NO317106B1 - 2-aryletyl-(piperidin-4-ylmetyl)aminderivater som muscarin-reseptor antagonister - Google Patents

Info

Publication number

NO317106B1

NO317106B1 NO20004261A NO20004261A NO317106B1 NO 317106 B1 NO317106 B1 NO 317106B1 NO 20004261 A NO20004261 A NO 20004261A NO 20004261 A NO20004261 A NO 20004261A NO 317106 B1 NO317106 B1 NO 317106B1

Authority

NO

Norway

Prior art keywords

methylethyl

ylmethyl

piperidin

amine

ethyl

Prior art date

1998-02-27

Links

• Espacenet
• Global Dossier
• Discuss

• -1 piperidin-4-ylmethyl Chemical group 0.000 title claims description 162
• 150000001412 amines Chemical class 0.000 title claims description 73
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 title abstract description 16
• 150000001875 compounds Chemical class 0.000 claims abstract description 283
• 239000000203 mixture Substances 0.000 claims abstract description 74
• 238000000034 method Methods 0.000 claims abstract description 67
• 150000003839 salts Chemical class 0.000 claims abstract description 22
• 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 14
• 239000003814 drug Substances 0.000 claims abstract description 12
• 238000002360 preparation method Methods 0.000 claims description 81
• 238000006243 chemical reaction Methods 0.000 claims description 80
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 46
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims description 25
• 239000001257 hydrogen Substances 0.000 claims description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 19
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims description 15
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 239000003638 chemical reducing agent Substances 0.000 claims description 13
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• 125000001424 substituent group Chemical group 0.000 claims description 11
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• 229940079593 drug Drugs 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• 230000004048 modification Effects 0.000 claims description 8
• 238000012986 modification Methods 0.000 claims description 8
• 229920006395 saturated elastomer Polymers 0.000 claims description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• 230000009467 reduction Effects 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
• 239000002253 acid Substances 0.000 claims description 5
• 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
• 229910052794 bromium Inorganic materials 0.000 claims description 5
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 239000000654 additive Substances 0.000 claims description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000002757 morpholinyl group Chemical group 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000001301 oxygen Substances 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
• YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 claims description 3
• RDJRIOZXPOIIJA-UHFFFAOYSA-N 4-methyl-n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide Chemical compound C=1C=CC(NC(=O)C=2C=CC(C)=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 RDJRIOZXPOIIJA-UHFFFAOYSA-N 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• 238000010511 deprotection reaction Methods 0.000 claims description 3
• QAHJUTBPGXSPCC-SFHVURJKSA-N n-[3-[4-[[[(2s)-1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl]-ethylamino]methyl]piperidin-1-yl]-3-oxopropyl]methanesulfonamide Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(C(=O)CCNS(C)(=O)=O)CC1 QAHJUTBPGXSPCC-SFHVURJKSA-N 0.000 claims description 3
• 230000008569 process Effects 0.000 claims description 3
• ALRQEPDILNRIMT-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-5-yl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-n-propylpropan-2-amine Chemical compound C=1C=C2OCCC2=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 ALRQEPDILNRIMT-UHFFFAOYSA-N 0.000 claims description 2
• VMPIQPNZNZOWAB-UHFFFAOYSA-N 4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]-n,n-dimethylpiperidine-1-carboxamide Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC1CCN(C(=O)N(C)C)CC1 VMPIQPNZNZOWAB-UHFFFAOYSA-N 0.000 claims description 2
• RIBAXXIYZLISAM-UHFFFAOYSA-N 4-methoxy-n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide Chemical compound C=1C=CC(NC(=O)C=2C=CC(OC)=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 RIBAXXIYZLISAM-UHFFFAOYSA-N 0.000 claims description 2
• RJSYPKWVIJGNLO-UHFFFAOYSA-N CCOClOC Chemical compound CCOClOC RJSYPKWVIJGNLO-UHFFFAOYSA-N 0.000 claims description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
• YRVAVJKNANTQRT-UHFFFAOYSA-N [4-[[1-(2,3-dihydro-1,4-benzodioxin-6-yl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C2OCCOC2=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 YRVAVJKNANTQRT-UHFFFAOYSA-N 0.000 claims description 2
• NPFVCJFOGGKLLC-UHFFFAOYSA-N [4-[[1-(2,3-dihydro-1-benzofuran-6-yl)propan-2-yl-propylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C2CCOC2=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 NPFVCJFOGGKLLC-UHFFFAOYSA-N 0.000 claims description 2
• HBVWMOGNXHPWGZ-UHFFFAOYSA-N [4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-piperidin-1-ylmethanone Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCCCC1 HBVWMOGNXHPWGZ-UHFFFAOYSA-N 0.000 claims description 2
• QISPLRIIUGYCCV-UHFFFAOYSA-N [4-[[ethyl-[1-[4-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-piperidin-1-ylmethanone Chemical compound C=1C=C(C(F)(F)F)C=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCCCC1 QISPLRIIUGYCCV-UHFFFAOYSA-N 0.000 claims description 2
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
• 239000004305 biphenyl Substances 0.000 claims description 2
• 235000010290 biphenyl Nutrition 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
• WADLOJAPSURZGG-UHFFFAOYSA-N morpholin-4-yl-[4-[[propyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]methanone Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 WADLOJAPSURZGG-UHFFFAOYSA-N 0.000 claims description 2
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 2
• 125000004193 piperazinyl group Chemical group 0.000 claims description 2
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• 125000001544 thienyl group Chemical group 0.000 claims description 2
• 125000001425 triazolyl group Chemical group 0.000 claims description 2
• HBIQGZJAYAPOFD-UHFFFAOYSA-N 3,4-dihydro-2h-1,5-naphthyridin-1-yl-[4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]methanone Chemical compound C1CN(C(=O)N2C3=CC=CN=C3CCC2)CCC1CN(CC)C(C)CC1=CC=CC(C(F)(F)F)=C1 HBIQGZJAYAPOFD-UHFFFAOYSA-N 0.000 claims 1
• UKWFQJXUZNUXMU-UHFFFAOYSA-N 4-[[ethyl-[1-[4-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]-n,n-dimethylpiperidine-1-carboxamide Chemical compound C=1C=C(C(F)(F)F)C=CC=1CC(C)N(CC)CC1CCN(C(=O)N(C)C)CC1 UKWFQJXUZNUXMU-UHFFFAOYSA-N 0.000 claims 1
