NO328600B1 - Substituerte sykloheksan-1,4-diaminderivater, anvendelse derav, fremgangsmate for fremstilling derav og legemidler inneholdende slike derivater - Google Patents
Substituerte sykloheksan-1,4-diaminderivater, anvendelse derav, fremgangsmate for fremstilling derav og legemidler inneholdende slike derivater Download PDFInfo
- Publication number
- NO328600B1 NO328600B1 NO20034930A NO20034930A NO328600B1 NO 328600 B1 NO328600 B1 NO 328600B1 NO 20034930 A NO20034930 A NO 20034930A NO 20034930 A NO20034930 A NO 20034930A NO 328600 B1 NO328600 B1 NO 328600B1
- Authority
- NO
- Norway
- Prior art keywords
- unsubstituted
- polysubstituted
- singly
- case
- saturated
- Prior art date
Links
- VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical class NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 title claims description 125
- 239000003814 drug Substances 0.000 title claims description 52
- 229940079593 drug Drugs 0.000 title claims description 34
- 238000000034 method Methods 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 12
- 230000008569 process Effects 0.000 title claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 548
- 125000001072 heteroaryl group Chemical group 0.000 claims description 535
- 125000003118 aryl group Chemical group 0.000 claims description 524
- 125000000217 alkyl group Chemical group 0.000 claims description 284
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 280
- -1 acenaphthyl Chemical group 0.000 claims description 260
- 239000000203 mixture Substances 0.000 claims description 140
- 150000003839 salts Chemical class 0.000 claims description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims description 106
- 229910052799 carbon Inorganic materials 0.000 claims description 88
- 125000002541 furyl group Chemical group 0.000 claims description 88
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 82
- 125000002947 alkylene group Chemical group 0.000 claims description 81
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
- 125000001544 thienyl group Chemical group 0.000 claims description 76
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 75
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 75
- 239000002253 acid Substances 0.000 claims description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 69
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 69
- 125000006239 protecting group Chemical group 0.000 claims description 65
- 150000007513 acids Chemical class 0.000 claims description 64
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 63
- 125000001041 indolyl group Chemical group 0.000 claims description 63
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 63
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 63
- 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 claims description 62
- 125000000623 heterocyclic group Chemical group 0.000 claims description 57
- 125000001624 naphthyl group Chemical group 0.000 claims description 57
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 50
- 125000004076 pyridyl group Chemical group 0.000 claims description 49
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 42
- 101100448208 Human herpesvirus 6B (strain Z29) U69 gene Proteins 0.000 claims description 40
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 38
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 36
- 150000001768 cations Chemical class 0.000 claims description 35
- 125000004429 atom Chemical group 0.000 claims description 34
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 32
- 238000002156 mixing Methods 0.000 claims description 31
- 150000004677 hydrates Chemical class 0.000 claims description 30
- 208000002193 Pain Diseases 0.000 claims description 29
- 239000012453 solvate Substances 0.000 claims description 29
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 28
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 26
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 25
- 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 25
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 25
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 25
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 125000005605 benzo group Chemical group 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000003914 fluoranthenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC=C4C1=C23)* 0.000 claims description 18
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 17
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 239000013543 active substance Substances 0.000 claims description 15
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 14
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 14
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 14
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 14
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 14
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 14
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 13
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
- 229940126601 medicinal product Drugs 0.000 claims description 13
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 12
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 230000036407 pain Effects 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- 238000011260 co-administration Methods 0.000 claims description 10
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 10
- 208000004296 neuralgia Diseases 0.000 claims description 10
- 208000021722 neuropathic pain Diseases 0.000 claims description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- 208000000094 Chronic Pain Diseases 0.000 claims description 9
- 229910003204 NH2 Inorganic materials 0.000 claims description 9
- 230000001154 acute effect Effects 0.000 claims description 9
- 208000005298 acute pain Diseases 0.000 claims description 9
- 239000000654 additive Substances 0.000 claims description 9
- 230000002981 neuropathic effect Effects 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- BWWVPRAFFGGRNT-UHFFFAOYSA-N 1-n,1-n-dimethyl-4-n-[(1-methylindol-3-yl)methyl]-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NCC=2C3=CC=CC=C3N(C)C=2)CCC1(N(C)C)C1=CC=CC=C1 BWWVPRAFFGGRNT-UHFFFAOYSA-N 0.000 claims description 8
- SIMLFUJOTUODCL-UHFFFAOYSA-N 4-n-(1h-indol-3-ylmethyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 SIMLFUJOTUODCL-UHFFFAOYSA-N 0.000 claims description 8
- GKKDBSVWRIIQDJ-UHFFFAOYSA-N 4-n-[2-(1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NCCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 GKKDBSVWRIIQDJ-UHFFFAOYSA-N 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 239000000014 opioid analgesic Substances 0.000 claims description 8
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 7
- SLROLMCJBPHLBQ-UHFFFAOYSA-N 4-n-[1-(1h-indol-3-yl)propan-2-yl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C=1NC2=CC=CC=C2C=1CC(C)NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 SLROLMCJBPHLBQ-UHFFFAOYSA-N 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 7
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 7
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 7
- 239000012964 benzotriazole Substances 0.000 claims description 7
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 7
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 7
- 229930192474 thiophene Natural products 0.000 claims description 7
- FTHZKCMAGMIUOU-UHFFFAOYSA-N 4-n-(1-benzothiophen-3-ylmethyl)-1-benzyl-1-n,1-n-dimethylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCC=2C3=CC=CC=C3SC=2)CCC1(N(C)C)CC1=CC=CC=C1 FTHZKCMAGMIUOU-UHFFFAOYSA-N 0.000 claims description 6
- YSIKTFCRHQNQEP-UHFFFAOYSA-N 4-n-(1-benzothiophen-3-ylmethyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCC=2C3=CC=CC=C3SC=2)CCC1(N(C)C)C1=CC=CC=C1 YSIKTFCRHQNQEP-UHFFFAOYSA-N 0.000 claims description 6
