DE60113719T2 - Chinuclidincarbamat derivate und deren verwendung als m3 antagonisten - Google Patents

Info

Publication number

DE60113719T2

DE60113719T2 DE60113719T DE60113719T DE60113719T2 DE 60113719 T2 DE60113719 T2 DE 60113719T2 DE 60113719 T DE60113719 T DE 60113719T DE 60113719 T DE60113719 T DE 60113719T DE 60113719 T2 DE60113719 T2 DE 60113719T2

Authority

DE

Germany

Prior art keywords

octane

azoniabicyclo

group

bromide

azabicyclo

Prior art date

2000-12-22

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.)

Expired - Lifetime

Links

• Espacenet
• Global Dossier
• DPMA
• Discuss

• 239000005557 antagonist Substances 0.000 title claims description 6
• 150000001875 compounds Chemical class 0.000 claims description 240
• 238000000034 method Methods 0.000 claims description 188
• -1 furan-2-ylmethyl Chemical group 0.000 claims description 141
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 124
• XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 claims description 53
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 239000000203 mixture Substances 0.000 claims description 20
• 125000000217 alkyl group Chemical group 0.000 claims description 19
• 125000004432 carbon atom Chemical group C* 0.000 claims description 18
• 238000002360 preparation method Methods 0.000 claims description 17
• 208000023504 respiratory system disease Diseases 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 13
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 125000005843 halogen group Chemical group 0.000 claims description 10
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 9
• 208000012931 Urologic disease Diseases 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 125000001544 thienyl group Chemical group 0.000 claims description 9
• 208000014001 urinary system disease Diseases 0.000 claims description 9
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 8
• 125000002723 alicyclic group Chemical group 0.000 claims description 8
• 150000001450 anions Chemical class 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 claims description 8
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 7
• 239000004480 active ingredient Substances 0.000 claims description 7
• 239000000556 agonist Substances 0.000 claims description 7
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 7
• 230000000241 respiratory effect Effects 0.000 claims description 7
• 150000003431 steroids Chemical class 0.000 claims description 7
• 102000007202 Muscarinic M3 Receptor Human genes 0.000 claims description 6
• 108010008405 Muscarinic M3 Receptor Proteins 0.000 claims description 6
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• 125000003118 aryl group Chemical group 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
• 239000002253 acid Substances 0.000 claims description 5
• WKFZHVFBHYHYAK-UHFFFAOYSA-N benzyl(phenyl)carbamic acid Chemical compound C=1C=CC=CC=1N(C(=O)O)CC1=CC=CC=C1 WKFZHVFBHYHYAK-UHFFFAOYSA-N 0.000 claims description 5
• 208000035475 disorder Diseases 0.000 claims description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• USPDKXJEZWRPBT-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-phenyl-N-(thiophen-2-ylmethyl)carbamate Chemical compound C1(=CC=CC=C1)N(C(=O)O[N+]12CCC(CC1)CC2)CC=1SC=CC=1 USPDKXJEZWRPBT-UHFFFAOYSA-N 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 229940100198 alkylating agent Drugs 0.000 claims description 4
• 239000002168 alkylating agent Substances 0.000 claims description 4
• 230000003266 anti-allergic effect Effects 0.000 claims description 4
• SNBFKFGZVPBMII-UHFFFAOYSA-N bis(thiophen-2-ylmethyl)carbamic acid Chemical compound C=1C=CSC=1CN(C(=O)O)CC1=CC=CS1 SNBFKFGZVPBMII-UHFFFAOYSA-N 0.000 claims description 4
• YQYXDECZRWZKKY-UHFFFAOYSA-N cyclopentyl(thiophen-2-ylmethyl)carbamic acid Chemical compound C1CCCC1N(C(=O)O)CC1=CC=CS1 YQYXDECZRWZKKY-UHFFFAOYSA-N 0.000 claims description 4
• 208000010643 digestive system disease Diseases 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
• 208000018685 gastrointestinal system disease Diseases 0.000 claims description 4
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• LURFOXLMBGTDCQ-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N,N-bis(furan-2-ylmethyl)carbamate Chemical compound O1C(=CC=C1)CN(C(=O)O[N+]12CCC(CC1)CC2)CC=1OC=CC=1 LURFOXLMBGTDCQ-UHFFFAOYSA-N 0.000 claims description 3
• OUJMNRNXTLOPJI-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-benzyl-N-phenylcarbamate Chemical compound C(C1=CC=CC=C1)N(C(=O)O[N+]12CCC(CC1)CC2)C1=CC=CC=C1 OUJMNRNXTLOPJI-UHFFFAOYSA-N 0.000 claims description 3
• GWQUOGDIWKSVOG-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-butyl-N-phenylcarbamate Chemical compound C(CCC)N(C(=O)O[N+]12CCC(CC1)CC2)C1=CC=CC=C1 GWQUOGDIWKSVOG-UHFFFAOYSA-N 0.000 claims description 3
• MQXGZORGNMOFQD-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-phenyl-N-(thiophen-3-ylmethyl)carbamate Chemical compound C1(=CC=CC=C1)N(C(=O)O[N+]12CCC(CC1)CC2)CC1=CSC=C1 MQXGZORGNMOFQD-UHFFFAOYSA-N 0.000 claims description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 3
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 241001465754 Metazoa Species 0.000 claims description 3
• KZGBMDVPRFXGCT-UHFFFAOYSA-N [3-(1-azabicyclo[2.2.2]octan-2-yl)phenyl]-benzylcarbamic acid hydrochloride Chemical compound Cl.N12C(CC(CC1)CC2)C=2C=C(C=CC2)N(C(O)=O)CC2=CC=CC=C2 KZGBMDVPRFXGCT-UHFFFAOYSA-N 0.000 claims description 3
• XWDAJKMDKMCFKY-UHFFFAOYSA-N bis(furan-2-ylmethyl)carbamic acid Chemical compound O1C(=CC=C1)CN(C(O)=O)CC=1OC=CC1 XWDAJKMDKMCFKY-UHFFFAOYSA-N 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 239000013066 combination product Substances 0.000 claims description 3