• WIFKFHIASQHPNT-UHFFFAOYSA-N [4-[[1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C2OCCC2=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 WIFKFHIASQHPNT-UHFFFAOYSA-N 0.000 claims 1
• DLMOQDVDJCDVCV-UHFFFAOYSA-N [4-[[1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl-propylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C2OCCC2=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 DLMOQDVDJCDVCV-UHFFFAOYSA-N 0.000 claims 1
• RPBIKTHAVXDAIP-UHFFFAOYSA-N [4-[[1-(3,3-dimethyl-2h-1-benzofuran-6-yl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C(C(CO2)(C)C)C2=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 RPBIKTHAVXDAIP-UHFFFAOYSA-N 0.000 claims 1
• BTSVMLPWCFPJJL-UHFFFAOYSA-N ethoxy-methoxy-propoxy-lambda3-chlorane Chemical compound CCCOCl(OC)OCC BTSVMLPWCFPJJL-UHFFFAOYSA-N 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 125000001624 naphthyl group Chemical group 0.000 claims 1
• 239000011593 sulfur Substances 0.000 claims 1
• 229910052717 sulfur Inorganic materials 0.000 claims 1
• 239000003149 muscarinic antagonist Substances 0.000 abstract description 3
• 229940124597 therapeutic agent Drugs 0.000 abstract description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 189
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 103
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
• 239000000243 solution Substances 0.000 description 77
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 62
• 239000002904 solvent Substances 0.000 description 59
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
• 230000002829 reductive effect Effects 0.000 description 45
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 23
• 239000003921 oil Substances 0.000 description 22
• 235000019198 oils Nutrition 0.000 description 22
• 239000003960 organic solvent Substances 0.000 description 21
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
• 239000012044 organic layer Substances 0.000 description 18
• 239000012074 organic phase Substances 0.000 description 18
• 239000002585 base Substances 0.000 description 17
• 239000000843 powder Substances 0.000 description 17
• 239000007787 solid Substances 0.000 description 17
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• 239000003795 chemical substances by application Substances 0.000 description 15
• 239000002775 capsule Substances 0.000 description 13
• 239000000543 intermediate Substances 0.000 description 13
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 239000000460 chlorine Substances 0.000 description 12
• 229910052801 chlorine Inorganic materials 0.000 description 12
• 238000010992 reflux Methods 0.000 description 12
• 239000000741 silica gel Substances 0.000 description 12
• 229910002027 silica gel Inorganic materials 0.000 description 12
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• 238000003818 flash chromatography Methods 0.000 description 11
• 239000012280 lithium aluminium hydride Substances 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• 238000006268 reductive amination reaction Methods 0.000 description 11
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• 239000004615 ingredient Substances 0.000 description 10
• 150000002576 ketones Chemical class 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 9
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
• 239000004480 active ingredient Substances 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• HRVXPXCISZSDCC-UHFFFAOYSA-N piperidine-4-carbaldehyde Chemical compound O=CC1CCNCC1 HRVXPXCISZSDCC-UHFFFAOYSA-N 0.000 description 9
• 229910000029 sodium carbonate Inorganic materials 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 150000008282 halocarbons Chemical class 0.000 description 8
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
• 229910052938 sodium sulfate Inorganic materials 0.000 description 8
• 235000011152 sodium sulphate Nutrition 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• 150000001299 aldehydes Chemical class 0.000 description 7
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• 238000002474 experimental method Methods 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• HYDZLHMFYXHQRK-HNNXBMFYSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-ethyl-n-(piperidin-4-ylmethyl)propan-2-amine Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCNCC1 HYDZLHMFYXHQRK-HNNXBMFYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 230000008602 contraction Effects 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 230000008020 evaporation Effects 0.000 description 6
• 230000002401 inhibitory effect Effects 0.000 description 6
• 230000028327 secretion Effects 0.000 description 6
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
• 241000282472 Canis lupus familiaris Species 0.000 description 5
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
• 230000010933 acylation Effects 0.000 description 5
• 238000005917 acylation reaction Methods 0.000 description 5
• 230000001476 alcoholic effect Effects 0.000 description 5
• 239000003937 drug carrier Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 210000001035 gastrointestinal tract Anatomy 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
• ISJUEAODZJCTHL-UHFFFAOYSA-N n-ethyl-1-(4-methoxyphenyl)-n-(piperidin-4-ylmethyl)propan-2-amine Chemical compound C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCNCC1 ISJUEAODZJCTHL-UHFFFAOYSA-N 0.000 description 5
• WVNSSOJONVOPEF-UHFFFAOYSA-N n-ethyl-1-(4-methoxyphenyl)-n-(piperidin-4-ylmethyl)propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCNCC1 WVNSSOJONVOPEF-UHFFFAOYSA-N 0.000 description 5
• 150000007524 organic acids Chemical class 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 238000006722 reduction reaction Methods 0.000 description 5
• 210000002345 respiratory system Anatomy 0.000 description 5
• 239000007921 spray Substances 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• DUHKKBBESXCBNM-INIZCTEOSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(S(C)(=O)=O)CC1 DUHKKBBESXCBNM-INIZCTEOSA-N 0.000 description 4
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 4
• 239000000908 ammonium hydroxide Substances 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
• 210000003169 central nervous system Anatomy 0.000 description 4
• 229940125810 compound 20 Drugs 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
• XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 4
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000012948 isocyanate Substances 0.000 description 4
• 150000002513 isocyanates Chemical class 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 235000019341 magnesium sulphate Nutrition 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 239000007922 nasal spray Substances 0.000 description 4
