SK286052B6 - 3,3-difenylpropylamíny, farmaceutické prostriedky, spôsob ich výroby a použitie - Google Patents
3,3-difenylpropylamíny, farmaceutické prostriedky, spôsob ich výroby a použitie Download PDFInfo
- Publication number
- SK286052B6 SK286052B6 SK1547-2000A SK15472000A SK286052B6 SK 286052 B6 SK286052 B6 SK 286052B6 SK 15472000 A SK15472000 A SK 15472000A SK 286052 B6 SK286052 B6 SK 286052B6
- Authority
- SK
- Slovakia
- Prior art keywords
- phenylpropyl
- diisopropylamino
- ester
- acid
- hydroxymethylphenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 29
- KISZTEOELCMZPY-UHFFFAOYSA-N 3,3-diphenylpropylamine Chemical class C=1C=CC=CC=1C(CCN)C1=CC=CC=C1 KISZTEOELCMZPY-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- -1 benzoylacyl Chemical group 0.000 claims description 162
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 40
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
- 150000002148 esters Chemical class 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 27
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 150000005690 diesters Chemical class 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 17
- 239000002585 base Substances 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 150000002170 ethers Chemical class 0.000 claims description 10
- 239000002207 metabolite Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Substances CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 8
- 230000001022 anti-muscarinic effect Effects 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 6
- 210000004185 liver Anatomy 0.000 claims description 6
- 150000007522 mineralic acids Chemical class 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 108090001060 Lipase Proteins 0.000 claims description 5
- 102000004882 Lipase Human genes 0.000 claims description 5
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 150000001720 carbohydrates Chemical class 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 229940043279 diisopropylamine Drugs 0.000 claims description 5
- 239000003149 muscarinic antagonist Substances 0.000 claims description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052805 deuterium Inorganic materials 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- 239000012948 isocyanate Substances 0.000 claims description 4
- 150000002513 isocyanates Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000001302 tertiary amino group Chemical group 0.000 claims description 4
- IOAGZOSRHBAGLF-UHFFFAOYSA-N 2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(ethoxymethyl)phenol Chemical compound CCOCC1=CC=C(O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 IOAGZOSRHBAGLF-UHFFFAOYSA-N 0.000 claims description 3
- ICRSOVOKENPWCQ-UHFFFAOYSA-N 2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(methoxymethyl)phenol Chemical compound COCC1=CC=C(O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 ICRSOVOKENPWCQ-UHFFFAOYSA-N 0.000 claims description 3
- CUBIWNOXCQKTST-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(formyloxymethyl)phenyl] benzoate Chemical compound C=1C(COC=O)=CC=C(OC(=O)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 CUBIWNOXCQKTST-UHFFFAOYSA-N 0.000 claims description 3
- KGNKBMFLHKBDSX-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] benzoate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 KGNKBMFLHKBDSX-UHFFFAOYSA-N 0.000 claims description 3
- KBCRQQPEPOQTFD-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] propanoate Chemical compound CCC(=O)OC1=CC=C(CO)C=C1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 KBCRQQPEPOQTFD-UHFFFAOYSA-N 0.000 claims description 3
- FQGQHOIIFPANBW-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-formyloxyphenyl]methyl formate Chemical compound C=1C(COC=O)=CC=C(OC=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 FQGQHOIIFPANBW-UHFFFAOYSA-N 0.000 claims description 3
- ONAYLBCJKSLQDV-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-hydroxyphenyl]methyl 2,2-dimethylpropanoate Chemical compound C=1C(COC(=O)C(C)(C)C)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 ONAYLBCJKSLQDV-UHFFFAOYSA-N 0.000 claims description 3
- KBQJPVIJGZHINT-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxyphenyl]methyl benzoate Chemical compound C=1C(COC(=O)C=2C=CC=CC=2)=CC=C(OCC=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 KBQJPVIJGZHINT-UHFFFAOYSA-N 0.000 claims description 3
- SEHCTGCUIKWNLH-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-trimethylsilyloxyphenyl]methanol Chemical compound C=1C(CO)=CC=C(O[Si](C)(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 SEHCTGCUIKWNLH-UHFFFAOYSA-N 0.000 claims description 3
- LRFPIHCDDAVNEG-UHFFFAOYSA-N [4-(acetyloxymethyl)-2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl] benzoate Chemical compound C=1C(COC(C)=O)=CC=C(OC(=O)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 LRFPIHCDDAVNEG-UHFFFAOYSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 150000008051 alkyl sulfates Chemical class 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 3
- 150000003938 benzyl alcohols Chemical class 0.000 claims description 3
- 150000007942 carboxylates Chemical class 0.000 claims description 3
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- PWXJULSLLONQHY-UHFFFAOYSA-N phenylcarbamic acid Chemical compound OC(=O)NC1=CC=CC=C1 PWXJULSLLONQHY-UHFFFAOYSA-N 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 claims description 3
- ZXOAYKHGVAAUQX-UHFFFAOYSA-N 2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(propan-2-yloxymethyl)phenol Chemical compound CC(C)OCC1=CC=C(O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 ZXOAYKHGVAAUQX-UHFFFAOYSA-N 0.000 claims description 2
- FVGOMOJXEFTVPO-UHFFFAOYSA-N 2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(trimethylsilyloxymethyl)phenol Chemical compound C=1C(CO[Si](C)(C)C)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 FVGOMOJXEFTVPO-UHFFFAOYSA-N 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- IJOGBZLVGHCYOQ-UHFFFAOYSA-N 4-[[2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenoxy]carbonylamino]butylcarbamic acid Chemical compound C=1C(CO)=CC=C(OC(=O)NCCCCNC(O)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 IJOGBZLVGHCYOQ-UHFFFAOYSA-N 0.000 claims description 2
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 claims description 2
- APRJFNLVTJWEPP-UHFFFAOYSA-N Diethylcarbamic acid Chemical compound CCN(CC)C(O)=O APRJFNLVTJWEPP-UHFFFAOYSA-N 0.000 claims description 2
- KGNKBMFLHKBDSX-AREMUKBSSA-N [2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] benzoate Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)OC(=O)C=2C=CC=CC=2)=CC=CC=C1 KGNKBMFLHKBDSX-AREMUKBSSA-N 0.000 claims description 2
- MBLCIBYXWDJRTL-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 4-chlorobenzoate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C=CC(Cl)=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 MBLCIBYXWDJRTL-UHFFFAOYSA-N 0.000 claims description 2
- YGQQSKRWISRYIE-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] cyclopentanecarboxylate Chemical compound C=1C(CO)=CC=C(OC(=O)C2CCCC2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 YGQQSKRWISRYIE-UHFFFAOYSA-N 0.000 claims description 2
- WXQIMMHESMEGJT-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(2-methylpropanoyloxy)phenyl]methyl 2-methylpropanoate Chemical compound C=1C(COC(=O)C(C)C)=CC=C(OC(=O)C(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 WXQIMMHESMEGJT-UHFFFAOYSA-N 0.000 claims description 2
- KOULVVBWHDZSHA-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-hydroxyphenyl]methyl benzoate Chemical compound C=1C(COC(=O)C=2C=CC=CC=2)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 KOULVVBWHDZSHA-UHFFFAOYSA-N 0.000 claims description 2
- FVJZAGORFDOLFR-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-hydroxyphenyl]methyl formate Chemical compound C=1C(COC=O)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 FVJZAGORFDOLFR-UHFFFAOYSA-N 0.000 claims description 2
- DDHZRAZIPFFORZ-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-hydroxyphenyl]methyl propanoate Chemical compound CCC(=O)OCC1=CC=C(O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 DDHZRAZIPFFORZ-UHFFFAOYSA-N 0.000 claims description 2