• 229940127555 combination product Drugs 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 238000002414 normal-phase solid-phase extraction Methods 0.000 claims description 3
• MZEJYTHCXCYSHD-UHFFFAOYSA-N phenyl(thiophen-2-ylmethyl)carbamic acid Chemical compound C=1C=CC=CC=1N(C(=O)O)CC1=CC=CS1 MZEJYTHCXCYSHD-UHFFFAOYSA-N 0.000 claims description 3
• HZOXALVFNQWNFV-UHFFFAOYSA-N phenyl(thiophen-3-ylmethyl)carbamic acid Chemical compound C=1C=CC=CC=1N(C(=O)O)CC=1C=CSC=1 HZOXALVFNQWNFV-UHFFFAOYSA-N 0.000 claims description 3
• 239000011541 reaction mixture Substances 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 3
• 229910052717 sulfur Inorganic materials 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• GDLWJBJOVTYAJR-GSEXTUOBSA-M [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 GDLWJBJOVTYAJR-GSEXTUOBSA-M 0.000 claims description 2
• JZCRAMPGFZJPOE-ZZNGFPBBSA-M [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 JZCRAMPGFZJPOE-ZZNGFPBBSA-M 0.000 claims description 2
• MSEFDPBADMQKQW-RARKWRLQSA-M [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CCC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 MSEFDPBADMQKQW-RARKWRLQSA-M 0.000 claims description 2
• RUMIBZGNGQBYPD-DSSKCDFUSA-M [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC3=CSC=C3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 RUMIBZGNGQBYPD-DSSKCDFUSA-M 0.000 claims description 2
• PIJFPTVLIXOHMJ-DSSKCDFUSA-M [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n,n-bis(thiophen-2-ylmethyl)carbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)CC=3SC=CC=3)[N+]21CCCC1=CC=CC=C1 PIJFPTVLIXOHMJ-DSSKCDFUSA-M 0.000 claims description 2
• RFHYCEHWBDUMOY-AEDYTTQKSA-M [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-(furan-2-ylmethyl)-n-phenylcarbamate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)N(CC=3OC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 RFHYCEHWBDUMOY-AEDYTTQKSA-M 0.000 claims description 2
• PNWQOMABRMWDMF-LVKSKBLHSA-M [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 PNWQOMABRMWDMF-LVKSKBLHSA-M 0.000 claims description 2
• ZEKWXBFSCSXDLQ-NRMJQQDLSA-M [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 ZEKWXBFSCSXDLQ-NRMJQQDLSA-M 0.000 claims description 2
• GNNJTNLPQMHFBR-DSSKCDFUSA-M [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-cyclopentyl-n-(thiophen-2-ylmethyl)carbamate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C3CCCC3)[N+]21CCCC1=CC=CC=C1 GNNJTNLPQMHFBR-DSSKCDFUSA-M 0.000 claims description 2
• ROECTEAZZKLWOE-MSZWFKHVSA-M [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n,n-bis(thiophen-2-ylmethyl)carbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)CC=3SC=CC=3)[N+]21CCCC1=CC=CS1 ROECTEAZZKLWOE-MSZWFKHVSA-M 0.000 claims description 2
• MCGSMQKZGMDZFT-AEDYTTQKSA-M [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 MCGSMQKZGMDZFT-AEDYTTQKSA-M 0.000 claims description 2
• FHESLQGDLROIOJ-SSVLGJNASA-M [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 FHESLQGDLROIOJ-SSVLGJNASA-M 0.000 claims description 2
• NBAFBTBCPVIPLO-OCJYMVTRSA-M [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 NBAFBTBCPVIPLO-OCJYMVTRSA-M 0.000 claims description 2
• WUXTWVZFGDCASM-ZZNGFPBBSA-M [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)N(CC3=CSC=C3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 WUXTWVZFGDCASM-ZZNGFPBBSA-M 0.000 claims description 2
• RRDGGSLRLZXWCU-CCOWBORGSA-N [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC(O)=C1 RRDGGSLRLZXWCU-CCOWBORGSA-N 0.000 claims description 2
• OEHUXJMRJMPURF-MNFPOUGWSA-M [(3r)-1-[3-(4-fluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCOC1=CC=C(F)C=C1 OEHUXJMRJMPURF-MNFPOUGWSA-M 0.000 claims description 2
• OJBOKNOKZXHCRK-SUPQUVAKSA-M [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(CCCC=C)C1=CC=CC=C1 OJBOKNOKZXHCRK-SUPQUVAKSA-M 0.000 claims description 2
• QPRWDHVZZSSIHZ-QMAMVGRZSA-M [Br-].C1CC([C@H](C2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CC[N+]12C(C)C1=CC=CC=C1 Chemical compound [Br-].C1CC([C@H](C2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CC[N+]12C(C)C1=CC=CC=C1 QPRWDHVZZSSIHZ-QMAMVGRZSA-M 0.000 claims description 2
• CQAMPEQWAJLGTK-UHFFFAOYSA-N benzyl-(4-fluorophenyl)carbamic acid Chemical compound C=1C=C(F)C=CC=1N(C(=O)O)CC1=CC=CC=C1 CQAMPEQWAJLGTK-UHFFFAOYSA-N 0.000 claims description 2
• 239000004305 biphenyl Substances 0.000 claims description 2
• 235000010290 biphenyl Nutrition 0.000 claims description 2
• 125000006267 biphenyl group Chemical group 0.000 claims description 2
• 150000007519 polyprotic acids Polymers 0.000 claims description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 1
• JENYYAPLTSERHI-UHFFFAOYSA-N N12CCC(CC1)(CC2)OC(N(C2=CC=CC=C2)CC2=CC=CC=C2)=O.N21CCC(CC2)(C1)OC(N(C1=CC=CC=C1)CC1=CC=CC=C1)=O Chemical compound N12CCC(CC1)(CC2)OC(N(C2=CC=CC=C2)CC2=CC=CC=C2)=O.N21CCC(CC2)(C1)OC(N(C1=CC=CC=C1)CC1=CC=CC=C1)=O JENYYAPLTSERHI-UHFFFAOYSA-N 0.000 claims 1
• HSGQPXOPCPJENX-CCOWBORGSA-M [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 HSGQPXOPCPJENX-CCOWBORGSA-M 0.000 claims 1
• 150000003840 hydrochlorides Chemical class 0.000 claims 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 108
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
• 239000000243 solution Substances 0.000 description 14
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 239000000725 suspension Substances 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 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 6
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 6