- YWKWGULBAVUUNJ-UHFFFAOYSA-N 4-n-(1h-indol-3-ylmethyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 YWKWGULBAVUUNJ-UHFFFAOYSA-N 0.000 claims description 6
- ZDSRRNGYNZJQML-UHFFFAOYSA-N 4-n-[2-(1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 ZDSRRNGYNZJQML-UHFFFAOYSA-N 0.000 claims description 6
- WZZNQPJROHVWBF-UHFFFAOYSA-N 4-n-benzyl-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NCC1=CC=CC=C1 WZZNQPJROHVWBF-UHFFFAOYSA-N 0.000 claims description 6
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 6
- 230000003444 anaesthetic effect Effects 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- GJDBQWAQDWEWLG-UHFFFAOYSA-N methyl 2-[[4-(dimethylamino)-4-phenylcyclohexyl]amino]-3-(1h-indol-3-yl)propanoate;dihydrochloride Chemical compound Cl.Cl.C=1NC2=CC=CC=C2C=1CC(C(=O)OC)NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 GJDBQWAQDWEWLG-UHFFFAOYSA-N 0.000 claims 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 claims description 6
- QHLWXDXBURXTFJ-UHFFFAOYSA-N n-[4-(dimethylamino)-4-phenylcyclohexyl]-n-propylbenzamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(=O)N(CCC)C(CC1)CCC1(N(C)C)C1=CC=CC=C1 QHLWXDXBURXTFJ-UHFFFAOYSA-N 0.000 claims description 6
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000006268 reductive amination reaction Methods 0.000 claims description 6
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 6
- LFPWQFOSDUIQPT-UHFFFAOYSA-N 1-n,1-n-dimethyl-4-n-[2-(7-methyl-1h-indol-3-yl)ethyl]-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC=CC(C)=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 LFPWQFOSDUIQPT-UHFFFAOYSA-N 0.000 claims description 5
- COKSNCUEIFGHPQ-UHFFFAOYSA-N 4-n-(1,2-dihydroacenaphthylen-1-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC2C=3C=CC=C4C=CC=C(C=34)C2)CCC1(N(C)C)C1=CC=CC=C1 COKSNCUEIFGHPQ-UHFFFAOYSA-N 0.000 claims description 5
- QCCXRNLUJPYHIT-UHFFFAOYSA-N 4-n-[2-(6-fluoro-1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC=C(F)C=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 QCCXRNLUJPYHIT-UHFFFAOYSA-N 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 5
- HASHIQANERBSQC-UHFFFAOYSA-N 1-n,1-n-dimethyl-1-phenyl-4-n-[2-(5-phenylmethoxy-1h-indol-3-yl)ethyl]cyclohexane-1,4-diamine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NCCC(C1=C2)=CNC1=CC=C2OCC1=CC=CC=C1 HASHIQANERBSQC-UHFFFAOYSA-N 0.000 claims description 4
- OTCYOBLTAQTFPW-UHFFFAOYSA-N 4-aminocyclohexan-1-one Chemical class NC1CCC(=O)CC1 OTCYOBLTAQTFPW-UHFFFAOYSA-N 0.000 claims description 4
- WCCMVPWCXQERET-UHFFFAOYSA-N 4-n-(2,3-dihydro-1h-inden-5-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C=C3CCCC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 WCCMVPWCXQERET-UHFFFAOYSA-N 0.000 claims description 4
- XCMBEDKJGGNRJD-UHFFFAOYSA-N 4-n-(2h-benzotriazol-5-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(NC=2C=C3NN=NC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 XCMBEDKJGGNRJD-UHFFFAOYSA-N 0.000 claims description 4
- GCWMSDSVVBVTSU-UHFFFAOYSA-N 4-n-(9h-fluoren-1-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC=2C3=C(C4=CC=CC=C4C3)C=CC=2)CCC1(N(C)C)C1=CC=CC=C1 GCWMSDSVVBVTSU-UHFFFAOYSA-N 0.000 claims description 4
- WTMUVVVADPHWFA-UHFFFAOYSA-N 4-n-[1-(1h-indol-3-yl)propan-2-yl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C=1NC2=CC=CC=C2C=1CC(C)NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 WTMUVVVADPHWFA-UHFFFAOYSA-N 0.000 claims description 4
- BCLWHBNQUOVGQP-UHFFFAOYSA-N 4-n-[2-(5-methoxy-1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=CC=C2NC=C1CCNC(CC1)CCC1(N(C)C)C1=CC=CC=C1 BCLWHBNQUOVGQP-UHFFFAOYSA-N 0.000 claims description 4
- 208000004880 Polyuria Diseases 0.000 claims description 4
- DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 claims description 4
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexyloxide Natural products O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 4
- 230000035619 diuresis Effects 0.000 claims description 4
- 206010015037 epilepsy Diseases 0.000 claims description 4
- 125000001979 organolithium group Chemical group 0.000 claims description 4
- 125000002524 organometallic group Chemical group 0.000 claims description 4
- 208000011117 substance-related disease Diseases 0.000 claims description 4
- AAAODFPLXSUBKU-UHFFFAOYSA-N 1-benzyl-4-n-(2,3-dihydro-1h-inden-5-yl)-1-n,1-n-dimethylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(NC=2C=C3CCCC3=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 AAAODFPLXSUBKU-UHFFFAOYSA-N 0.000 claims description 3
- IWVNYVJAAMLZKE-UHFFFAOYSA-N 3-[2-[[4-(dimethylamino)-4-phenylcyclohexyl]amino]ethyl]-1h-indol-5-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC(O)=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 IWVNYVJAAMLZKE-UHFFFAOYSA-N 0.000 claims description 3
- KMHBGBIDIAWFBZ-UHFFFAOYSA-N 4-n,1-dibenzyl-1-n,1-n,4-n-trimethylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(CC=2C=CC=CC=2)(N(C)C)CCC1N(C)CC1=CC=CC=C1 KMHBGBIDIAWFBZ-UHFFFAOYSA-N 0.000 claims description 3
- XVRYIRJXMFEBHH-UHFFFAOYSA-N 4-n,1-dibenzyl-1-n,1-n-dimethylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(NCC=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 XVRYIRJXMFEBHH-UHFFFAOYSA-N 0.000 claims description 3
- KYZPFENNMLVYHV-UHFFFAOYSA-N 4-n-(1-benzothiophen-5-yl)-1-benzyl-1-n,1-n-dimethylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC=2C=C3C=CSC3=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 KYZPFENNMLVYHV-UHFFFAOYSA-N 0.000 claims description 3
- QZUSOBGSEVLKEN-UHFFFAOYSA-N 4-n-(1-benzothiophen-5-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(NC=2C=C3C=CSC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 QZUSOBGSEVLKEN-UHFFFAOYSA-N 0.000 claims description 3
- DLYJAIUIOAWQNN-UHFFFAOYSA-N 4-n-(2,1,3-benzothiadiazol-4-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC=2C3=NSN=C3C=CC=2)CCC1(N(C)C)C1=CC=CC=C1 DLYJAIUIOAWQNN-UHFFFAOYSA-N 0.000 claims description 3
- CMONLYZORAQLSA-UHFFFAOYSA-N 4-n-(2,3-dihydro-1h-inden-1-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC2C3=CC=CC=C3CC2)CCC1(N(C)C)C1=CC=CC=C1 CMONLYZORAQLSA-UHFFFAOYSA-N 0.000 claims description 3
- UVDJEWBPNJXYBU-UHFFFAOYSA-N 4-n-(2,3-dihydro-1h-inden-2-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC2CC3=CC=CC=C3C2)CCC1(N(C)C)C1=CC=CC=C1 UVDJEWBPNJXYBU-UHFFFAOYSA-N 0.000 claims description 3
- DDMOTXNBRFKZEJ-UHFFFAOYSA-N 4-n-(9h-fluoren-9-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC2C3=CC=CC=C3C3=CC=CC=C32)CCC1(N(C)C)C1=CC=CC=C1 DDMOTXNBRFKZEJ-UHFFFAOYSA-N 0.000 claims description 3
- SULRCGGASUOCOH-UHFFFAOYSA-N 4-n-(9h-fluoren-9-yl)-1-n,1-n-dimethyl-1-thiophen-2-ylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC2C3=CC=CC=C3C3=CC=CC=C32)CCC1(N(C)C)C1=CC=CS1 SULRCGGASUOCOH-UHFFFAOYSA-N 0.000 claims description 3
- CUXOURJGJJPDMN-UHFFFAOYSA-N 4-n-[1-(1h-indol-3-yl)propan-2-yl]-1-n,1-n-dimethyl-1-thiophen-2-ylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C=1NC2=CC=CC=C2C=1CC(C)NC(CC1)CCC1(N(C)C)C1=CC=CS1 CUXOURJGJJPDMN-UHFFFAOYSA-N 0.000 claims description 3
- NFYSFGUGMVMSNF-UHFFFAOYSA-N 4-n-[2-(1-benzothiophen-3-yl)ethyl]-1-benzyl-1-n,1-n-dimethylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC=CC=C3SC=2)CCC1(N(C)C)CC1=CC=CC=C1 NFYSFGUGMVMSNF-UHFFFAOYSA-N 0.000 claims description 3
- VAHPDRGYKXZMQO-UHFFFAOYSA-N 4-n-[2-(1-benzothiophen-3-yl)ethyl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC=CC=C3SC=2)CCC1(N(C)C)C1=CC=CC=C1 VAHPDRGYKXZMQO-UHFFFAOYSA-N 0.000 claims description 3
- ZWAUCSZYTUGMNU-UHFFFAOYSA-N 4-n-[2-(5-fluoro-1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC(F)=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 ZWAUCSZYTUGMNU-UHFFFAOYSA-N 0.000 claims description 3