- LRFPIHCDDAVNEG-MUUNZHRXSA-N [4-(acetyloxymethyl)-2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl] benzoate Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(COC(C)=O)C=2)OC(=O)C=2C=CC=CC=2)=CC=CC=C1 LRFPIHCDDAVNEG-MUUNZHRXSA-N 0.000 claims description 2
- VSQHRRCGQPXSBF-UHFFFAOYSA-N [4-acetyloxy-3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl]methyl 2,2-dimethylpropanoate Chemical compound C=1C(COC(=O)C(C)(C)C)=CC=C(OC(C)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 VSQHRRCGQPXSBF-UHFFFAOYSA-N 0.000 claims description 2
- OOHFNCCDLJCABN-UHFFFAOYSA-N [4-benzoyloxy-3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl]methyl benzoate Chemical compound C=1C(COC(=O)C=2C=CC=CC=2)=CC=C(OC(=O)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 OOHFNCCDLJCABN-UHFFFAOYSA-N 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
- NCWUEGVAVOURMO-UHFFFAOYSA-N bis[2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] hexanedioate Chemical compound C=1C(CO)=CC=C(OC(=O)CCCCC(=O)OC=2C(=CC(CO)=CC=2)C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 NCWUEGVAVOURMO-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 2
- DWLVWMUCHSLGSU-UHFFFAOYSA-N dimethylcarbamic acid Chemical compound CN(C)C(O)=O DWLVWMUCHSLGSU-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 claims description 2
- 150000002540 isothiocyanates Chemical class 0.000 claims description 2
- 150000002561 ketenes Chemical class 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 claims 2
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical compound COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- JZPBSPBDNUCJNY-UHFFFAOYSA-N 2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(propoxymethyl)phenol Chemical compound CCCOCC1=CC=C(O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 JZPBSPBDNUCJNY-UHFFFAOYSA-N 0.000 claims 1
- JVPZKVIYSYEUID-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenol Chemical compound C=1C(O)=CC=C(O[Si](C)(C)C(C)(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 JVPZKVIYSYEUID-UHFFFAOYSA-N 0.000 claims 1
- FKMVNGWJGSSDCF-UHFFFAOYSA-N 4-acetoxybenzyl alcohol Chemical compound CC(=O)OC1=CC=C(CO)C=C1 FKMVNGWJGSSDCF-UHFFFAOYSA-N 0.000 claims 1
- QCFAHQNRWPIQFK-UHFFFAOYSA-N C(C)OCC1=CC=C(C=C1)OC(CC(CCN(C(C)C)C(C)C)C1=CC=CC=C1)=O Chemical compound C(C)OCC1=CC=C(C=C1)OC(CC(CCN(C(C)C)C(C)C)C1=CC=CC=C1)=O QCFAHQNRWPIQFK-UHFFFAOYSA-N 0.000 claims 1
- QCLYHRFCZQZNSP-UHFFFAOYSA-N C1(=CC=CC=C1)C(CCN)C1=CC=CC=C1.C(C)(=O)O Chemical class C1(=CC=CC=C1)C(CCN)C1=CC=CC=C1.C(C)(=O)O QCLYHRFCZQZNSP-UHFFFAOYSA-N 0.000 claims 1
- NKTQJFGDIPUASC-UHFFFAOYSA-N CC(C)N(CCC(C1=CC=CC=C1)C2=C(C=CC(=C2)OC(=O)C)OC(=O)C(C)(C)C)C(C)C Chemical compound CC(C)N(CCC(C1=CC=CC=C1)C2=C(C=CC(=C2)OC(=O)C)OC(=O)C(C)(C)C)C(C)C NKTQJFGDIPUASC-UHFFFAOYSA-N 0.000 claims 1
- WROISCKUKFSJKG-AREMUKBSSA-N CC(C)N(CC[C@H](C1=CC=C(C=C1)COC(=O)C)C(C)(C)C(=O)OC2=CC=CC=C2)C(C)C Chemical compound CC(C)N(CC[C@H](C1=CC=C(C=C1)COC(=O)C)C(C)(C)C(=O)OC2=CC=CC=C2)C(C)C WROISCKUKFSJKG-AREMUKBSSA-N 0.000 claims 1
- 241001255854 Teras Species 0.000 claims 1
- YITIBBWTPPPIBU-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(ethoxycarbonyloxymethyl)phenyl] ethyl carbonate Chemical compound CCOC(=O)OCC1=CC=C(OC(=O)OCC)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 YITIBBWTPPPIBU-UHFFFAOYSA-N 0.000 claims 1
- UUQZJCVJLILIBJ-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2,2-dimethylpropanoate Chemical compound C=1C(CO)=CC=C(OC(=O)C(C)(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 UUQZJCVJLILIBJ-UHFFFAOYSA-N 0.000 claims 1
- ORGQWJPFPNJJMJ-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-acetamidoacetate Chemical compound C=1C(CO)=CC=C(OC(=O)CNC(C)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 ORGQWJPFPNJJMJ-UHFFFAOYSA-N 0.000 claims 1
- DCCSDBARQIPTGU-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methylpropanoate Chemical compound C=1C(CO)=CC=C(OC(=O)C(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 DCCSDBARQIPTGU-UHFFFAOYSA-N 0.000 claims 1
- COQSZSOHODRSCC-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] cyclohexanecarboxylate Chemical compound C=1C(CO)=CC=C(OC(=O)C2CCCCC2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 COQSZSOHODRSCC-UHFFFAOYSA-N 0.000 claims 1
- PYJGAVVIWWRPCC-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] formate Chemical compound C=1C(CO)=CC=C(OC=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 PYJGAVVIWWRPCC-UHFFFAOYSA-N 0.000 claims 1
- VEVRXYWNXTUOPG-UHFFFAOYSA-N [4-(2,2-dimethylpropanoyloxy)-3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl]methyl 2,2-dimethylpropanoate Chemical compound C=1C(COC(=O)C(C)(C)C)=CC=C(OC(=O)C(C)(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 VEVRXYWNXTUOPG-UHFFFAOYSA-N 0.000 claims 1
- OOHFNCCDLJCABN-JGCGQSQUSA-N [4-benzoyloxy-3-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl]methyl benzoate Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(COC(=O)C=3C=CC=CC=3)C=2)OC(=O)C=2C=CC=CC=2)=CC=CC=C1 OOHFNCCDLJCABN-JGCGQSQUSA-N 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000005129 aryl carbonyl group Chemical group 0.000 claims 1
- XMKWCYAHVZZBKW-UHFFFAOYSA-N benzoic acid;2-methylpropanoic acid Chemical compound CC(C)C(O)=O.OC(=O)C1=CC=CC=C1 XMKWCYAHVZZBKW-UHFFFAOYSA-N 0.000 claims 1
- 229940007550 benzyl acetate Drugs 0.000 claims 1
- GCTPMLUUWLLESL-UHFFFAOYSA-N benzyl prop-2-enoate Chemical compound C=CC(=O)OCC1=CC=CC=C1 GCTPMLUUWLLESL-UHFFFAOYSA-N 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- DCCSDBARQIPTGU-HSZRJFAPSA-N fesoterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)OC(=O)C(C)C)=CC=CC=C1 DCCSDBARQIPTGU-HSZRJFAPSA-N 0.000 claims 1
- KWBIXTIBYFUAGV-UHFFFAOYSA-M n-ethylcarbamate Chemical compound CCNC([O-])=O KWBIXTIBYFUAGV-UHFFFAOYSA-M 0.000 claims 1
- LQVYKEXVMZXOAH-UHFFFAOYSA-N oct-4-enedioic acid Chemical compound OC(=O)CCC=CCCC(O)=O LQVYKEXVMZXOAH-UHFFFAOYSA-N 0.000 claims 1
- QIIPQYDSKRYMFG-UHFFFAOYSA-M phenyl carbonate Chemical compound [O-]C(=O)OC1=CC=CC=C1 QIIPQYDSKRYMFG-UHFFFAOYSA-M 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- 206010046543 Urinary incontinence Diseases 0.000 abstract description 8
- 238000011282 treatment Methods 0.000 abstract description 7
- 208000013403 hyperactivity Diseases 0.000 abstract description 4
- 230000002496 gastric effect Effects 0.000 abstract description 2
- 210000002460 smooth muscle Anatomy 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 114
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- 239000000543 intermediate Substances 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- 239000007858 starting material Substances 0.000 description 28
- 239000003921 oil Substances 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 23
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 23
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- 239000012230 colorless oil Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 229910021529 ammonia Inorganic materials 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 14
- 125000001309 chloro group Chemical group Cl* 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 125000000026 trimethylsilyl group Chemical class [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 239000006188 syrup Substances 0.000 description 10
- 235000020357 syrup Nutrition 0.000 description 10
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 10
- DUXZAXCGJSBGDW-UHFFFAOYSA-N 2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenol Chemical compound C=1C(CO)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 DUXZAXCGJSBGDW-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 229960004045 tolterodine Drugs 0.000 description 8
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 8
- 239000005711 Benzoic acid Substances 0.000 description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000005917 acylation reaction Methods 0.000 description 6
- 235000010233 benzoic acid Nutrition 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- IFBPJCUUTXMZLB-LJQANCHMSA-N (3r)-3-(5-bromo-2-phenylmethoxyphenyl)-3-phenylpropanoic acid Chemical compound C1([C@@H](CC(=O)O)C=2C(=CC=C(Br)C=2)OCC=2C=CC=CC=2)=CC=CC=C1 IFBPJCUUTXMZLB-LJQANCHMSA-N 0.000 description 5
