AU2009228647B2 - Substituted spirocyclic cyclohexane derivatives - Google Patents
Substituted spirocyclic cyclohexane derivatives Download PDFInfo
- Publication number
- AU2009228647B2 AU2009228647B2 AU2009228647A AU2009228647A AU2009228647B2 AU 2009228647 B2 AU2009228647 B2 AU 2009228647B2 AU 2009228647 A AU2009228647 A AU 2009228647A AU 2009228647 A AU2009228647 A AU 2009228647A AU 2009228647 B2 AU2009228647 B2 AU 2009228647B2
- Authority
- AU
- Australia
- Prior art keywords
- cyclohexane
- indole
- amine
- phenyl
- dimethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- 125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 148
- 229940079593 drug Drugs 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 130
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 95
- 239000000203 mixture Substances 0.000 claims description 54
- RERZNCLIYCABFS-UHFFFAOYSA-N harmaline Chemical compound C1CN=C(C)C2=C1C1=CC=C(OC)C=C1N2 RERZNCLIYCABFS-UHFFFAOYSA-N 0.000 claims description 52
- 125000003118 aryl group Chemical group 0.000 claims description 51
- -1 4-(dimethylamino)-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1' pyrano[3,4-b]indole]-2-yl Chemical group 0.000 claims description 46
- DULBEIKUQPJAST-UHFFFAOYSA-N pyrano[3,4-b]indole Chemical compound O1C=CC2=C3C=CC=CC3=NC2=C1 DULBEIKUQPJAST-UHFFFAOYSA-N 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 27
- 125000001931 aliphatic group Chemical group 0.000 claims description 25
- 229920006395 saturated elastomer Polymers 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 20
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 16
- 208000002193 Pain Diseases 0.000 claims description 16
- 229910052740 iodine Inorganic materials 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 229940005483 opioid analgesics Drugs 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 8
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 229910052727 yttrium Inorganic materials 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- ZRVFZCWVNBOHAP-UHFFFAOYSA-N 3'-[(3-fluorophenyl)methyl]-n,n-dimethyl-1'-phenylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC=CC=C4N3)CCN2)C1CC1=CC=CC(F)=C1 ZRVFZCWVNBOHAP-UHFFFAOYSA-N 0.000 claims description 5
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 5
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 claims description 5
- 230000003444 anaesthetic effect Effects 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- RGRFHXRVKJVFOG-UHFFFAOYSA-N 3',6-difluoro-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)C(F)CC1(N(C)C)C1=CC=CC=C1 RGRFHXRVKJVFOG-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- LEZGTFHHHFCMIE-UHFFFAOYSA-N 3'-[(3-fluorophenyl)methyl]-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC=CC=C4N3)CCO2)C1CC1=CC=CC(F)=C1 LEZGTFHHHFCMIE-UHFFFAOYSA-N 0.000 claims description 3
- YRDMRECBXVVXCE-UHFFFAOYSA-N 6-fluoro-3'-[(3-fluorophenyl)methyl]-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)C1CC1=CC=CC(F)=C1 YRDMRECBXVVXCE-UHFFFAOYSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