- ZZMYTCPYYUIZJM-UHFFFAOYSA-N 4-n-anthracen-2-yl-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(NC=2C=C3C=C4C=CC=CC4=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 ZZMYTCPYYUIZJM-UHFFFAOYSA-N 0.000 claims description 3
- YWOYUMIIQSIDFN-UHFFFAOYSA-N 4-n-cyclooctyl-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NC1CCCCCCC1 YWOYUMIIQSIDFN-UHFFFAOYSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 206010061428 decreased appetite Diseases 0.000 claims description 3
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000008991 intestinal motility Effects 0.000 claims description 3
- 229960005181 morphine Drugs 0.000 claims description 3
- OVADDRWFNTZZCO-UHFFFAOYSA-N n-[4-benzyl-4-(dimethylamino)cyclohexyl]-n-ethylbenzamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(=O)N(CC)C(CC1)CCC1(N(C)C)CC1=CC=CC=C1 OVADDRWFNTZZCO-UHFFFAOYSA-N 0.000 claims description 3
- 230000001777 nootropic effect Effects 0.000 claims description 3
- 235000015816 nutrient absorption Nutrition 0.000 claims description 3
- 150000002923 oximes Chemical class 0.000 claims description 3
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 2
- FTCXWNUJMSGUKP-UHFFFAOYSA-N 1-amino-4-oxocyclohexane-1-carbonitrile Chemical class N#CC1(N)CCC(=O)CC1 FTCXWNUJMSGUKP-UHFFFAOYSA-N 0.000 claims description 2
- KGLIDWVKHUHIJM-UHFFFAOYSA-N 1-benzyl-4-n-(1h-indol-3-ylmethyl)-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)CC1=CC=CC=C1 KGLIDWVKHUHIJM-UHFFFAOYSA-N 0.000 claims description 2
- WRDKADLIWSANTL-UHFFFAOYSA-N 1-benzyl-4-n-(2,3-dihydro-1h-inden-1-yl)-1-n,1-n-dimethylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC2C3=CC=CC=C3CC2)CCC1(N(C)C)CC1=CC=CC=C1 WRDKADLIWSANTL-UHFFFAOYSA-N 0.000 claims description 2
- IVXIJWTXWOZACU-UHFFFAOYSA-N 1-benzyl-4-n-(9h-fluoren-9-yl)-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NC2C3=CC=CC=C3C3=CC=CC=C32)CCC1(N(C)C)CC1=CC=CC=C1 IVXIJWTXWOZACU-UHFFFAOYSA-N 0.000 claims description 2
- VERWNSPZGOPLPB-UHFFFAOYSA-N 1-n,1-n-dimethyl-1-phenyl-4-n-[2-(7-phenylmethoxy-1h-indol-3-yl)ethyl]cyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NCCC(C1=CC=C2)=CNC1=C2OCC1=CC=CC=C1 VERWNSPZGOPLPB-UHFFFAOYSA-N 0.000 claims description 2
- KVIJZAWRBNJWBL-UHFFFAOYSA-N 1-n,1-n-dimethyl-4-n-[2-(5-methyl-1h-indol-3-yl)ethyl]-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCCC=2C3=CC(C)=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 KVIJZAWRBNJWBL-UHFFFAOYSA-N 0.000 claims description 2
- IAEFCRNPARONRL-UHFFFAOYSA-N 4-n-(1,2-dihydroacenaphthylen-5-ylmethyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCC=2C=3C=CC=C4CCC(C=34)=CC=2)CCC1(N(C)C)C1=CC=CC=C1 IAEFCRNPARONRL-UHFFFAOYSA-N 0.000 claims description 2
- OWKQCJIZRRHOLK-UHFFFAOYSA-N 4-n-(1,3-benzothiazol-6-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC=2C=C3SC=NC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 OWKQCJIZRRHOLK-UHFFFAOYSA-N 0.000 claims description 2
- LJRRJZFALGBNMO-UHFFFAOYSA-N 4-n-(2-adamantyl)-1-n,1-n-dimethyl-1-thiophen-2-ylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC2C3CC4CC(C3)CC2C4)CCC1(N(C)C)C1=CC=CS1 LJRRJZFALGBNMO-UHFFFAOYSA-N 0.000 claims description 2
- CORLCBVHAIZVBU-UHFFFAOYSA-N 4-n-[1-(1h-indol-3-yl)propan-2-yl]-1-n,1-n-dimethyl-1-naphthalen-2-ylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1=CC=CC2=CC(C3(N(C)C)CCC(CC3)NC(CC=3C4=CC=CC=C4NC=3)C)=CC=C21 CORLCBVHAIZVBU-UHFFFAOYSA-N 0.000 claims description 2
- RCZZQVRYROAITB-UHFFFAOYSA-N 4-n-cyclooctyl-1-n,1-n-dimethyl-1-thiophen-2-ylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)(C=2SC=CC=2)CCC1NC1CCCCCCC1 RCZZQVRYROAITB-UHFFFAOYSA-N 0.000 claims description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 2
- 239000005695 Ammonium acetate Substances 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- NNFCFDBSQPBMEM-UHFFFAOYSA-N C(C1=CC=CC=C1)C1(CCC(CC1)NC(CC1=CNC2=CC=CC=C12)C)N(C)C.Cl.Cl.C(C1=CC=CC=C1)C1(CCC(CC1)NCC1=CNC2=CC=CC=C12)N(C)C Chemical compound C(C1=CC=CC=C1)C1(CCC(CC1)NC(CC1=CNC2=CC=CC=C12)C)N(C)C.Cl.Cl.C(C1=CC=CC=C1)C1(CCC(CC1)NCC1=CNC2=CC=CC=C12)N(C)C NNFCFDBSQPBMEM-UHFFFAOYSA-N 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 2
- 206010013654 Drug abuse Diseases 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 206010048865 Hypoacusis Diseases 0.000 claims description 2
- 208000001953 Hypotension Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000003251 Pruritus Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000009205 Tinnitus Diseases 0.000 claims description 2
- 125000005219 aminonitrile group Chemical group 0.000 claims description 2
- 235000019257 ammonium acetate Nutrition 0.000 claims description 2
- 229940043376 ammonium acetate Drugs 0.000 claims description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 206010013663 drug dependence Diseases 0.000 claims description 2
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 claims description 2
- 229960003132 halothane Drugs 0.000 claims description 2
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 claims description 2
- 229960002456 hexobarbital Drugs 0.000 claims description 2
- 230000036543 hypotension Effects 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 230000003137 locomotive effect Effects 0.000 claims description 2
- YXIZFWDUIVPYEF-UHFFFAOYSA-N methyl 2-[[4-(dimethylamino)-4-phenylcyclohexyl]amino]-3-(5-fluoro-1h-indol-3-yl)propanoate;dihydrochloride Chemical compound Cl.Cl.C=1NC2=CC=C(F)C=C2C=1CC(C(=O)OC)NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 YXIZFWDUIVPYEF-UHFFFAOYSA-N 0.000 claims description 2
- ACKUCEDPKWPOFN-UHFFFAOYSA-N methyl 2-[[4-(dimethylamino)-4-phenylcyclohexyl]amino]-3-(6-fluoro-1h-indol-3-yl)propanoate;dihydrochloride Chemical compound Cl.Cl.C=1NC2=CC(F)=CC=C2C=1CC(C(=O)OC)NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 ACKUCEDPKWPOFN-UHFFFAOYSA-N 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- OWCATVHFFAQXKR-UHFFFAOYSA-N n-[4-(dimethylamino)-4-phenylcyclohexyl]-2-(1h-indol-3-yl)acetamide;hydrochloride Chemical compound Cl.C1CC(NC(=O)CC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 OWCATVHFFAQXKR-UHFFFAOYSA-N 0.000 claims description 2
- FPPQHVZGMYOKIL-UHFFFAOYSA-N n-[4-(dimethylamino)-4-phenylcyclohexyl]-2-(5-methoxy-1h-indol-3-yl)acetamide;hydrochloride Chemical compound Cl.C12=CC(OC)=CC=C2NC=C1CC(=O)NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 FPPQHVZGMYOKIL-UHFFFAOYSA-N 0.000 claims description 2
- RKTKBXMRPPLWKR-UHFFFAOYSA-N n-[4-(dimethylamino)-4-phenylcyclohexyl]-n-(3-phenylpropyl)acetamide;hydrochloride Chemical compound Cl.C1CC(N(C)C)(C=2C=CC=CC=2)CCC1N(C(C)=O)CCCC1=CC=CC=C1 RKTKBXMRPPLWKR-UHFFFAOYSA-N 0.000 claims description 2
- BCRGUZOQAFKHAS-UHFFFAOYSA-N n-[4-benzyl-4-(dimethylamino)cyclohexyl]-n-methylbenzamide;hydrochloride Chemical compound Cl.C1CC(N(C)C(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 BCRGUZOQAFKHAS-UHFFFAOYSA-N 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 230000002829 reductive effect 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
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 231100000886 tinnitus Toxicity 0.000 claims description 2
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 claims description 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 3
- JVLZDVPESJBVJK-UHFFFAOYSA-N 4-N-(2-adamantyl)-1-N,1-N-dimethyl-1-phenylcyclohexane-1,4-diamine 4-N-(9-ethylcarbazol-3-yl)-1-N,1-N-dimethyl-1-phenylcyclohexane-1,4-diamine tetrahydrochloride Chemical compound Cl.Cl.C(C)N1C2=CC=CC=C2C=2C=C(C=CC12)NC1CCC(CC1)(N(C)C)C1=CC=CC=C1.Cl.Cl.C12C(C3CC(CC(C1)C3)C2)NC2CCC(CC2)(N(C)C)C2=CC=CC=C2 JVLZDVPESJBVJK-UHFFFAOYSA-N 0.000 claims 1