• 229940097496 nasal spray Drugs 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 description 4
• 229910052697 platinum Inorganic materials 0.000 description 4
• GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• 239000006188 syrup Substances 0.000 description 4
• 235000020357 syrup Nutrition 0.000 description 4
• 239000002562 thickening agent Substances 0.000 description 4
• 230000000699 topical effect Effects 0.000 description 4
• WDKWVYKURJCBFY-UHFFFAOYSA-N (1-methylsulfonylpiperidin-4-yl)methanol Chemical compound CS(=O)(=O)N1CCC(CO)CC1 WDKWVYKURJCBFY-UHFFFAOYSA-N 0.000 description 3
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 3
• URCSNIJPBZTMBH-UHFFFAOYSA-N 1-(morpholine-4-carbonyl)piperidine-4-carbaldehyde Chemical compound C1CC(C=O)CCN1C(=O)N1CCOCC1 URCSNIJPBZTMBH-UHFFFAOYSA-N 0.000 description 3
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 3
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 3
• HRPDHOOLRWLRAR-UHFFFAOYSA-N 1-methylsulfonylpiperidine-4-carbaldehyde Chemical compound CS(=O)(=O)N1CCC(C=O)CC1 HRPDHOOLRWLRAR-UHFFFAOYSA-N 0.000 description 3
• VHCSBTPOPKFYIU-UHFFFAOYSA-N 2-chloroethanesulfonyl chloride Chemical compound ClCCS(Cl)(=O)=O VHCSBTPOPKFYIU-UHFFFAOYSA-N 0.000 description 3
• OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 3
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
• BRNXXXCBZXNYEW-HNNXBMFYSA-N 4-[[[(2s)-1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl]-ethylamino]methyl]piperidine-1-sulfonyl chloride Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(S(Cl)(=O)=O)CC1 BRNXXXCBZXNYEW-HNNXBMFYSA-N 0.000 description 3
• 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 description 3
• 241000220479 Acacia Species 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 229930003347 Atropine Natural products 0.000 description 3
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 239000007868 Raney catalyst Substances 0.000 description 3
• 229910000564 Raney nickel Inorganic materials 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 3
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000007900 aqueous suspension Substances 0.000 description 3
• 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 3
• 229960000396 atropine Drugs 0.000 description 3
• SJSWRKNSCWKNIR-UHFFFAOYSA-N azane;dihydrochloride Chemical compound N.Cl.Cl SJSWRKNSCWKNIR-UHFFFAOYSA-N 0.000 description 3
• 230000027455 binding Effects 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 150000001805 chlorine compounds Chemical class 0.000 description 3
• 235000015165 citric acid Nutrition 0.000 description 3
• 239000003086 colorant Substances 0.000 description 3
• 229940127204 compound 29 Drugs 0.000 description 3
• 239000006071 cream Substances 0.000 description 3
• RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• ZEISHOJDDIABID-UHFFFAOYSA-N ethyl 1-methylsulfonylpiperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN(S(C)(=O)=O)CC1 ZEISHOJDDIABID-UHFFFAOYSA-N 0.000 description 3
• 230000000763 evoking effect Effects 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 235000013355 food flavoring agent Nutrition 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 3
• SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 3
• 239000007937 lozenge Substances 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• 229910052749 magnesium Inorganic materials 0.000 description 3
• 230000004899 motility Effects 0.000 description 3
• 210000005036 nerve Anatomy 0.000 description 3
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 210000003296 saliva Anatomy 0.000 description 3
• 210000002460 smooth muscle Anatomy 0.000 description 3
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
• 150000003461 sulfonyl halides Chemical class 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• SVUVJFRHSCTKBT-KRWDZBQOSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-[(1-ethenylsulfonylpiperidin-4-yl)methyl]-n-ethylpropan-2-amine Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(S(=O)(=O)C=C)CC1 SVUVJFRHSCTKBT-KRWDZBQOSA-N 0.000 description 2
• RTMLDMNOFWWYEC-YYLIZZNMSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-[(1s)-1-phenylethyl]propan-2-amine;hydrochloride Chemical compound Cl.C1([C@H](C)N[C@H](CC=2C=C3CCOC3=CC=2)C)=CC=CC=C1 RTMLDMNOFWWYEC-YYLIZZNMSA-N 0.000 description 2
• LBJMQEAGQQCSDW-IRXDYDNUSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-ethyl-n-[(1s)-1-phenylethyl]propan-2-amine Chemical compound C1([C@H](C)N([C@@H](C)CC=2C=C3CCOC3=CC=2)CC)=CC=CC=C1 LBJMQEAGQQCSDW-IRXDYDNUSA-N 0.000 description 2
• DIUULXJKNRMJEH-JTQLQIEISA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-ethylpropan-2-amine Chemical compound CCN[C@@H](C)CC1=CC=C2OCCC2=C1 DIUULXJKNRMJEH-JTQLQIEISA-N 0.000 description 2
• ISJUEAODZJCTHL-HNNXBMFYSA-N (2s)-n-ethyl-1-(4-methoxyphenyl)-n-(piperidin-4-ylmethyl)propan-2-amine Chemical compound CCN([C@@H](C)CC=1C=CC(OC)=CC=1)CC1CCNCC1 ISJUEAODZJCTHL-HNNXBMFYSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
• 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 2
• CCHJWKALXQOFEE-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-one Chemical compound CC(=O)CC1=CC=C2OCCC2=C1 CCHJWKALXQOFEE-UHFFFAOYSA-N 0.000 description 2
• TYFVYHHUWTVZTM-UHFFFAOYSA-N 1-(3-nitrophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=CC([N+]([O-])=O)=C1 TYFVYHHUWTVZTM-UHFFFAOYSA-N 0.000 description 2
• WFWKNGZODAOLEO-UHFFFAOYSA-N 1-(4-Methoxyphenyl)-2-propanone Chemical compound COC1=CC=C(CC(C)=O)C=C1 WFWKNGZODAOLEO-UHFFFAOYSA-N 0.000 description 2
• JXNFENHXHCBSQA-UHFFFAOYSA-N 1-(cyclohexanecarbonyl)piperidine-4-carbaldehyde Chemical compound C1CC(C=O)CCN1C(=O)C1CCCCC1 JXNFENHXHCBSQA-UHFFFAOYSA-N 0.000 description 2
• JWOHBPPVVDQMKB-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)CC1 JWOHBPPVVDQMKB-UHFFFAOYSA-N 0.000 description 2
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 2
• PIAOLBVUVDXHHL-UHFFFAOYSA-N 2-nitroethenylbenzene Chemical compound [O-][N+](=O)C=CC1=CC=CC=C1 PIAOLBVUVDXHHL-UHFFFAOYSA-N 0.000 description 2
• USEGQJLHQSTGHW-UHFFFAOYSA-N 3-bromo-2-methylprop-1-ene Chemical compound CC(=C)CBr USEGQJLHQSTGHW-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
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• MTAGZSVRKHRTEV-IAGOWNOFSA-N 4-[(2r)-2-[[(1r)-1-phenylethyl]-propylamino]propyl]aniline Chemical compound C([C@@H](C)N(CCC)[C@H](C)C=1C=CC=CC=1)C1=CC=C(N)C=C1 MTAGZSVRKHRTEV-IAGOWNOFSA-N 0.000 description 2
• IRJVHZXTHBPUSX-UHFFFAOYSA-N 4-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]aniline Chemical compound C=1C=C(N)C=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 IRJVHZXTHBPUSX-UHFFFAOYSA-N 0.000 description 2
• ZVKYNHQGWSLBEC-OAHLLOKOSA-N 4-methoxy-n-[3-[(2r)-2-(propylamino)propyl]phenyl]benzamide Chemical compound CCCN[C@H](C)CC1=CC=CC(NC(=O)C=2C=CC(OC)=CC=2)=C1 ZVKYNHQGWSLBEC-OAHLLOKOSA-N 0.000 description 2