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- 206010006895 Cachexia Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010012335 Dependence Diseases 0.000 claims description 3
- 208000020401 Depressive disease Diseases 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 208000030814 Eating disease Diseases 0.000 claims description 3
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- 206010020772 Hypertension Diseases 0.000 claims description 3
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- 208000019695 Migraine disease Diseases 0.000 claims description 3
- 208000003251 Pruritus Diseases 0.000 claims description 3
- 206010039966 Senile dementia Diseases 0.000 claims description 3
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 208000022531 anorexia Diseases 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 206010061428 decreased appetite Diseases 0.000 claims description 3
- 230000002950 deficient Effects 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 235000014632 disordered eating Nutrition 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 208000016354 hearing loss disease Diseases 0.000 claims description 3
- 230000036543 hypotension Effects 0.000 claims description 3
- 230000008991 intestinal motility Effects 0.000 claims description 3
- 206010027599 migraine Diseases 0.000 claims description 3
- LYLYGYZNYSHTPY-UHFFFAOYSA-N n,n-dimethyl-1'-phenyl-3'-phenylsulfanylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC=CC=C4N3)CCO2)C1SC1=CC=CC=C1 LYLYGYZNYSHTPY-UHFFFAOYSA-N 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 230000001777 nootropic effect Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000003367 polycyclic group Chemical group 0.000 claims description 3
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- QERFEDFJCNNUNU-UHFFFAOYSA-N 2',2',6-trifluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCN2)CC(F)(F)C1(N(C)C)C1=CC=CC(F)=C1 QERFEDFJCNNUNU-UHFFFAOYSA-N 0.000 claims description 2
- PRYJGPVLQGEIHP-UHFFFAOYSA-N 2',6-difluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCN2)CC(F)C1(N(C)C)C1=CC=CC(F)=C1 PRYJGPVLQGEIHP-UHFFFAOYSA-N 0.000 claims description 2
- KRSPNUVHHWJPBX-UHFFFAOYSA-N 2'-[(dimethylamino)methyl]-n,n-dimethyl-1'-phenylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound CN(C)CC1CC2(C3=C(C4=CC=CC=C4N3)CCN2)CCC1(N(C)C)C1=CC=CC=C1 KRSPNUVHHWJPBX-UHFFFAOYSA-N 0.000 claims description 2
- ZTOKBWFOPCUIQE-UHFFFAOYSA-N 2'-[(dimethylamino)methyl]-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound CN(C)CC1CC2(C3=C(C4=CC=CC=C4N3)CCO2)CCC1(N(C)C)C1=CC=CC=C1 ZTOKBWFOPCUIQE-UHFFFAOYSA-N 0.000 claims description 2
- VMWCVNRWKYXQMS-UHFFFAOYSA-N 2'-fluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC=CC=C4N3)CCN2)CC(F)C1(N(C)C)C1=CC=CC(F)=C1 VMWCVNRWKYXQMS-UHFFFAOYSA-N 0.000 claims description 2
- YZTKCOYZTZVEIJ-UHFFFAOYSA-N 3',3'-difluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC=CC=C4N3)CCN2)C(F)(F)CC1(N(C)C)C1=CC=CC(F)=C1 YZTKCOYZTZVEIJ-UHFFFAOYSA-N 0.000 claims description 2