- RNNCHCQTLQFRIU-UHFFFAOYSA-N Cl.CN(C1(CCC(CC1)NCCC)C1=CC=CC=C1)C.Cl.C(C1=CC=CC=C1)C1(CCC(CC1)N(C(C1=CC=CC=C1)=O)CCC)N(C)C Chemical compound Cl.CN(C1(CCC(CC1)NCCC)C1=CC=CC=C1)C.Cl.C(C1=CC=CC=C1)C1(CCC(CC1)N(C(C1=CC=CC=C1)=O)CCC)N(C)C RNNCHCQTLQFRIU-UHFFFAOYSA-N 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- XEODMJOSKRMLIM-UHFFFAOYSA-N methyl 2-[[4-(dimethylamino)-4-thiophen-2-ylcyclohexyl]amino]-3-(1h-indol-3-yl)propanoate;dihydrochloride Chemical compound Cl.Cl.C=1NC2=CC=CC=C2C=1CC(C(=O)OC)NC(CC1)CCC1(N(C)C)C1=CC=CS1 XEODMJOSKRMLIM-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 219
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 166
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 162
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 106
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 98
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- 235000019439 ethyl acetate Nutrition 0.000 description 73
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- 238000010626 work up procedure Methods 0.000 description 56
- 235000011121 sodium hydroxide Nutrition 0.000 description 54
- 239000007787 solid Substances 0.000 description 54
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 52
- 229910052938 sodium sulfate Inorganic materials 0.000 description 51
- 235000011152 sodium sulphate Nutrition 0.000 description 51
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
- 239000000243 solution Substances 0.000 description 49
- 229960000583 acetic acid Drugs 0.000 description 47
- 239000000284 extract Substances 0.000 description 47
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 45
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 44
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 44
- 239000012362 glacial acetic acid Substances 0.000 description 43
- 229910052786 argon Inorganic materials 0.000 description 42
- 239000012043 crude product Substances 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- 239000000741 silica gel Substances 0.000 description 38
- 229910002027 silica gel Inorganic materials 0.000 description 38
- 239000008346 aqueous phase Substances 0.000 description 35
- 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 32
- 239000012071 phase Substances 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 20
- 239000002585 base Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 18
- 108010020615 nociceptin receptor Proteins 0.000 description 16
- SOQQQHJQTOJEOW-UHFFFAOYSA-N 4-benzyl-4-(dimethylamino)cyclohexan-1-one Chemical compound C=1C=CC=CC=1CC1(N(C)C)CCC(=O)CC1 SOQQQHJQTOJEOW-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- JXYGLMATGAAIBU-UHFFFAOYSA-N indol-3-ylmethylamine Chemical compound C1=CC=C2C(CN)=CNC2=C1 JXYGLMATGAAIBU-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 108090000622 Nociceptin Proteins 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- 102000048266 Nociceptin Human genes 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 8
- PULGYDLMFSFVBL-SMFNREODSA-N nociceptin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 PULGYDLMFSFVBL-SMFNREODSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 7
- 238000010792 warming Methods 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 150000001450 anions Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- 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 5
- 241000124008 Mammalia Species 0.000 description 5
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- HWARGPOVTVVFTR-UHFFFAOYSA-N 1-n,1-n-dimethyl-1-phenyl-4-n-propylcyclohexane-1,4-diamine Chemical compound C1CC(NCCC)CCC1(N(C)C)C1=CC=CC=C1 HWARGPOVTVVFTR-UHFFFAOYSA-N 0.000 description 4
- YWXDBWNXMZHMFX-UHFFFAOYSA-N 2-(1-benzothiophen-3-yl)ethanamine Chemical compound C1=CC=C2C(CCN)=CSC2=C1 YWXDBWNXMZHMFX-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- QSQQQURBVYWZKJ-UHFFFAOYSA-N alpha-methyltryptamine Chemical compound C1=CC=C2C(CC(N)C)=CNC2=C1 QSQQQURBVYWZKJ-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- NULYUPNMIHVJPM-UHFFFAOYSA-N n-[4-benzyl-4-(dimethylamino)cyclohexyl]-n-propylbenzamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(=O)N(CCC)C(CC1)CCC1(N(C)C)CC1=CC=CC=C1 NULYUPNMIHVJPM-UHFFFAOYSA-N 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- LEWZOBYWGWKNCK-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-amine Chemical compound NC1=CC=C2CCCC2=C1 LEWZOBYWGWKNCK-UHFFFAOYSA-N 0.000 description 3
- AVKONLBRDWNBAO-UHFFFAOYSA-N 4-(dimethylamino)-4-naphthalen-2-ylcyclohexan-1-one Chemical compound C=1C=C2C=CC=CC2=CC=1C1(N(C)C)CCC(=O)CC1 AVKONLBRDWNBAO-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 229940049906 glutamate Drugs 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 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 3
- OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- DUDAKCCDHRNMDJ-UHFFFAOYSA-N thiophen-3-ylmethanamine Chemical compound NCC=1C=CSC=1 DUDAKCCDHRNMDJ-UHFFFAOYSA-N 0.000 description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 2
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 2
- ZUPYTANKWDPRDP-UHFFFAOYSA-N 1-benzothiophen-5-amine Chemical compound NC1=CC=C2SC=CC2=C1 ZUPYTANKWDPRDP-UHFFFAOYSA-N 0.000 description 2
- HLNVBAJJWXNTMS-UHFFFAOYSA-N 1-benzyl-1-n,1-n,4-n-trimethylcyclohexane-1,4-diamine Chemical compound C1CC(NC)CCC1(N(C)C)CC1=CC=CC=C1 HLNVBAJJWXNTMS-UHFFFAOYSA-N 0.000 description 2
- NZMDILYGANEMQL-UHFFFAOYSA-N 1-benzyl-4-n-ethyl-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NCC)CCC1(N(C)C)CC1=CC=CC=C1 NZMDILYGANEMQL-UHFFFAOYSA-N 0.000 description 2
- DSAMTIPDNZRRDB-UHFFFAOYSA-N 1-n,1-n-dimethyl-1-phenyl-4-n-propylcyclohexane-1,4-diamine;hydrochloride Chemical compound Cl.C1CC(NCCC)CCC1(N(C)C)C1=CC=CC=C1 DSAMTIPDNZRRDB-UHFFFAOYSA-N 0.000 description 2
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 description 2
- FFFIRKXTFQCCKJ-UHFFFAOYSA-N 2,4,6-trimethylbenzoic acid Chemical compound CC1=CC(C)=C(C(O)=O)C(C)=C1 FFFIRKXTFQCCKJ-UHFFFAOYSA-N 0.000 description 2
- VIKBNMWOLLIQPG-UHFFFAOYSA-N 2-methyldecanedioic acid Chemical compound OC(=O)C(C)CCCCCCCC(O)=O VIKBNMWOLLIQPG-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 2
- OBSXGVVLMVFMBC-UHFFFAOYSA-N 4-n,1-dibenzyl-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NCC=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 OBSXGVVLMVFMBC-UHFFFAOYSA-N 0.000 description 2
- QYHIFMRFGPPAOT-UHFFFAOYSA-N 4-n-(1,2-dihydroacenaphthylen-1-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC2C=3C=CC=C4C=CC=C(C=34)C2)CCC1(N(C)C)C1=CC=CC=C1 QYHIFMRFGPPAOT-UHFFFAOYSA-N 0.000 description 2
- BZIPJWXOSHIROA-UHFFFAOYSA-N 4-n-(1,3-benzodioxol-5-ylmethyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCC=2C=C3OCOC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 BZIPJWXOSHIROA-UHFFFAOYSA-N 0.000 description 2
- GLKSFRZAINOTGG-UHFFFAOYSA-N 4-n-(1-benzothiophen-3-ylmethyl)-1-benzyl-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NCC=2C3=CC=CC=C3SC=2)CCC1(N(C)C)CC1=CC=CC=C1 GLKSFRZAINOTGG-UHFFFAOYSA-N 0.000 description 2
- ALPOFWUHZWSPBT-UHFFFAOYSA-N 4-n-(1h-indol-5-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C=C3C=CNC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 ALPOFWUHZWSPBT-UHFFFAOYSA-N 0.000 description 2
- MMIAYYVOOAENHV-UHFFFAOYSA-N 4-n-(2h-benzotriazol-5-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C=C3NN=NC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 MMIAYYVOOAENHV-UHFFFAOYSA-N 0.000 description 2
- FNYVYGDTRKLTQD-UHFFFAOYSA-N 4-n-(9-ethylcarbazol-3-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 FNYVYGDTRKLTQD-UHFFFAOYSA-N 0.000 description 2
- IIUSKEPMLRPHSS-UHFFFAOYSA-N 4-n-[2-(6-fluoro-1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NCCC=2C3=CC=C(F)C=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 IIUSKEPMLRPHSS-UHFFFAOYSA-N 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 2
- VAHHNSVLAMERNE-UHFFFAOYSA-N 8-benzyl-n,n-dimethyl-1,4-dioxaspiro[4.5]decan-8-amine Chemical compound C1CC2(OCCO2)CCC1(N(C)C)CC1=CC=CC=C1 VAHHNSVLAMERNE-UHFFFAOYSA-N 0.000 description 2