• VDYXSGARTADIQY-FGZHOGPDSA-N 4-methoxy-n-[3-[(2r)-2-[[(1r)-1-phenylethyl]-propylamino]propyl]phenyl]benzamide Chemical compound C([C@@H](C)N(CCC)[C@H](C)C=1C=CC=CC=1)C(C=1)=CC=CC=1NC(=O)C1=CC=C(OC)C=C1 VDYXSGARTADIQY-FGZHOGPDSA-N 0.000 description 2
• 206010002091 Anaesthesia Diseases 0.000 description 2
• 208000019901 Anxiety disease Diseases 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• 206010012735 Diarrhoea Diseases 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 208000023783 Genitourinary tract disease Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 208000019695 Migraine disease Diseases 0.000 description 2
• 208000006550 Mydriasis Diseases 0.000 description 2
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
• RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 208000028017 Psychotic disease Diseases 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 206010039424 Salivary hypersecretion Diseases 0.000 description 2
• 206010040741 Sinus bradycardia Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
• 229960004373 acetylcholine Drugs 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000000996 additive effect Effects 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 230000037005 anaesthesia Effects 0.000 description 2
• 230000001022 anti-muscarinic effect Effects 0.000 description 2
• 230000036506 anxiety Effects 0.000 description 2
• 230000004872 arterial blood pressure Effects 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• UCAGLBKTLXCODC-UHFFFAOYSA-N carzenide Chemical compound NS(=O)(=O)C1=CC=C(C(O)=O)C=C1 UCAGLBKTLXCODC-UHFFFAOYSA-N 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 229940125898 compound 5 Drugs 0.000 description 2
• 239000000470 constituent Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 230000001186 cumulative effect Effects 0.000 description 2
• 150000001913 cyanates Chemical class 0.000 description 2
• 201000000255 cycloplegia Diseases 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 208000037765 diseases and disorders Diseases 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
• 238000007327 hydrogenolysis reaction Methods 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 239000012442 inert solvent Substances 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 230000036724 intravesical pressure Effects 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 150000002540 isothiocyanates Chemical class 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 239000006210 lotion Substances 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
• 238000004519 manufacturing process Methods 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 206010027599 migraine Diseases 0.000 description 2
• TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical group OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
• RSAFAYLZKCYUQW-UHFFFAOYSA-N n,n-di(propan-2-yl)carbamoyl chloride Chemical compound CC(C)N(C(C)C)C(Cl)=O RSAFAYLZKCYUQW-UHFFFAOYSA-N 0.000 description 2
• SPVAGCCMLGXRDN-UHFFFAOYSA-N n-ethyl-n-[1-(4-methoxyphenyl)propan-2-yl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)N(CC)C(C)CC1=CC=C(OC)C=C1 SPVAGCCMLGXRDN-UHFFFAOYSA-N 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• 210000003928 nasal cavity Anatomy 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 210000001002 parasympathetic nervous system Anatomy 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 235000010603 pastilles Nutrition 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 229920006316 polyvinylpyrrolidine Polymers 0.000 description 2
• 239000013641 positive control Substances 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 2
• 235000019260 propionic acid Nutrition 0.000 description 2
• 239000002287 radioligand Substances 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 208000023504 respiratory system disease Diseases 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical group OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 208000026451 salivation Diseases 0.000 description 2
• 150000003335 secondary amines Chemical class 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• XEOQRCLPHLWMGC-UHFFFAOYSA-N tert-butyl 4-[[1-(4-methoxyphenyl)propan-2-ylamino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1CC(C)NCC1CCN(C(=O)OC(C)(C)C)CC1 XEOQRCLPHLWMGC-UHFFFAOYSA-N 0.000 description 2
• VTYODXPIVJZGCC-SFHVURJKSA-N tert-butyl 4-[[[(2s)-1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl]-ethylamino]methyl]piperidine-1-carboxylate Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(C(=O)OC(C)(C)C)CC1 VTYODXPIVJZGCC-SFHVURJKSA-N 0.000 description 2
• WQSDHVBEUMXOSU-UHFFFAOYSA-N tert-butyl 4-[[ethyl-[1-(4-methoxyphenyl)propan-2-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCN(C(=O)OC(C)(C)C)CC1 WQSDHVBEUMXOSU-UHFFFAOYSA-N 0.000 description 2
• JYUQEWCJWDGCRX-UHFFFAOYSA-N tert-butyl 4-formylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=O)CC1 JYUQEWCJWDGCRX-UHFFFAOYSA-N 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
• RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• WXSRUQJXUYPIPU-PPHPATTJSA-N (2S)-1-(2,3-dihydro-1-benzofuran-5-yl)-N-ethylpropan-2-amine hydrochloride Chemical compound Cl.CCN[C@@H](C)CC1=CC=C2OCCC2=C1 WXSRUQJXUYPIPU-PPHPATTJSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• NHDFFJOAECJVNN-PKLMIRHRSA-N (2r)-n-ethyl-1-(4-methoxyphenyl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.CCN([C@H](C)CC=1C=CC(OC)=CC=1)CC1CCN(S(C)(=O)=O)CC1 NHDFFJOAECJVNN-PKLMIRHRSA-N 0.000 description 1
• FHYLLQHPCSYJDM-XFULWGLBSA-N (2r)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-1-[3-(trifluoromethyl)phenyl]propan-2-amine;hydrochloride Chemical compound Cl.CCN([C@H](C)CC=1C=C(C=CC=1)C(F)(F)F)CC1CCN(S(C)(=O)=O)CC1 FHYLLQHPCSYJDM-XFULWGLBSA-N 0.000 description 1
• WMTTTXMRJKGYBR-LMOVPXPDSA-N (2s)-1-(2,2-dimethyl-3h-1-benzofuran-5-yl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.CCN([C@@H](C)CC=1C=C2CC(C)(C)OC2=CC=1)CC1CCN(S(C)(=O)=O)CC1 WMTTTXMRJKGYBR-LMOVPXPDSA-N 0.000 description 1
• RJUZRBMVABZEBD-LMOVPXPDSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-n-propylpropan-2-amine;hydrochloride Chemical compound Cl.CCCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(S(C)(=O)=O)CC1 RJUZRBMVABZEBD-LMOVPXPDSA-N 0.000 description 1
• SGGXNZZBBCCAFW-FYZYNONXSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-[[1-[(1,1-dioxo-1,4-thiazinan-4-yl)sulfonyl]piperidin-4-yl]methyl]-n-ethylpropan-2-amine;hydrochloride Chemical compound Cl.CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC(CC1)CCN1S(=O)(=O)N1CCS(=O)(=O)CC1 SGGXNZZBBCCAFW-FYZYNONXSA-N 0.000 description 1