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
• 229910052708 sodium Inorganic materials 0.000 description 6
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
• 239000011737 fluorine Substances 0.000 description 5
• 229910052731 fluorine Inorganic materials 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• 208000006673 asthma Diseases 0.000 description 4
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 4
• 201000010099 disease Diseases 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 150000002431 hydrogen Chemical class 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 238000010561 standard procedure Methods 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• IVLICPVPXWEGCA-ZETCQYMHSA-N (3r)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@@H](O)CN1CC2 IVLICPVPXWEGCA-ZETCQYMHSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 208000009079 Bronchial Spasm Diseases 0.000 description 3
• 208000014181 Bronchial disease Diseases 0.000 description 3
• 206010006482 Bronchospasm Diseases 0.000 description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
• 206010063057 Cystitis noninfective Diseases 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 206010020853 Hypertonic bladder Diseases 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 3
• 206010029279 Neurogenic bladder Diseases 0.000 description 3
• 206010046543 Urinary incontinence Diseases 0.000 description 3
• 239000000443 aerosol Substances 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000000043 antiallergic agent Substances 0.000 description 3
• 230000027455 binding Effects 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 201000003139 chronic cystitis Diseases 0.000 description 3
• 206010009887 colitis Diseases 0.000 description 3
• 239000012141 concentrate Substances 0.000 description 3
• 208000007784 diverticulitis Diseases 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 235000019441 ethanol Nutrition 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 239000007941 film coated tablet Substances 0.000 description 3
• 229910052736 halogen Inorganic materials 0.000 description 3
• 150000002367 halogens Chemical group 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 3
• 208000002551 irritable bowel syndrome Diseases 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 206010039083 rhinitis Diseases 0.000 description 3
• 239000002904 solvent Substances 0.000 description 3
• 230000001148 spastic effect Effects 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 2
• DSNGLKATJGBVIX-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptan-4-ol Chemical compound C1CN2CCC1(O)C2 DSNGLKATJGBVIX-UHFFFAOYSA-N 0.000 description 2
• JMOPKEVUVYGKRW-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptan-4-yl n-benzyl-n-phenylcarbamate Chemical compound C1CN(C2)CCC12OC(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 JMOPKEVUVYGKRW-UHFFFAOYSA-N 0.000 description 2
• QLPCBFZOKBZFEV-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-4-yl n-benzyl-n-phenylcarbamate Chemical compound C1CN(CC2)CCC12OC(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 QLPCBFZOKBZFEV-UHFFFAOYSA-N 0.000 description 2
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 206010066091 Bronchial Hyperreactivity Diseases 0.000 description 2
• 0 CCC(C)(C)C1(C)C2N=C(*3)C(*C)C3C12 Chemical compound CCC(C)(C)C1(C)C2N=C(*3)C(*C)C3C12 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 241000700198 Cavia Species 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 208000008967 Enuresis Diseases 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 229910002651 NO3 Inorganic materials 0.000 description 2
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
• 208000008469 Peptic Ulcer Diseases 0.000 description 2
• 206010036018 Pollakiuria Diseases 0.000 description 2
• 206010040741 Sinus bradycardia Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 2
• JEEPGBSHIOBHQN-GDWJQBMWSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 JEEPGBSHIOBHQN-GDWJQBMWSA-N 0.000 description 2
• POQLGGZHQBVJBA-OTBAGVBSSA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n,n-bis(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)CC=3SC=CC=3)[N+]21CCCC1=CC=CS1 POQLGGZHQBVJBA-OTBAGVBSSA-N 0.000 description 2
• HDGRBVFLKPMNIN-RXFKJLCSSA-N [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(C=1C=CC=CC=1)CC=1C=CSC=1 HDGRBVFLKPMNIN-RXFKJLCSSA-N 0.000 description 2
• 150000004703 alkoxides Chemical class 0.000 description 2
• IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 230000001022 anti-muscarinic effect Effects 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 230000036427 bronchial hyperreactivity Effects 0.000 description 2
• 206010006451 bronchitis Diseases 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 230000007717 exclusion Effects 0.000 description 2
• 210000004907 gland Anatomy 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• UTGDDKPFAFNFJS-UHFFFAOYSA-N n-cyclopentyl-n-(thiophen-2-ylmethyl)carbamoyl chloride Chemical compound C1CCCC1N(C(=O)Cl)CC1=CC=CS1 UTGDDKPFAFNFJS-UHFFFAOYSA-N 0.000 description 2
• 208000005346 nocturnal enuresis Diseases 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 230000001734 parasympathetic effect Effects 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical group CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 210000002460 smooth muscle Anatomy 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001425 triazolyl group Chemical group 0.000 description 2
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