- KJRIQDNHVYBMSO-UHFFFAOYSA-N 3',5',6-trifluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(F)C2(C3=C(C4=CC(F)=CC=C4N3)CCN2)C(F)CC1(N(C)C)C1=CC=CC(F)=C1 KJRIQDNHVYBMSO-UHFFFAOYSA-N 0.000 claims description 2
- KRZPNWSAXBSKRL-UHFFFAOYSA-N 3',5'-difluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(F)C2(C3=C(C4=CC=CC=C4N3)CCN2)C(F)CC1(N(C)C)C1=CC=CC(F)=C1 KRZPNWSAXBSKRL-UHFFFAOYSA-N 0.000 claims description 2
- MELMNECKASPRRB-UHFFFAOYSA-N 3',6-difluoro-n,n-dimethyl-1'-thiophen-2-ylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)C(F)CC1(N(C)C)C1=CC=CS1 MELMNECKASPRRB-UHFFFAOYSA-N 0.000 claims description 2
- HNRGFZLGEXVUCB-UHFFFAOYSA-N 3'-fluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC=CC=C4N3)CCN2)C(F)CC1(N(C)C)C1=CC=CC(F)=C1 HNRGFZLGEXVUCB-UHFFFAOYSA-N 0.000 claims description 2
- ILNCEOIGYRKHIT-UHFFFAOYSA-N 3'-fluoro-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC=CC=C4N3)CCO2)C(F)CC1(N(C)C)C1=CC=CC=C1 ILNCEOIGYRKHIT-UHFFFAOYSA-N 0.000 claims description 2
- 208000004880 Polyuria Diseases 0.000 claims description 2
- 125000002723 alicyclic group Chemical group 0.000 claims description 2
- 230000002082 anti-convulsion Effects 0.000 claims description 2
- 230000035619 diuresis Effects 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- NNHQQQAFJCVHTJ-UHFFFAOYSA-N n,n-dimethyl-1'-phenyl-3'-phenylsulfanylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC=CC=C4N3)CCN2)C1SC1=CC=CC=C1 NNHQQQAFJCVHTJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000003957 neurotransmitter release Effects 0.000 claims description 2
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- 125000003003 spiro group Chemical group 0.000 claims description 2
- 208000009205 Tinnitus Diseases 0.000 claims 2
- 231100000886 tinnitus Toxicity 0.000 claims 2
- NWNVIDLCAYEQJL-FOCLMDBBSA-N (e)-1-[1'-(dimethylamino)-2'-fluoro-1'-(3-fluorophenyl)spiro[4,9-dihydro-3h-pyrido[3,4-b]indole-1,4'-cyclohexane]-2-yl]-3-phenylprop-2-en-1-one Chemical compound C1C(F)C(N(C)C)(C=2C=C(F)C=CC=2)CCC1(C1=C(C2=CC=CC=C2N1)CC1)N1C(=O)\C=C\C1=CC=CC=C1 NWNVIDLCAYEQJL-FOCLMDBBSA-N 0.000 claims 1
- QSIWIUOGISVJRD-FOCLMDBBSA-N (e)-1-[4'-(dimethylamino)-2'-fluoro-4'-(3-fluorophenyl)spiro[4,9-dihydro-3h-pyrido[3,4-b]indole-1,1'-cyclohexane]-2-yl]-3-phenylprop-2-en-1-one Chemical compound FC1CC(N(C)C)(C=2C=C(F)C=CC=2)CCC1(C1=C(C2=CC=CC=C2N1)CC1)N1C(=O)\C=C\C1=CC=CC=C1 QSIWIUOGISVJRD-FOCLMDBBSA-N 0.000 claims 1
- ZWAFHWCKPOMXPK-UHFFFAOYSA-N 1'-butyl-2',2',6-trifluoro-n,n-dimethylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(F)(F)C(CCCC)(N(C)C)CCC21C(NC=1C3=CC(F)=CC=1)=C3CCO2 ZWAFHWCKPOMXPK-UHFFFAOYSA-N 0.000 claims 1
- GUWAEAUYDRHBRM-UHFFFAOYSA-N 1'-butyl-3',5',6-trifluoro-n,n-dimethylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound FC1CC(CCCC)(N(C)C)CC(F)C11C(NC=2C3=CC(F)=CC=2)=C3CCO1 GUWAEAUYDRHBRM-UHFFFAOYSA-N 0.000 claims 1
- LZFDDVHXABBJPX-UHFFFAOYSA-N 2',2',6-trifluoro-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)CC(F)(F)C1(N(C)C)C1=CC=CC=C1 LZFDDVHXABBJPX-UHFFFAOYSA-N 0.000 claims 1