• SURJVFASQDLOLQ-IBGZPJMESA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-ethyl-n-[(1-morpholin-4-ylsulfonylpiperidin-4-yl)methyl]propan-2-amine Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC(CC1)CCN1S(=O)(=O)N1CCOCC1 SURJVFASQDLOLQ-IBGZPJMESA-N 0.000 description 1
• UKWJOTGDTMMDAN-FYZYNONXSA-N (2s)-1-(2,3-dihydro-1-benzofuran-5-yl)-n-ethyl-n-[(1-thiomorpholin-4-ylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC(CC1)CCN1S(=O)(=O)N1CCSCC1 UKWJOTGDTMMDAN-FYZYNONXSA-N 0.000 description 1
• BBPYJTDLBUIKNE-NTISSMGPSA-N (2s)-1-(3,4-dimethoxyphenyl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.CCN([C@@H](C)CC=1C=C(OC)C(OC)=CC=1)CC1CCN(S(C)(=O)=O)CC1 BBPYJTDLBUIKNE-NTISSMGPSA-N 0.000 description 1
• QBSBABILDKSBHW-RSAXXLAASA-N (2s)-1-(3-chlorophenyl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.CCN([C@@H](C)CC=1C=C(Cl)C=CC=1)CC1CCN(S(C)(=O)=O)CC1 QBSBABILDKSBHW-RSAXXLAASA-N 0.000 description 1
• OQBPURBYLUEFOZ-PPHPATTJSA-N (2s)-1-(4-chlorophenyl)-n-propylpropan-2-amine;hydrochloride Chemical compound Cl.CCCN[C@@H](C)CC1=CC=C(Cl)C=C1 OQBPURBYLUEFOZ-PPHPATTJSA-N 0.000 description 1
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
• KWQLOEWGKCQLPR-PPHPATTJSA-N (2s)-n-ethyl-1-(4-methoxyphenyl)propan-2-amine;hydrochloride Chemical compound Cl.CCN[C@@H](C)CC1=CC=C(OC)C=C1 KWQLOEWGKCQLPR-PPHPATTJSA-N 0.000 description 1
• FHYLLQHPCSYJDM-RSAXXLAASA-N (2s)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-1-[3-(trifluoromethyl)phenyl]propan-2-amine;hydrochloride Chemical compound Cl.CCN([C@@H](C)CC=1C=C(C=CC=1)C(F)(F)F)CC1CCN(S(C)(=O)=O)CC1 FHYLLQHPCSYJDM-RSAXXLAASA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• GXTSJSXEUCLGEO-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2OCOC2=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 GXTSJSXEUCLGEO-UHFFFAOYSA-N 0.000 description 1
• SMKHYULRXXOSGM-UHFFFAOYSA-N 1-(1-benzofuran-5-yl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2OC=CC2=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 SMKHYULRXXOSGM-UHFFFAOYSA-N 0.000 description 1
• KEHYRMWPEFEFJT-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-n-propan-2-ylpropan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2OCCOC2=CC=1CC(C)N(C(C)C)CC1CCN(S(C)(=O)=O)CC1 KEHYRMWPEFEFJT-UHFFFAOYSA-N 0.000 description 1
• BFKLAWTZFOQYTK-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2OCCOC2=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 BFKLAWTZFOQYTK-UHFFFAOYSA-N 0.000 description 1
• RJUZRBMVABZEBD-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-5-yl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-n-propylpropan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2OCCC2=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 RJUZRBMVABZEBD-UHFFFAOYSA-N 0.000 description 1
• SQSRPOOEPAKODL-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-6-yl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-n-propylpropan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2CCOC2=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 SQSRPOOEPAKODL-UHFFFAOYSA-N 0.000 description 1
• TVYBTKTWPIWSJP-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-6-yl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2CCOC2=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 TVYBTKTWPIWSJP-UHFFFAOYSA-N 0.000 description 1
• JQQUHDYNNPCXBI-UHFFFAOYSA-N 1-(3,4-dihydro-2h-chromen-6-yl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2OCCCC2=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 JQQUHDYNNPCXBI-UHFFFAOYSA-N 0.000 description 1
• QBSBABILDKSBHW-UHFFFAOYSA-N 1-(3-chlorophenyl)-n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=CC(Cl)=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 QBSBABILDKSBHW-UHFFFAOYSA-N 0.000 description 1
• HPHJIDVLKJJTQL-UHFFFAOYSA-N 1-(4-bromophenyl)-n-ethylpropan-2-amine;hydrochloride Chemical compound Cl.CCNC(C)CC1=CC=C(Br)C=C1 HPHJIDVLKJJTQL-UHFFFAOYSA-N 0.000 description 1
• CFMMTXJMIJRUSH-UHFFFAOYSA-N 1-(4-bromophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=C(Br)C=C1 CFMMTXJMIJRUSH-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• RUCHULLNCOPNQD-UHFFFAOYSA-N 1-[2-[2-[ethyl-[(1-methylsulfonylpiperidin-4-yl)methyl]amino]propyl]phenyl]-3-propan-2-ylurea;hydrochloride Chemical compound Cl.C=1C=CC=C(NC(=O)NC(C)C)C=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 RUCHULLNCOPNQD-UHFFFAOYSA-N 0.000 description 1
• PDLAPSHMQFXQPL-UHFFFAOYSA-N 1-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]-3-phenylurea;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)NC=2C=CC=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 PDLAPSHMQFXQPL-UHFFFAOYSA-N 0.000 description 1
• YOYDPSHNYRKJHM-UHFFFAOYSA-N 1-[4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidine-1-carbonyl]-2-methylpiperidine-2-carboxylic acid hydrochloride Chemical compound CCN(CC1CCN(CC1)C(=O)N2CCCCC2(C)C(=O)O)C(C)CC3=CC(=CC=C3)C(F)(F)F.Cl YOYDPSHNYRKJHM-UHFFFAOYSA-N 0.000 description 1
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
• AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
• NUDMYXJXBUZNNO-UHFFFAOYSA-N 1-methylsulfonylpiperidine-4-carbonyl chloride Chemical compound CS(=O)(=O)N1CCC(C(Cl)=O)CC1 NUDMYXJXBUZNNO-UHFFFAOYSA-N 0.000 description 1
• KHSYYLCXQKCYQX-UHFFFAOYSA-N 1-naphthalen-2-ylethanamine Chemical compound C1=CC=CC2=CC(C(N)C)=CC=C21 KHSYYLCXQKCYQX-UHFFFAOYSA-N 0.000 description 1
• RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
• IHOYSEGVBAXLFX-UHFFFAOYSA-N 2,2,2-trifluoro-1-[4-[4-[[1-(4-nitrophenyl)propan-2-yl-propylamino]methyl]piperidine-1-carbonyl]-2h-pyridin-1-yl]ethanone;dihydrochloride Chemical compound Cl.Cl.C=1C=C([N+]([O-])=O)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)C1=CCN(C(=O)C(F)(F)F)C=C1 IHOYSEGVBAXLFX-UHFFFAOYSA-N 0.000 description 1
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical group C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
• QYNIWAXTDRAODF-UHFFFAOYSA-N 2-methoxy-5-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]benzenesulfonamide;hydrochloride Chemical compound Cl.C=1C=C(OC)C(S(N)(=O)=O)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 QYNIWAXTDRAODF-UHFFFAOYSA-N 0.000 description 1
• PEXSKFKBLLRDMS-UHFFFAOYSA-N 2-methyl-n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]propanamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C(C)C)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 PEXSKFKBLLRDMS-UHFFFAOYSA-N 0.000 description 1
• UVKQFTMBPPLKTD-UHFFFAOYSA-N 3,4-dihydro-2h-quinolin-1-yl-[4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]methanone;hydrochloride Chemical compound Cl.C1CN(C(=O)N2C3=CC=CC=C3CCC2)CCC1CN(CC)C(C)CC1=CC=CC(C(F)(F)F)=C1 UVKQFTMBPPLKTD-UHFFFAOYSA-N 0.000 description 1
• XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
• ROXNGYJOKSANKT-UHFFFAOYSA-N 3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]aniline Chemical compound C=1C=CC(N)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 ROXNGYJOKSANKT-UHFFFAOYSA-N 0.000 description 1