• FSNYTEYOTCTPSO-ZETCQYMHSA-N (2s)-1-azabicyclo[2.2.2]octan-2-ol Chemical compound C1CN2[C@@H](O)CC1CC2 FSNYTEYOTCTPSO-ZETCQYMHSA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• RQRSQXFVRUWISR-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-4-ol Chemical compound C1CN2CCC1(O)CC2 RQRSQXFVRUWISR-UHFFFAOYSA-N 0.000 description 1
• WFQKPCLZQMECEZ-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N,N-bis(thiophen-2-ylmethyl)carbamate Chemical compound S1C(=CC=C1)CN(C(=O)O[N+]12CCC(CC1)CC2)CC=1SC=CC=1 WFQKPCLZQMECEZ-UHFFFAOYSA-N 0.000 description 1
• RAKWUKMOMDBGAO-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-(furan-2-ylmethyl)-N-(thiophen-2-ylmethyl)carbamate Chemical compound O1C(=CC=C1)CN(C(=O)O[N+]12CCC(CC1)CC2)CC=1SC=CC=1 RAKWUKMOMDBGAO-UHFFFAOYSA-N 0.000 description 1
• HOCYEGVIHOEMKD-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-(furan-2-ylmethyl)-N-phenylcarbamate Chemical compound O1C(=CC=C1)CN(C(=O)O[N+]12CCC(CC1)CC2)C1=CC=CC=C1 HOCYEGVIHOEMKD-UHFFFAOYSA-N 0.000 description 1
• OWZBDOUVXLXXDT-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-benzyl-N-(4-methylphenyl)carbamate Chemical compound C(C1=CC=CC=C1)N(C(=O)O[N+]12CCC(CC1)CC2)C1=CC=C(C=C1)C OWZBDOUVXLXXDT-UHFFFAOYSA-N 0.000 description 1
• QANNJABNODULAJ-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-butyl-N-(thiophen-2-ylmethyl)carbamate Chemical compound C(CCC)N(C(=O)O[N+]12CCC(CC1)CC2)CC=1SC=CC=1 QANNJABNODULAJ-UHFFFAOYSA-N 0.000 description 1
• OMSMCCHDUVXQDC-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-cyclopentyl-N-(thiophen-2-ylmethyl)carbamate Chemical compound C1(CCCC1)N(C(=O)O[N+]12CCC(CC1)CC2)CC=1SC=CC=1 OMSMCCHDUVXQDC-UHFFFAOYSA-N 0.000 description 1
• LQPFYXOOYCSMEN-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-pent-4-enyl-N-phenylcarbamate Chemical compound C=CCCCN(C(=O)O[N+]12CCC(CC1)CC2)c1ccccc1 LQPFYXOOYCSMEN-UHFFFAOYSA-N 0.000 description 1
• DOYFIBKVLYOACR-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-pentyl-N-phenylcarbamate Chemical compound C(CCCC)N(C(=O)O[N+]12CCC(CC1)CC2)C1=CC=CC=C1 DOYFIBKVLYOACR-UHFFFAOYSA-N 0.000 description 1
• YCYGAQICBXNSCT-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octan-1-yl N-phenyl-N-(2-phenylethyl)carbamate Chemical compound C(CC1=CC=CC=C1)N(C(=O)O[N+]12CCC(CC1)CC2)C1=CC=CC=C1 YCYGAQICBXNSCT-UHFFFAOYSA-N 0.000 description 1
• DSTLXMSUVMLNBP-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octane;carbamate Chemical class NC(O)=O.C1CC2CCN1CC2 DSTLXMSUVMLNBP-UHFFFAOYSA-N 0.000 description 1
• LSXKDWGTSHCFPP-UHFFFAOYSA-N 1-bromoheptane Chemical compound CCCCCCCBr LSXKDWGTSHCFPP-UHFFFAOYSA-N 0.000 description 1
• MMZJZOAVHSPESP-UHFFFAOYSA-N 2-(3-bromopropyl)thiophene Chemical compound BrCCCC1=CC=CS1 MMZJZOAVHSPESP-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
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• TZLFTWUXUMJFQT-MUZWYTLNSA-N 4-[(3r)-3-[benzyl(phenyl)carbamoyl]oxy-1-azoniabicyclo[2.2.2]octan-1-yl]butyl acetate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCOC(=O)C)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 TZLFTWUXUMJFQT-MUZWYTLNSA-N 0.000 description 1
• UIGWFDUVUFIVPI-JEPVQIMHSA-N 4-[(3r)-3-[butyl(phenyl)carbamoyl]oxy-1-azoniabicyclo[2.2.2]octan-1-yl]butyl acetate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCCOC(C)=O)C1)C(=O)N(CCCC)C1=CC=CC=C1 UIGWFDUVUFIVPI-JEPVQIMHSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 229930003347 Atropine Natural products 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 206010006458 Bronchitis chronic Diseases 0.000 description 1
• 102000017925 CHRM3 Human genes 0.000 description 1
• 101150060249 CHRM3 gene Proteins 0.000 description 1
• CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical class NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
• RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
• 229940126083 M3 antagonist Drugs 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• KJSQDELEDLJGHZ-UUTHKHQDSA-N [(3R)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] N-butyl-N-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21C(C)C1=CC=CC=C1 KJSQDELEDLJGHZ-UUTHKHQDSA-N 0.000 description 1
• FTARAIZZZVPUJB-XBXIBHRUSA-N [(3r)-1-(1-phenylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C1CC([C@H](C2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CC[N+]12C(C)C1=CC=CC=C1 FTARAIZZZVPUJB-XBXIBHRUSA-N 0.000 description 1
• OKQIFWNEQUZLKZ-CRIAOJQNSA-N [(3r)-1-(2-ethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCOCC)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 OKQIFWNEQUZLKZ-CRIAOJQNSA-N 0.000 description 1
• UCEFDQPFTNRJOI-MMPATGFWSA-N [(3r)-1-(2-ethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCOCC)C1)C(=O)N(CCCC)C1=CC=CC=C1 UCEFDQPFTNRJOI-MMPATGFWSA-N 0.000 description 1
• RKAJVTVMICVPJE-GPQFNORQSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 RKAJVTVMICVPJE-GPQFNORQSA-N 0.000 description 1
• CXRIFSPGYWTKPW-OKBRVIPFSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 CXRIFSPGYWTKPW-OKBRVIPFSA-N 0.000 description 1
• FEAAEXOAAKGNBO-JOMKWTIYSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC=C)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 FEAAEXOAAKGNBO-JOMKWTIYSA-N 0.000 description 1
• MKNMXMNMHVEQPO-JOMKWTIYSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCCC)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 MKNMXMNMHVEQPO-JOMKWTIYSA-N 0.000 description 1
• NJCVUBFVVNHWHH-IIIFQBMYSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 NJCVUBFVVNHWHH-IIIFQBMYSA-N 0.000 description 1
• FWPIWVUMKDFZSR-JOMKWTIYSA-N [(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC3=CSC=C3)C=3C=CC=CC=3)[N+]21CCOC1=CC=CC=C1 FWPIWVUMKDFZSR-JOMKWTIYSA-N 0.000 description 1
