ES2797904T3 - Derivados de 3-((hetero)aril)alquil-8-amino-2-oxo-1,3-diazaespiro-[4.5]-decano - Google Patents

Info

Publication number

ES2797904T3

ES2797904T3 ES17701638T ES17701638T ES2797904T3 ES 2797904 T3 ES2797904 T3 ES 2797904T3 ES 17701638 T ES17701638 T ES 17701638T ES 17701638 T ES17701638 T ES 17701638T ES 2797904 T3 ES2797904 T3 ES 2797904T3

Authority

ES

Spain

Prior art keywords

diazaspiro

cis

decan

phenyl

methyl

Prior art date

2016-01-13

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.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 125000003118 aryl group Chemical group 0.000 title claims abstract description 29
• 125000005842 heteroatom Chemical group 0.000 title description 13
• 229920006395 saturated elastomer Polymers 0.000 claims abstract description 151
• 150000001875 compounds Chemical class 0.000 claims abstract description 143
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 86
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 64
• 125000001424 substituent group Chemical group 0.000 claims abstract description 59
• 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims abstract description 51
• 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims abstract description 41
• 125000006707 (C3-C12) heterocycloalkyl group Chemical group 0.000 claims abstract description 38
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims abstract description 36
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 25
• 150000003839 salts Chemical class 0.000 claims abstract description 24
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 22
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 14
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
• -1 -OH Chemical group 0.000 claims description 69
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 26
• ZAJNGDIORYACQU-UHFFFAOYSA-N decan-2-one Chemical compound CCCCCCCCC(C)=O ZAJNGDIORYACQU-UHFFFAOYSA-N 0.000 claims description 26
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
• 125000000217 alkyl group Chemical group 0.000 claims description 19
• BHNBGYKHHFLUSJ-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2)=O)CC2=CC=C(C=C2)OC)CC1)C1=CC=CC=C1)C BHNBGYKHHFLUSJ-UHFFFAOYSA-N 0.000 claims description 18
• 208000002193 Pain Diseases 0.000 claims description 15
• 239000002253 acid Substances 0.000 claims description 13
• 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 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
• 230000036407 pain Effects 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• BGEAEALXBNWGJY-UHFFFAOYSA-N 8-(dimethylamino)-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3cccc(F)c3)NC2=O)cc1 BGEAEALXBNWGJY-UHFFFAOYSA-N 0.000 claims description 7
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 7
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 6
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
• GMXJRLCDFKLCGY-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[(3-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)(C1=CC=CC=C1)N(C)C)CC1=CC(=CC=C1)OC)=O GMXJRLCDFKLCGY-UHFFFAOYSA-N 0.000 claims description 5
• RABKZFCSZJSVIG-UHFFFAOYSA-N 1-[(1-hydroxycyclobutyl)methyl]-3-[(4-methoxyphenyl)methyl]-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CNC1(CCC2(CN(Cc3ccc(OC)cc3)C(=O)N2CC2(O)CCC2)CC1)c1ccccc1 RABKZFCSZJSVIG-UHFFFAOYSA-N 0.000 claims description 5
• BFAKENXZKHGIGE-UHFFFAOYSA-N bis(2,3,5,6-tetrafluoro-4-iodophenyl)diazene Chemical compound FC1=C(C(=C(C(=C1F)I)F)F)N=NC1=C(C(=C(C(=C1F)F)I)F)F BFAKENXZKHGIGE-UHFFFAOYSA-N 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• QNBCHHJSUDHSIL-UHFFFAOYSA-N 1-(cyclobutylmethyl)-3-[(3-methoxyphenyl)methyl]-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)(C1=CC=CC=C1)NC)CC1=CC(=CC=C1)OC)=O QNBCHHJSUDHSIL-UHFFFAOYSA-N 0.000 claims description 4
• HDACKSUZWAPUAP-UHFFFAOYSA-N 1-(cyclobutylmethyl)-3-[(4-methoxyphenyl)methyl]-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)(C1=CC=CC=C1)NC)CC1=CC=C(C=C1)OC)=O HDACKSUZWAPUAP-UHFFFAOYSA-N 0.000 claims description 4
• PNGFHKYHCNALQP-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[(4-hydroxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3ccc(O)cc3)C(=O)N2CC2CCC2)CC1)c1ccccc1 PNGFHKYHCNALQP-UHFFFAOYSA-N 0.000 claims description 4
• LTWIXTDRAFZAPF-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC3CCC3)C2=O)cc1 LTWIXTDRAFZAPF-UHFFFAOYSA-N 0.000 claims description 4
• WRLWEGOEFBBBJN-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-8-(3-fluorophenyl)-3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)(C1=CC(=CC=C1)F)N(C)C)CC1=CC=C(C=C1)OC)=O WRLWEGOEFBBBJN-UHFFFAOYSA-N 0.000 claims description 4
• SFVUCTQOKPNATA-UHFFFAOYSA-N 8-(dimethylamino)-1-(2-methoxy-2-methylpropyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2CC(C)(C)OC)=O)CC2=CC=C(C=C2)OC)CC1)C1=CC=CC=C1)C SFVUCTQOKPNATA-UHFFFAOYSA-N 0.000 claims description 4
• NQNSOTSTQRWEFA-UHFFFAOYSA-N 2-[[1-(cyclobutylmethyl)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-8-yl]-methylamino]acetonitrile Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)CC#N)c3ccccc3)N(CC3CCC3)C2=O)cc1 NQNSOTSTQRWEFA-UHFFFAOYSA-N 0.000 claims description 3
• JPPRWNMMGJNQBN-UHFFFAOYSA-N 8-(dimethylamino)-1-(2-hydroxyethyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2CCO)=O)CC2=CC=C(C=C2)OC)CC1)C1=CC=CC=C1)C JPPRWNMMGJNQBN-UHFFFAOYSA-N 0.000 claims description 3
• CZVLUFVYJXQKHZ-UHFFFAOYSA-N 8-(dimethylamino)-1-(3-hydroxy-3-methylbutyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CCC(C)(C)O)C2=O)cc1 CZVLUFVYJXQKHZ-UHFFFAOYSA-N 0.000 claims description 3
• VFVLDDWIJAMRTA-UHFFFAOYSA-N 8-(dimethylamino)-1-[(1-hydroxycyclobutyl)methyl]-8-phenyl-3-(2-phenylethyl)-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(CCC3=CC=CC=C3)C(=O)N2CC2(O)CCC2)CC1)C1=CC=CC=C1 VFVLDDWIJAMRTA-UHFFFAOYSA-N 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 6
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 4
• QUVDCWLEMFTCQX-UHFFFAOYSA-N 8-(dimethylamino)-1-ethyl-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 QUVDCWLEMFTCQX-UHFFFAOYSA-N 0.000 claims 2
• SGGMATVTIPUWKX-UHFFFAOYSA-N 1-(2-cyclobutylethyl)-8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CCC3CCC3)C2=O)cc1 SGGMATVTIPUWKX-UHFFFAOYSA-N 0.000 claims 1
• RQOVYXMPEPGWDI-UHFFFAOYSA-N 1-(cyclobutylmethyl)-3-[[1-(2-hydroxyethyl)triazol-4-yl]methyl]-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CNC1(CCC2(CN(CC3=CN(CCO)N=N3)C(=O)N2CC2CCC2)CC1)C1=CC=CC=C1 RQOVYXMPEPGWDI-UHFFFAOYSA-N 0.000 claims 1
• PEPORJMKLNYBKB-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[(3-methylsulfonylphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3cccc(c3)S(C)(=O)=O)C(=O)N2CC2CCC2)CC1)c1ccccc1 PEPORJMKLNYBKB-UHFFFAOYSA-N 0.000 claims 1
• RAODKODTBAFUCM-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-(3-methoxypropyl)-1,3-diazaspiro[4.5]decan-2-one Chemical compound COCCCC1(CCC2(CN(Cc3ccc(OC)cc3)C(=O)N2CC2CCC2)CC1)N(C)C RAODKODTBAFUCM-UHFFFAOYSA-N 0.000 claims 1