• YDBURRVFWABAFA-KRWDZBQOSA-N 3-amino-1-[4-[[[(2s)-1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl]-ethylamino]methyl]piperidin-1-yl]propan-1-one Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(C(=O)CCN)CC1 YDBURRVFWABAFA-KRWDZBQOSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• GPKDGVXBXQTHRY-UHFFFAOYSA-N 3-chloropropane-1-sulfonyl chloride Chemical compound ClCCCS(Cl)(=O)=O GPKDGVXBXQTHRY-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• YUYFWMMSKWFXBD-UHFFFAOYSA-N 3-methoxy-n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide Chemical compound C=1C=CC(NC(=O)C=2C=C(OC)C=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 YUYFWMMSKWFXBD-UHFFFAOYSA-N 0.000 description 1
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 description 1
• DKTUJINXJITHRT-UHFFFAOYSA-N 4-[[1-(2,3-dihydro-1,4-benzodioxin-6-yl)propan-2-yl-ethylamino]methyl]-n,n-dimethylpiperidine-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=C2OCCOC2=CC=1CC(C)N(CC)CC1CCN(C(=O)N(C)C)CC1 DKTUJINXJITHRT-UHFFFAOYSA-N 0.000 description 1
• LVZIFHXIUJGBFM-UHFFFAOYSA-N 4-[[1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl-ethylamino]methyl]-n,n-dimethylpiperidine-1-carboxamide Chemical compound C=1C=C2OCCC2=CC=1CC(C)N(CC)CC1CCN(C(=O)N(C)C)CC1 LVZIFHXIUJGBFM-UHFFFAOYSA-N 0.000 description 1
• NWRNSALAOJMELG-UHFFFAOYSA-N 4-[[1-[3-(3h-1,2-benzodioxole-5-carbonylamino)phenyl]propan-2-yl-propylamino]methyl]-n-methylpiperidine-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=C3COOC3=CC=2)=CC=1CC(C)N(CCC)CC1CCN(C(=O)NC)CC1 NWRNSALAOJMELG-UHFFFAOYSA-N 0.000 description 1
• HDDXRXXFPZJUOY-UHFFFAOYSA-N 4-[[1-[3-[(4-tert-butylbenzoyl)amino]phenyl]propan-2-yl-propylamino]methyl]-n-methylpiperidine-1-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC1CCN(C(=O)NC)CC1 HDDXRXXFPZJUOY-UHFFFAOYSA-N 0.000 description 1
• MWKYONDTBVMDKB-UHFFFAOYSA-N 4-[[1-[3-[(4-tert-butylbenzoyl)amino]phenyl]propan-2-yl-propylamino]methyl]-n-propan-2-ylpiperidine-1-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC1CCN(C(=O)NC(C)C)CC1 MWKYONDTBVMDKB-UHFFFAOYSA-N 0.000 description 1
• AEYNVFQFUBIHBI-UHFFFAOYSA-N 4-[[1-[3-[(4-tert-butylbenzoyl)amino]phenyl]propan-2-yl-propylamino]methyl]piperidine-1-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC1CCN(C(N)=O)CC1 AEYNVFQFUBIHBI-UHFFFAOYSA-N 0.000 description 1
• LHTCPKXIIAMQCY-UHFFFAOYSA-N 4-[[ethyl-[1-(4-methoxyphenyl)propan-2-yl]amino]methyl]-n,n-dimethylpiperidine-1-carboxamide Chemical compound C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCN(C(=O)N(C)C)CC1 LHTCPKXIIAMQCY-UHFFFAOYSA-N 0.000 description 1
• NOCHGSHQSFTHMJ-UHFFFAOYSA-N 4-[[ethyl-[1-(4-methoxyphenyl)propan-2-yl]amino]methyl]-n,n-dimethylpiperidine-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCN(C(=O)N(C)C)CC1 NOCHGSHQSFTHMJ-UHFFFAOYSA-N 0.000 description 1
• YKDPOGUSEZPQRP-UHFFFAOYSA-N 4-[[ethyl-[1-(4-methoxyphenyl)propan-2-yl]amino]methyl]-n-methylpiperidine-1-carboxamide Chemical compound C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCN(C(=O)NC)CC1 YKDPOGUSEZPQRP-UHFFFAOYSA-N 0.000 description 1
• LCCPKSRRJHCSFA-UHFFFAOYSA-N 4-[[ethyl-[1-(4-methoxyphenyl)propan-2-yl]amino]methyl]piperidine-1-carbonyl chloride;hydrochloride Chemical compound Cl.C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCN(C(Cl)=O)CC1 LCCPKSRRJHCSFA-UHFFFAOYSA-N 0.000 description 1
• AXRRJGCAJTYPBS-UHFFFAOYSA-N 4-chloro-n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide Chemical compound C=1C=CC(NC(=O)C=2C=CC(Cl)=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 AXRRJGCAJTYPBS-UHFFFAOYSA-N 0.000 description 1
• GWYGYUVEDDTZPU-ZMBIFBSDSA-N 4-cyano-n-[3-[(2r)-2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]benzamide;hydrochloride Chemical compound Cl.CCCN([C@H](C)CC=1C=C(NC(=O)C=2C=CC(=CC=2)C#N)C=CC=1)CC1CCN(S(C)(=O)=O)CC1 GWYGYUVEDDTZPU-ZMBIFBSDSA-N 0.000 description 1
• LGFNKMFLRCJGHX-UHFFFAOYSA-N 4-ethyl-n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=CC(CC)=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 LGFNKMFLRCJGHX-UHFFFAOYSA-N 0.000 description 1
• UXCGHFVSJBZTES-FQEVSTJZSA-N 4-fluoro-n-[3-[(2s)-2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]benzamide Chemical compound CCCN([C@@H](C)CC=1C=C(NC(=O)C=2C=CC(F)=CC=2)C=CC=1)CC1CCN(S(C)(=O)=O)CC1 UXCGHFVSJBZTES-FQEVSTJZSA-N 0.000 description 1
• FFDQDQZMSLGMSD-QHCPKHFHSA-N 4-fluoro-n-[3-[(2s)-2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide Chemical compound CCCN([C@@H](C)CC=1C=C(NC(=O)C=2C=CC(F)=CC=2)C=CC=1)CC(CC1)CCN1C(=O)N1CCOCC1 FFDQDQZMSLGMSD-QHCPKHFHSA-N 0.000 description 1
• RIBAXXIYZLISAM-XMMPIXPASA-N 4-methoxy-n-[3-[(2r)-2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide Chemical compound CCCN([C@H](C)CC=1C=C(NC(=O)C=2C=CC(OC)=CC=2)C=CC=1)CC(CC1)CCN1C(=O)N1CCOCC1 RIBAXXIYZLISAM-XMMPIXPASA-N 0.000 description 1
• HCJOZVDPIQYERY-UHFFFAOYSA-N 4-methyl-n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]benzenesulfonamide Chemical compound C=1C=CC(NS(=O)(=O)C=2C=CC(C)=CC=2)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 HCJOZVDPIQYERY-UHFFFAOYSA-N 0.000 description 1
• GVWXATKZQKYECR-UHFFFAOYSA-N 4-methylsulfonyl-n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propan-2-ylamino]propyl]phenyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=CC(=CC=2)S(C)(=O)=O)=CC=1CC(C)N(C(C)C)CC(CC1)CCN1C(=O)N1CCOCC1 GVWXATKZQKYECR-UHFFFAOYSA-N 0.000 description 1
• GVXMXVLTPCPYNN-GNAFDRTKSA-N 4-tert-butyl-n-[3-[(2r)-2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]benzamide;hydrochloride Chemical compound Cl.CCCN([C@H](C)CC=1C=C(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)C=CC=1)CC1CCN(S(C)(=O)=O)CC1 GVXMXVLTPCPYNN-GNAFDRTKSA-N 0.000 description 1
• LDKOFGPSMABAEW-UHFFFAOYSA-N 4-tert-butyl-n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 LDKOFGPSMABAEW-UHFFFAOYSA-N 0.000 description 1
• SETDSEPADSSXOG-UHFFFAOYSA-N 4-tert-butyl-n-[3-[2-[[1-(4-methylphenyl)sulfonylpiperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC(CC1)CCN1S(=O)(=O)C1=CC=C(C)C=C1 SETDSEPADSSXOG-UHFFFAOYSA-N 0.000 description 1
• LBXZIGSDFHRSSP-UHFFFAOYSA-N 4-tert-butyl-n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 LBXZIGSDFHRSSP-UHFFFAOYSA-N 0.000 description 1
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
• UDWFSJAYXTXMLM-UHFFFAOYSA-N 5-bromo-2,3-dihydro-1-benzofuran Chemical compound BrC1=CC=C2OCCC2=C1 UDWFSJAYXTXMLM-UHFFFAOYSA-N 0.000 description 1
• HBNQOSYHNZYHJF-UHFFFAOYSA-N 6-[2-[ethyl-[(1-methylsulfonylpiperidin-4-yl)methyl]amino]propyl]-4h-1,4-benzoxazin-3-one;hydrochloride Chemical compound Cl.C=1C=C2OCC(=O)NC2=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 HBNQOSYHNZYHJF-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 206010002660 Anoxia Diseases 0.000 description 1