• ZJEJXXJLUQDWDN-HAMJSAHASA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOCC1=CC=CC=C1 ZJEJXXJLUQDWDN-HAMJSAHASA-N 0.000 description 1
• YVQPLISEZIVWIU-MUZWYTLNSA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCOCC1=CC=CC=C1 YVQPLISEZIVWIU-MUZWYTLNSA-N 0.000 description 1
• VPQPEPPKQPUSKQ-KGBLJUBMSA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC=C)C=3C=CC=CC=3)[N+]21CCOCC1=CC=CC=C1 VPQPEPPKQPUSKQ-KGBLJUBMSA-N 0.000 description 1
• GRGDCRSUFUFSRY-KGBLJUBMSA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCCC)C=3C=CC=CC=3)[N+]21CCOCC1=CC=CC=C1 GRGDCRSUFUFSRY-KGBLJUBMSA-N 0.000 description 1
• QPOYDCASJDUGLJ-FUFAFYGISA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOCC1=CC=CC=C1 QPOYDCASJDUGLJ-FUFAFYGISA-N 0.000 description 1
• SYRVXBDLMMPFEM-ROTRRZJSSA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C=3C=CC=CC=3)[N+]21CCOCC1=CC=CC=C1 SYRVXBDLMMPFEM-ROTRRZJSSA-N 0.000 description 1
• QXBQBQGAGIWXEC-KGBLJUBMSA-N [(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC3=CSC=C3)C=3C=CC=CC=3)[N+]21CCOCC1=CC=CC=C1 QXBQBQGAGIWXEC-KGBLJUBMSA-N 0.000 description 1
• PZTHGNBCWQXWTQ-IYUIPRCHSA-N [(3r)-1-(3-cyanopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC#N)C1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 PZTHGNBCWQXWTQ-IYUIPRCHSA-N 0.000 description 1
• HGKJUCQDXWXVOK-XWGIXXMPSA-N [(3r)-1-(3-cyanopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC#N)C1)C(=O)N(CCCC)C1=CC=CC=C1 HGKJUCQDXWXVOK-XWGIXXMPSA-N 0.000 description 1
• PYYUKXSJSGWLCT-JEPVQIMHSA-N [(3r)-1-(3-hydroxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCO)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 PYYUKXSJSGWLCT-JEPVQIMHSA-N 0.000 description 1
• NATRMGUMFWTHML-WWAKMMQFSA-N [(3r)-1-(3-hydroxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCO)C1)C(=O)N(CCCC)C1=CC=CC=C1 NATRMGUMFWTHML-WWAKMMQFSA-N 0.000 description 1
• DTMXVPKMCOKRPA-YFGMWWGUSA-N [(3r)-1-(3-naphthalen-1-yloxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C3=CC=CC=C3C=CC=2)C1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 DTMXVPKMCOKRPA-YFGMWWGUSA-N 0.000 description 1
• CRNULVRCQATHCB-IIIFQBMYSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 CRNULVRCQATHCB-IIIFQBMYSA-N 0.000 description 1
• KNWXPALPEQWKCD-JOMKWTIYSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 KNWXPALPEQWKCD-JOMKWTIYSA-N 0.000 description 1
• PUGIKYDNVSBIIG-ROTRRZJSSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC=C)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 PUGIKYDNVSBIIG-ROTRRZJSSA-N 0.000 description 1
• HQLQUEMRGIWKLH-ROTRRZJSSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCCC)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 HQLQUEMRGIWKLH-ROTRRZJSSA-N 0.000 description 1
• GHZYQKPSKBWUHY-GEMBBTIOSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 GHZYQKPSKBWUHY-GEMBBTIOSA-N 0.000 description 1
• FPJVJMRSCSFKQC-VTIINTLQSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 FPJVJMRSCSFKQC-VTIINTLQSA-N 0.000 description 1
• MGFCTKPXCQNKNU-ROTRRZJSSA-N [(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC3=CSC=C3)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC=C1 MGFCTKPXCQNKNU-ROTRRZJSSA-N 0.000 description 1
• VUHQMSADHNNCSR-JOMKWTIYSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n,n-bis(furan-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3OC=CC=3)CC=3OC=CC=3)[N+]21CCCC1=CC=CC=C1 VUHQMSADHNNCSR-JOMKWTIYSA-N 0.000 description 1
• VJIRAXKGKHTNIX-JOMKWTIYSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n,n-bis(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)CC=3SC=CC=3)[N+]21CCCC1=CC=CC=C1 VJIRAXKGKHTNIX-JOMKWTIYSA-N 0.000 description 1
• WTNLGMPEHYXWHQ-JOMKWTIYSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-(furan-2-ylmethyl)-n-(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3OC=CC=3)CC=3SC=CC=3)[N+]21CCCC1=CC=CC=C1 WTNLGMPEHYXWHQ-JOMKWTIYSA-N 0.000 description 1
• VEJNOGRBRWFHDD-ROTRRZJSSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-(furan-2-ylmethyl)-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3OC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 VEJNOGRBRWFHDD-ROTRRZJSSA-N 0.000 description 1
• UFUXGTXGCTXVQR-DQXUUOSFSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-(4-fluorophenyl)carbamate Chemical compound C1=CC(F)=CC=C1N(C(=O)O[C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)CC1=CC=CC=C1 UFUXGTXGCTXVQR-DQXUUOSFSA-N 0.000 description 1
• QUQTWSOKVZEVEI-FUFAFYGISA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-(4-methylphenyl)carbamate Chemical compound C1=CC(C)=CC=C1N(C(=O)O[C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)CC1=CC=CC=C1 QUQTWSOKVZEVEI-FUFAFYGISA-N 0.000 description 1
• ZUICJRIEMALFLN-HAMJSAHASA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 ZUICJRIEMALFLN-HAMJSAHASA-N 0.000 description 1
• GIJJGEVWDCNFDZ-RXFKJLCSSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCC=2C=CC=CC=2)C1)C(=O)N(CCCC)CC1=CC=CS1 GIJJGEVWDCNFDZ-RXFKJLCSSA-N 0.000 description 1
• XMVZKWJSNYQWPQ-MUZWYTLNSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 XMVZKWJSNYQWPQ-MUZWYTLNSA-N 0.000 description 1
• FGNIEKZMIIAKNK-JOMKWTIYSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-cyclopentyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C3CCCC3)[N+]21CCCC1=CC=CC=C1 FGNIEKZMIIAKNK-JOMKWTIYSA-N 0.000 description 1
• WERBGHGJBVUKIF-KGBLJUBMSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC=C)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 WERBGHGJBVUKIF-KGBLJUBMSA-N 0.000 description 1
• LJXVDPHXVLQJQF-KGBLJUBMSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCCC)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 LJXVDPHXVLQJQF-KGBLJUBMSA-N 0.000 description 1