- OUGMRQJTULXVDC-UHFFFAOYSA-N 9h-fluoren-9-amine Chemical compound C1=CC=C2C(N)C3=CC=CC=C3C2=C1 OUGMRQJTULXVDC-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 230000003502 anti-nociceptive effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000001767 cationic compounds Chemical class 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- FYAQQULBLMNGAH-UHFFFAOYSA-N hexane-1-sulfonic acid Chemical compound CCCCCCS(O)(=O)=O FYAQQULBLMNGAH-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910001411 inorganic cation Inorganic materials 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 235000019136 lipoic acid Nutrition 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- AJXKMSUIFIQZDT-UHFFFAOYSA-N n,n-dimethyl-8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC21OCCO2 AJXKMSUIFIQZDT-UHFFFAOYSA-N 0.000 description 2
- NDBVJJLRQIIXEH-UHFFFAOYSA-N n-(1-benzothiophen-3-ylmethylidene)hydroxylamine Chemical compound C1=CC=C2C(C=NO)=CSC2=C1 NDBVJJLRQIIXEH-UHFFFAOYSA-N 0.000 description 2
- RHBYRDSWUAGYDI-UHFFFAOYSA-N n-[4-benzyl-4-(dimethylamino)cyclohexyl]-n-methylbenzamide Chemical compound C1CC(N(C)C(=O)C=2C=CC=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 RHBYRDSWUAGYDI-UHFFFAOYSA-N 0.000 description 2
- NCIKQJBVUNUXLW-UHFFFAOYSA-N n-omega-methyltryptamine Natural products C1=CC=C2C(CCNC)=CNC2=C1 NCIKQJBVUNUXLW-UHFFFAOYSA-N 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960002663 thioctic acid Drugs 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- WHUUTDBJXJRKMK-BMCPPWMHSA-N (2S)-2-amino-2-tritiopentanedioic acid Chemical compound [3H][C@](N)(CCC(O)=O)C(O)=O WHUUTDBJXJRKMK-BMCPPWMHSA-N 0.000 description 1
- 125000006702 (C1-C18) alkyl group Chemical group 0.000 description 1
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- LCYNDXQWJAMEAI-UHFFFAOYSA-N 1,2-dihydroacenaphthylen-1-amine Chemical compound C1=CC(C(N)C2)=C3C2=CC=CC3=C1 LCYNDXQWJAMEAI-UHFFFAOYSA-N 0.000 description 1
- XBYRMPXUBGMOJC-UHFFFAOYSA-N 1,2-dihydropyrazol-3-one Chemical compound OC=1C=CNN=1 XBYRMPXUBGMOJC-UHFFFAOYSA-N 0.000 description 1
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 1
- FAYAYUOZWYJNBD-UHFFFAOYSA-N 1,3-benzothiazol-6-amine Chemical compound NC1=CC=C2N=CSC2=C1 FAYAYUOZWYJNBD-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 1
- WDJLPQCBTBZTRH-UHFFFAOYSA-N 1-benzothiophene-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CSC2=C1 WDJLPQCBTBZTRH-UHFFFAOYSA-N 0.000 description 1
- KBMCRYZXXGTTKB-UHFFFAOYSA-N 1-benzyl-1-n,1-n-dimethyl-4-n-propylcyclohexane-1,4-diamine Chemical compound C1CC(NCCC)CCC1(N(C)C)CC1=CC=CC=C1 KBMCRYZXXGTTKB-UHFFFAOYSA-N 0.000 description 1
- LBWSOVWOGOLPCV-UHFFFAOYSA-N 1-benzyl-4-N-(2,3-dihydro-1H-inden-1-yl)-1-N,1-N-dimethylcyclohexane-1,4-diamine 1-benzyl-4-N-(2,3-dihydro-1H-inden-5-yl)-1-N,1-N-dimethylcyclohexane-1,4-diamine trihydrochloride Chemical compound Cl.Cl.C(C1=CC=CC=C1)C1(CCC(CC1)NC1CCC2=CC=CC=C12)N(C)C.Cl.C(C1=CC=CC=C1)C1(CCC(CC1)NC=1C=C2CCCC2=CC1)N(C)C LBWSOVWOGOLPCV-UHFFFAOYSA-N 0.000 description 1
- QQDBYNAPOFMHOC-UHFFFAOYSA-N 1-benzyl-4-n-(1h-indol-3-ylmethyl)-1-n,1-n-dimethylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)CC1=CC=CC=C1 QQDBYNAPOFMHOC-UHFFFAOYSA-N 0.000 description 1
- XIIPIDMLKHUSTJ-UHFFFAOYSA-N 1-benzyl-4-n-(2,3-dihydro-1h-inden-1-yl)-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NC2C3=CC=CC=C3CC2)CCC1(N(C)C)CC1=CC=CC=C1 XIIPIDMLKHUSTJ-UHFFFAOYSA-N 0.000 description 1
- MMHJRVGQUWLOCI-UHFFFAOYSA-N 1-benzyl-4-n-(2,3-dihydro-1h-inden-5-yl)-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C=C3CCCC3=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 MMHJRVGQUWLOCI-UHFFFAOYSA-N 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- DRLGIZIAMHIQHL-UHFFFAOYSA-N 2,1,3-benzothiadiazol-4-amine Chemical compound NC1=CC=CC2=NSN=C12 DRLGIZIAMHIQHL-UHFFFAOYSA-N 0.000 description 1
- DEELHLMCCWZFFE-UHFFFAOYSA-N 2-(1-benzothiophen-3-yl)acetonitrile Chemical compound C1=CC=C2C(CC#N)=CSC2=C1 DEELHLMCCWZFFE-UHFFFAOYSA-N 0.000 description 1
- BQTOKMYKZPCPRW-UHFFFAOYSA-N 2-(6-fluoro-1h-indol-3-yl)ethanamine Chemical compound FC1=CC=C2C(CCN)=CNC2=C1 BQTOKMYKZPCPRW-UHFFFAOYSA-N 0.000 description 1
- SGGBZKQTWMKXHD-UHFFFAOYSA-N 2-(7-methyl-1h-indol-3-yl)ethanamine Chemical compound CC1=CC=CC2=C1NC=C2CCN SGGBZKQTWMKXHD-UHFFFAOYSA-N 0.000 description 1
- LMHHFZAXSANGGM-UHFFFAOYSA-N 2-aminoindane Chemical compound C1=CC=C2CC(N)CC2=C1 LMHHFZAXSANGGM-UHFFFAOYSA-N 0.000 description 1
- APSMUYYLXZULMS-UHFFFAOYSA-N 2-bromonaphthalene Chemical compound C1=CC=CC2=CC(Br)=CC=C21 APSMUYYLXZULMS-UHFFFAOYSA-N 0.000 description 1
- ROIMNSWDOJCBFR-UHFFFAOYSA-N 2-iodothiophene Chemical compound IC1=CC=CS1 ROIMNSWDOJCBFR-UHFFFAOYSA-N 0.000 description 1
- XSFHICWNEBCMNN-UHFFFAOYSA-N 2h-benzotriazol-5-amine Chemical compound NC1=CC=C2NN=NC2=C1 XSFHICWNEBCMNN-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OULGAZMZZIDMCY-UHFFFAOYSA-N 4-N-(2,3-dihydro-1H-inden-1-yl)-1-N,1-N-dimethyl-1-phenylcyclohexane-1,4-diamine 4-N-(1H-indol-5-yl)-1-N,1-N-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound N1C=CC2=CC(=CC=C12)NC1CCC(CC1)(N(C)C)C1=CC=CC=C1.C1(CCC2=CC=CC=C12)NC1CCC(CC1)(N(C)C)C1=CC=CC=C1 OULGAZMZZIDMCY-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- JRXTZRUCMCYLII-UHFFFAOYSA-N 4-n,1-dibenzyl-1-n,1-n,4-n-trimethylcyclohexane-1,4-diamine Chemical compound C1CC(CC=2C=CC=CC=2)(N(C)C)CCC1N(C)CC1=CC=CC=C1 JRXTZRUCMCYLII-UHFFFAOYSA-N 0.000 description 1
- LNHWZXISBVYROA-UHFFFAOYSA-N 4-n-(1,3-benzodioxol-5-ylmethyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NCC=2C=C3OCOC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 LNHWZXISBVYROA-UHFFFAOYSA-N 0.000 description 1
- BAOCHHXJEAXNDO-UHFFFAOYSA-N 4-n-(1,3-benzothiazol-6-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C=C3SC=NC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 BAOCHHXJEAXNDO-UHFFFAOYSA-N 0.000 description 1
- YYTHUTVELNNMHQ-UHFFFAOYSA-N 4-n-(1-benzothiophen-3-ylmethyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NCC=2C3=CC=CC=C3SC=2)CCC1(N(C)C)C1=CC=CC=C1 YYTHUTVELNNMHQ-UHFFFAOYSA-N 0.000 description 1
- LYJZJYOOQHNIPY-UHFFFAOYSA-N 4-n-(1-benzothiophen-5-yl)-1-benzyl-1-n,1-n-dimethylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C=C3C=CSC3=CC=2)CCC1(N(C)C)CC1=CC=CC=C1 LYJZJYOOQHNIPY-UHFFFAOYSA-N 0.000 description 1
- YQTASMBBNSLTER-UHFFFAOYSA-N 4-n-(2,1,3-benzothiadiazol-4-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C3=NSN=C3C=CC=2)CCC1(N(C)C)C1=CC=CC=C1 YQTASMBBNSLTER-UHFFFAOYSA-N 0.000 description 1
- ASWTVCDCNXSEAW-UHFFFAOYSA-N 4-n-(2,3-dihydro-1h-inden-2-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC2CC3=CC=CC=C3C2)CCC1(N(C)C)C1=CC=CC=C1 ASWTVCDCNXSEAW-UHFFFAOYSA-N 0.000 description 1
- SLFJLTILXWHFBQ-UHFFFAOYSA-N 4-n-(2-adamantyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC2C3CC4CC(C3)CC2C4)CCC1(N(C)C)C1=CC=CC=C1 SLFJLTILXWHFBQ-UHFFFAOYSA-N 0.000 description 1
- SYZNUPMARGJOMF-UHFFFAOYSA-N 4-n-(2-adamantyl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC2C3CC4CC(C3)CC2C4)CCC1(N(C)C)C1=CC=CC=C1 SYZNUPMARGJOMF-UHFFFAOYSA-N 0.000 description 1
- AWLQWXPCBOCBNR-UHFFFAOYSA-N 4-n-(9-ethylcarbazol-3-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 AWLQWXPCBOCBNR-UHFFFAOYSA-N 0.000 description 1
- LRIMUGDYKHEVMV-UHFFFAOYSA-N 4-n-(9h-fluoren-1-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C3=C(C4=CC=CC=C4C3)C=CC=2)CCC1(N(C)C)C1=CC=CC=C1 LRIMUGDYKHEVMV-UHFFFAOYSA-N 0.000 description 1
- WMSCZUMVTNKIIQ-UHFFFAOYSA-N 4-n-(9h-fluoren-9-yl)-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC2C3=CC=CC=C3C3=CC=CC=C32)CCC1(N(C)C)C1=CC=CC=C1 WMSCZUMVTNKIIQ-UHFFFAOYSA-N 0.000 description 1
- MLDWHVNEHMZKOD-UHFFFAOYSA-N 4-n-(9h-fluoren-9-yl)-1-n,1-n-dimethyl-1-thiophen-2-ylcyclohexane-1,4-diamine Chemical compound C1CC(NC2C3=CC=CC=C3C3=CC=CC=C32)CCC1(N(C)C)C1=CC=CS1 MLDWHVNEHMZKOD-UHFFFAOYSA-N 0.000 description 1