• 241000976983 Anoxia Species 0.000 description 1
• 206010056948 Automatic bladder Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 206010006458 Bronchitis chronic Diseases 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• 229920000742 Cotton Polymers 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical group OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 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
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• 208000012258 Diverticular disease Diseases 0.000 description 1
• 206010013554 Diverticulum Diseases 0.000 description 1
• 208000014094 Dystonic disease Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014561 Emphysema Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 1
• 208000000289 Esophageal Achalasia Diseases 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 206010052402 Gastrointestinal hypermotility Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical group OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• 241000557766 Guthriea Species 0.000 description 1
• 238000006842 Henry reaction Methods 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 206010020853 Hypertonic bladder Diseases 0.000 description 1
• 206010021036 Hyponatraemia Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
• 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 229920000881 Modified starch Polymers 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Chemical group OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
• 208000008238 Muscle Spasticity Diseases 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• JAXHQTHCMSJMAS-UHFFFAOYSA-N N-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]pyridine-3-carboxamide dihydrochloride Chemical compound Cl.Cl.C=1C=CC(NC(=O)C=2C=NC=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 JAXHQTHCMSJMAS-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 206010029458 Nodal arrhythmia Diseases 0.000 description 1
• 206010030136 Oesophageal achalasia Diseases 0.000 description 1
• 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 206010066218 Stress Urinary Incontinence Diseases 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 239000005864 Sulphur Chemical group 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• QHCMBOIUNKHMPS-UHFFFAOYSA-N [4-[[1-(2,3-dihydro-1,4-benzodioxin-6-yl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-(oxan-4-yl)methanone;hydrochloride Chemical compound Cl.C=1C=C2OCCOC2=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)C1CCOCC1 QHCMBOIUNKHMPS-UHFFFAOYSA-N 0.000 description 1
• IQHQMJGUAMLOMI-UHFFFAOYSA-N [4-[[1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone;hydrochloride Chemical compound Cl.C=1C=C2OCCC2=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 IQHQMJGUAMLOMI-UHFFFAOYSA-N 0.000 description 1
• RWCFSBMVQYXYHX-UHFFFAOYSA-N [4-[[1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl-propylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone;hydrochloride Chemical compound Cl.C=1C=C2OCCC2=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 RWCFSBMVQYXYHX-UHFFFAOYSA-N 0.000 description 1
• NPYJOKVTKGDQGM-UHFFFAOYSA-N [4-[[1-(3-chlorophenyl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-cyclohexylmethanone Chemical compound C=1C=CC(Cl)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)C1CCCCC1 NPYJOKVTKGDQGM-UHFFFAOYSA-N 0.000 description 1
• GZIQFPQJYOMQCC-UHFFFAOYSA-N [4-[[1-(3-chlorophenyl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone;hydrochloride Chemical compound Cl.C=1C=CC(Cl)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 GZIQFPQJYOMQCC-UHFFFAOYSA-N 0.000 description 1
• PLJVGHYPEMWTCT-UHFFFAOYSA-N [4-[[1-(3-chlorophenyl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-piperidin-1-ylmethanone Chemical compound C=1C=CC(Cl)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCCCC1 PLJVGHYPEMWTCT-UHFFFAOYSA-N 0.000 description 1
• BXMNCDZRVJIBLO-UHFFFAOYSA-N [4-[[1-(3-chlorophenyl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-piperidin-1-ylmethanone;hydrochloride Chemical compound Cl.C=1C=CC(Cl)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCCCC1 BXMNCDZRVJIBLO-UHFFFAOYSA-N 0.000 description 1
• KERUEBKPMZLAEB-UHFFFAOYSA-N [4-[[1-(4-aminophenyl)propan-2-yl-propylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C(N)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 KERUEBKPMZLAEB-UHFFFAOYSA-N 0.000 description 1
• PZTKQNQHWFOHGW-UHFFFAOYSA-N [4-[[1-(4-nitrophenyl)propan-2-yl-propylamino]methyl]piperidin-1-yl]-piperidin-4-ylmethanone;dihydrochloride Chemical compound Cl.Cl.C=1C=C([N+]([O-])=O)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)C1CCNCC1 PZTKQNQHWFOHGW-UHFFFAOYSA-N 0.000 description 1
• IDWKNMKZIUYIHY-UHFFFAOYSA-N [4-[[1-[4-(dimethylamino)phenyl]propan-2-yl-propylamino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone;dihydrochloride Chemical compound Cl.Cl.C=1C=C(N(C)C)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 IDWKNMKZIUYIHY-UHFFFAOYSA-N 0.000 description 1
• BUZZMFZQJXNLLO-UHFFFAOYSA-N [4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-(oxan-4-yl)methanone;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)C1CCOCC1 BUZZMFZQJXNLLO-UHFFFAOYSA-N 0.000 description 1
• FHBYZVZPZZUPKP-UHFFFAOYSA-N [4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 FHBYZVZPZZUPKP-UHFFFAOYSA-N 0.000 description 1
• HHGAZWUUSCIXGP-UHFFFAOYSA-N [4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-morpholin-4-ylmethanone;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 HHGAZWUUSCIXGP-UHFFFAOYSA-N 0.000 description 1
• BKFCMNPBVNRRIT-UHFFFAOYSA-N [4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-piperidin-1-ylmethanone;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCCCC1 BKFCMNPBVNRRIT-UHFFFAOYSA-N 0.000 description 1
• 201000000621 achalasia Diseases 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 150000001266 acyl halides Chemical class 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 239000004411 aluminium Substances 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 238000001949 anaesthesia Methods 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
• 230000007953 anoxia Effects 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 238000000889 atomisation Methods 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• SPQJPMVGTJZXQM-UHFFFAOYSA-N benzyl 4-[ethyl-[1-(4-methoxyphenyl)propan-2-yl]carbamoyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC=2C=CC=CC=2)CCC1C(=O)N(CC)C(C)CC1=CC=C(OC)C=C1 SPQJPMVGTJZXQM-UHFFFAOYSA-N 0.000 description 1
• KUBUQFFBRSHOMJ-UHFFFAOYSA-N benzyl 4-carbonochloridoylpiperidine-1-carboxylate Chemical compound C1CC(C(=O)Cl)CCN1C(=O)OCC1=CC=CC=C1 KUBUQFFBRSHOMJ-UHFFFAOYSA-N 0.000 description 1