• BARLHUVNIVYXMO-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[(4-methylsulfonylphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3ccc(cc3)S(C)(=O)=O)C(=O)N2CC2CCC2)CC1)c1ccccc1 BARLHUVNIVYXMO-UHFFFAOYSA-N 0.000 claims 1
• VBLSOCKFYRCTFP-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[[1-(2-hydroxyethyl)triazol-4-yl]methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3cn(CCO)nn3)C(=O)N2CC2CCC2)CC1)c1ccccc1 VBLSOCKFYRCTFP-UHFFFAOYSA-N 0.000 claims 1
• DJFZBCVQEHKNNP-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-8-(3-methoxyphenyl)-3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3cccc(OC)c3)N(CC3CCC3)C2=O)cc1 DJFZBCVQEHKNNP-UHFFFAOYSA-N 0.000 claims 1
• ZJSRAQNSQCIMIR-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-8-(4-fluorophenyl)-3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccc(F)cc3)N(CC3CCC3)C2=O)cc1 ZJSRAQNSQCIMIR-UHFFFAOYSA-N 0.000 claims 1
• IKOPGFJXCMHTLG-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-8-(4-methoxyphenyl)-3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)(C1=CC=C(C=C1)OC)N(C)C)CC1=CC=C(C=C1)OC)=O IKOPGFJXCMHTLG-UHFFFAOYSA-N 0.000 claims 1
• LTJOZEQCCDXJDH-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-8-phenyl-3-[[6-(trifluoromethyl)pyridin-3-yl]methyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3ccc(nc3)C(F)(F)F)C(=O)N2CC2CCC2)CC1)c1ccccc1 LTJOZEQCCDXJDH-UHFFFAOYSA-N 0.000 claims 1
• ODGKMJBDZAKEOJ-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-[2-methoxyethyl(methyl)amino]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COCCN(C)C1(CCC2(CN(Cc3ccc(OC)cc3)C(=O)N2CC2CCC2)CC1)c1ccccc1 ODGKMJBDZAKEOJ-UHFFFAOYSA-N 0.000 claims 1
• LOYKRVWFMCWRDF-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-[ethyl(methyl)amino]-3-[(3-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCN(C)C1(CCC2(CN(Cc3cccc(OC)c3)C(=O)N2CC2CCC2)CC1)c1ccccc1 LOYKRVWFMCWRDF-UHFFFAOYSA-N 0.000 claims 1
• NVWJPWMESOJBIQ-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-[ethyl(methyl)amino]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCN(C)C1(CCC2(CN(Cc3ccc(OC)cc3)C(=O)N2CC2CCC2)CC1)c1ccccc1 NVWJPWMESOJBIQ-UHFFFAOYSA-N 0.000 claims 1
• XGTYIJYODNDKSI-UHFFFAOYSA-N 1-(cyclohexylmethyl)-8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC3CCCCC3)C2=O)cc1 XGTYIJYODNDKSI-UHFFFAOYSA-N 0.000 claims 1
• LBRBAUKQYWJZGV-UHFFFAOYSA-N 1-(cyclopropylmethyl)-8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CC1)CN1C(N(CC11CCC(CC1)(C1=CC=CC=C1)N(C)C)CC1=CC=C(C=C1)OC)=O LBRBAUKQYWJZGV-UHFFFAOYSA-N 0.000 claims 1
• UAUMNBLPPCLQJI-UHFFFAOYSA-N 1-[(1-hydroxycyclobutyl)methyl]-3-[[1-(2-hydroxyethyl)triazol-4-yl]methyl]-8-(methylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CNC1(CCC2(CN(Cc3cn(CCO)nn3)C(=O)N2CC2(O)CCC2)CC1)c1ccccc1 UAUMNBLPPCLQJI-UHFFFAOYSA-N 0.000 claims 1
• MLZNGXHVSPBQRK-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COC1=CC=C(C=C1)CN1C(NCC11CCC(CC1)C1=CC=CC=C1)=O MLZNGXHVSPBQRK-UHFFFAOYSA-N 0.000 claims 1
• MPXOSRRFFZVJAB-UHFFFAOYSA-N 1-benzyl-8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(Cc3ccccc3)C2=O)cc1 MPXOSRRFFZVJAB-UHFFFAOYSA-N 0.000 claims 1
• AXVAABMMWSPIFS-UHFFFAOYSA-N 1-butyl-8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCCCN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 AXVAABMMWSPIFS-UHFFFAOYSA-N 0.000 claims 1
• IKOYSWCQXDHCDO-UHFFFAOYSA-N 2-[4-[[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]triazol-1-yl]acetamide Chemical compound CN(C)C1(CCC2(CN(Cc3cn(CC(N)=O)nn3)C(=O)N2CC2CCC2)CC1)c1ccccc1 IKOYSWCQXDHCDO-UHFFFAOYSA-N 0.000 claims 1
• YLNLBILMQYDBCG-UHFFFAOYSA-N 2-[4-[[1-(cyclobutylmethyl)-8-(methylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]triazol-1-yl]acetamide Chemical compound CNC1(CCC2(CN(Cc3cn(CC(N)=O)nn3)C(=O)N2CC2CCC2)CC1)c1ccccc1 YLNLBILMQYDBCG-UHFFFAOYSA-N 0.000 claims 1
• FFZAIIYNXSFMCO-UHFFFAOYSA-N 2-[4-[[8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]triazol-1-yl]acetamide Chemical compound CN(C)C1(CCC2(CN(CC3=CN(CC(N)=O)N=N3)C(=O)N2)CC1)C1=CC=CC=C1 FFZAIIYNXSFMCO-UHFFFAOYSA-N 0.000 claims 1
• ZXRRGVGLHHARAT-UHFFFAOYSA-N 2-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N,N-dimethylacetamide Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(=O)N(C)C)C2=O)cc1 ZXRRGVGLHHARAT-UHFFFAOYSA-N 0.000 claims 1
• FDCCYBJKYXVZMA-UHFFFAOYSA-N 2-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N-methylacetamide Chemical compound CNC(=O)CN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 FDCCYBJKYXVZMA-UHFFFAOYSA-N 0.000 claims 1
• MZYWTWUHEDBUPO-UHFFFAOYSA-N 2-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]acetic acid Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(O)=O)C2=O)cc1 MZYWTWUHEDBUPO-UHFFFAOYSA-N 0.000 claims 1
• KLRNHYAAJDBCDZ-UHFFFAOYSA-N 2-[[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzamide Chemical compound CN(C)C1(CCC2(CN(Cc3ccccc3C(N)=O)C(=O)N2CC2CCC2)CC1)c1ccccc1 KLRNHYAAJDBCDZ-UHFFFAOYSA-N 0.000 claims 1
• COXCTWQMLFTBNV-UHFFFAOYSA-N 2-[[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzonitrile Chemical compound CN(C)C1(CCC2(CN(Cc3ccccc3C#N)C(=O)N2CC2CCC2)CC1)c1ccccc1 COXCTWQMLFTBNV-UHFFFAOYSA-N 0.000 claims 1
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims 1
• PROZJMQQFSDKGS-UHFFFAOYSA-N 3-[(3-cyclopropylphenyl)methyl]-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3cccc(c3)C3CC3)C(=O)N2)CC1)c1ccccc1 PROZJMQQFSDKGS-UHFFFAOYSA-N 0.000 claims 1
• BAVUHYFEHNCBQJ-UHFFFAOYSA-N 3-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]-2,2-dimethylpropanenitrile Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(C)(C)C#N)C2=O)cc1 BAVUHYFEHNCBQJ-UHFFFAOYSA-N 0.000 claims 1
• KGCKWOLCQQVPIU-UHFFFAOYSA-N 3-[[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzamide Chemical compound CN(C)C1(CCC2(CN(Cc3cccc(c3)C(N)=O)C(=O)N2CC2CCC2)CC1)c1ccccc1 KGCKWOLCQQVPIU-UHFFFAOYSA-N 0.000 claims 1
• FULKUJGTRBNCGE-UHFFFAOYSA-N 3-[[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzonitrile Chemical compound CN(C)C1(CCC2(CN(Cc3cccc(c3)C#N)C(=O)N2CC2CCC2)CC1)c1ccccc1 FULKUJGTRBNCGE-UHFFFAOYSA-N 0.000 claims 1
• KHVBGQXIDHWYFR-UHFFFAOYSA-N 3-[[1-(cyclobutylmethyl)-8-[ethyl(methyl)amino]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzonitrile Chemical compound CCN(C)C1(CCC2(CN(Cc3cccc(c3)C#N)C(=O)N2CC2CCC2)CC1)c1ccccc1 KHVBGQXIDHWYFR-UHFFFAOYSA-N 0.000 claims 1
• CZQIMPJTMOJZOC-UHFFFAOYSA-N 3-[[1-[(5-cyano-2-methoxyphenyl)methyl]-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]-4-methoxybenzonitrile Chemical compound COc1ccc(cc1CN1CC2(CCC(CC2)(N(C)C)c2ccccc2)N(Cc2cc(ccc2OC)C#N)C1=O)C#N CZQIMPJTMOJZOC-UHFFFAOYSA-N 0.000 claims 1
• ZIWDDEMSWAXPOA-UHFFFAOYSA-N 3-[[8-(dimethylamino)-1-[(1-hydroxycyclobutyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzamide Chemical compound CN(C)C1(CCC2(CN(Cc3cccc(c3)C(N)=O)C(=O)N2CC2(O)CCC2)CC1)c1ccccc1 ZIWDDEMSWAXPOA-UHFFFAOYSA-N 0.000 claims 1
• DCYJVBMOSCLZEW-UHFFFAOYSA-N 3-benzyl-8-(dimethylamino)-1-ethyl-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCN1C(=O)N(Cc2ccccc2)CC11CCC(CC1)(N(C)C)c1ccccc1 DCYJVBMOSCLZEW-UHFFFAOYSA-N 0.000 claims 1