- IFBPJCUUTXMZLB-UHFFFAOYSA-N 3-(5-bromo-2-phenylmethoxyphenyl)-3-phenylpropanoic acid Chemical compound C=1C(Br)=CC=C(OCC=2C=CC=CC=2)C=1C(CC(=O)O)C1=CC=CC=C1 IFBPJCUUTXMZLB-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 229920001577 copolymer Polymers 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 102000017925 CHRM3 Human genes 0.000 description 4
- 101150060249 CHRM3 gene Proteins 0.000 description 4
- 241000700198 Cavia Species 0.000 description 4
- XIQVNETUBQGFHX-UHFFFAOYSA-N Ditropan Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCC#CCN(CC)CC)C1CCCCC1 XIQVNETUBQGFHX-UHFFFAOYSA-N 0.000 description 4
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 4
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000005227 gel permeation chromatography Methods 0.000 description 4
- MSJGQLPLCOBFNR-CSKARUKUSA-N methyl 3-[(e)-3-[di(propan-2-yl)amino]-3-oxoprop-1-enyl]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(\C=C\C(=O)N(C(C)C)C(C)C)=C1 MSJGQLPLCOBFNR-CSKARUKUSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical class CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 3
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 3
- KJMCZWJBHWBPNB-UHFFFAOYSA-N 3-(5-bromo-2-phenylmethoxyphenyl)-3-phenylpropan-1-ol Chemical compound C=1C(Br)=CC=C(OCC=2C=CC=CC=2)C=1C(CCO)C1=CC=CC=C1 KJMCZWJBHWBPNB-UHFFFAOYSA-N 0.000 description 3
- LXYOEDGDQBDZFK-UHFFFAOYSA-N 5-bromo-2-phenylmethoxybenzaldehyde Chemical compound O=CC1=CC(Br)=CC=C1OCC1=CC=CC=C1 LXYOEDGDQBDZFK-UHFFFAOYSA-N 0.000 description 3
- KFKFQGCDFMGUCH-UHFFFAOYSA-N 6-bromo-4-phenyl-3,4-dihydrochromen-2-one Chemical compound C12=CC(Br)=CC=C2OC(=O)CC1C1=CC=CC=C1 KFKFQGCDFMGUCH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 239000004367 Lipase 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
- 238000010521 absorption reaction Methods 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 235000019421 lipase Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- SXFFQILYKHDSIZ-UHFFFAOYSA-N methyl 3-(5-bromo-2-phenylmethoxyphenyl)-3-phenylpropanoate Chemical compound C=1C(Br)=CC=C(OCC=2C=CC=CC=2)C=1C(CC(=O)OC)C1=CC=CC=C1 SXFFQILYKHDSIZ-UHFFFAOYSA-N 0.000 description 3
- LJDGPIHWEJMCHJ-UHFFFAOYSA-N methyl 3-[3-[di(propan-2-yl)amino]-3-oxo-1-phenylpropyl]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(C(CC(=O)N(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 LJDGPIHWEJMCHJ-UHFFFAOYSA-N 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 229960001383 methylscopolamine Drugs 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000007738 vacuum evaporation Methods 0.000 description 3
- 229920001567 vinyl ester resin Polymers 0.000 description 3
- DEYSPWMSQMLCDN-XCZPVHLTSA-N (4r)-3-[(3s)-3-(5-bromo-2-phenylmethoxyphenyl)-3-phenylpropanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C1([C@@H](CC(=O)N2C(OC[C@H]2C=2C=CC=CC=2)=O)C=2C=CC=CC=2)=CC(Br)=CC=C1OCC1=CC=CC=C1 DEYSPWMSQMLCDN-XCZPVHLTSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- UCYJWCSOSZIQLQ-UHFFFAOYSA-N 3-(5-bromo-2-phenylmethoxyphenyl)-3-phenyl-n,n-di(propan-2-yl)propan-1-amine Chemical compound C=1C(Br)=CC=C(OCC=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 UCYJWCSOSZIQLQ-UHFFFAOYSA-N 0.000 description 2
- JMUYVFMRSLESOK-UHFFFAOYSA-N 3-(5-bromo-2-phenylmethoxyphenyl)-3-phenyl-n,n-di(propan-2-yl)propanamide Chemical compound C=1C(Br)=CC=C(OCC=2C=CC=CC=2)C=1C(CC(=O)N(C(C)C)C(C)C)C1=CC=CC=C1 JMUYVFMRSLESOK-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-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
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102000007202 Muscarinic M3 Receptor Human genes 0.000 description 2
- 108010008405 Muscarinic M3 Receptor Proteins 0.000 description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- AXPHWDWOHXSWLO-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(formyloxymethyl)phenyl] acetate Chemical compound C=1C(COC=O)=CC=C(OC(C)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 AXPHWDWOHXSWLO-UHFFFAOYSA-N 0.000 description 2
- GGBRJVDMIAIYQE-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methoxybenzoate Chemical compound COC1=CC=CC=C1C(=O)OC1=CC=C(CO)C=C1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 GGBRJVDMIAIYQE-UHFFFAOYSA-N 0.000 description 2
- HSCRYMUWADSZNR-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(methoxymethyl)phenyl] acetate Chemical compound COCC1=CC=C(OC(C)=O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 HSCRYMUWADSZNR-UHFFFAOYSA-N 0.000 description 2
- VKPPGRKDENBKHV-NRKMYXNYSA-N [2H]C([2H])C(C([C@H](CCN(C(C)C)C(C)C)C1=CC=CC=C1)=C(C=C1)O)=C1O Chemical compound [2H]C([2H])C(C([C@H](CCN(C(C)C)C(C)C)C1=CC=CC=C1)=C(C=C1)O)=C1O VKPPGRKDENBKHV-NRKMYXNYSA-N 0.000 description 2
- MRPQPFZQDZLULY-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-hydroxyphenyl]methyl acetate Chemical compound C=1C(COC(C)=O)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 MRPQPFZQDZLULY-UHFFFAOYSA-N 0.000 description 2
- GVKBRMPULOEHLO-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxyphenyl]methanol Chemical compound C=1C(CO)=CC=C(OCC=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 GVKBRMPULOEHLO-UHFFFAOYSA-N 0.000 description 2
- ZYYOQPPGPQQGCU-UHFFFAOYSA-N [4-(acetyloxymethyl)-2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl] 2-methylpropanoate Chemical compound C=1C(COC(C)=O)=CC=C(OC(=O)C(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 ZYYOQPPGPQQGCU-UHFFFAOYSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000001078 anti-cholinergic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000000837 carbohydrate group Chemical group 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 125000005442 diisocyanate group Chemical group 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- KWBIXTIBYFUAGV-UHFFFAOYSA-N ethylcarbamic acid Chemical compound CCNC(O)=O KWBIXTIBYFUAGV-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000001145 hydrido group Chemical group *[H] 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- YRJYQILAWNHFTB-UHFFFAOYSA-N methyl 3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxybenzoate Chemical compound C=1C=CC=CC=1C(CCN(C(C)C)C(C)C)C1=CC(C(=O)OC)=CC=C1OCC1=CC=CC=C1 YRJYQILAWNHFTB-UHFFFAOYSA-N 0.000 description 2
- ZREVPFANJBZHEU-UHFFFAOYSA-N methyl 3-bromo-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(Br)=C1 ZREVPFANJBZHEU-UHFFFAOYSA-N 0.000 description 2
- 230000003551 muscarinic effect Effects 0.000 description 2
- YHOSNAAUPKDRMI-UHFFFAOYSA-N n,n-di(propan-2-yl)prop-2-enamide Chemical compound CC(C)N(C(C)C)C(=O)C=C YHOSNAAUPKDRMI-UHFFFAOYSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- HVAMZGADVCBITI-UHFFFAOYSA-N pent-4-enoic acid Chemical compound OC(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000001525 receptor binding assay Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000003033 spasmogenic effect Effects 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000000825 ultraviolet detection Methods 0.000 description 2
- KWGRBVOPPLSCSI-PSASIEDQSA-N (1s,2r)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-PSASIEDQSA-N 0.000 description 1
- UCYJWCSOSZIQLQ-AREMUKBSSA-N (3r)-3-(5-bromo-2-phenylmethoxyphenyl)-3-phenyl-n,n-di(propan-2-yl)propan-1-amine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(Br)C=2)OCC=2C=CC=CC=2)=CC=CC=C1 UCYJWCSOSZIQLQ-AREMUKBSSA-N 0.000 description 1
- WOGITNXCNOTRLK-VOTSOKGWSA-N (e)-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CC=C1 WOGITNXCNOTRLK-VOTSOKGWSA-N 0.000 description 1
- LQVYKEXVMZXOAH-OWOJBTEDSA-N (e)-oct-4-enedioic acid Chemical compound OC(=O)CC\C=C\CCC(O)=O LQVYKEXVMZXOAH-OWOJBTEDSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- CWIFYQQOFPQJEW-JOCHJYFZSA-N 2-[2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl]-2-methylpropanoic acid Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)C(C)(C)C(O)=O)=CC=CC=C1 CWIFYQQOFPQJEW-JOCHJYFZSA-N 0.000 description 1
- LELZKBBTNYTEJN-UHFFFAOYSA-N 2-[3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-hydroxyphenyl]acetic acid Chemical compound C=1C(CC(O)=O)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 LELZKBBTNYTEJN-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical class Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000003541 2-chlorobenzoyl group Chemical group ClC1=C(C(=O)*)C=CC=C1 0.000 description 1