- WYEZTUIJZFLRTP-UHFFFAOYSA-N 2',2'-difluoro-n,n-dimethyl-1'-phenylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC=CC=C4N3)CCN2)CC(F)(F)C1(N(C)C)C1=CC=CC=C1 WYEZTUIJZFLRTP-UHFFFAOYSA-N 0.000 claims 1
- WALZLZQINUMROW-UHFFFAOYSA-N 2',6-difluoro-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)CC(F)C1(N(C)C)C1=CC=CC=C1 WALZLZQINUMROW-UHFFFAOYSA-N 0.000 claims 1
- RJLKEYGXHXIEMB-UHFFFAOYSA-N 2-[5'-(dimethylamino)-5'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,2'-cyclohexane]-1'-yl]acetonitrile Chemical compound C1CC2(C3=C(C4=CC=CC=C4N3)CCO2)C(CC#N)CC1(N(C)C)C1=CC=CC=C1 RJLKEYGXHXIEMB-UHFFFAOYSA-N 0.000 claims 1
- DBWJRYDBOSDJPY-UHFFFAOYSA-N 3',3',6-trifluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCN2)C(F)(F)CC1(N(C)C)C1=CC=CC(F)=C1 DBWJRYDBOSDJPY-UHFFFAOYSA-N 0.000 claims 1
- BWWFSITUFBMPKV-UHFFFAOYSA-N 3',3',6-trifluoro-n,n-dimethyl-1'-thiophen-2-ylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)C(F)(F)CC1(N(C)C)C1=CC=CS1 BWWFSITUFBMPKV-UHFFFAOYSA-N 0.000 claims 1
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- MPELBLISKJKROZ-UHFFFAOYSA-N 3',6-difluoro-1'-(3-fluorophenyl)-n,n-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1CC2(C3=C(C4=CC(F)=CC=C4N3)CCN2)C(F)CC1(N(C)C)C1=CC=CC(F)=C1 MPELBLISKJKROZ-UHFFFAOYSA-N 0.000 claims 1
- QBVIWHPHZCVHMP-UHFFFAOYSA-N 3'-(4-fluorophenyl)-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC=CC=C4N3)CCO2)C1C1=CC=C(F)C=C1 QBVIWHPHZCVHMP-UHFFFAOYSA-N 0.000 claims 1
- AUDCNKWQWXLRMW-UHFFFAOYSA-N 3'-[(4-fluorophenyl)methyl]-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC=CC=C4N3)CCO2)C1CC1=CC=C(F)C=C1 AUDCNKWQWXLRMW-UHFFFAOYSA-N 0.000 claims 1
- NFUDCFAJVQICOZ-UHFFFAOYSA-N 3'-benzyl-6-fluoro-n,n-dimethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(N(C)C)(C=2C=CC=CC=2)CCC2(C3=C(C4=CC(F)=CC=C4N3)CCO2)C1CC1=CC=CC=C1 NFUDCFAJVQICOZ-UHFFFAOYSA-N 0.000 claims 1
- 206010010904 Convulsion Diseases 0.000 claims 1
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- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- SBJZSFPMOHWNID-UHFFFAOYSA-N n,n,3',5'-tetramethyl-1'-phenylspiro[4,9-dihydro-3h-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine Chemical compound C1C(C)C2(C3=C(C4=CC=CC=C4N3)CCO2)C(C)CC1(N(C)C)C1=CC=CC=C1 SBJZSFPMOHWNID-UHFFFAOYSA-N 0.000 claims 1
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- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
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- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
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| AR071067A1 (es) * | 2008-03-27 | 2010-05-26 | Gruenenthal Chemie | Ciclohexildiaminas sustituidas |
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| BR112012006648A2 (pt) | 2009-09-23 | 2019-09-24 | Medivation Neurology Inc | composto,método de tratamento de um distúrbio cognitivo, distúrbio psicótico, distúrbio mediado por neurotransmissor ou um distúrbio neuronal, composição farmacêutica e kit |
| UA107943C2 (xx) * | 2009-11-16 | 2015-03-10 | Lilly Co Eli | Сполуки спіропіперидину як антагоністи рецептора orl-1 |