• NGQNIEGSHBVLIB-FUFAFYGISA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 NGQNIEGSHBVLIB-FUFAFYGISA-N 0.000 description 1
• DNGHZTDKLBJRPI-ROTRRZJSSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 DNGHZTDKLBJRPI-ROTRRZJSSA-N 0.000 description 1
• LQYINUYCLXSNNX-KGBLJUBMSA-N [(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC3=CSC=C3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 LQYINUYCLXSNNX-KGBLJUBMSA-N 0.000 description 1
• DQUOPWPTYBNISH-IIIFQBMYSA-N [(3r)-1-(3-phenylsulfanylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCSC1=CC=CC=C1 DQUOPWPTYBNISH-IIIFQBMYSA-N 0.000 description 1
• KRQWWJKJMBKOEK-IYUIPRCHSA-N [(3r)-1-(3-pyrrol-1-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCN1C=CC=C1 KRQWWJKJMBKOEK-IYUIPRCHSA-N 0.000 description 1
• JNJKTGYSCZXDCF-ROTRRZJSSA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 JNJKTGYSCZXDCF-ROTRRZJSSA-N 0.000 description 1
• WRRKXJXJKFCUCR-BMMPOPSUSA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 WRRKXJXJKFCUCR-BMMPOPSUSA-N 0.000 description 1
• XHONDBFNYXSIDM-OKBRVIPFSA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC=C)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 XHONDBFNYXSIDM-OKBRVIPFSA-N 0.000 description 1
• GHGXEKZZCDTJHT-OKBRVIPFSA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCCC)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 GHGXEKZZCDTJHT-OKBRVIPFSA-N 0.000 description 1
• BOUIEQCLPBGZOL-GPQFNORQSA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 BOUIEQCLPBGZOL-GPQFNORQSA-N 0.000 description 1
• ZGAIDOGAKIQCJU-FJOOJYTASA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3SC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 ZGAIDOGAKIQCJU-FJOOJYTASA-N 0.000 description 1
• DIQXIWJNNCBKDZ-OKBRVIPFSA-N [(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC3=CSC=C3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CS1 DIQXIWJNNCBKDZ-OKBRVIPFSA-N 0.000 description 1
• WZOMXRTVBFDJPD-MUZWYTLNSA-N [(3r)-1-(4-methylpent-3-enyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCC=C(C)C)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 WZOMXRTVBFDJPD-MUZWYTLNSA-N 0.000 description 1
• BIGKVGNUQGNIIK-JEPVQIMHSA-N [(3r)-1-(4-methylpent-3-enyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC=C(C)C)C1)C(=O)N(CCCC)C1=CC=CC=C1 BIGKVGNUQGNIIK-JEPVQIMHSA-N 0.000 description 1
• VJWIOXAVZUSCES-GEMBBTIOSA-N [(3r)-1-(4-oxo-4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCC(=O)C=1C=CC=CC=1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 VJWIOXAVZUSCES-GEMBBTIOSA-N 0.000 description 1
• PBEUVUYKCAADTE-FYKVLBHHSA-N [(3r)-1-(4-oxo-4-thiophen-2-ylbutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCC(=O)C=1SC=CC=1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 PBEUVUYKCAADTE-FYKVLBHHSA-N 0.000 description 1
• MXWTXHAECXYZMB-CJQCTXEWSA-N [(3r)-1-(4-oxo-4-thiophen-2-ylbutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCC(=O)C1=CC=CS1 MXWTXHAECXYZMB-CJQCTXEWSA-N 0.000 description 1
• HLVAALPZDHYGFR-FUFAFYGISA-N [(3r)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCCC1=CC=CC=C1 HLVAALPZDHYGFR-FUFAFYGISA-N 0.000 description 1
• KRFAYJZMZMKWAE-KGBLJUBMSA-N [(3r)-1-(4-phenylbutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCCC1=CC=CC=C1 KRFAYJZMZMKWAE-KGBLJUBMSA-N 0.000 description 1
• PANZZNJSRYFNJN-CRIAOJQNSA-N [(3r)-1-(cyclopropylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC1CC1 PANZZNJSRYFNJN-CRIAOJQNSA-N 0.000 description 1
• RCTUKMFNNCBVGM-MMPATGFWSA-N [(3r)-1-(cyclopropylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CC1CC1 RCTUKMFNNCBVGM-MMPATGFWSA-N 0.000 description 1
• AQQCLPGRJNJCHI-RXFKJLCSSA-N [(3r)-1-[2-(2-methoxyethoxy)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCOCCOC)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 AQQCLPGRJNJCHI-RXFKJLCSSA-N 0.000 description 1
• SAQHUZWTXIFWGY-CVCZCXRASA-N [(3r)-1-[2-(2-methoxyethoxy)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCOCCOC)C1)C(=O)N(CCCC)C1=CC=CC=C1 SAQHUZWTXIFWGY-CVCZCXRASA-N 0.000 description 1
• UYMHACUGWKANKD-HLJRPHAASA-N [(3r)-1-[3-(1,3-benzodioxol-5-yloxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=C3OCOC3=CC=2)C1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 UYMHACUGWKANKD-HLJRPHAASA-N 0.000 description 1
• FFARTKVMUGKDJW-JWNAFBRWSA-N [(3r)-1-[3-(2,4,6-trimethylphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound CC1=CC(C)=CC(C)=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 FFARTKVMUGKDJW-JWNAFBRWSA-N 0.000 description 1
• PWLNYYLLSJKGPC-JCBDZXOXSA-N [(3r)-1-[3-(2,4-difluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound FC1=CC(F)=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 PWLNYYLLSJKGPC-JCBDZXOXSA-N 0.000 description 1
• FAVVGJGQYQWYFV-PGSWAALUSA-O [(3r)-1-[3-(2-carbamoylphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound NC(=O)C1=CC=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 FAVVGJGQYQWYFV-PGSWAALUSA-O 0.000 description 1
• ZMYAWMOOPIUDQM-YGRPKTSXSA-N [(3r)-1-[3-(3-cyanophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC(C#N)=C1 ZMYAWMOOPIUDQM-YGRPKTSXSA-N 0.000 description 1
• YCWQBKLGBCCWNC-KCTUUFLGSA-O [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound OC1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)N(CC=2C=CC=CC=2)C=2C=CC=CC=2)=C1 YCWQBKLGBCCWNC-KCTUUFLGSA-O 0.000 description 1
• DVJHMGKXVDCRJI-GDWJQBMWSA-O [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC(O)=C1 DVJHMGKXVDCRJI-GDWJQBMWSA-O 0.000 description 1