• UGMHTGXNTSNAJX-UHFFFAOYSA-N 3-benzyl-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2)=O)CC2=CC=CC=C2)CC1)C1=CC=CC=C1)C UGMHTGXNTSNAJX-UHFFFAOYSA-N 0.000 claims 1
• YDBCFLZEMCMGGF-UHFFFAOYSA-N 4-[[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzamide Chemical compound CN(C)C1(CCC2(CN(Cc3ccc(cc3)C(N)=O)C(=O)N2CC2CCC2)CC1)c1ccccc1 YDBCFLZEMCMGGF-UHFFFAOYSA-N 0.000 claims 1
• OMKDSWPCDJXLHL-UHFFFAOYSA-N 4-[[8-(dimethylamino)-3-[(2-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzonitrile Chemical compound COc1ccccc1CN1CC2(CCC(CC2)(N(C)C)c2ccccc2)N(Cc2ccc(cc2)C#N)C1=O OMKDSWPCDJXLHL-UHFFFAOYSA-N 0.000 claims 1
• IIWPFIOGXDEILF-UHFFFAOYSA-N 8-(dimethylamino)-1,3-bis[(2-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccccc1CN1CC2(CCC(CC2)(N(C)C)c2ccccc2)N(Cc2ccccc2OC)C1=O IIWPFIOGXDEILF-UHFFFAOYSA-N 0.000 claims 1
• IHTLAUCEENRUEU-UHFFFAOYSA-N 8-(dimethylamino)-1-(2,2-dimethylpropyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(C)(C)C)C2=O)cc1 IHTLAUCEENRUEU-UHFFFAOYSA-N 0.000 claims 1
• QWTRCFJREFKNLA-UHFFFAOYSA-N 8-(dimethylamino)-1-(2-methoxyethyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COCCN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 QWTRCFJREFKNLA-UHFFFAOYSA-N 0.000 claims 1
• SIGOICSVLIYHOG-UHFFFAOYSA-N 8-(dimethylamino)-1-(3-hydroxypropyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2CCCO)=O)CC2=CC=C(C=C2)OC)CC1)C1=CC=CC=C1)C SIGOICSVLIYHOG-UHFFFAOYSA-N 0.000 claims 1
• GABIRMYMQDJWCZ-UHFFFAOYSA-N 8-(dimethylamino)-1-(3-methoxy-3-methylbutyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CCC(C)(C)OC)C2=O)cc1 GABIRMYMQDJWCZ-UHFFFAOYSA-N 0.000 claims 1
• KDLYBOULYFJNGG-UHFFFAOYSA-N 8-(dimethylamino)-1-(4-methoxybutyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2CCCCOC)=O)CC2=CC=C(C=C2)OC)CC1)C1=CC=CC=C1)C KDLYBOULYFJNGG-UHFFFAOYSA-N 0.000 claims 1
• NZNKTAQYGWAKRG-UHFFFAOYSA-N 8-(dimethylamino)-1-[(1-hydroxycyclobutyl)methyl]-3-[[1-(2-hydroxyethyl)triazol-4-yl]methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3cn(CCO)nn3)C(=O)N2CC2(O)CCC2)CC1)c1ccccc1 NZNKTAQYGWAKRG-UHFFFAOYSA-N 0.000 claims 1
• SQVUGTPGSWROSO-UHFFFAOYSA-N 8-(dimethylamino)-1-[(1-hydroxycyclobutyl)methyl]-8-phenyl-3-(1-phenylcyclopropyl)-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(C(=O)N2CC2(O)CCC2)C2(CC2)c2ccccc2)CC1)c1ccccc1 SQVUGTPGSWROSO-UHFFFAOYSA-N 0.000 claims 1
• YHFRDHDYJQGFCO-UHFFFAOYSA-N 8-(dimethylamino)-1-[(1-methoxycyclobutyl)methyl]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC3(CCC3)OC)C2=O)cc1 YHFRDHDYJQGFCO-UHFFFAOYSA-N 0.000 claims 1
• FQWQSNXRVLAODG-QJYLRPAKSA-N 8-(dimethylamino)-1-[(2R)-2-hydroxypropyl]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(C[C@@H](C)O)C2=O)cc1 FQWQSNXRVLAODG-QJYLRPAKSA-N 0.000 claims 1
• FQWQSNXRVLAODG-HTFLBPPUSA-N 8-(dimethylamino)-1-[(2S)-2-hydroxypropyl]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2C[C@H](C)O)=O)CC2=CC=C(C=C2)OC)CC1)C1=CC=CC=C1)C FQWQSNXRVLAODG-HTFLBPPUSA-N 0.000 claims 1
• YGKSGVSDBCEYFA-UHFFFAOYSA-N 8-(dimethylamino)-1-ethyl-3-[(4-methylsulfonylphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCN1C(=O)N(Cc2ccc(cc2)S(C)(=O)=O)CC11CCC(CC1)(N(C)C)c1ccccc1 YGKSGVSDBCEYFA-UHFFFAOYSA-N 0.000 claims 1
• LNOCBRQVXASBHM-UHFFFAOYSA-N 8-(dimethylamino)-1-hexyl-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCCCCCN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 LNOCBRQVXASBHM-UHFFFAOYSA-N 0.000 claims 1
• ZCLDCJBPOKYYLS-UHFFFAOYSA-N 8-(dimethylamino)-3-(2-imidazol-1-ylethyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(CCn3ccnc3)C(=O)N2)CC1)c1ccccc1 ZCLDCJBPOKYYLS-UHFFFAOYSA-N 0.000 claims 1
• BNKDNWQCAAKLJI-UHFFFAOYSA-N 8-(dimethylamino)-3-[(2-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccccc1CN1CC2(CCC(CC2)(N(C)C)c2ccccc2)NC1=O BNKDNWQCAAKLJI-UHFFFAOYSA-N 0.000 claims 1
• IIXIYAOBXURUSH-UHFFFAOYSA-N 8-(dimethylamino)-3-[(3-methylsulfonylphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3cccc(c3)S(C)(=O)=O)C(=O)N2)CC1)c1ccccc1 IIXIYAOBXURUSH-UHFFFAOYSA-N 0.000 claims 1
• ZFDFQROBUBTCCD-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-1-(2-methylpropyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(C)C)C2=O)cc1 ZFDFQROBUBTCCD-UHFFFAOYSA-N 0.000 claims 1
• FOGFBFFNNUETQN-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-1-(2-methylsulfinylethyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CCS(C)=O)C2=O)cc1 FOGFBFFNNUETQN-UHFFFAOYSA-N 0.000 claims 1
• NBJAQPQZTRCRMT-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-1-(2-methylsulfonylethyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CCS(C)(=O)=O)C2=O)cc1 NBJAQPQZTRCRMT-UHFFFAOYSA-N 0.000 claims 1
• BXZLRTCXNRQVCW-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-1-(3-methoxypropyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COCCCN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 BXZLRTCXNRQVCW-UHFFFAOYSA-N 0.000 claims 1
• KHOAUVUZRCUBHZ-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-1-(3-methylbutyl)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CCC(C)C)C2=O)cc1 KHOAUVUZRCUBHZ-UHFFFAOYSA-N 0.000 claims 1
• RHAGFGQMVKOAOQ-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-1-[(1-methylcyclobutyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC3(C)CCC3)C2=O)cc1 RHAGFGQMVKOAOQ-UHFFFAOYSA-N 0.000 claims 1
• XEYHRCKUXCHABL-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-1-methyl-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(C)C2=O)cc1 XEYHRCKUXCHABL-UHFFFAOYSA-N 0.000 claims 1
• ZDOKCQISPIJWSQ-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1-[3-(trifluoromethoxy)propyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CCCOC(F)(F)F)C2=O)cc1 ZDOKCQISPIJWSQ-UHFFFAOYSA-N 0.000 claims 1
• YKJRFMZLGSIQRX-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1-propan-2-yl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(C(C)C)C2=O)cc1 YKJRFMZLGSIQRX-UHFFFAOYSA-N 0.000 claims 1
• SXFLFVXSZGMVAC-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1-propyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CCCN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 SXFLFVXSZGMVAC-UHFFFAOYSA-N 0.000 claims 1
• IHUFDVVXUQAUSC-UHFFFAOYSA-N 8-(dimethylamino)-3-[[1-(2-hydroxyethyl)triazol-4-yl]methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(CC3=CN(CCO)N=N3)C(=O)N2)CC1)C1=CC=CC=C1 IHUFDVVXUQAUSC-UHFFFAOYSA-N 0.000 claims 1
• SEOUKLLRFIWGEE-UHFFFAOYSA-N 8-(dimethylamino)-3-[[2-(4-methylpiperazin-1-yl)pyridin-4-yl]methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(Cc3ccnc(c3)N3CCN(C)CC3)C(=O)N2)CC1)c1ccccc1 SEOUKLLRFIWGEE-UHFFFAOYSA-N 0.000 claims 1
• AJPXHRMJMSUXJS-UHFFFAOYSA-N 8-(dimethylamino)-8-phenyl-3-(1-phenylcyclopropyl)-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(C(=O)N2)C2(CC2)c2ccccc2)CC1)c1ccccc1 AJPXHRMJMSUXJS-UHFFFAOYSA-N 0.000 claims 1
• OYBWOVGHVZVZSD-UHFFFAOYSA-N 8-(dimethylamino)-8-phenyl-3-(2-phenylpropan-2-yl)-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C)C1(CCC2(CN(C(=O)N2)C(C)(C)c2ccccc2)CC1)c1ccccc1 OYBWOVGHVZVZSD-UHFFFAOYSA-N 0.000 claims 1