- FAXNXBBXCNTHJS-UHFFFAOYSA-N 4-n-[1-(1h-indol-3-yl)propan-2-yl]-1-n,1-n-dimethyl-1-naphthalen-2-ylcyclohexane-1,4-diamine Chemical compound C1=CC=CC2=CC(C3(N(C)C)CCC(CC3)NC(CC=3C4=CC=CC=C4NC=3)C)=CC=C21 FAXNXBBXCNTHJS-UHFFFAOYSA-N 0.000 description 1
- ICHZGUNHOOYSHU-UHFFFAOYSA-N 4-n-[2-(1h-indol-3-yl)ethyl]-1-n,1-n,4-n-trimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C=1NC2=CC=CC=C2C=1CCN(C)C(CC1)CCC1(N(C)C)C1=CC=CC=C1 ICHZGUNHOOYSHU-UHFFFAOYSA-N 0.000 description 1
- IOOGAVARHSDDFH-UHFFFAOYSA-N 4-n-[2-(1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-naphthalen-2-ylcyclohexane-1,4-diamine Chemical compound C1=CC=CC2=CC(C3(CCC(CC3)NCCC=3C4=CC=CC=C4NC=3)N(C)C)=CC=C21 IOOGAVARHSDDFH-UHFFFAOYSA-N 0.000 description 1
- MVTDSEVJBUWTFI-UHFFFAOYSA-N 4-n-[2-(1h-indol-3-yl)ethyl]-1-n,1-n-dimethyl-1-naphthalen-2-ylcyclohexane-1,4-diamine;dihydrochloride Chemical compound Cl.Cl.C1=CC=CC2=CC(C3(CCC(CC3)NCCC=3C4=CC=CC=C4NC=3)N(C)C)=CC=C21 MVTDSEVJBUWTFI-UHFFFAOYSA-N 0.000 description 1
- JSKGOQUFCTWPPL-UHFFFAOYSA-N 4-n-anthracen-2-yl-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(NC=2C=C3C=C4C=CC=CC4=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 JSKGOQUFCTWPPL-UHFFFAOYSA-N 0.000 description 1
- PATHEPDFFMCKDD-UHFFFAOYSA-N 4-n-benzyl-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NCC1=CC=CC=C1 PATHEPDFFMCKDD-UHFFFAOYSA-N 0.000 description 1
- VGXXOCIFAFWQJX-UHFFFAOYSA-N 4-n-cyclooctyl-1-n,1-n-dimethyl-1-phenylcyclohexane-1,4-diamine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCC1NC1CCCCCCC1 VGXXOCIFAFWQJX-UHFFFAOYSA-N 0.000 description 1
- WKPDXBXNJWWWGQ-UHFFFAOYSA-N 5-benzyloxytryptamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1OCC1=CC=CC=C1 WKPDXBXNJWWWGQ-UHFFFAOYSA-N 0.000 description 1
- OXEUETBFKVCRNP-UHFFFAOYSA-N 9-ethyl-3-carbazolamine Chemical compound NC1=CC=C2N(CC)C3=CC=CC=C3C2=C1 OXEUETBFKVCRNP-UHFFFAOYSA-N 0.000 description 1
- CYSPWCARDHRYJX-UHFFFAOYSA-N 9h-fluoren-1-amine Chemical compound C12=CC=CC=C2CC2=C1C=CC=C2N CYSPWCARDHRYJX-UHFFFAOYSA-N 0.000 description 1
- 101100277337 Arabidopsis thaliana DDM1 gene Proteins 0.000 description 1
- 241001609773 Campion Species 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 description 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000001490 Opioid Peptides Human genes 0.000 description 1
- 108010093625 Opioid Peptides Proteins 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- QZWNXXINFABALM-UHFFFAOYSA-N adamantan-2-amine Chemical compound C1C(C2)CC3CC1C(N)C2C3 QZWNXXINFABALM-UHFFFAOYSA-N 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000578 anorexic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- YCSBALJAGZKWFF-UHFFFAOYSA-N anthracen-2-amine Chemical compound C1=CC=CC2=CC3=CC(N)=CC=C3C=C21 YCSBALJAGZKWFF-UHFFFAOYSA-N 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- DMSMPAJRVJJAGA-UHFFFAOYSA-N benzo[d]isothiazol-3-one Chemical compound C1=CC=C2C(=O)NSC2=C1 DMSMPAJRVJJAGA-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GMBHLHMRHUMBHU-UHFFFAOYSA-N butan-2-one;hydrochloride Chemical compound Cl.CCC(C)=O GMBHLHMRHUMBHU-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 101150113676 chr1 gene Proteins 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- HSOHBWMXECKEKV-UHFFFAOYSA-N cyclooctanamine Chemical compound NC1CCCCCCC1 HSOHBWMXECKEKV-UHFFFAOYSA-N 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 230000002825 dopamine reuptake Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 230000000917 hyperalgesic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- NBKQRVSGHYZUOR-UHFFFAOYSA-N indoline-3-carbaldehyde Natural products C1=CC=C2C(C=O)CNC2=C1 NBKQRVSGHYZUOR-UHFFFAOYSA-N 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 1
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- KCUNTYMNJVXYKZ-JTQLQIEISA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 KCUNTYMNJVXYKZ-JTQLQIEISA-N 0.000 description 1
- PNTDYQFUWSJEQX-UHFFFAOYSA-N methyl 2-[[4-(dimethylamino)-4-phenylcyclohexyl]amino]-3-(1h-indol-3-yl)propanoate Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)OC)NC(CC1)CCC1(N(C)C)C1=CC=CC=C1 PNTDYQFUWSJEQX-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 230000036453 micturition reflex Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- SDRHXSAHBXQABX-UHFFFAOYSA-N n,n-dimethyl-8-naphthalen-2-yl-1,4-dioxaspiro[4.5]decan-8-amine Chemical compound C1CC(N(C)C)(C=2C=C3C=CC=CC3=CC=2)CCC21OCCO2.C1CC(N(C)C)(C=2C=C3C=CC=CC3=CC=2)CCC21OCCO2 SDRHXSAHBXQABX-UHFFFAOYSA-N 0.000 description 1
- WOJHNPPRAKHDFQ-UHFFFAOYSA-N n,n-dimethyl-8-naphthalen-2-yl-1,4-dioxaspiro[4.5]decan-8-amine;hydrochloride Chemical compound Cl.C1CC(N(C)C)(C=2C=C3C=CC=CC3=CC=2)CCC21OCCO2 WOJHNPPRAKHDFQ-UHFFFAOYSA-N 0.000 description 1
- PCDFJRPNSKFUFX-UHFFFAOYSA-N n,n-dimethyl-8-thiophen-2-yl-1,4-dioxaspiro[4.5]decan-8-amine;hydrochloride Chemical compound Cl.C1CC(N(C)C)(C=2SC=CC=2)CCC21OCCO2 PCDFJRPNSKFUFX-UHFFFAOYSA-N 0.000 description 1
- YNMRZDJUGRBDAN-UHFFFAOYSA-N n-[4-(dimethylamino)-4-phenylcyclohexyl]-n-[2-(4-fluorophenyl)ethyl]acetamide;hydrochloride Chemical compound Cl.C1CC(N(C)C)(C=2C=CC=CC=2)CCC1N(C(C)=O)CCC1=CC=C(F)C=C1 YNMRZDJUGRBDAN-UHFFFAOYSA-N 0.000 description 1
- WCSLMUJUJBHNML-UHFFFAOYSA-N n-[4-benzyl-4-(dimethylamino)cyclohexyl]-n-propylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(CCC)C(CC1)CCC1(N(C)C)CC1=CC=CC=C1 WCSLMUJUJBHNML-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- FLMVYEYCNBKTNO-UHFFFAOYSA-N n-methylthiophen-3-amine;hydrochloride Chemical compound Cl.CNC=1C=CSC=1 FLMVYEYCNBKTNO-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 235000021231 nutrient uptake Nutrition 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003399 opiate peptide Substances 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- 230000002400 pro-nociceptive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- DNTVKOMHCDKATN-UHFFFAOYSA-N pyrazolidine-3,5-dione Chemical compound O=C1CC(=O)NN1 DNTVKOMHCDKATN-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000010409 stress-induced analgesia Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/36—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton containing at least two amino groups bound to the carbon skeleton
-
- 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
- A61K31/13—Amines
-
- 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
- A61K31/13—Amines
- A61K31/132—Amines having two or more amino groups, e.g. spermidine, putrescine
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- 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
-
- 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
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- 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
-
- 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
- A61P15/18—Feminine contraceptives
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Anesthesiology (AREA)
- Vascular Medicine (AREA)
- Nutrition Science (AREA)
- Child & Adolescent Psychology (AREA)
- Dermatology (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10123163A DE10123163A1 (de) | 2001-05-09 | 2001-05-09 | Substituierte Cyclohexan-1,4-diaminderivate |
PCT/EP2002/005051 WO2002090317A1 (de) | 2001-05-09 | 2002-05-08 | Substituierte cyclohexan-1,4-diaminderivate |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20034930D0 NO20034930D0 (no) | 2003-11-05 |
NO20034930L NO20034930L (no) | 2004-01-05 |
NO328600B1 true NO328600B1 (no) | 2010-03-29 |
Family
ID=7684562
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20034931A NO326784B1 (no) | 2001-05-09 | 2003-11-05 | Substituerte 2-pyridin-cykloheksan-1,4-diaminderivater, fremgangsmåte for deres fremstilling, anvendelser samt legemiddel |