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 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
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 description 1
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
- DOZZSWAOPDYVLH-UHFFFAOYSA-N 2-phenylpropanamide Chemical compound NC(=O)C(C)C1=CC=CC=C1 DOZZSWAOPDYVLH-UHFFFAOYSA-N 0.000 description 1
- KTQCYOABVYGDNK-UHFFFAOYSA-N 3-(5-bromo-2-phenylmethoxyphenyl)prop-2-enoic acid Chemical compound OC(=O)C=CC1=CC(Br)=CC=C1OCC1=CC=CC=C1 KTQCYOABVYGDNK-UHFFFAOYSA-N 0.000 description 1
- KHTAIVJFQGLEFQ-UHFFFAOYSA-N 3-[2-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]phenyl]-3-phenyl-n,n-di(propan-2-yl)propan-1-amine Chemical compound C=1C(CO[Si](C)(C)C(C)(C)C)=CC=C(O[Si](C)(C)C(C)(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 KHTAIVJFQGLEFQ-UHFFFAOYSA-N 0.000 description 1
- KJWIVHKZEWPBJI-UHFFFAOYSA-N 3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxybenzoic acid Chemical compound C=1C(C(O)=O)=CC=C(OCC=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 KJWIVHKZEWPBJI-UHFFFAOYSA-N 0.000 description 1
- YWQSBJFSXVRFOA-UHFFFAOYSA-N 3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxybenzoic acid;hydrochloride Chemical compound Cl.C=1C(C(O)=O)=CC=C(OCC=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 YWQSBJFSXVRFOA-UHFFFAOYSA-N 0.000 description 1
- FEKBGCMJPISLFY-UHFFFAOYSA-N 4-(butoxymethyl)-2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenol Chemical compound CCCCOCC1=CC=C(O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 FEKBGCMJPISLFY-UHFFFAOYSA-N 0.000 description 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
- DYWPOVCJMDENAE-UHFFFAOYSA-N 4-[4-(5-bromo-2-phenylmethoxyphenyl)-4-phenylbutyl]benzenesulfonic acid Chemical compound C(C1=CC=CC=C1)OC1=C(C=C(C=C1)Br)C(CCCC1=CC=C(C=C1)S(=O)(=O)O)C1=CC=CC=C1 DYWPOVCJMDENAE-UHFFFAOYSA-N 0.000 description 1
- QYSOLIUQGINJSE-UHFFFAOYSA-N 4-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenol Chemical compound C=1C(CO[Si](C)(C)C(C)(C)C)=CC=C(O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 QYSOLIUQGINJSE-UHFFFAOYSA-N 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 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
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- GHXHUAPJSUZZMB-UHFFFAOYSA-N C(C)(C)N(CCC(C1=CC=CC=C1)C1=C(C=CC(=C1)CO)C(C(=O)O)NC(C)=O)C(C)C.C(C)(C)N(CCC(C1=CC=CC=C1)C1=C(C=CC(=C1)CO)OC(CNC(C)=O)=O)C(C)C Chemical compound C(C)(C)N(CCC(C1=CC=CC=C1)C1=C(C=CC(=C1)CO)C(C(=O)O)NC(C)=O)C(C)C.C(C)(C)N(CCC(C1=CC=CC=C1)C1=C(C=CC(=C1)CO)OC(CNC(C)=O)=O)C(C)C GHXHUAPJSUZZMB-UHFFFAOYSA-N 0.000 description 1
- QXYIXAYTCABDLP-UHFFFAOYSA-N C(C)(C)N(CCC(C1=CC=CC=C1)C1=C(C=CC(=C1)CO)OC(N(C1=CC=CC=C1)C1=CC=CC=C1)=O)C(C)C Chemical compound C(C)(C)N(CCC(C1=CC=CC=C1)C1=C(C=CC(=C1)CO)OC(N(C1=CC=CC=C1)C1=CC=CC=C1)=O)C(C)C QXYIXAYTCABDLP-UHFFFAOYSA-N 0.000 description 1
- QULNJNROVBOLDC-UHFFFAOYSA-N C(C)(C)N(CCC(C1=CC=CC=C1)C=1C=C(CC(C(=O)O)(C)C)C=CC1O)C(C)C Chemical compound C(C)(C)N(CCC(C1=CC=CC=C1)C=1C=C(CC(C(=O)O)(C)C)C=CC1O)C(C)C QULNJNROVBOLDC-UHFFFAOYSA-N 0.000 description 1
- FDACOTFCDLEPOG-UHFFFAOYSA-N C(C)(C)N(CCC(C1=CC=CC=C1)C=1C=C(CC(C(=O)O)C)C=CC1O)C(C)C Chemical compound C(C)(C)N(CCC(C1=CC=CC=C1)C=1C=C(CC(C(=O)O)C)C=CC1O)C(C)C FDACOTFCDLEPOG-UHFFFAOYSA-N 0.000 description 1
- IQJUUTZTDVFTPR-UHFFFAOYSA-N C(C)(C)N(CCC(C1=CC=CC=C1)C=1C=C(CC(C(=O)O)CC)C=CC1O)C(C)C Chemical compound C(C)(C)N(CCC(C1=CC=CC=C1)C=1C=C(CC(C(=O)O)CC)C=CC1O)C(C)C IQJUUTZTDVFTPR-UHFFFAOYSA-N 0.000 description 1
- VREUQBUHYINEAU-UHFFFAOYSA-N C1=CC(CO)=CC=C1OC(=O)C1CCCC1 Chemical compound C1=CC(CO)=CC=C1OC(=O)C1CCCC1 VREUQBUHYINEAU-UHFFFAOYSA-N 0.000 description 1
- BQTGKYFWBCHLAS-UHFFFAOYSA-N CC(C)N(CCC(C1=CC=CC=C1)C2=CC=CC=C2CO[Si](C)(C)C)C(C)C Chemical compound CC(C)N(CCC(C1=CC=CC=C1)C2=CC=CC=C2CO[Si](C)(C)C)C(C)C BQTGKYFWBCHLAS-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- DUXZAXCGJSBGDW-HXUWFJFHSA-N Desfesoterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)O)=CC=CC=C1 DUXZAXCGJSBGDW-HXUWFJFHSA-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
- UFHFLCQGNIYNRP-VVKOMZTBSA-N Dideuterium Chemical compound [2H][2H] UFHFLCQGNIYNRP-VVKOMZTBSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 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
- 206010020853 Hypertonic bladder Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 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 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 108010048733 Lipozyme Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- OKJIRPAQVSHGFK-UHFFFAOYSA-M N-acetylglycinate Chemical compound CC(=O)NCC([O-])=O OKJIRPAQVSHGFK-UHFFFAOYSA-M 0.000 description 1
- LYAVXWPXKIFHBU-UHFFFAOYSA-N N-{2-[(1,2-diphenylhydrazinyl)carbonyl]-2-hydroxyhexanoyl}-6-aminohexanoic acid Chemical compound C=1C=CC=CC=1N(C(=O)C(O)(C(=O)NCCCCCC(O)=O)CCCC)NC1=CC=CC=C1 LYAVXWPXKIFHBU-UHFFFAOYSA-N 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 206010048010 Withdrawal syndrome Diseases 0.000 description 1
- XRDRVDDMLLSKLV-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(ethoxymethyl)phenyl] acetate Chemical compound CCOCC1=CC=C(OC(C)=O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 XRDRVDDMLLSKLV-UHFFFAOYSA-N 0.000 description 1
- HQFAUISFJSCISA-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-acetyloxybenzoate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C(=CC=CC=2)OC(C)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 HQFAUISFJSCISA-UHFFFAOYSA-N 0.000 description 1
- SIVIXAOLMWQGHP-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methylbenzoate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C(=CC=CC=2)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 SIVIXAOLMWQGHP-UHFFFAOYSA-N 0.000 description 1
- NRGLGVDLGIWGQI-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-nitrobenzoate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C(=CC=CC=2)[N+]([O-])=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 NRGLGVDLGIWGQI-UHFFFAOYSA-N 0.000 description 1
- CTYLBYQJDFJQHD-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 4-methylbenzoate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C=CC(C)=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 CTYLBYQJDFJQHD-UHFFFAOYSA-N 0.000 description 1
- ZQCOFHZGQGRBCO-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 4-nitrobenzoate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C=CC(=CC=2)[N+]([O-])=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 ZQCOFHZGQGRBCO-UHFFFAOYSA-N 0.000 description 1
- COPIGDPPLIVQTA-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] acetate Chemical compound C=1C(CO)=CC=C(OC(C)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 COPIGDPPLIVQTA-UHFFFAOYSA-N 0.000 description 1
- ZHMZAZQYTLBIMY-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] butanoate Chemical compound CCCC(=O)OC1=CC=C(CO)C=C1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 ZHMZAZQYTLBIMY-UHFFFAOYSA-N 0.000 description 1
- IVADPYCBTYELHZ-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] hydrogen carbonate Chemical compound C=1C(CO)=CC=C(OC(O)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 IVADPYCBTYELHZ-UHFFFAOYSA-N 0.000 description 1
- PVZNVGVWHLOLTC-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] n,n-diethylcarbamate Chemical compound CCN(CC)C(=O)OC1=CC=C(CO)C=C1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 PVZNVGVWHLOLTC-UHFFFAOYSA-N 0.000 description 1
- BVEKXWODCHFMIT-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] n,n-dimethylcarbamate Chemical compound C=1C(CO)=CC=C(OC(=O)N(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 BVEKXWODCHFMIT-UHFFFAOYSA-N 0.000 description 1
- BQDMLRYPFNRUIQ-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] n-[4-[[2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenoxy]carbonylamino]butyl]carbamate Chemical compound C=1C(CO)=CC=C(OC(=O)NCCCCNC(=O)OC=2C(=CC(CO)=CC=2)C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 BQDMLRYPFNRUIQ-UHFFFAOYSA-N 0.000 description 1