• PBOMZZBWZTYARW-UHFFFAOYSA-N N-(1-cyanocyclopropyl)-2-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]acetamide Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(=O)NC3(CC3)C#N)C2=O)cc1 PBOMZZBWZTYARW-UHFFFAOYSA-N 0.000 claims 1
• HIPWFIJDSIDRID-UHFFFAOYSA-N N-(cyanomethyl)-2-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]acetamide Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(=O)NCC#N)C2=O)cc1 HIPWFIJDSIDRID-UHFFFAOYSA-N 0.000 claims 1
• SNELALVEGSICQC-UHFFFAOYSA-N benzyl 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decane-1-carboxylate Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(C(=O)OCc3ccccc3)C2=O)cc1 SNELALVEGSICQC-UHFFFAOYSA-N 0.000 claims 1
• UYRRUFWQQVZIOQ-UHFFFAOYSA-N methyl 2-[[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]methyl]benzoate Chemical compound COC(=O)c1ccccc1CN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 UYRRUFWQQVZIOQ-UHFFFAOYSA-N 0.000 claims 1
• 150000004702 methyl esters Chemical class 0.000 claims 1
• ZLBZEQAPQMBMTC-UHFFFAOYSA-N tert-butyl 2-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]acetate Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(=O)OC(C)(C)C)C2=O)cc1 ZLBZEQAPQMBMTC-UHFFFAOYSA-N 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 301
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 232
• 102000005962 receptors Human genes 0.000 description 188
• 108020003175 receptors Proteins 0.000 description 188
• 239000011541 reaction mixture Substances 0.000 description 182
• 230000000694 effects Effects 0.000 description 171
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 157
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 134
• 239000000243 solution Substances 0.000 description 109
• 239000000556 agonist Substances 0.000 description 100
• 239000007787 solid Substances 0.000 description 94
• 230000002829 reductive effect Effects 0.000 description 92
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 90
• 238000003786 synthesis reaction Methods 0.000 description 90
• 230000015572 biosynthetic process Effects 0.000 description 89
• 239000007832 Na2SO4 Substances 0.000 description 86
• 229910052938 sodium sulfate Inorganic materials 0.000 description 86
• 235000011152 sodium sulphate Nutrition 0.000 description 86
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 85
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 77
• 238000004809 thin layer chromatography Methods 0.000 description 70
• 235000019439 ethyl acetate Nutrition 0.000 description 67
• 239000000203 mixture Substances 0.000 description 65
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 63
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
• 102000051367 mu Opioid Receptors Human genes 0.000 description 56
• 108020001612 μ-opioid receptors Proteins 0.000 description 56
• 239000012044 organic layer Substances 0.000 description 53
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 46
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
• 239000000047 product Substances 0.000 description 44
• 238000000746 purification Methods 0.000 description 38
• 239000000741 silica gel Substances 0.000 description 35
• 229910002027 silica gel Inorganic materials 0.000 description 35
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
• 238000006243 chemical reaction Methods 0.000 description 29
• 239000012267 brine Substances 0.000 description 28
• 238000003818 flash chromatography Methods 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• 239000000284 extract Substances 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
• 238000000034 method Methods 0.000 description 24
• 238000004440 column chromatography Methods 0.000 description 23
• 235000017557 sodium bicarbonate Nutrition 0.000 description 23
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 23
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 22
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
• 238000003756 stirring Methods 0.000 description 21
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
• 239000005557 antagonist Substances 0.000 description 18
• 238000003556 assay Methods 0.000 description 18
• 239000000706 filtrate Substances 0.000 description 18
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
• 102000003840 Opioid Receptors Human genes 0.000 description 17
• 108090000137 Opioid Receptors Proteins 0.000 description 17
• 235000019270 ammonium chloride Nutrition 0.000 description 17
• 230000027455 binding Effects 0.000 description 17
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 17
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
• 239000003480 eluent Substances 0.000 description 16
• 238000002821 scintillation proximity assay Methods 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 239000012071 phase Substances 0.000 description 15
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• 238000012360 testing method Methods 0.000 description 14
• 239000012300 argon atmosphere Substances 0.000 description 13
• 239000012074 organic phase Substances 0.000 description 13
• 238000005160 1H NMR spectroscopy Methods 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 210000001428 peripheral nervous system Anatomy 0.000 description 12
• 239000003208 petroleum Substances 0.000 description 12
• 101100322888 Escherichia coli (strain K12) metL gene Proteins 0.000 description 10
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 10
• 239000012043 crude product Substances 0.000 description 10
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
• 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 10
• 239000008194 pharmaceutical composition Substances 0.000 description 10
• 125000006413 ring segment Chemical group 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 229960000583 acetic acid Drugs 0.000 description 9
• 210000003169 central nervous system Anatomy 0.000 description 9
• 239000013067 intermediate product Substances 0.000 description 9
• 239000012280 lithium aluminium hydride Substances 0.000 description 9
• 229940005483 opioid analgesics Drugs 0.000 description 9
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
• 229910010084 LiAlH4 Inorganic materials 0.000 description 8
• 230000003042 antagnostic effect Effects 0.000 description 8
• 229910052786 argon Inorganic materials 0.000 description 8
• 239000011324 bead Substances 0.000 description 8
• 125000005647 linker group Chemical group 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 239000002480 mineral oil Substances 0.000 description 8
• 235000010446 mineral oil Nutrition 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 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 7
• 102000048266 Nociceptin Human genes 0.000 description 7
• 108090000622 Nociceptin Proteins 0.000 description 7
• 101100485158 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) wzzE gene Proteins 0.000 description 7