• JHKMWVOLJZNNLJ-VTIINTLQSA-O [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound OC1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)N(CCCC=C)C=2C=CC=CC=2)=C1 JHKMWVOLJZNNLJ-VTIINTLQSA-O 0.000 description 1
• DBWGXIVARZJXDU-VTIINTLQSA-O [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCCC)C=3C=CC=CC=3)[N+]21CCCOC1=CC=CC(O)=C1 DBWGXIVARZJXDU-VTIINTLQSA-O 0.000 description 1
• DONMTVHZXYHUGU-GYNTZMJKSA-O [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound OC1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)N(CCC=2C=CC=CC=2)C=2C=CC=CC=2)=C1 DONMTVHZXYHUGU-GYNTZMJKSA-O 0.000 description 1
• CXTDREZIFCNIQA-AUSLDBMVSA-O [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound OC1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)N(CC=2SC=CC=2)C=2C=CC=CC=2)=C1 CXTDREZIFCNIQA-AUSLDBMVSA-O 0.000 description 1
• OLZIGXQADUFNMR-VTIINTLQSA-O [(3r)-1-[3-(3-hydroxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound OC1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)N(CC2=CSC=C2)C=2C=CC=CC=2)=C1 OLZIGXQADUFNMR-VTIINTLQSA-O 0.000 description 1
• IOEQBIZZTMJIOX-OGQZCOGXSA-O [(3r)-1-[3-(4-acetamidophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C1=CC(NC(=O)C)=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 IOEQBIZZTMJIOX-OGQZCOGXSA-O 0.000 description 1
• HWEHPSONIGSNOS-PAQIEUDPSA-N [(3r)-1-[3-(4-fluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C1=CC(F)=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 HWEHPSONIGSNOS-PAQIEUDPSA-N 0.000 description 1
• WRFYJTUKCQJARJ-VOHYGNEJSA-N [(3r)-1-[3-(4-fluorophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CCCC)C=3C=CC=CC=3)[N+]21CCCOC1=CC=C(F)C=C1 WRFYJTUKCQJARJ-VOHYGNEJSA-N 0.000 description 1
• NMVSLNFFVPUNBH-GYNTZMJKSA-N [(3r)-1-[3-(4-methoxyphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C1=CC(OC)=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 NMVSLNFFVPUNBH-GYNTZMJKSA-N 0.000 description 1
• HNJJZBGQKLSMEJ-PAQIEUDPSA-N [(3r)-1-[3-(4-nitrophenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 HNJJZBGQKLSMEJ-PAQIEUDPSA-N 0.000 description 1
• WINGGJASQUSDDW-BWFJTVLFSA-N [(3r)-1-[3-(4-phenylphenoxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCOC(C=C1)=CC=C1C1=CC=CC=C1 WINGGJASQUSDDW-BWFJTVLFSA-N 0.000 description 1
• OAUGUNJWIHEVGN-YFGMWWGUSA-N [(3r)-1-[3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCOC=2C=C3CCCCC3=CC=2)C1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 OAUGUNJWIHEVGN-YFGMWWGUSA-N 0.000 description 1
• NJLRKWWHEPWZAQ-YGRPKTSXSA-N [(3r)-1-[3-(n-methylanilino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCN(C)C=1C=CC=CC=1)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 NJLRKWWHEPWZAQ-YGRPKTSXSA-N 0.000 description 1
• WOLZQBNTZSFZDY-OGQZCOGXSA-N [(3r)-1-[3-[3-(dimethylamino)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound CN(C)C1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)N(CC=2C=CC=CC=2)C=2C=CC=CC=2)=C1 WOLZQBNTZSFZDY-OGQZCOGXSA-N 0.000 description 1
• UJZOYTRXQXQLMV-YQUUDUBZSA-N [(3r)-1-[3-[3-(trifluoromethyl)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound FC(F)(F)C1=CC=CC(OCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)N(CC=2C=CC=CC=2)C=2C=CC=CC=2)=C1 UJZOYTRXQXQLMV-YQUUDUBZSA-N 0.000 description 1
• AMYPPPYVTXQXKB-GEMBBTIOSA-N [(3r)-1-[3-[4-(hydroxymethyl)phenoxy]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C1=CC(CO)=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 AMYPPPYVTXQXKB-GEMBBTIOSA-N 0.000 description 1
• JZXJMFOSRNVGHQ-SFHVURJKSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)N(C=1C=CC=CC=1)CC=1C=CSC=1 JZXJMFOSRNVGHQ-SFHVURJKSA-N 0.000 description 1
• OYPHGGHOVVOVKM-KGBLJUBMSA-N [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 OYPHGGHOVVOVKM-KGBLJUBMSA-N 0.000 description 1
• FMSQASUZXQGXMN-CRIAOJQNSA-N [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(CCCC)C1=CC=CC=C1 FMSQASUZXQGXMN-CRIAOJQNSA-N 0.000 description 1
• LMDUVRPXNAFSFL-RXFKJLCSSA-N [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(CCCC=C)C1=CC=CC=C1 LMDUVRPXNAFSFL-RXFKJLCSSA-N 0.000 description 1
• PIHGTIQAXQGHRB-RXFKJLCSSA-N [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(CCCCC)C1=CC=CC=C1 PIHGTIQAXQGHRB-RXFKJLCSSA-N 0.000 description 1
• HLOOIXKQBFHCMC-ZYOFUYEDSA-N [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(C=1C=CC=CC=1)CCC1=CC=CC=C1 HLOOIXKQBFHCMC-ZYOFUYEDSA-N 0.000 description 1
• SBEIYPSLNPSUJX-OKBRVIPFSA-N [(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)N(C=1C=CC=CC=1)CC1=CC=CS1 SBEIYPSLNPSUJX-OKBRVIPFSA-N 0.000 description 1
• ZBDPTPGWTQLPMM-MMPATGFWSA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 ZBDPTPGWTQLPMM-MMPATGFWSA-N 0.000 description 1
• KWXUBQOLGJJRDI-JGCRXCKMSA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C)C1)C(=O)N(CCCC)C1=CC=CC=C1 KWXUBQOLGJJRDI-JGCRXCKMSA-N 0.000 description 1
• DXJBKJXMLAUFLT-OZWAEMERSA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-pent-4-enyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)N(CCCC=C)C1=CC=CC=C1 DXJBKJXMLAUFLT-OZWAEMERSA-N 0.000 description 1
• UZIWTUOJYJFRFZ-OZWAEMERSA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-pentyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C)C1)C(=O)N(CCCCC)C1=CC=CC=C1 UZIWTUOJYJFRFZ-OZWAEMERSA-N 0.000 description 1
• ALBUZAHYKAKMPQ-CVCZCXRASA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(2-phenylethyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)N(C=1C=CC=CC=1)CCC1=CC=CC=C1 ALBUZAHYKAKMPQ-CVCZCXRASA-N 0.000 description 1
• XJQLVERVBPRFET-UEUGHCDMSA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-2-ylmethyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)N(C=1C=CC=CC=1)CC1=CC=CS1 XJQLVERVBPRFET-UEUGHCDMSA-N 0.000 description 1