- ZZJSLWQZSGYEPC-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] n-ethylcarbamate Chemical compound CCNC(=O)OC1=CC=C(CO)C=C1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 ZZJSLWQZSGYEPC-UHFFFAOYSA-N 0.000 description 1
- HKUGDRYPCZTPID-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] naphthalene-1-carboxylate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C3=CC=CC=C3C=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 HKUGDRYPCZTPID-UHFFFAOYSA-N 0.000 description 1
- MEKUIJXCWXWTDS-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] naphthalene-2-carboxylate Chemical compound C=1C(CO)=CC=C(OC(=O)C=2C=C3C=CC=CC3=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 MEKUIJXCWXWTDS-UHFFFAOYSA-N 0.000 description 1
- BEDSMQJGXDJAFB-UHFFFAOYSA-N [2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(sulfooxymethyl)phenyl] benzoate Chemical compound C=1C(COS(O)(=O)=O)=CC=C(OC(=O)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 BEDSMQJGXDJAFB-UHFFFAOYSA-N 0.000 description 1
- GVKBRMPULOEHLO-HHHXNRCGSA-N [3-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxyphenyl]methanol Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(CO)C=2)OCC=2C=CC=CC=2)=CC=CC=C1 GVKBRMPULOEHLO-HHHXNRCGSA-N 0.000 description 1
- AWSAXDSHDDRXDH-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-hydroxyphenyl]methyl butanoate Chemical compound CCCC(=O)OCC1=CC=C(O)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 AWSAXDSHDDRXDH-UHFFFAOYSA-N 0.000 description 1
- XFTUDCJRXMYXDL-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxyphenyl]methyl 2-methylpropanoate Chemical compound C=1C(COC(=O)C(C)C)=CC=C(OCC=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 XFTUDCJRXMYXDL-UHFFFAOYSA-N 0.000 description 1
- IDYNFCRMUDQBTD-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-phenylmethoxyphenyl]methyl acetate Chemical compound C=1C(COC(C)=O)=CC=C(OCC=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 IDYNFCRMUDQBTD-UHFFFAOYSA-N 0.000 description 1
- INCOYGJLNTWJRS-UHFFFAOYSA-N [3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-propanoyloxyphenyl]methyl propanoate Chemical compound CCC(=O)OCC1=CC=C(OC(=O)CC)C(C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)=C1 INCOYGJLNTWJRS-UHFFFAOYSA-N 0.000 description 1
- ZYYOQPPGPQQGCU-RUZDIDTESA-N [4-(acetyloxymethyl)-2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl] 2-methylpropanoate Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(COC(C)=O)C=2)OC(=O)C(C)C)=CC=CC=C1 ZYYOQPPGPQQGCU-RUZDIDTESA-N 0.000 description 1
- SGRHEKPPVGNDJJ-UHFFFAOYSA-N [4-[tert-butyl(dimethyl)silyl]oxy-3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl]methanol Chemical compound C=1C(CO)=CC=C(O[Si](C)(C)C(C)(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 SGRHEKPPVGNDJJ-UHFFFAOYSA-N 0.000 description 1
- XRMSLYWKSBFYHP-UHFFFAOYSA-N [4-[tert-butyl(diphenyl)silyl]oxy-3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl]methanol Chemical compound C=1C(CO)=CC=C(O[Si](C=2C=CC=CC=2)(C=2C=CC=CC=2)C(C)(C)C)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 XRMSLYWKSBFYHP-UHFFFAOYSA-N 0.000 description 1
- WSFRISHKDDRIBV-UHFFFAOYSA-N [4-acetyloxy-3-[3-[di(propan-2-yl)amino]-1-phenylpropyl]phenyl]methyl acetate Chemical compound C=1C(COC(C)=O)=CC=C(OC(C)=O)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 WSFRISHKDDRIBV-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- WJGAPUXHSQQWQF-UHFFFAOYSA-N acetic acid;hydrochloride Chemical compound Cl.CC(O)=O WJGAPUXHSQQWQF-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- VRAIHTAYLFXSJJ-UHFFFAOYSA-N alumane Chemical compound [AlH3].[AlH3] VRAIHTAYLFXSJJ-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 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
- 230000008901 benefit Effects 0.000 description 1
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 description 1
- 238000006480 benzoylation reaction Methods 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-L benzylidene(dichloro)ruthenium;tricyclohexylphosphane Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1P(C1CCCCC1)C1CCCCC1.C1CCCCC1P(C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-L 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 1
- YJNYGULGSGQMLB-UHFFFAOYSA-N bis[2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] propanedioate Chemical compound C=1C(CO)=CC=C(OC(=O)CC(=O)OC=2C(=CC(CO)=CC=2)C(CCN(C(C)C)C(C)C)C=2C=CC=CC=2)C=1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 YJNYGULGSGQMLB-UHFFFAOYSA-N 0.000 description 1
- 210000005068 bladder tissue Anatomy 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- XNRHTMDHGDWBGP-UHFFFAOYSA-N carbamic acid;hydrochloride Chemical compound Cl.NC(O)=O XNRHTMDHGDWBGP-UHFFFAOYSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- UWCHSDIUMBNDLT-UHFFFAOYSA-L copper;methylsulfanylmethane;dibromide Chemical compound CSC.Br[Cu]Br UWCHSDIUMBNDLT-UHFFFAOYSA-L 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000002178 crystalline material Substances 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
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000005828 desilylation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 108700003601 dimethylglycine Proteins 0.000 description 1
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical class C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229960002854 ephedrine hydrate Drugs 0.000 description 1
- 229960002534 ephedrine hydrochloride Drugs 0.000 description 1
- VEXUDELPDQBTKZ-UHFFFAOYSA-N ethyl 2-[[2-[3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenoxy]carbonylamino]acetate;hydrochloride Chemical compound Cl.CCOC(=O)CNC(=O)OC1=CC=C(CO)C=C1C(CCN(C(C)C)C(C)C)C1=CC=CC=C1 VEXUDELPDQBTKZ-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000002367 glucuronosyl group Chemical group 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- BCDGQXUMWHRQCB-UHFFFAOYSA-N glycine methyl ketone Natural products CC(=O)CN BCDGQXUMWHRQCB-UHFFFAOYSA-N 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical class C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 1
- 150000007928 imidazolide derivatives Chemical class 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002485 inorganic esters Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- FCCDDURTIIUXBY-UHFFFAOYSA-N lipoamide Chemical compound NC(=O)CCCCC1CCSS1 FCCDDURTIIUXBY-UHFFFAOYSA-N 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
- 229960002329 methacholine Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000002032 methanolic fraction Substances 0.000 description 1
- LZCOQTDXKCNBEE-IKIFYQGPSA-N methscopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-IKIFYQGPSA-N 0.000 description 1
- MSJGQLPLCOBFNR-UHFFFAOYSA-N methyl 3-[3-[di(propan-2-yl)amino]-3-oxoprop-1-enyl]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(C=CC(=O)N(C(C)C)C(C)C)=C1 MSJGQLPLCOBFNR-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-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
- 230000027939 micturition Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940078490 n,n-dimethylglycine Drugs 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 150000008379 phenol ethers Chemical class 0.000 description 1
- QIIPQYDSKRYMFG-UHFFFAOYSA-N phenyl hydrogen carbonate Chemical compound OC(=O)OC1=CC=CC=C1 QIIPQYDSKRYMFG-UHFFFAOYSA-N 0.000 description 1
- 125000000405 phenylalanyl group Chemical group 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- NIXKBAZVOQAHGC-UHFFFAOYSA-N phenylmethanesulfonic acid Chemical compound OS(=O)(=O)CC1=CC=CC=C1 NIXKBAZVOQAHGC-UHFFFAOYSA-N 0.000 description 1
- 229950009195 phenylpropanol Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 231100000245 skin permeability Toxicity 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical group CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 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