• 125000002947 alkylene group Chemical group 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 239000003446 ligand Substances 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• 101150089110 metN gene Proteins 0.000 description 7
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
• 238000012746 preparative thin layer chromatography Methods 0.000 description 7
• 238000001525 receptor binding assay Methods 0.000 description 7
• 238000005406 washing Methods 0.000 description 7
• XLYLQUQHYUOPIW-UHFFFAOYSA-N 3-oxo-Tetradecanal Chemical compound CCCCCCCCCCCC(=O)CC=O XLYLQUQHYUOPIW-UHFFFAOYSA-N 0.000 description 6
• RYGXCMJMVYJVGM-UHFFFAOYSA-N 4-oxo-1-pyridin-2-ylcyclohexane-1-carbonitrile Chemical compound C1CC(=O)CCC1(C#N)C1=CC=CC=N1 RYGXCMJMVYJVGM-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• 125000002619 bicyclic group Chemical group 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
• 238000001816 cooling Methods 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 6
• 239000003921 oil Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
• VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 5
• IEVQOYQXKCFWOT-UHFFFAOYSA-N 3-[(2-chloropyridin-4-yl)methyl]-8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound ClC1=NC=CC(=C1)CN1C(NC2(C1)CCC(CC2)(C1=CC=CC=C1)N(C)C)=O IEVQOYQXKCFWOT-UHFFFAOYSA-N 0.000 description 5
• QKFQOTCUAXJMNN-UHFFFAOYSA-N 3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decane-2,8-dione Chemical compound COC1=CC=C(C=C1)CN1C(NC2(C1)CCC(CC2)=O)=O QKFQOTCUAXJMNN-UHFFFAOYSA-N 0.000 description 5
• LUTOSMMOQSDXDA-UHFFFAOYSA-N 4-(dimethylamino)-4-pyridin-2-ylcyclohexan-1-one Chemical compound C=1C=CC=NC=1C1(N(C)C)CCC(=O)CC1 LUTOSMMOQSDXDA-UHFFFAOYSA-N 0.000 description 5
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 239000000018 receptor agonist Substances 0.000 description 5
• 238000000611 regression analysis Methods 0.000 description 5
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• OCHYRSKMMMYUMI-UHFFFAOYSA-N tetradecan-3-one Chemical compound CCCCCCCCCCCC(=O)CC OCHYRSKMMMYUMI-UHFFFAOYSA-N 0.000 description 5
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 4
• VXOYQGDCUZXHBD-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-8-(3-hydroxyphenyl)-3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3cccc(O)c3)N(CC3CCC3)C2=O)cc1 VXOYQGDCUZXHBD-UHFFFAOYSA-N 0.000 description 4
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 4
• HHGXOPVSTPLHET-UHFFFAOYSA-N 4-(ethylamino)-4-phenylcyclohexan-1-one Chemical compound C(C)NC1(CCC(CC1)=O)C1=CC=CC=C1 HHGXOPVSTPLHET-UHFFFAOYSA-N 0.000 description 4
• JDYPYUQIRJOJOP-UHFFFAOYSA-N 8-(dimethylamino)-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile Chemical compound CN(C1(CCC2(CNC(N2)=O)CC1)C#N)C JDYPYUQIRJOJOP-UHFFFAOYSA-N 0.000 description 4
• JYPRSWRUJGRICL-UHFFFAOYSA-N 8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound CN(C1(CCC2(C(NC(N2)=O)=O)CC1)C1=CC=CC=C1)C JYPRSWRUJGRICL-UHFFFAOYSA-N 0.000 description 4
• DXHKKVXZOKPTBB-UHFFFAOYSA-N 8-pyridin-2-yl-1,4-dioxaspiro[4.5]decan-8-amine Chemical compound N1=C(C=CC=C1)C1(CCC2(OCCO2)CC1)N DXHKKVXZOKPTBB-UHFFFAOYSA-N 0.000 description 4
• HZUHLTNOXQNJSY-UHFFFAOYSA-N 8-pyridin-2-yl-1,4-dioxaspiro[4.5]decane-8-carbonitrile Chemical compound C1CC(C#N)(C=2N=CC=CC=2)CCC21OCCO2 HZUHLTNOXQNJSY-UHFFFAOYSA-N 0.000 description 4
• FSHAYQCLNOUYFO-UHFFFAOYSA-N 8-pyridin-2-yl-1,4-dioxaspiro[4.5]decane-8-carboxamide Chemical compound N1=C(C=CC=C1)C1(CCC2(OCCO2)CC1)C(=O)N FSHAYQCLNOUYFO-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 4
• 229940035676 analgesics Drugs 0.000 description 4
• 239000000730 antalgic agent Substances 0.000 description 4
• 239000012131 assay buffer Substances 0.000 description 4
• FLHFTXCMKFVKRP-UHFFFAOYSA-N bromomethylcyclobutane Chemical compound BrCC1CCC1 FLHFTXCMKFVKRP-UHFFFAOYSA-N 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 4
• 229960004127 naloxone Drugs 0.000 description 4
• 229940044601 receptor agonist Drugs 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 201000009032 substance abuse Diseases 0.000 description 4
• 208000011117 substance-related disease Diseases 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• 239000003039 volatile agent Substances 0.000 description 4
• KPVMALJBWBDEAK-UHFFFAOYSA-N 1,3-diazaspiro[4.5]decane-2,8-dione Chemical compound N1C(NCC11CCC(CC1)=O)=O KPVMALJBWBDEAK-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• GIGRWGTZFONRKA-UHFFFAOYSA-N 1-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CBr)C=C1 GIGRWGTZFONRKA-UHFFFAOYSA-N 0.000 description 3
• FPFPSEBIOFRNAQ-UHFFFAOYSA-N 1-amino-4-(dimethylamino)-4-phenylcyclohexane-1-carbonitrile Chemical compound NC1(CCC(CC1)(C1=CC=CC=C1)N(C)C)C#N FPFPSEBIOFRNAQ-UHFFFAOYSA-N 0.000 description 3
• XXZDHFVKLHNUMC-UHFFFAOYSA-N 2-[[8-(dimethylamino)-1-[(1-hydroxycyclobutyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]methyl]benzamide Chemical compound CN(C)C1(CCC2(CN(Cc3ccccc3C(N)=O)C(=O)N2CC2(O)CCC2)CC1)c1ccccc1 XXZDHFVKLHNUMC-UHFFFAOYSA-N 0.000 description 3
• CWHHBXPULGNVNR-UHFFFAOYSA-N 2-methyl-N-(8-phenyl-1,4-dioxaspiro[4.5]decan-8-yl)propane-2-sulfinamide Chemical compound CC(C)(C)S(=O)NC1(CCC2(OCCO2)CC1)C1=CC=CC=C1 CWHHBXPULGNVNR-UHFFFAOYSA-N 0.000 description 3
• FQWWQHBAKRPCBO-UHFFFAOYSA-N 4-(cyclobutylmethyl)-2-[(4-methoxyphenyl)methyl]-9,12-dioxa-2,4-diazadispiro[4.2.48.25]tetradecan-3-one Chemical compound C1(CCC1)CN1C(N(CC11CCC2(OCCO2)CC1)CC1=CC=C(C=C1)OC)=O FQWWQHBAKRPCBO-UHFFFAOYSA-N 0.000 description 3
• 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 3
• PBPZBSGDULGZKX-UHFFFAOYSA-N 8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile Chemical compound CN(C1(CCC2(CN(C(N2)=O)CC2=CC=C(C=C2)OC)CC1)C#N)C PBPZBSGDULGZKX-UHFFFAOYSA-N 0.000 description 3
• GOIAOUOIXPHVQJ-UHFFFAOYSA-N 8-(ethylamino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound C(C)NC1(CCC2(C(NC(N2)=O)=O)CC1)C1=CC=CC=C1 GOIAOUOIXPHVQJ-UHFFFAOYSA-N 0.000 description 3
• BLIXSOVLQOJZEW-UHFFFAOYSA-N 8-[methyl(oxolan-3-ylmethyl)amino]-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound CN(C1(CCC2(C(NC(N2)=O)=O)CC1)C1=CC=CC=C1)CC1COCC1 BLIXSOVLQOJZEW-UHFFFAOYSA-N 0.000 description 3
• FVXOGNXUZZJKFT-UHFFFAOYSA-N 8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine;hydrochloride Chemical compound Cl.C1CC(N)(C=2C=CC=CC=2)CCC21OCCO2 FVXOGNXUZZJKFT-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 0 COc1ccc(CN(C[C@](CC2)(CC[C@]2(*)N(*)*)N2)C2=O)cc1 Chemical compound COc1ccc(CN(C[C@](CC2)(CC[C@]2(*)N(*)*)N2)C2=O)cc1 0.000 description 3
• 208000000094 Chronic Pain Diseases 0.000 description 3
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 239000007821 HATU Substances 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• UIUQDGWKUXEFTI-UHFFFAOYSA-N N-(oxolan-3-ylmethyl)-8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine Chemical compound C1(=CC=CC=C1)C1(CCC2(OCCO2)CC1)NCC1COCC1 UIUQDGWKUXEFTI-UHFFFAOYSA-N 0.000 description 3