NO20034930A NO328600B1 (no) | 2001-05-09 | 2003-11-05 | Substituerte sykloheksan-1,4-diaminderivater, anvendelse derav, fremgangsmate for fremstilling derav og legemidler inneholdende slike derivater |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20034931A NO326784B1 (no) | 2001-05-09 | 2003-11-05 | Substituerte 2-pyridin-cykloheksan-1,4-diaminderivater, fremgangsmåte for deres fremstilling, anvendelser samt legemiddel |
Country Status (31)
Country | Link |
---|---|
US (3) | US6998409B2 (es) |
EP (3) | EP1392641B1 (es) |
JP (3) | JP2004533439A (es) |
KR (2) | KR20040002943A (es) |
CN (2) | CN1307158C (es) |
AR (1) | AR035883A1 (es) |
AT (2) | ATE359260T1 (es) |
AU (3) | AU2002312883B2 (es) |
BR (2) | BR0209580A (es) |
CA (3) | CA2446463C (es) |
CO (2) | CO5540300A2 (es) |
CY (2) | CY1106468T1 (es) |
CZ (2) | CZ20033005A3 (es) |
DE (3) | DE10123163A1 (es) |
DK (2) | DK1392641T3 (es) |
EC (2) | ECSP034830A (es) |
ES (2) | ES2291486T3 (es) |
HK (2) | HK1062911A1 (es) |
HU (3) | HU228253B1 (es) |
IL (4) | IL158784A0 (es) |
MX (3) | MXPA03010134A (es) |
NO (2) | NO326784B1 (es) |
NZ (2) | NZ529334A (es) |
PE (1) | PE20021094A1 (es) |
PL (3) | PL220595B1 (es) |
PT (2) | PT1392641E (es) |
RU (2) | RU2321579C2 (es) |
SI (2) | SI1385825T1 (es) |
SK (2) | SK286617B6 (es) |
WO (3) | WO2002090330A1 (es) |
ZA (2) | ZA200309522B (es) |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10252665A1 (de) | 2002-11-11 | 2004-06-03 | Grünenthal GmbH | 4-Aminomethyl-1-aryl-cyclohexylamin-Derivate |
DE10252650A1 (de) * | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Cyclohexyl-Harnstoff-Derivate |
WO2004043902A1 (de) | 2002-11-12 | 2004-05-27 | Grünenthal GmbH | 4-hydroxymethyl-1-aryl-cyclohexylamin-derivative |
JP4206382B2 (ja) * | 2002-11-19 | 2009-01-07 | アキリオン ファーマシューティカルズ,インコーポレーテッド | 置換されたアリールチオウレアおよび関連化合物;ウイルス複製のインヒビター |
US7378409B2 (en) * | 2003-08-21 | 2008-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkylamine derivatives as modulators of chemokine receptor activity |
DE10360793A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
DE10360792A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
DE102004023501A1 (de) | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Oxosubstituierte Cyclohexyl-1,4-diamin-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 |
DE102004023508A1 (de) * | 2004-05-10 | 2005-12-08 | Grünenthal GmbH | Säurederivate substituierter Cyclohexyl-1,4-diamine |
DE102004023506A1 (de) | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Kettenverlängerte substituierte Cyclohexyl-1,4-diamin-Derivate |
DE102004023507A1 (de) | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Substituierte Cyclohexylessigsäure-Derivate |
DE102004023522A1 (de) * | 2004-05-10 | 2005-12-01 | Grünenthal GmbH | Substituierte Cyclohexyl-1,4-diamin-Derivate |
TW200600492A (en) * | 2004-05-18 | 2006-01-01 | Achillion Pharmaceuticals Inc | Substituted aryl acylthioureas and related compounds; inhibitors of viral replication |
DE102005061428A1 (de) | 2005-12-22 | 2007-08-16 | Grünenthal GmbH | Substituierte Cyclohexylmethyl-Derivate |
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 |
DE102006035787A1 (de) | 2006-07-28 | 2008-03-13 | Tesa Ag | Verfahren zum Stanzen von bei Raumtemperatur nicht tackigen hitzeaktivierbaren Klebmassen |
US20080194557A1 (en) * | 2007-01-18 | 2008-08-14 | Joseph Barbosa | Methods and compositions for the treatment of pain, inflammation and cancer |
US8003692B2 (en) * | 2007-06-15 | 2011-08-23 | Board Of Regents, The University Of Texas System | Methods and compositions to inhibit edema factor and adenylyl cyclase |
US20090215725A1 (en) * | 2008-02-26 | 2009-08-27 | Grunenthal Gmbh | Substituted 4-aminocyclohexane derivatives |
CN102046633B (zh) | 2008-03-27 | 2015-03-25 | 格吕伦塔尔有限公司 | 取代的螺环状环己烷衍生物 |
WO2009118174A1 (de) * | 2008-03-27 | 2009-10-01 | Grünenthal GmbH | Substituierte cyclohexyldiamine |
JP5542119B2 (ja) | 2008-03-27 | 2014-07-09 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | スピロ(5.5)ウンデカン誘導体 |
BR122013017393A2 (pt) | 2008-03-27 | 2019-10-15 | Grünenthal GmbH | Compostos derivados substituídos de 4-aminociclohexano, medicamentos contendo pelo menos um composto e uso dos referidos compostos |
CN102046591B (zh) | 2008-03-27 | 2014-12-03 | 格吕伦塔尔有限公司 | 羟甲基环己胺 |
HUE026184T2 (en) | 2008-03-27 | 2016-05-30 | Gruenenthal Gmbh | (Hetero-) aryl-cyclohexane derivatives |
DK2324013T6 (en) | 2008-07-21 | 2014-12-15 | Purdue Pharma Lp | Substituted bridged piperidine compounds of quinoxalintype and uses thereof |
WO2010084160A1 (en) | 2009-01-21 | 2010-07-29 | Oryzon Genomics S.A. | Phenylcyclopropylamine derivatives and their medical use |
US8859555B2 (en) | 2009-09-25 | 2014-10-14 | Oryzon Genomics S.A. | Lysine Specific Demethylase-1 inhibitors and their use |
US8946296B2 (en) | 2009-10-09 | 2015-02-03 | Oryzon Genomics S.A. | Substituted heteroaryl- and aryl-cyclopropylamine acetamides and their use |
WO2011106574A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Inhibitors for antiviral use |
WO2011106106A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with hepadnaviridae |
RS55348B1 (sr) | 2010-04-19 | 2017-03-31 | Oryzon Gnomics S A | Inhibitori lizin specifične demetilaze-1 i njihova upotreba |
EP2598482B1 (en) | 2010-07-29 | 2018-04-04 | Oryzon Genomics, S.A. | Arylcyclopropylamine based demethylase inhibitors of lsd1 and their medical use |
EP2598480B1 (en) | 2010-07-29 | 2019-04-24 | Oryzon Genomics, S.A. | Cyclopropylamine derivatives useful as lsd1 inhibitors |
WO2012045883A1 (en) | 2010-10-08 | 2012-04-12 | Oryzon Genomics S.A. | Cyclopropylamine inhibitors of oxidases |
WO2012072713A2 (en) | 2010-11-30 | 2012-06-07 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with flaviviridae |
WO2012107498A1 (en) | 2011-02-08 | 2012-08-16 | Oryzon Genomics S.A. | Lysine demethylase inhibitors for myeloproliferative disorders |
IN2014CN03337A (es) | 2011-10-20 | 2015-07-03 | Oryzon Genomics Sa | |
MX356344B (es) | 2011-10-20 | 2018-05-23 | Oryzon Genomics Sa | Compuestos de (hetero)arilciclopropilamina como inhibidores de lsd1. |
US12084472B2 (en) | 2015-12-18 | 2024-09-10 | Ardelyx, Inc. | Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists |
TWI773657B (zh) | 2015-12-18 | 2022-08-11 | 美商亞德利克斯公司 | 作爲非全身tgr5促效劑之經取代之4-苯基吡啶化合物 |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU172460B (hu) * | 1975-10-03 | 1978-09-28 | Chinoin Gyogyszer Es Vegyeszet | Sposob poluchenija novykh proizvodnykh 5,6-digidro-3h-pirimidin-4-ona |
US4065573A (en) * | 1976-06-03 | 1977-12-27 | The Upjohn Company | 4-Amino-4-phenylcyclohexanone ketal compositions and process of use |
US4113866A (en) * | 1977-04-01 | 1978-09-12 | The Upjohn Company | Analgetic compounds, compositions and process of treatment |
US4447454A (en) * | 1977-04-01 | 1984-05-08 | The Upjohn Company | Analgetic compounds, compositions and process of treatment |
US5877277A (en) | 1987-09-24 | 1999-03-02 | Biomeasure, Inc. | Octapeptide bombesin analogs |
US4906655A (en) | 1989-01-24 | 1990-03-06 | Warner-Lambert Company | Novel 1,2-cyclohexylaminoaryl amides useful as analgesic agents |
US5153226A (en) | 1989-08-31 | 1992-10-06 | Warner-Lambert Company | Acat inhibitors for treating hypocholesterolemia |
FR2687147A1 (fr) | 1992-02-11 | 1993-08-13 | Union Pharma Scient Appl | Nouveaux derives d'alpha-amino n-pyridyl benzene propanamide, leurs procedes de preparation, compositions pharmaceutiques les contenant. |
US5620955A (en) | 1993-06-18 | 1997-04-15 | Peptide Technologies Corporation | Bombesin receptor antagonists and uses thereof |
US5565568A (en) | 1995-04-06 | 1996-10-15 | Eli Lilly And Company | 2-acylaminopropanamides as tachykinin receptor antagonists |