- 238000011200 topical administration Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- KOZCZZVUFDCZGG-UHFFFAOYSA-N vinyl benzoate Chemical compound C=COC(=O)C1=CC=CC=C1 KOZCZZVUFDCZGG-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/62—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C219/28—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton having amino groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/42—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/44—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/42—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/52—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C307/02—Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Luminescent Compositions (AREA)
- Heat Sensitive Colour Forming Recording (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Photoreceptors In Electrophotography (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98108608A EP0957073A1 (en) | 1998-05-12 | 1998-05-12 | Novel derivatives of 3,3-diphenylpropylamines |
PCT/EP1999/003212 WO1999058478A1 (en) | 1998-05-12 | 1999-05-11 | Novel derivatives of 3,3-diphenylpropylamines |
Publications (2)
Publication Number | Publication Date |
---|---|
SK15472000A3 SK15472000A3 (sk) | 2001-06-11 |
SK286052B6 true SK286052B6 (sk) | 2008-02-05 |
Family
ID=8231918
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1547-2000A SK286052B6 (sk) | 1998-05-12 | 1999-05-11 | 3,3-difenylpropylamíny, farmaceutické prostriedky, spôsob ich výroby a použitie |
Country Status (32)
Country | Link |
---|---|
US (6) | US6713464B1 (pt) |
EP (3) | EP0957073A1 (pt) |
JP (3) | JP3929702B2 (pt) |
KR (1) | KR100599004B1 (pt) |
CN (2) | CN1207268C (pt) |
AT (1) | ATE220056T1 (pt) |
AU (1) | AU748057B2 (pt) |
BR (1) | BRPI9910406B8 (pt) |
CA (1) | CA2328920C (pt) |
CY (1) | CY2007024I2 (pt) |
CZ (2) | CZ299721B6 (pt) |
DE (2) | DE122007000065I2 (pt) |
DK (1) | DK1077912T3 (pt) |
ES (1) | ES2181443T3 (pt) |
FR (1) | FR07C0050I2 (pt) |
GE (1) | GEP20084461B (pt) |
HK (2) | HK1046269B (pt) |
HU (2) | HU226490B1 (pt) |
IL (1) | IL139110A0 (pt) |
IS (1) | IS2044B (pt) |
LU (1) | LU91365I2 (pt) |
MX (1) | MXPA00011096A (pt) |
NL (1) | NL300293I2 (pt) |
NO (2) | NO326872B1 (pt) |
NZ (1) | NZ507487A (pt) |
PL (3) | PL218882B1 (pt) |
PT (1) | PT1077912E (pt) |
RU (1) | RU2199525C2 (pt) |
SK (1) | SK286052B6 (pt) |
TR (1) | TR200003319T2 (pt) |
WO (1) | WO1999058478A1 (pt) |
ZA (1) | ZA200005728B (pt) |
Families Citing this family (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0957073A1 (en) | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
DE19955190A1 (de) * | 1999-11-16 | 2001-06-21 | Sanol Arznei Schwarz Gmbh | Stabile Salze neuartiger Derivate von 3,3-Diphenylpropylaminen |
SE9904850D0 (sv) * | 1999-12-30 | 1999-12-30 | Pharmacia & Upjohn Ab | Novel process and intermediates |
DE10028443C1 (de) * | 2000-06-14 | 2002-05-29 | Sanol Arznei Schwarz Gmbh | Verfahren zur Herstellung von 3,3-Diarylpropylaminen, (R,S)- und (R)-4-Phenyl-2-chromanon-6-carbonsäure sowie (R)-4-Phenyl-2-chromanon-carbonsäure-cinchonidinsalz und deren Verwendung zur Herstellung eines rechtsdrehenden Hydroxybenzylalkohols und von pharmazeutischen Zusammensetzungen |
DE10033016A1 (de) * | 2000-07-07 | 2002-01-24 | Sanol Arznei Schwarz Gmbh | Verfahren zur Herstellung von 3,3-Diarylpropylaminen |
EP1424079A1 (en) * | 2002-11-27 | 2004-06-02 | Boehringer Ingelheim International GmbH | Combination of a beta-3-receptor agonist and of a reuptake inhibitor of serotonin and/or norepinephrine |
DE10315878B4 (de) * | 2003-04-08 | 2009-06-04 | Schwarz Pharma Ag | Vorrichtung zur transdermalen Verabreichung von Fesoterodin und Verwendung |
DE10315917A1 (de) | 2003-04-08 | 2004-11-18 | Schwarz Pharma Ag | Hochreine Basen von 3,3-Diphenylpropylaminmonoestern |
WO2004091597A2 (en) * | 2003-04-15 | 2004-10-28 | Pharmacia & Upjohn Company Llc | Method of treating irritable bowel syndrome (ibs) |
EP1620389A1 (en) * | 2003-04-25 | 2006-02-01 | Pharmacia & Upjohn Company LLC | Halogen substituted 3,3-diphenylpropylamines (tolterodine) having antimuscarinic activity |
ATE545627T1 (de) | 2003-05-23 | 2012-03-15 | Bridge Pharma Inc | Glattmuskelspasmolytika |
WO2005012227A2 (en) * | 2003-08-05 | 2005-02-10 | Ranbaxy Laboratories Limited | Process for preparation of 2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxymethyl-phenol, a metabolite of tolterodine |
WO2007039918A1 (en) * | 2005-10-06 | 2007-04-12 | Natco Pharma Limited | Novel process for the preparation of tolterodine |
KR20080076961A (ko) * | 2005-12-20 | 2008-08-20 | 화이자 프로덕츠 인크. | Pde5 억제제 및 무스카린성 길항제를 포함하는luts의 치료를 위한 약제학적 조합물 |
US8119667B2 (en) * | 2005-12-29 | 2012-02-21 | Schering-Plough Animal Health Corporation | Carbonates of fenicol antibiotics |
US8067594B2 (en) * | 2006-05-24 | 2011-11-29 | Pfizer Inc. | Process for the production of benzopyran-2-ol derivatives |
CN101454273B (zh) * | 2006-05-31 | 2013-08-21 | 施瓦茨制药有限公司 | 取代的羟甲基苯酚的合成方法 |
EP1862449A1 (en) * | 2006-05-31 | 2007-12-05 | Schwarz Pharma Ltd. | A shortened synthesis of substituted hydroxymethyl phenols |
IES20060424A2 (en) | 2006-06-08 | 2007-10-31 | Schwarz Pharma Ltd | Accelerated synthesis of (3-Diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)phenol and its phenolic monoesters |
CA2648333C (en) * | 2006-06-09 | 2014-04-29 | Schwarz Pharma Ltd | Synthesis of phenolic esters of hydroxymethyl phenols |
US7807715B2 (en) | 2006-06-09 | 2010-10-05 | Ucb Pharma Gmbh | Pharmaceutical compositions comprising fesoterodine |
ES2370943T3 (es) * | 2006-06-09 | 2011-12-23 | Ucb Pharma Gmbh | Composiciones farmacéuticas estabilizadas que comprenden fesoterodina. |
CA2647990C (en) * | 2006-06-12 | 2014-02-04 | Claus Meese | New chiral intermediate, process for producing the same and its use in the manufacture of tolterodine, fesoterodine, or the active metabolite thereof |
IES20060435A2 (en) | 2006-06-12 | 2007-12-12 | Schwarz Pharma Ltd | Shortened synthesis using paraformaldehyde or trioxane |
CZ298448B6 (cs) * | 2006-08-09 | 2007-10-03 | Zentiva, A. S. | Farmaceutická kompozice s obsahem tolterodinu |
JP4859255B2 (ja) * | 2006-11-17 | 2012-01-25 | 旭化成ケミカルズ株式会社 | イソシアネートの製造方法 |
TW200844080A (en) | 2007-01-11 | 2008-11-16 | Asahi Kasei Chemicals Corp | Process for producing isocyanate |
WO2008144602A1 (en) * | 2007-05-18 | 2008-11-27 | Auspex Pharmaceuticals, Inc. | Deuterated zamifenacin derivatives |
WO2009006413A1 (en) * | 2007-06-30 | 2009-01-08 | Auspex Pharmaceuticals, Inc. | Substituted pyrrolidines |
US20090062385A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched fesoterodine |
US20090062398A1 (en) * | 2007-08-29 | 2009-03-05 | Protia, Llc | Deuterium-enriched tolterodine |
WO2009037569A2 (en) * | 2007-09-21 | 2009-03-26 | Actavis Group Ptc Ehf | An improved process for the preparation of fesoterodine |
WO2009044278A1 (en) * | 2007-10-01 | 2009-04-09 | Actavis Group Ptc Ehf | Amorphous fesoterodine fumarate |
WO2009058216A1 (en) * | 2007-11-01 | 2009-05-07 | Acucela, Inc. | Amine derivative compounds for treating ophthalmic diseases and disorders |
US20110086103A1 (en) * | 2008-04-04 | 2011-04-14 | Actavis Group Ptc Ehf | Novel mandelate salt of fesoterodine |
EP2275405B1 (en) | 2008-05-15 | 2019-04-24 | Asahi Kasei Kabushiki Kaisha | Process for producing isocyanate using diaryl carbonate |
CN102026965B (zh) | 2008-05-15 | 2014-02-26 | 旭化成化学株式会社 | 异氰酸酯的制造方法 |
US20110171274A1 (en) * | 2008-07-21 | 2011-07-14 | Actavis Group Ptc Ehf | Fesoterodine Substantially Free of Dehydroxy Impurity |
JP5381086B2 (ja) * | 2008-10-06 | 2014-01-08 | 日本電気株式会社 | 通信システム及び通信制御方法 |
PL2416761T3 (pl) | 2009-05-11 | 2015-07-31 | Ratiopharm Gmbh | Desfezoterodyna w postaci soli kwasu winowego |
IT1394219B1 (it) | 2009-05-15 | 2012-06-01 | Chemi Spa | Metodo di preparazione di fesoterodina fumarato di elevata purezza. |
IT1394217B1 (it) | 2009-05-15 | 2012-06-01 | Chemi Spa | Metodo di preparazione di fesoterodina e/o fesoterodina fumarato. |
EP2281801B1 (en) | 2009-07-27 | 2014-01-08 | Crystal Pharma, S.A.U. | Process for obtaining 3,3-diphenylpropylamines |
IT1396373B1 (it) | 2009-10-29 | 2012-11-19 | Dipharma Francis Srl | Procedimento per la preparazione di fesoterodina. |
EP2316432A1 (de) | 2009-10-30 | 2011-05-04 | ratiopharm GmbH | Zusammensetzung enthaltend Fesoterodin und Ballaststoffe |
US20110124903A1 (en) * | 2009-11-20 | 2011-05-26 | Actavis Group Ptc Ehf | Solid state forms of fesoterodine intermediates |