• LTQNPOMQWJISGM-UHFFFAOYSA-N N-[1-cyano-4-(dimethylamino)-4-phenylcyclohexyl]-2,2,2-trifluoroacetamide Chemical compound C(#N)C1(CCC(CC1)(C1=CC=CC=C1)N(C)C)NC(C(F)(F)F)=O LTQNPOMQWJISGM-UHFFFAOYSA-N 0.000 description 3
• SYVCQVOEYNVAGD-UHFFFAOYSA-N N-methyl-N-(oxolan-3-ylmethyl)-8-phenyl-1,4-dioxaspiro[4.5]decan-8-amine Chemical compound CN(C1(CCC2(OCCO2)CC1)C1=CC=CC=C1)CC1COCC1 SYVCQVOEYNVAGD-UHFFFAOYSA-N 0.000 description 3
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 230000036592 analgesia Effects 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 150000001450 anions Chemical class 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• GFBLFDSCAKHHGX-UHFFFAOYSA-N cyclobutanecarbonitrile Chemical compound N#CC1CCC1 GFBLFDSCAKHHGX-UHFFFAOYSA-N 0.000 description 3
• MFNYBOWJWGPXFM-UHFFFAOYSA-N cyclobutanecarboxamide Chemical compound NC(=O)C1CCC1 MFNYBOWJWGPXFM-UHFFFAOYSA-N 0.000 description 3
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 3
• 125000005879 dioxolanyl group Chemical group 0.000 description 3
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• KDJLTJLQYHNGGV-UHFFFAOYSA-N methyl N-(8-pyridin-2-yl-1,4-dioxaspiro[4.5]decan-8-yl)carbamate Chemical compound N1=C(C=CC=C1)C1(CCC2(OCCO2)CC1)NC(OC)=O KDJLTJLQYHNGGV-UHFFFAOYSA-N 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 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 3
• 230000007935 neutral effect Effects 0.000 description 3
• 108010020615 nociceptin receptor Proteins 0.000 description 3
• 230000009871 nonspecific binding Effects 0.000 description 3
• 102000014187 peptide receptors Human genes 0.000 description 3
• 108010011903 peptide receptors Proteins 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
• ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• LFILDSDQMSCNBV-LURJTMIESA-N propane-2-sulfinamide Chemical compound CC(C)[S@@](N)=O LFILDSDQMSCNBV-LURJTMIESA-N 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 230000002441 reversible effect Effects 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• HPZJMUBDEAMBFI-WTNAPCKOSA-N (D-Ala(2)-mephe(4)-gly-ol(5))enkephalin Chemical compound C([C@H](N)C(=O)N[C@H](C)C(=O)NCC(=O)N(C)[C@@H](CC=1C=CC=CC=1)C(=O)NCCO)C1=CC=C(O)C=C1 HPZJMUBDEAMBFI-WTNAPCKOSA-N 0.000 description 2
• NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical group C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 description 2
• POTIYWUALSJREP-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline Chemical group N1CCCC2CCCCC21 POTIYWUALSJREP-UHFFFAOYSA-N 0.000 description 2
• MDEXMBGPIZUUBI-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoxaline Chemical compound N1CCNC2CCCCC21 MDEXMBGPIZUUBI-UHFFFAOYSA-N 0.000 description 2
• OBLFDAAENCOHLA-UHFFFAOYSA-N 1-(aminomethyl)-4-N,4-N-dimethyl-4-phenyl-1-N-(2,2,2-trifluoroethyl)cyclohexane-1,4-diamine Chemical compound NCC1(CCC(CC1)(N(C)C)C1=CC=CC=C1)NCC(F)(F)F OBLFDAAENCOHLA-UHFFFAOYSA-N 0.000 description 2
• DFHLAJIJSLWLGN-UHFFFAOYSA-N 1-(cyclobutylmethyl)-3-[(4-methoxyphenyl)methyl]-1,3-diazaspiro[4.5]decane-2,8-dione Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)=O)CC1=CC=C(C=C1)OC)=O DFHLAJIJSLWLGN-UHFFFAOYSA-N 0.000 description 2
• BQBFEYSEHRFJRE-UHFFFAOYSA-N 1-(cyclobutylmethyl)-3-[(4-methoxyphenyl)methyl]-8-[methyl(2-methylpropyl)amino]-2-oxo-1,3-diazaspiro[4.5]decane-8-carbonitrile Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)(C#N)N(C)CC(C)C)CC1=CC=C(C=C1)OC)=O BQBFEYSEHRFJRE-UHFFFAOYSA-N 0.000 description 2
• QJAIUODYPSAJPR-UHFFFAOYSA-N 1-(cyclobutylmethyl)-3-[(4-methoxyphenyl)methyl]-8-[methyl(prop-2-enyl)amino]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)CC=C)c3ccccc3)N(CC3CCC3)C2=O)cc1 QJAIUODYPSAJPR-UHFFFAOYSA-N 0.000 description 2
• GFTBNQDZJMFSDP-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-3-[[4-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]phenyl]methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCOc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC3CCC3)C2=O)cc1 GFTBNQDZJMFSDP-UHFFFAOYSA-N 0.000 description 2
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical group C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 2
• PDELQDSYLBLPQO-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-indole Chemical group C1CCCC2NCCC21 PDELQDSYLBLPQO-UHFFFAOYSA-N 0.000 description 2
• VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical group OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 2
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
• QLCCLFSQGSEYDK-UHFFFAOYSA-N 2-[8-(dimethylamino)-3-[(4-methoxyphenyl)methyl]-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-1-yl]-N-propylacetamide Chemical compound CCCNC(=O)CN1C(=O)N(Cc2ccc(OC)cc2)CC11CCC(CC1)(N(C)C)c1ccccc1 QLCCLFSQGSEYDK-UHFFFAOYSA-N 0.000 description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• KQWVAUSXZDRQPZ-UMTXDNHDSA-N 4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enyl-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1[C@H](C=1C=C(OC)C=CC=1)N1[C@@H](C)CN(CC=C)[C@H](C)C1 KQWVAUSXZDRQPZ-UMTXDNHDSA-N 0.000 description 2
• QVTUQHFWKQYGFJ-UHFFFAOYSA-N 4-[methyl(oxolan-3-ylmethyl)amino]-4-phenylcyclohexan-1-one Chemical compound CN(C1(CCC(CC1)=O)C1=CC=CC=C1)CC1COCC1 QVTUQHFWKQYGFJ-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• DXJKRLHHCGXHMB-UHFFFAOYSA-N 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine Chemical compound C1NCCN2N=CN=C21 DXJKRLHHCGXHMB-UHFFFAOYSA-N 0.000 description 2
• SMSHIXOEBWOYJS-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinazoline Chemical group C1=NC=C2CCCCC2=N1 SMSHIXOEBWOYJS-UHFFFAOYSA-N 0.000 description 2
• YQDGQEKUTLYWJU-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinoline Chemical group C1=CC=C2CCCCC2=N1 YQDGQEKUTLYWJU-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• JNVNMRNNXAYZDI-UHFFFAOYSA-N 8-(dimethylamino)-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CNC(N2)=O)CC1)C1=CC=CC=C1)C JNVNMRNNXAYZDI-UHFFFAOYSA-N 0.000 description 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• 108700022183 Ala(2)-MePhe(4)-Gly(5)- Enkephalin Proteins 0.000 description 2
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
• 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 239000012448 Lithium borohydride Substances 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
• 102000001490 Opioid Peptides Human genes 0.000 description 2
• 108010093625 Opioid Peptides Proteins 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
• 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-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
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
• 239000001099 ammonium carbonate Substances 0.000 description 2
• 230000000202 analgesic effect Effects 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 230000008499 blood brain barrier function Effects 0.000 description 2
• 210000001218 blood-brain barrier Anatomy 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
• VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical compound NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
• LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
• 108700023159 delta Opioid Receptors Proteins 0.000 description 2
• 102000048124 delta Opioid Receptors Human genes 0.000 description 2
• SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 2
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 2
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 230000000155 isotopic effect Effects 0.000 description 2
• 102000048260 kappa Opioid Receptors Human genes 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Substances [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 230000003040 nociceptive effect Effects 0.000 description 2
• 239000003399 opiate peptide Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 235000011837 pasties Nutrition 0.000 description 2
• 230000003285 pharmacodynamic effect Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 239000011343 solid material Substances 0.000 description 2
• 231100000736 substance abuse Toxicity 0.000 description 2
• 201000006152 substance dependence Diseases 0.000 description 2
• 238000007910 systemic administration Methods 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 108020001588 κ-opioid receptors Proteins 0.000 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• UUZJJNBYJDFQHL-UHFFFAOYSA-N 1,2,3-triazolidine Chemical compound C1CNNN1 UUZJJNBYJDFQHL-UHFFFAOYSA-N 0.000 description 1
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
• CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 1
• AFXUAEAIXDBZOX-UHFFFAOYSA-N 1,3-diazaspiro[4.5]decan-2-one Chemical compound N1C(=O)NCC11CCCCC1 AFXUAEAIXDBZOX-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
• WAUNFWSVXRPCDQ-UHFFFAOYSA-N 1-(bromomethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CBr WAUNFWSVXRPCDQ-UHFFFAOYSA-N 0.000 description 1
• ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 1
• NMERHTBBQWPUKW-UHFFFAOYSA-N 1-(bromomethyl)cyclobutane-1-carbonitrile Chemical compound BrCC1(CCC1)C#N NMERHTBBQWPUKW-UHFFFAOYSA-N 0.000 description 1
• PEWXZFSEKJFKOF-UHFFFAOYSA-N 1-(cyclobutylmethyl)-3-[(3-methoxyphenyl)methyl]-8-[methyl(propyl)amino]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CCC1)CN1C(N(CC11CCC(CC1)(C1=CC=CC=C1)N(CCC)C)CC1=CC(=CC=C1)OC)=O PEWXZFSEKJFKOF-UHFFFAOYSA-N 0.000 description 1
• DKIMZULFRMEMRG-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-(dimethylamino)-8-(3-fluorophenyl)-1,3-diazaspiro[4.5]decan-2-one Chemical compound C1(CCC1)CN1C(NCC11CCC(CC1)(C1=CC(=CC=C1)F)N(C)C)=O DKIMZULFRMEMRG-UHFFFAOYSA-N 0.000 description 1
• UYGFTRRNEDTVAD-UHFFFAOYSA-N 1-(cyclobutylmethyl)-8-[2-hydroxyethyl(methyl)amino]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)CCO)c3ccccc3)N(CC3CCC3)C2=O)cc1 UYGFTRRNEDTVAD-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 1
• MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
• APUDJEBZDAGSQY-UHFFFAOYSA-N 1-oxaspiro[2.3]hexane Chemical compound C1OC11CCC1 APUDJEBZDAGSQY-UHFFFAOYSA-N 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• JJAOOEWOCRVIDR-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid 8-(ethylamino)-8-phenyl-1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound OC(C(O)C(O)=O)C(O)=O.CCNC1(CCC2(CC1)NC(=O)NC2=O)c1ccccc1 JJAOOEWOCRVIDR-UHFFFAOYSA-N 0.000 description 1
• AEQWOBMWSBGOFE-UHFFFAOYSA-N 2-(1-methoxycyclobutyl)ethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OCCC1(CCC1)OC AEQWOBMWSBGOFE-UHFFFAOYSA-N 0.000 description 1
• JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
• FQSQUIZMCHSWNK-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-9,12-dioxa-2,4-diazadispiro[4.2.48.25]tetradecan-3-one Chemical compound COC1=CC=C(CN2C(NC3(C2)CCC2(OCCO2)CC3)=O)C=C1 FQSQUIZMCHSWNK-UHFFFAOYSA-N 0.000 description 1
• SZGNWRSFHADOMY-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCO SZGNWRSFHADOMY-UHFFFAOYSA-N 0.000 description 1
• PAXJFLMMCORNQI-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OCCOCCOCCOCCOCCOCCOCCOCCOC PAXJFLMMCORNQI-UHFFFAOYSA-N 0.000 description 1
• JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 1
• QELZCGMVHLQNSO-UHFFFAOYSA-N 2-chloro-4-(chloromethyl)pyridine Chemical compound ClCC1=CC=NC(Cl)=C1 QELZCGMVHLQNSO-UHFFFAOYSA-N 0.000 description 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
• VODKOOOHHCAWFR-UHFFFAOYSA-N 2-iodoacetonitrile Chemical compound ICC#N VODKOOOHHCAWFR-UHFFFAOYSA-N 0.000 description 1
• 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• KDFDOINBXBEOLZ-UHFFFAOYSA-N 2-phenylpropan-2-amine Chemical compound CC(C)(N)C1=CC=CC=C1 KDFDOINBXBEOLZ-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• UKVQBONVSSLJBB-UHFFFAOYSA-N 2-pyridin-2-ylacetonitrile Chemical compound N#CCC1=CC=CC=N1 UKVQBONVSSLJBB-UHFFFAOYSA-N 0.000 description 1
• YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 1
• AGYZKRGPZJEWPN-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-benzo[b][1,4]oxazine Chemical group O1CCNC2CCCCC21 AGYZKRGPZJEWPN-UHFFFAOYSA-N 0.000 description 1
• 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• WHNQTHDJEZTVHS-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)propanoic acid Chemical compound C1=CC=C2SC(CCC(=O)O)=NC2=C1 WHNQTHDJEZTVHS-UHFFFAOYSA-N 0.000 description 1
• UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
• WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
• GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 1
• 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 1
• VAJUUDUWDNCECT-UHFFFAOYSA-N 4-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=NC=C1 VAJUUDUWDNCECT-UHFFFAOYSA-N 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• CWNVRGJEWVHJCP-UHFFFAOYSA-N 8-(dimethylamino)-1-(2-hydroxy-2-methylpropyl)-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound COc1ccc(CN2CC3(CCC(CC3)(N(C)C)c3ccccc3)N(CC(C)(C)O)C2=O)cc1 CWNVRGJEWVHJCP-UHFFFAOYSA-N 0.000 description 1
• RBFQZGNYIFKKCL-UHFFFAOYSA-N 8-(dimethylamino)-1-[2-(1-methoxycyclobutyl)ethyl]-3-[(4-methoxyphenyl)methyl]-8-phenyl-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CN(C(N2CCC2(CCC2)OC)=O)CC2=CC=C(C=C2)OC)CC1)C1=CC=CC=C1)C RBFQZGNYIFKKCL-UHFFFAOYSA-N 0.000 description 1
• APBLAQTUWHYWTM-UHFFFAOYSA-N 8-(dimethylamino)-8-(3-methylphenyl)-1,3-diazaspiro[4.5]decan-2-one Chemical compound CN(C1(CCC2(CNC(N2)=O)CC1)C=1C=C(C=CC=1)C)C APBLAQTUWHYWTM-UHFFFAOYSA-N 0.000 description 1
• GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• AZHKLNYAAAVWGU-UHFFFAOYSA-N C1(=CC(=CC=C1)[Mg])C.[Br] Chemical compound C1(=CC(=CC=C1)[Mg])C.[Br] AZHKLNYAAAVWGU-UHFFFAOYSA-N 0.000 description 1
• PYZKUSXTFANYAK-UHFFFAOYSA-N CC1=CC=CC([Mg])=C1 Chemical compound CC1=CC=CC([Mg])=C1 PYZKUSXTFANYAK-UHFFFAOYSA-N 0.000 description 1
• FKEJPEWXXLBTOV-UHFFFAOYSA-N CCC(C)(CC1)CCC1(C)c1ccccc1 Chemical compound CCC(C)(CC1)CCC1(C)c1ccccc1 FKEJPEWXXLBTOV-UHFFFAOYSA-N 0.000 description 1
• SXWUIDOQKQNILZ-UHFFFAOYSA-N CCOC(C[n]1nnc(CN(CC(CC2)(CCC2(c2ccccc2)N(C)C)N2)C2=O)c1)=O Chemical compound CCOC(C[n]1nnc(CN(CC(CC2)(CCC2(c2ccccc2)N(C)C)N2)C2=O)c1)=O SXWUIDOQKQNILZ-UHFFFAOYSA-N 0.000 description 1