AU6772996A (en) | 1995-08-21 | 1997-03-12 | Eli Lilly And Company | 2-acylaminopropanamides as growth hormone secretagogues |
ES2253782T3 (es) | 1996-08-22 | 2006-06-01 | Warner-Lambert Company Llc | Antagonistas de receptor de bombesina no peptidicos. |
PT1049689E (pt) * | 1998-01-19 | 2002-09-30 | Pfizer | Compostos de 4-(2-ceto-1-benzimidazolinil)piperidina como agonistas do receptor orl1 |
US20020169101A1 (en) | 1999-05-10 | 2002-11-14 | Gonzalez Maria Isabel | Treatment of sexual dysfunction |
GB0006289D0 (en) | 2000-03-15 | 2000-05-03 | Smithkline Beecham Plc | New use |
GB0012240D0 (en) * | 2000-05-19 | 2000-07-12 | Merck Sharp & Dohme | Therapeutic agents |
US20020028799A1 (en) | 2000-07-06 | 2002-03-07 | Naylor Alasdair Mark | Treatment of male sexual dysfunction |
US6991916B2 (en) | 2000-07-14 | 2006-01-31 | Pfizer Inc. | Compounds for the treatment of sexual dysfunction |
US7138397B2 (en) * | 2000-10-06 | 2006-11-21 | Tanabe Seiyaku Co., Ltd. | Nitrogenous 5-membered ring compounds |
US20020055759A1 (en) | 2000-11-06 | 2002-05-09 | Shibuya Terry Y. | Bioactive surgical suture |
AU2002225730A1 (en) | 2000-11-16 | 2002-05-27 | Smith Kline Beecham Corporation | Compounds |
BR0115364A (pt) | 2000-11-17 | 2003-09-23 | Warner Lambert Co | Tratamento de disfunção sexual |
GB2369117A (en) | 2000-11-17 | 2002-05-22 | Warner Lambert Co | Bombesin receptor antagonists |
KR20040062416A (ko) | 2000-11-17 | 2004-07-07 | 워너-램버트 캄파니 엘엘씨 | 봄베신 길항제를 이용한 성기능 장애의 치료 |
GB2369118A (en) | 2000-11-17 | 2002-05-22 | Warner Lambert Co | Bombesin receptor antagonists |
EP1333824B1 (en) | 2000-11-17 | 2005-09-07 | Warner-Lambert Company LLC | Treatment of sexual dysfunction with bombesin receptor antagonists |
US20030119714A1 (en) | 2000-12-15 | 2003-06-26 | Naylor Alasdair Mark | Treatment of male sexual dysfunction |
-
2001
- 2001-05-09 DE DE10123163A patent/DE10123163A1/de not_active Withdrawn
-
2002
- 2002-05-08 ES ES02750900T patent/ES2291486T3/es not_active Expired - Lifetime
- 2002-05-08 IL IL15878402A patent/IL158784A0/xx unknown
- 2002-05-08 NZ NZ529334A patent/NZ529334A/en not_active IP Right Cessation
- 2002-05-08 NZ NZ529147A patent/NZ529147A/en not_active IP Right Cessation
- 2002-05-08 JP JP2002587399A patent/JP2004533439A/ja active Pending
- 2002-05-08 AT AT02738038T patent/ATE359260T1/de active
- 2002-05-08 SI SI200230627T patent/SI1385825T1/sl unknown
- 2002-05-08 CZ CZ20033005A patent/CZ20033005A3/cs unknown
- 2002-05-08 IL IL15878202A patent/IL158782A0/xx unknown
- 2002-05-08 DE DE50210707T patent/DE50210707D1/de not_active Expired - Lifetime
- 2002-05-08 PT PT02738038T patent/PT1392641E/pt unknown
- 2002-05-08 DK DK02738038T patent/DK1392641T3/da active
- 2002-05-08 HU HU0400888A patent/HU228253B1/hu not_active IP Right Cessation
- 2002-05-08 EP EP02738038A patent/EP1392641B1/de not_active Expired - Lifetime
- 2002-05-08 ES ES02738038T patent/ES2284876T3/es not_active Expired - Lifetime
- 2002-05-08 PT PT02750900T patent/PT1385825E/pt unknown
- 2002-05-08 SI SI200230571T patent/SI1392641T1/sl unknown
- 2002-05-08 PL PL366662A patent/PL220595B1/pl unknown
- 2002-05-08 CZ CZ20032995A patent/CZ20032995A3/cs unknown
- 2002-05-08 BR BR0209580-7A patent/BR0209580A/pt not_active Application Discontinuation
- 2002-05-08 KR KR10-2003-7014530A patent/KR20040002943A/ko not_active Application Discontinuation
- 2002-05-08 WO PCT/EP2002/005078 patent/WO2002090330A1/de active IP Right Grant
- 2002-05-08 RU RU2003134147/04A patent/RU2321579C2/ru not_active IP Right Cessation
- 2002-05-08 SK SK1378-2003A patent/SK286617B6/sk not_active IP Right Cessation
- 2002-05-08 WO PCT/EP2002/005051 patent/WO2002090317A1/de active IP Right Grant
- 2002-05-08 CA CA2446463A patent/CA2446463C/en not_active Expired - Fee Related
- 2002-05-08 SK SK1379-2003A patent/SK287319B6/sk not_active IP Right Cessation
- 2002-05-08 AU AU2002312883A patent/AU2002312883B2/en not_active Ceased
- 2002-05-08 CN CNB028135571A patent/CN1307158C/zh not_active Expired - Fee Related
- 2002-05-08 AT AT02750900T patent/ATE370120T1/de active
- 2002-05-08 RU RU2003134145/04A patent/RU2287523C2/ru not_active IP Right Cessation
- 2002-05-08 DE DE50209929T patent/DE50209929D1/de not_active Expired - Lifetime
- 2002-05-08 KR KR1020037014568A patent/KR100895778B1/ko not_active IP Right Cessation
- 2002-05-08 MX MXPA03010134A patent/MXPA03010134A/es active IP Right Grant
- 2002-05-08 DK DK02750900T patent/DK1385825T3/da active
- 2002-05-08 PL PL368851A patent/PL212887B1/pl unknown
- 2002-05-08 EP EP02750900A patent/EP1385825B1/de not_active Expired - Lifetime
- 2002-05-08 MX MXPA03010201A patent/MXPA03010201A/es active IP Right Grant
- 2002-05-08 HU HU0400989A patent/HU229288B1/hu not_active IP Right Cessation
- 2002-05-08 BR BR0209579-3A patent/BR0209579A/pt active Search and Examination
- 2002-05-08 JP JP2002587410A patent/JP2004528374A/ja active Pending
- 2002-05-08 CA CA2446461A patent/CA2446461C/en not_active Expired - Fee Related
- 2002-05-08 AU AU2002341195A patent/AU2002341195B2/en not_active Ceased
- 2002-05-08 CN CN028137531A patent/CN1533374B/zh not_active Expired - Fee Related
- 2002-05-09 MX MXPA03010195A patent/MXPA03010195A/es unknown
- 2002-05-09 HU HU0400963A patent/HUP0400963A2/hu unknown
- 2002-05-09 EP EP02769145A patent/EP1385493A1/de not_active Withdrawn
- 2002-05-09 PL PL02366631A patent/PL366631A1/xx not_active Application Discontinuation
- 2002-05-09 JP JP2002586920A patent/JP2005515959A/ja not_active Withdrawn
- 2002-05-09 WO PCT/EP2002/005122 patent/WO2002089783A1/de not_active Application Discontinuation
- 2002-05-09 PE PE2002000388A patent/PE20021094A1/es not_active Application Discontinuation
- 2002-05-09 CA CA002446735A patent/CA2446735A1/en not_active Abandoned
- 2002-05-10 AR ARP020101704A patent/AR035883A1/es unknown
-
2003
- 2003-11-05 NO NO20034931A patent/NO326784B1/no not_active IP Right Cessation
- 2003-11-05 NO NO20034930A patent/NO328600B1/no not_active IP Right Cessation
- 2003-11-06 IL IL158782A patent/IL158782A/en not_active IP Right Cessation
- 2003-11-06 IL IL158784A patent/IL158784A/en not_active IP Right Cessation
- 2003-11-07 CO CO03098846A patent/CO5540300A2/es active IP Right Grant
- 2003-11-07 EC EC2003004830A patent/ECSP034830A/es unknown
- 2003-11-07 EC EC2003004831A patent/ECSP034831A/es unknown
- 2003-11-07 CO CO03098857A patent/CO5700725A2/es not_active Application Discontinuation
- 2003-11-10 US US10/704,200 patent/US6998409B2/en not_active Expired - Fee Related
- 2003-11-10 US US10/704,524 patent/US20040229872A1/en not_active Abandoned
- 2003-11-10 US US10/704,329 patent/US7276518B2/en not_active Expired - Fee Related
- 2003-12-08 ZA ZA2003/09522A patent/ZA200309522B/en unknown
- 2003-12-08 ZA ZA200309521A patent/ZA200309521B/xx unknown
-
2004
- 2004-08-03 HK HK04105744A patent/HK1062911A1/xx not_active IP Right Cessation
-
2005
- 2005-03-29 HK HK05102616.5A patent/HK1070049A1/xx not_active IP Right Cessation
-
2007
- 2007-05-07 AU AU2007202033A patent/AU2007202033B8/en not_active Ceased
- 2007-05-10 CY CY20071100630T patent/CY1106468T1/el unknown
- 2007-10-25 CY CY20071101374T patent/CY1108067T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO328600B1 (no) | Substituerte sykloheksan-1,4-diaminderivater, anvendelse derav, fremgangsmate for fremstilling derav og legemidler inneholdende slike derivater | |
US20050277674A1 (en) | 4-substituted 1-aminocyclohexane compounds for utilization as ORL1-receptor and mu-opiate receptor ligands | |
US20050245593A1 (en) | 4-Aminomethyl-1-aryl-cyclohexylamine compounds | |
ES2340766T3 (es) | Derivados de 4-hidroximetil-1-aril-ciclohexilamina. | |
CA2453901C (en) | Substituted 4-aminocyclohexanols | |
CA2480038C (en) | Substituted 4-aminocyclohexanols | |
AU2002328894B2 (en) | Substituted 4-aminocyclohexanol derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |