | 2008-03-27 | 2016-08-02 | Gruenenthal Gmbh | Substituted 4-aminocyclohexane derivatives |
| US9580386B2 (en) | 2008-03-27 | 2017-02-28 | Grünenthal | Substituted 4-aminocyclohexane derivatives |
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 |
| ES2544488T3 (es) | 2015-08-31 |
| 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 |
| 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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