• LKVDANQGJAPXND-PSWAGMNNSA-N CC[IH]1=CC=C(CN(C[C@](CC2)(CC[C@]2(c2ccccc2)N(C)C)N2)C2=O)C=C1Cl Chemical compound CC[IH]1=CC=C(CN(C[C@](CC2)(CC[C@]2(c2ccccc2)N(C)C)N2)C2=O)C=C1Cl LKVDANQGJAPXND-PSWAGMNNSA-N 0.000 description 1
• VNVWBVUXTNXHJW-UHFFFAOYSA-N CN(C)C(CC1)(CCC1(CN1C=C=C)NC1=O)c1ccccc1 Chemical compound CN(C)C(CC1)(CCC1(CN1C=C=C)NC1=O)c1ccccc1 VNVWBVUXTNXHJW-UHFFFAOYSA-N 0.000 description 1
• JNVNMRNNXAYZDI-IYBDPMFKSA-N CN(C)[C@](CC1)(CC[C@@]1(CN1)NC1=O)c1ccccc1 Chemical compound CN(C)[C@](CC1)(CC[C@@]1(CN1)NC1=O)c1ccccc1 JNVNMRNNXAYZDI-IYBDPMFKSA-N 0.000 description 1
• JVXLMBHVUZDVFU-UHFFFAOYSA-N CNC(CC1)(CCC11OCCO1)N(C)C Chemical compound CNC(CC1)(CCC11OCCO1)N(C)C JVXLMBHVUZDVFU-UHFFFAOYSA-N 0.000 description 1
• HKALLVNXLQXSHJ-UHFFFAOYSA-N COc1ccc(CNC(NCC(N)=O)=O)cc1 Chemical compound COc1ccc(CNC(NCC(N)=O)=O)cc1 HKALLVNXLQXSHJ-UHFFFAOYSA-N 0.000 description 1
• 206010010774 Constipation Diseases 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
• 102000034354 Gi proteins Human genes 0.000 description 1
• 108091006101 Gi proteins Proteins 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101500026210 Homo sapiens Nociceptin Proteins 0.000 description 1
• 101100462200 Homo sapiens OPN4 gene Proteins 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 206010065390 Inflammatory pain Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 102100028646 Nociceptin receptor Human genes 0.000 description 1
• 108070000021 Opioid peptides receptors Proteins 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
• 206010038678 Respiratory depression Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 239000005708 Sodium hypochlorite Substances 0.000 description 1
• 206010041349 Somnolence Diseases 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• PGZRDDYTKFZSFR-ONTIZHBOSA-N U69593 Chemical compound C([C@@H]([C@H](C1)N2CCCC2)N(C)C(=O)CC=2C=CC=CC=2)C[C@]21CCCO2 PGZRDDYTKFZSFR-ONTIZHBOSA-N 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 208000005298 acute pain Diseases 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 230000003502 anti-nociceptive effect Effects 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• RPHLNRIJHROTSF-UHFFFAOYSA-N azanium;acetonitrile;hydrogen carbonate Chemical compound [NH4+].CC#N.OC([O-])=O RPHLNRIJHROTSF-UHFFFAOYSA-N 0.000 description 1
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 125000005997 bromomethyl group Chemical group 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000006630 butoxycarbonylamino group Chemical group 0.000 description 1
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
• 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
• 229910052593 corundum Inorganic materials 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• LEQCYZPSDVXIJZ-UHFFFAOYSA-N cumene hydrochloride Chemical compound Cl.CC(C)C1=CC=CC=C1 LEQCYZPSDVXIJZ-UHFFFAOYSA-N 0.000 description 1
• 229940045803 cuprous chloride Drugs 0.000 description 1
• CFBGXYDUODCMNS-UHFFFAOYSA-N cyclobutene Chemical compound C1CC=C1 CFBGXYDUODCMNS-UHFFFAOYSA-N 0.000 description 1
• UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 1
• PNZXMIKHJXIPEK-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1CCCCC1 PNZXMIKHJXIPEK-UHFFFAOYSA-N 0.000 description 1
• WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
• 239000004914 cyclooctane Substances 0.000 description 1
• OOXWYYGXTJLWHA-UHFFFAOYSA-N cyclopropene Chemical compound C1C=C1 OOXWYYGXTJLWHA-UHFFFAOYSA-N 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical compound C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 1
• JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 239000006274 endogenous ligand Substances 0.000 description 1
• LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• HVJJYOAPXBPQQV-UHFFFAOYSA-N ethyl 2-azidoacetate Chemical compound CCOC(=O)CN=[N+]=[N-] HVJJYOAPXBPQQV-UHFFFAOYSA-N 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
• BNRNAKTVFSZAFA-UHFFFAOYSA-N hydrindane Chemical compound C1CCCC2CCCC21 BNRNAKTVFSZAFA-UHFFFAOYSA-N 0.000 description 1
• MBVAHHOKMIRXLP-UHFFFAOYSA-N imidazo[1,2-a]pyrazine Chemical compound C1=CN=CC2=NC=CN21 MBVAHHOKMIRXLP-UHFFFAOYSA-N 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 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
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• DBYQHFPBWKKZAT-UHFFFAOYSA-N lithium;benzene Chemical compound [Li+].C1=CC=[C-]C=C1 DBYQHFPBWKKZAT-UHFFFAOYSA-N 0.000 description 1
• 238000004020 luminiscence type Methods 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• DTKMKZYEOXZPQZ-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=C[C-]=C1 DTKMKZYEOXZPQZ-UHFFFAOYSA-M 0.000 description 1
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
• 229940126601 medicinal product Drugs 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• QKYWADPCTHTJHQ-UHFFFAOYSA-N n,2-dimethylpropan-1-amine Chemical compound CNCC(C)C QKYWADPCTHTJHQ-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 108010081490 naloxone receptor Proteins 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 230000002981 neuropathic effect Effects 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
• TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
• GSUBXIVOZXWGKF-UHFFFAOYSA-N oxolane-3-carbaldehyde Chemical compound O=CC1CCOC1 GSUBXIVOZXWGKF-UHFFFAOYSA-N 0.000 description 1
• BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
• 210000005223 peripheral sensory neuron Anatomy 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 238000011809 primate model Methods 0.000 description 1
• 230000002400 pro-nociceptive effect Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 238000010926 purge Methods 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 230000003014 reinforcing effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000007789 sealing 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
• 230000020341 sensory perception of pain Effects 0.000 description 1
• PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
• 235000010378 sodium ascorbate Nutrition 0.000 description 1
• 229960005055 sodium ascorbate Drugs 0.000 description 1
• 235000017550 sodium carbonate Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
• SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
• RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
• PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• ZYXWYDDFNXBTFO-UHFFFAOYSA-N tetrazolidine Chemical compound C1NNNN1 ZYXWYDDFNXBTFO-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• RLTPJVKHGBFGQA-UHFFFAOYSA-N thiadiazolidine Chemical compound C1CSNN1 RLTPJVKHGBFGQA-UHFFFAOYSA-N 0.000 description 1
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
• XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 1
• 238000007070 tosylation reaction Methods 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
• PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 229910001845 yogo sapphire Inorganic materials 0.000 description 1