IT1397521B1 (it) | 2009-12-21 | 2013-01-16 | Dipharma Francis Srl | Procedimento per la preparazione di fesoterodina con un basso contenuto di impurezze. |
EP2364966A1 (en) | 2010-03-09 | 2011-09-14 | LEK Pharmaceuticals d.d. | Process for preparation of 3-(2-hydroxy-5-substituted phenyl)-3-phenylpropylamines, intermediates for making hydroxytolterodine |
WO2011117884A1 (en) | 2010-03-22 | 2011-09-29 | Cadila Healthcare Limited | Stable pharmaceutical compositions comprising fesoterodine |
ES2604705T3 (es) | 2010-03-31 | 2017-03-08 | Ono Pharmaceutical Co., Ltd. | Agente preventivo y/o remedio para el síndrome mano-pie |
AU2011245499B2 (en) | 2010-04-30 | 2014-09-25 | Merck Sharp & Dohme Corp. | Novel beta 3 adrenergic receptor agonists |
US20110282094A1 (en) | 2010-05-11 | 2011-11-17 | Intas Pharmaceuticals Limited | Process for preparation of phenolic monoesters of hydroxymethyl phenols |
IT1401451B1 (it) | 2010-06-10 | 2013-07-26 | Chemi Spa | Nuovo processo di preparazione di 2-idrossi-4-fenil-3,4-diidro-2h-cromen-6-il-metanolo e (r)-2-[3-(diisopropilammino)-1-fenilpropil]-4-(idrossimetil)fenolo. |
WO2011158257A1 (en) | 2010-06-18 | 2011-12-22 | Panacea Biotec Ltd | Preparation process of fesoterodine and intermediates |
US9012678B2 (en) * | 2010-08-25 | 2015-04-21 | Cadila Healthcare Limited | Processes for the preparation of fesoterodine |
US8492557B2 (en) * | 2010-09-16 | 2013-07-23 | Allergan, Inc. | Ester pro-drugs of [3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl] methanol |
IT1403094B1 (it) | 2010-12-09 | 2013-10-04 | Dipharma Francis Srl | Procedimento per la preparazione di fesoterodina o un suo sale |
WO2012098560A2 (en) * | 2011-01-17 | 2012-07-26 | Msn Laboratories Limited | Process for the preparation of muscarinic receptor antagonist |
TWI520732B (zh) | 2011-01-18 | 2016-02-11 | 輝瑞有限公司 | 固體分子分散液 |
US9085509B2 (en) | 2011-04-07 | 2015-07-21 | Alembic Pharmaceuticals Limited | Process for preparing fesoterodine |
EP2508173A1 (en) | 2011-04-08 | 2012-10-10 | LEK Pharmaceuticals d.d. | Stabilized pharmaceutical composition comprising fesoterodine |
EP2508175A1 (en) | 2011-04-08 | 2012-10-10 | LEK Pharmaceuticals d.d. | Pharmaceutical composition comprising fesoterodine or a salt or a solvate thereof |
WO2013021343A1 (en) | 2011-08-05 | 2013-02-14 | Ranbaxy Laboratories Limited | Process for the optical resolution of () -3- (2 -benzyloxy- 5 - bromophenyl) - 3 - phenylpropionic |
WO2013046135A1 (en) | 2011-09-26 | 2013-04-04 | Ranbaxy Laboratories Limited | Process for the preparation of fesoterodine or its salts |
EP2800735B1 (en) | 2012-01-07 | 2016-03-30 | Alembic Pharmaceuticals Limited | Process for the preparation of fesoterodine |
CN103304356B (zh) * | 2012-03-12 | 2016-01-20 | 北京乐威泰克医药技术有限公司 | 羟胺的合成方法 |
WO2013113946A2 (en) | 2012-05-04 | 2013-08-08 | Crystal Pharma, S.A.U. | Process for the preparation of optically active 3,3-diphenylpropylamines |
WO2013046194A2 (en) | 2012-05-18 | 2013-04-04 | Alembic Pharmaceuticals Limited | The novel reference markers for fesoterodine fumarate |
ES2569201T3 (es) | 2012-06-14 | 2016-05-09 | Ratiopharm Gmbh | Sales de desfesoterodina |
ITMI20121232A1 (it) * | 2012-07-16 | 2014-01-17 | Cambrex Profarmaco Milano Srl | Procedimento per la preparazione di 2-(3-n,n-diisopropilamino-1-fenilpropil)-4-idrossimetil-fenolo e suoi derivati |
CZ2014400A3 (cs) | 2014-06-09 | 2015-12-16 | Zentiva, K.S. | Stabilizovaná formulace fesoterodinu |
US9751828B2 (en) | 2014-07-30 | 2017-09-05 | Dipharma Francis S.R.L. | Antimuscarinic compound having a low content of impurities |
TR201721437A2 (tr) | 2017-12-25 | 2019-07-22 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Fesoterodi̇ni̇n modi̇fi̇ye salim sağlayan formülasyonlari |
Family Cites Families (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE766207C (de) | 1940-07-08 | 1952-12-22 | Ig Farbenindustrie Ag | Verfahren zur Herstellung von basischen Verbindungen der Diarylmethanreihe |
DE925468C (de) | 1941-08-13 | 1955-03-21 | Hoechst Ag | Verfahren zur Herstellung von ª†, ª†-Diaryl-propyl-aminen |
GB624117A (en) | 1946-12-07 | 1949-05-27 | Wellcome Found | Improvements in and relating to the preparation of substituted allylamines and propylamines |
GB627139A (en) | 1947-05-28 | 1949-07-29 | Wellcome Found | Improvements in and relating to the preparation of quaternary ammonium salts of substituted propanolamines, allylamines and propylamines |
BE497819A (pt) | 1947-10-28 | |||
US2567245A (en) | 1948-05-10 | 1951-09-11 | Schering Corp | Aryl-(2-pyridyl)-amino alkanes and their production |
US2556636A (en) | 1948-06-23 | 1951-06-12 | Schering Corp | gamma-substituted propylamine type antihistamines |
DE830193C (de) | 1948-11-09 | 1952-02-04 | Farbwerke Hoechst Vormals Meis | Verfahren zur Herstellung von basischen Verbindungen |
CH287776A (de) | 1948-11-09 | 1952-12-15 | Michael Dr Erlenbach | Verfahren zur Herstellung einer basischen Verbindung. |
GB685696A (en) | 1948-11-23 | 1953-01-07 | Schering Corp | Process for the manufacture of anti-histaminic compounds |
NL74271C (pt) | 1949-09-05 | |||
US2676964A (en) | 1950-06-07 | 1954-04-27 | Schering Corp | 3-pyridyl propylamine antihistamine substances |
US3261841A (en) | 1961-05-03 | 1966-07-19 | Sterling Drug Inc | N-substituted 1,5-iminocycloalkanes and -alkenes |
US3216841A (en) * | 1962-04-30 | 1965-11-09 | Clevite Corp | Metal slip casting composition |
DK111894A (pt) | 1962-11-15 | |||
GB1025041A (en) | 1964-02-21 | 1966-04-06 | Hoechst Ag | Process for the manufacture of diphenylalkylamines |
GB1169945A (en) | 1966-08-25 | 1969-11-05 | Geistlich Soehne Ag | Pharmaceutical Compositions containing Diphenylalkyl-amine Derivatives |
GB1169944A (en) | 1966-08-25 | 1969-11-05 | Geistlich Soehne Ag | Novel 3,3-Diphenylpropylamines and processes for the preparation thereof |
HU200591B (en) | 1986-07-11 | 1990-07-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing new diphenyl propylamine derivatives and pharmaceutical compositions comprising such compounds |
US5382600A (en) | 1988-01-22 | 1995-01-17 | Pharmacia Aktiebolag | 3,3-diphenylpropylamines and pharmaceutical compositions thereof |
SE8800207D0 (sv) | 1988-01-22 | 1988-01-22 | Kabivitrum Ab | Nya aminer, deras anvendning och framstellning |
US5693144A (en) * | 1990-03-19 | 1997-12-02 | 3D Systems, Inc. | Vibrationally enhanced stereolithographic recoating |
ATE185694T1 (de) | 1992-05-13 | 1999-11-15 | Alza Corp | Oxybutynin zur transdermalen verabreichung |
SE9203318D0 (sv) * | 1992-11-06 | 1992-11-06 | Kabi Pharmacia Ab | Novel 3,3-diphenylpropylamines, their use and preparation |
US6071970A (en) | 1993-02-08 | 2000-06-06 | Nps Pharmaceuticals, Inc. | Compounds active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases |
AU7994694A (en) | 1994-10-21 | 1996-05-15 | Leiras Oy | Controlled release oral delivery system containing oxybutynin |
WO1998003067A1 (en) | 1996-07-19 | 1998-01-29 | Gunnar Aberg | S(-)-tolterodine in the treatment of urinary and gastrointestinal disorders |
WO1998025590A2 (de) | 1996-12-12 | 1998-06-18 | Dds Drug Delivery Service Gesellschaft Zur Förderung Der Forschung In Pharmazeutischer Technologie Und Biopharmazie Mbh | Zubereitung in form eines wahlweise wirkstoffhaltigen matrixmaterial-hilfsstoff compounds |
KR20000057548A (ko) | 1996-12-13 | 2000-09-25 | 알프레드 엘. 미첼슨 | 광학적 전송물질 및 결합재 |
SE9701144D0 (sv) | 1997-03-27 | 1997-03-27 | Pharmacia & Upjohn Ab | Novel compounds, their use and preparation |
EP0872233A1 (en) | 1997-04-14 | 1998-10-21 | Janssen Pharmaceutica N.V. | Antiretroviral compositions with improved bioavailability |
WO1998056359A2 (de) | 1997-06-13 | 1998-12-17 | Roland Bodmeier | Zusammensetzungen, die die wirkstofffreisetzung verzögern |
EP0957073A1 (en) | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
SE9802864D0 (sv) | 1998-08-27 | 1998-08-27 | Pharmacia & Upjohn Ab | Transdermally administered tolterodine as antimuscarinic agent for the treatment of overactive bladder |
SE9803871D0 (sv) | 1998-11-11 | 1998-11-11 | Pharmacia & Upjohn Ab | Therapeutic method and formulation |
CA2311755C (en) | 1998-08-27 | 2010-03-23 | Pharmacia & Upjohn Ab | Therapeutic formulation for administering tolterodine with controlled release |
DE19922662C1 (de) | 1999-05-18 | 2000-12-28 | Sanol Arznei Schwarz Gmbh | Transdermales therapeutisches System (TTS) Tolterodin enthaltend |
ES2245320T3 (es) | 1999-11-11 | 2006-01-01 | Pfizer Health Ab | Formulacion farmaceutica que contiene tolterodina y su uso. |
DE19955190A1 (de) | 1999-11-16 | 2001-06-21 | Sanol Arznei Schwarz Gmbh | Stabile Salze neuartiger Derivate von 3,3-Diphenylpropylaminen |
US6566537B2 (en) | 1999-12-30 | 2003-05-20 | Pharmacia Ab | Process and intermediates |
SE9904850D0 (sv) | 1999-12-30 | 1999-12-30 | Pharmacia & Upjohn Ab | Novel process and intermediates |
DE10028443C1 (de) | 2000-06-14 | 2002-05-29 | Sanol Arznei Schwarz Gmbh | Verfahren zur Herstellung von 3,3-Diarylpropylaminen, (R,S)- und (R)-4-Phenyl-2-chromanon-6-carbonsäure sowie (R)-4-Phenyl-2-chromanon-carbonsäure-cinchonidinsalz und deren Verwendung zur Herstellung eines rechtsdrehenden Hydroxybenzylalkohols und von pharmazeutischen Zusammensetzungen |
DE10033016A1 (de) | 2000-07-07 | 2002-01-24 | Sanol Arznei Schwarz Gmbh | Verfahren zur Herstellung von 3,3-Diarylpropylaminen |
US20030086972A1 (en) | 2000-08-09 | 2003-05-08 | Appel Leah E. | Hydrogel-driven drug dosage form |
AR033711A1 (es) | 2001-05-09 | 2004-01-07 | Novartis Ag | Composiciones farmaceuticas |
US20030027856A1 (en) | 2001-06-29 | 2003-02-06 | Aberg A.K. Gunnar | Tolterodine metabolites |
GB0117619D0 (en) | 2001-07-19 | 2001-09-12 | Phoqus Ltd | Pharmaceutical dosage form |
EP1423700A2 (en) | 2001-09-04 | 2004-06-02 | Pfizer Limited | Affinity-assay for the human erg potassium channel |
JP2005506323A (ja) | 2001-09-05 | 2005-03-03 | ベクトゥラ・リミテッド | 経口送達用機能性散剤 |
WO2003026564A2 (en) | 2001-09-27 | 2003-04-03 | Pharmacia Ab | Pharmaceutical compositions for the treatment of urinary disorders |
JP3981357B2 (ja) | 2001-10-26 | 2007-09-26 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 第4級アンモニウム化合物および抗ムスカリン剤としてのそれらの使用 |
JP2005511582A (ja) | 2001-11-05 | 2005-04-28 | ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー | 抗ムスカリン・エアゾール |
US20030152624A1 (en) | 2001-12-20 | 2003-08-14 | Aldrich Dale S. | Controlled release dosage form having improved drug release properties |
KR100540035B1 (ko) | 2002-02-01 | 2005-12-29 | 주식회사 태평양 | 다단계 경구 약물 방출 제어 시스템 |
DE10224107A1 (de) | 2002-05-29 | 2003-12-11 | Gruenenthal Gmbh | Kombination ausgewählter Opioide mit anderen Wirkstoffen zur Therapie der Harninkontinenz |
CN1674877A (zh) | 2002-06-07 | 2005-09-28 | 兰贝克赛实验室有限公司 | 控释的多单位药物释放系统 |
ITMI20021329A1 (it) | 2002-06-14 | 2003-12-15 | Recordati Chem Pharm | Nuove ossialchilammine sostituite |
WO2004019892A2 (en) | 2002-08-30 | 2004-03-11 | Watson Pharmaceuticals, Inc. | Drug delivery system for treating urinary incontinence |
TW200408955A (en) | 2002-09-30 | 2004-06-01 | Advent Networks Inc | Implementing request/reply programming semantics using publish/subscribe middleware |
DE10315917A1 (de) * | 2003-04-08 | 2004-11-18 | Schwarz Pharma Ag | Hochreine Basen von 3,3-Diphenylpropylaminmonoestern |
DE10315878B4 (de) * | 2003-04-08 | 2009-06-04 | Schwarz Pharma Ag | Vorrichtung zur transdermalen Verabreichung von Fesoterodin und Verwendung |
EP1620389A1 (en) | 2003-04-25 | 2006-02-01 | Pharmacia & Upjohn Company LLC | Halogen substituted 3,3-diphenylpropylamines (tolterodine) having antimuscarinic activity |
-
1998
- 1998-05-12 EP EP98108608A patent/EP0957073A1/en not_active Withdrawn
-
1999
- 1999-05-11 RU RU2000125813/04A patent/RU2199525C2/ru active Protection Beyond IP Right Term
- 1999-05-11 CN CNB998060380A patent/CN1207268C/zh not_active Expired - Lifetime
- 1999-05-11 HU HU0100779A patent/HU226490B1/hu active Protection Beyond IP Right Term
- 1999-05-11 JP JP2000548284A patent/JP3929702B2/ja not_active Expired - Lifetime
- 1999-05-11 DE DE122007000065C patent/DE122007000065I2/de active Active
- 1999-05-11 HU HU0600760A patent/HU230434B1/hu unknown
- 1999-05-11 CA CA002328920A patent/CA2328920C/en not_active Expired - Lifetime
- 1999-05-11 MX MXPA00011096A patent/MXPA00011096A/es unknown
- 1999-05-11 IL IL13911099A patent/IL139110A0/xx active Protection Beyond IP Right Term
- 1999-05-11 NZ NZ507487A patent/NZ507487A/xx not_active IP Right Cessation
- 1999-05-11 PT PT99924929T patent/PT1077912E/pt unknown
- 1999-05-11 PL PL380733A patent/PL218882B1/pl unknown
- 1999-05-11 PL PL99347823A patent/PL195581B1/pl unknown
- 1999-05-11 KR KR1020007012653A patent/KR100599004B1/ko active IP Right Grant
- 1999-05-11 CN CNB2005100702999A patent/CN100491336C/zh not_active Expired - Lifetime
- 1999-05-11 EP EP99924929A patent/EP1077912B1/en not_active Expired - Lifetime
- 1999-05-11 DE DE69902037T patent/DE69902037T2/de not_active Expired - Lifetime
- 1999-05-11 SK SK1547-2000A patent/SK286052B6/sk not_active IP Right Cessation
- 1999-05-11 EP EP02013481A patent/EP1254890A1/en not_active Withdrawn
- 1999-05-11 US US09/700,094 patent/US6713464B1/en not_active Expired - Lifetime
- 1999-05-11 ES ES99924929T patent/ES2181443T3/es not_active Expired - Lifetime
- 1999-05-11 CZ CZ20060029A patent/CZ299721B6/cs not_active IP Right Cessation
- 1999-05-11 TR TR2000/03319T patent/TR200003319T2/xx unknown
- 1999-05-11 WO PCT/EP1999/003212 patent/WO1999058478A1/en active IP Right Grant
- 1999-05-11 DK DK99924929T patent/DK1077912T3/da active
- 1999-05-11 PL PL380081A patent/PL202489B1/pl unknown
- 1999-05-11 BR BRPI9910406A patent/BRPI9910406B8/pt not_active IP Right Cessation
- 1999-05-11 CZ CZ20003774A patent/CZ296605B6/cs not_active IP Right Cessation
- 1999-05-11 AT AT99924929T patent/ATE220056T1/de active
- 1999-05-11 AU AU41412/99A patent/AU748057B2/en not_active Expired
-
2000
- 2000-10-17 ZA ZA200005728A patent/ZA200005728B/xx unknown
- 2000-10-17 IS IS5670A patent/IS2044B/is unknown
- 2000-11-10 NO NO20005669A patent/NO326872B1/no not_active IP Right Cessation
-
2002
- 2002-10-30 HK HK02107859.3A patent/HK1046269B/zh not_active IP Right Cessation
-
2004
- 2004-01-27 US US10/766,263 patent/US7230030B2/en not_active Expired - Lifetime
-
2005
- 2005-08-10 US US11/201,756 patent/US7384980B2/en not_active Expired - Fee Related
-
2006
- 2006-04-11 HK HK06104367.1A patent/HK1084099A1/xx not_active IP Right Cessation
- 2006-10-18 JP JP2006283861A patent/JP4658895B2/ja not_active Expired - Lifetime
-
2007
- 2007-02-20 JP JP2007039857A patent/JP4833884B2/ja not_active Expired - Lifetime
- 2007-09-10 GE GEAP200710260A patent/GEP20084461B/en unknown
- 2007-09-13 NL NL300293C patent/NL300293I2/nl unknown
- 2007-09-14 LU LU91365C patent/LU91365I2/fr unknown
- 2007-10-04 FR FR07C0050C patent/FR07C0050I2/fr active Active
- 2007-10-15 CY CY2007024C patent/CY2007024I2/el unknown
-
2008
- 2008-04-17 US US12/105,016 patent/US7855230B2/en not_active Expired - Fee Related
-
2009
- 2009-07-17 NO NO2009015C patent/NO2009015I2/no unknown
-
2010
- 2010-06-14 US US12/814,982 patent/US7985772B2/en not_active Expired - Fee Related
-
2011
- 2011-06-15 US US13/161,049 patent/US8338478B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SK286052B6 (sk) | 3,3-difenylpropylamíny, farmaceutické prostriedky, spôsob ich výroby a použitie | |
JP2007084552A5 (pt) | ||
US6894076B2 (en) | Esters derived from (RR,SS)-2-hydroxybenzoate of 3-(2-dimethylaminomethyl-1-hydroxycyclohexyl)phenyl | |
US8258179B2 (en) | Crystalline form of a (3S)-aminomethyl-5-methyl-hexanoic acid prodrug and methods of use | |
US9309215B2 (en) | Chiral intermediate, process for producing the same and its use in the manufacture of tolterodine, fesoterodine, or the active metabolite thereof | |
SK10632003A3 (sk) | Inhibítor príjmu monoamínov | |
BRPI9917910B1 (pt) | 3,3-diphenylpropylamine compounds, use of the same, process for the production of phenolic monoesters, process for the preparation of carbonates and carbamates and pharmaceutical composition |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
QB4A | Licence contract registered or granted |
Free format text: EXCLUSIVE LICENCE Name of requester: PFIZER INC., NEW YORK, NY, US Effective date: 20060412 |
|
TC4A | Change of owner's name |
Owner name: UCB PHARMA GMBH, MONHEIM, DE Effective date: 20180502 |
|
MK4A | Patent expired |
Expiry date: 20190511 |