• QJXVTEOOJFOGNB-OZWAEMERSA-N [(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-phenyl-n-(thiophen-3-ylmethyl)carbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)N(C=1C=CC=CC=1)CC=1C=CSC=1 QJXVTEOOJFOGNB-OZWAEMERSA-N 0.000 description 1
• XAPJEQRFWBXQJS-JEPVQIMHSA-N [(3r)-1-propan-2-yl-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C(C)C)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 XAPJEQRFWBXQJS-JEPVQIMHSA-N 0.000 description 1
• RBWNIIRYXXFSSA-WWAKMMQFSA-N [(3r)-1-propan-2-yl-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)C(C)C)C(=O)N(CCCC)C1=CC=CC=C1 RBWNIIRYXXFSSA-WWAKMMQFSA-N 0.000 description 1
• HLAPWENLDHLTNZ-JEPVQIMHSA-N [(3r)-1-propyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCC)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 HLAPWENLDHLTNZ-JEPVQIMHSA-N 0.000 description 1
• YYULGIDZMDGLTP-WWAKMMQFSA-N [(3r)-1-propyl-1-azoniabicyclo[2.2.2]octan-3-yl] n-butyl-n-phenylcarbamate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCC)C1)C(=O)N(CCCC)C1=CC=CC=C1 YYULGIDZMDGLTP-WWAKMMQFSA-N 0.000 description 1
• ZUICJRIEMALFLN-GPMJGTCWSA-N [(3s)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] n-benzyl-n-phenylcarbamate Chemical compound C([C@H](C(CC1)CC2)OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC1=CC=CC=C1 ZUICJRIEMALFLN-GPMJGTCWSA-N 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
• 229960000396 atropine Drugs 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• AYDJYLCIIXDOPZ-UHFFFAOYSA-N benzyl(phenyl)carbamic acid hydrochloride Chemical compound Cl.C(C1=CC=CC=C1)N(C(O)=O)C1=CC=CC=C1 AYDJYLCIIXDOPZ-UHFFFAOYSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 229940124630 bronchodilator Drugs 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• CEWKHVQYIATTIC-UHFFFAOYSA-N butyl(phenyl)carbamic acid Chemical compound CCCCN(C(O)=O)C1=CC=CC=C1 CEWKHVQYIATTIC-UHFFFAOYSA-N 0.000 description 1
• AIRBJINEBYGVJZ-UHFFFAOYSA-N butyl(thiophen-2-ylmethyl)carbamic acid Chemical compound CCCCN(C(O)=O)CC1=CC=CS1 AIRBJINEBYGVJZ-UHFFFAOYSA-N 0.000 description 1
• VCJUJZHGRYCPGJ-UHFFFAOYSA-N butyl-(4-fluorophenyl)carbamic acid Chemical compound CCCCN(C(O)=O)C1=CC=C(F)C=C1 VCJUJZHGRYCPGJ-UHFFFAOYSA-N 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 150000001793 charged compounds Chemical class 0.000 description 1
• 239000000812 cholinergic antagonist Substances 0.000 description 1
• 208000023819 chronic asthma Diseases 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 230000008602 contraction Effects 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 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 1
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
• KTEUFNULQYZGHB-OUZZWEIQSA-N ethyl 5-[(3r)-3-[benzyl(phenyl)carbamoyl]oxy-1-azoniabicyclo[2.2.2]octan-1-yl]pentanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCCC(=O)OCC)C(=O)N(C=1C=CC=CC=1)CC1=CC=CC=C1 KTEUFNULQYZGHB-OUZZWEIQSA-N 0.000 description 1
• OVCNHFMQAYOFMB-DWNDAPBDSA-N ethyl 5-[(3r)-3-[butyl(phenyl)carbamoyl]oxy-1-azoniabicyclo[2.2.2]octan-1-yl]pentanoate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCCCC(=O)OCC)C1)C(=O)N(CCCC)C1=CC=CC=C1 OVCNHFMQAYOFMB-DWNDAPBDSA-N 0.000 description 1
• 230000002964 excitative effect Effects 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 230000000762 glandular Effects 0.000 description 1
• 125000005059 halophenyl group Chemical group 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• QNAQPWIVPNCFAW-OEGWBVIWSA-N methyl 4-[3-[(3r)-3-[benzyl(phenyl)carbamoyl]oxy-1-azoniabicyclo[2.2.2]octan-1-yl]propoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OCCC[N+]1(C[C@@H]2OC(=O)N(CC=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 QNAQPWIVPNCFAW-OEGWBVIWSA-N 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 238000000465 moulding Methods 0.000 description 1
• RYTAWEJFPWUHAM-UHFFFAOYSA-N n-(4-phenylbutyl)carbamoyl chloride Chemical compound ClC(=O)NCCCCC1=CC=CC=C1 RYTAWEJFPWUHAM-UHFFFAOYSA-N 0.000 description 1
• CRLHPNUFQXBBAO-UHFFFAOYSA-N n-(thiophen-2-ylmethyl)cyclopentanamine Chemical compound C=1C=CSC=1CNC1CCCC1 CRLHPNUFQXBBAO-UHFFFAOYSA-N 0.000 description 1
• UANSQQFYKHHDJM-KRWDZBQOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(N[C@@H]3C4CCN(CC4)C3)=O)=CC=CC2=C1 UANSQQFYKHHDJM-KRWDZBQOSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• KVNPRHJSNCFLEG-UHFFFAOYSA-N n-benzyl-n-phenylcarbamoyl chloride Chemical compound C=1C=CC=CC=1N(C(=O)Cl)CC1=CC=CC=C1 KVNPRHJSNCFLEG-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
• JVKPGXHNRQRNEO-UHFFFAOYSA-N n-butyl-n-phenylcarbamoyl chloride Chemical compound CCCCN(C(Cl)=O)C1=CC=CC=C1 JVKPGXHNRQRNEO-UHFFFAOYSA-N 0.000 description 1
• VSHTWPWTCXQLQN-UHFFFAOYSA-N n-butylaniline Chemical compound CCCCNC1=CC=CC=C1 VSHTWPWTCXQLQN-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 230000001272 neurogenic effect Effects 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
• 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
• 238000012856 packing Methods 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• OLTPKMBOLARPFC-UHFFFAOYSA-N phenyl(2-phenylethyl)carbamic acid Chemical compound C=1C=CC=CC=1N(C(=O)O)CCC1=CC=CC=C1 OLTPKMBOLARPFC-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 229920000075 poly(4-vinylpyridine) Polymers 0.000 description 1
• 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 230000016160 smooth muscle contraction Effects 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 230000002048 spasmolytic effect Effects 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000009278 visceral effect Effects 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1