| TWI582092B (zh) * | 2010-07-28 | 2017-05-11 | 歌林達股份有限公司 | 順式－四氫－螺旋（環己烷－１,１’－吡啶［３,４－b］吲哚）－４－胺－衍生物 |
| DK2600851T3 (en) | 2010-08-04 | 2018-06-25 | Gruenenthal Gmbh | PHARMACEUTICAL DOSAGE FORM CONTAINING 6'-FLUORO- (N-METHYL OR N, N-DIMETHYL -) - 4-PHENYL-4 ', 9'-DIHYDRO-3'H-SPIRO [CYCLOHEXAN-1,1'-PYRANO [3,4, B] INDOL] -4-AMINE FOR TREATMENT OF NEUROPATHIC PAIN |
| SI2649044T1 (en) * | 2010-12-08 | 2018-01-31 | Gruenenthal Gmbh | A process for the synthesis of substituted aminocyclohexanone derivatives |
| WO2012154261A1 (en) | 2011-02-18 | 2012-11-15 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| PL2688403T3 (pl) | 2011-03-23 | 2017-09-29 | Trevena, Inc. | Ligandy receptora opioidowego oraz sposoby ich stosowania i wytwarzania |
| HUE029406T2 (hu) * | 2011-12-12 | 2017-03-28 | Gruenenthal Gmbh | (1R,4R)-6'-fluor-N,N-dimetil-4-fenil-4',9'-dihidro-3'H-spiro-[ciklohexán-1,1'- pirano[3,4,B]indol]-4-amin-hidroklorid szilárd formái |
| ES2686326T3 (es) | 2014-07-15 | 2018-10-17 | Grünenthal GmbH | Derivados de azaspiro(4,5)decano sustituidos |
| TW201607923A (zh) | 2014-07-15 | 2016-03-01 | 歌林達有限公司 | 被取代之氮螺環（４．５）癸烷衍生物 |
| CA3007020A1 (en) | 2015-12-14 | 2017-06-22 | Trevena, Inc. | Methods of treating hyperalgesia |
| CN116284027B (zh) * | 2023-01-10 | 2025-07-11 | 云南大学 | 一种多取代五环螺吲哚啉衍生物及其制备方法 |
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| DE102005061427A1 (de) | 2005-12-22 | 2007-06-28 | Grünenthal GmbH | Substituierte Oxadiazol-Derivate |
| DE102005061430A1 (de) | 2005-12-22 | 2007-07-05 | Grünenthal GmbH | Substituierte Imidazolin-Derivate |
| DE102006019597A1 (de) | 2006-04-27 | 2007-10-31 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE102006033114A1 (de) | 2006-07-18 | 2008-01-24 | Grünenthal GmbH | Spirocyclische Azaindol-Derivate |
| DE102006033109A1 (de) | 2006-07-18 | 2008-01-31 | Grünenthal GmbH | Substituierte Heteroaryl-Derivate |
| DE102006046745A1 (de) | 2006-09-29 | 2008-04-03 | Grünenthal GmbH | Gemischte ORL1/µ-Agonisten zur Behandlung von Schmerz |
| DE102007009235A1 (de) | 2007-02-22 | 2008-09-18 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| DE102007009319A1 (de) | 2007-02-22 | 2008-08-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
| CA2719736C (en) | 2008-03-27 | 2016-02-09 | Gruenenthal Gmbh | Spiro(5.5)undecane derivatives |
| WO2009118163A1 (de) | 2008-03-27 | 2009-10-01 | Grünenthal GmbH | (hetero-)aryl-cyclohexan-derivate |
| PL2271613T3 (pl) | 2008-03-27 | 2014-09-30 | Gruenenthal Gmbh | Hydroksymetylocykloheksyloaminy |
| PT2260042E (pt) | 2008-03-27 | 2011-12-06 | Gruenenthal Gmbh | Derivados de ciclo-hexano espirocíclicos substituídos |
| EP2502907B1 (de) | 2008-03-27 | 2018-08-29 | Grünenthal GmbH | Substituierte 4-Aminocyclohexan-Derivate |
| AR071067A1 (es) | 2008-03-27 | 2010-05-26 | Gruenenthal Chemie | Ciclohexildiaminas sustituidas |
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2009
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7547707B2 (en) * | 2002-11-11 | 2009-06-16 | Gruenenthal Gmbh | Spirocyclic cyclohexane compounds |
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