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• 208000006218 bradycardia Diseases 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 229940124630 bronchodilator Drugs 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
• 150000001722 carbon compounds Chemical class 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 229960004424 carbon dioxide Drugs 0.000 description 1
• 150000003857 carboxamides Chemical class 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 208000007451 chronic bronchitis Diseases 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 239000000306 component Substances 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126086 compound 21 Drugs 0.000 description 1
• 229940126208 compound 22 Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940125846 compound 25 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• MOCVJUQLSWDWKI-UHFFFAOYSA-N cyclohexyl-[4-[[ethyl-[1-[4-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]methanone Chemical compound C=1C=C(C(F)(F)F)C=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)C1CCCCC1 MOCVJUQLSWDWKI-UHFFFAOYSA-N 0.000 description 1
• NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical group CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 208000010118 dystonia Diseases 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• JOXWSDNHLSQKCC-UHFFFAOYSA-N ethenesulfonamide Chemical compound NS(=O)(=O)C=C JOXWSDNHLSQKCC-UHFFFAOYSA-N 0.000 description 1
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
• YDAMCXZRQUEJKE-UHFFFAOYSA-N ethyl 4-[[1-[3-[(4-tert-butylbenzoyl)amino]phenyl]propan-2-yl-propylamino]methyl]piperidine-1-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC1CCN(C(=O)OCC)CC1 YDAMCXZRQUEJKE-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 1
• 238000013265 extended release Methods 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 210000000609 ganglia Anatomy 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 239000003349 gelling agent Substances 0.000 description 1
• 239000003193 general anesthetic agent Substances 0.000 description 1
• 229940005494 general anesthetics Drugs 0.000 description 1
• 210000004392 genitalia Anatomy 0.000 description 1
• 230000000762 glandular Effects 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 239000000174 gluconic acid Chemical group 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Chemical group 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 244000144993 groups of animals Species 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• UUBJKHVFGWGJKX-UHFFFAOYSA-N hydrate tetrahydrochloride Chemical compound O.Cl.Cl.Cl.Cl UUBJKHVFGWGJKX-UHFFFAOYSA-N 0.000 description 1
• 239000000852 hydrogen donor Substances 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 239000005414 inactive ingredient Substances 0.000 description 1
• 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 208000002551 irritable bowel syndrome Diseases 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 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
• MASZZCMOOVIWNP-UHFFFAOYSA-N methyl 4-[[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]carbamoyl]benzoate Chemical compound C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(=O)OC)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 MASZZCMOOVIWNP-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 229960001383 methylscopolamine Drugs 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 235000019426 modified starch Nutrition 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N mono-n-propyl amine Natural products CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
• BBWFKYMMTWOUIE-UHFFFAOYSA-N morpholin-4-yl-[4-[[1-(3-nitrophenyl)propan-2-yl-propylamino]methyl]piperidin-1-yl]methanone;hydrochloride Chemical compound Cl.C=1C=CC([N+]([O-])=O)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 BBWFKYMMTWOUIE-UHFFFAOYSA-N 0.000 description 1
• DGFODHSNTUFBNT-UHFFFAOYSA-N morpholin-4-yl-[4-[[1-(4-nitrophenyl)propan-2-yl-propylamino]methyl]piperidin-1-yl]methanone Chemical compound C=1C=C([N+]([O-])=O)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 DGFODHSNTUFBNT-UHFFFAOYSA-N 0.000 description 1
• UALCJNDMZGTGHW-UHFFFAOYSA-N morpholin-4-yl-[4-[[propyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]methanone;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 UALCJNDMZGTGHW-UHFFFAOYSA-N 0.000 description 1
• XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 201000003152 motion sickness Diseases 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 229940051866 mouthwash Drugs 0.000 description 1
• 230000003551 muscarinic effect Effects 0.000 description 1
• 230000004220 muscle function Effects 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• HGFRWUXXNAOTCH-UHFFFAOYSA-N n,n-diethyl-4-[[ethyl-[1-(4-methoxyphenyl)propan-2-yl]amino]methyl]piperidine-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCN(C(=O)N(CC)CC)CC1 HGFRWUXXNAOTCH-UHFFFAOYSA-N 0.000 description 1
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
• JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
• ACTQPNZUGFDAHO-UHFFFAOYSA-N n-(cyclopropylmethyl)-1-(2,3-dihydro-1-benzofuran-6-yl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2CCOC2=CC=1CC(C)N(CC1CCN(CC1)S(C)(=O)=O)CC1CC1 ACTQPNZUGFDAHO-UHFFFAOYSA-N 0.000 description 1
• RJASJOJQSLXLNG-UHFFFAOYSA-N n-(piperidin-4-ylmethyl)ethanamine Chemical class CCNCC1CCNCC1 RJASJOJQSLXLNG-UHFFFAOYSA-N 0.000 description 1
• YPMWEBRBJXXUEJ-UHFFFAOYSA-N n-[(1-methylsulfonylpiperidin-4-yl)methyl]-1-(3-nitrophenyl)-n-propylpropan-2-amine;hydrochloride Chemical compound Cl.C=1C=CC([N+]([O-])=O)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 YPMWEBRBJXXUEJ-UHFFFAOYSA-N 0.000 description 1
• POHBFCSJSNLQSY-UHFFFAOYSA-N n-[(1-methylsulfonylpiperidin-4-yl)methyl]-1-(4-nitrophenyl)-n-propylpropan-2-amine;hydrochloride Chemical compound Cl.C=1C=C([N+]([O-])=O)C=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 POHBFCSJSNLQSY-UHFFFAOYSA-N 0.000 description 1
• OMAAUWNFYWIYPU-GEBXLFFOSA-N n-[(2s)-1-[4-[[1-(3-chlorophenyl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-4-methylsulfinyl-1-oxobutan-2-yl]methanesulfonamide;hydrochloride Chemical compound Cl.C=1C=CC(Cl)=CC=1CC(C)N(CC)CC1CCN(C(=O)[C@H](CCS(C)=O)NS(C)(=O)=O)CC1 OMAAUWNFYWIYPU-GEBXLFFOSA-N 0.000 description 1
• MOGPGQLCPKXQLW-KJIPLLCSSA-N n-[(2s)-1-[4-[[1-(3-chlorophenyl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]-4-methylsulfonyl-1-oxobutan-2-yl]methanesulfonamide;hydrochloride Chemical compound Cl.C=1C=CC(Cl)=CC=1CC(C)N(CC)CC1CCN(C(=O)[C@H](CCS(C)(=O)=O)NS(C)(=O)=O)CC1 MOGPGQLCPKXQLW-KJIPLLCSSA-N 0.000 description 1
• HKSNTAGHEWZGSX-GGYWPGCISA-N n-[(2s)-2-[4-[[1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl-ethylamino]methyl]piperidin-1-yl]sulfonylpropyl]methanesulfonamide Chemical compound C=1C=C2OCCC2=CC=1CC(C)N(CC)CC1CCN(S(=O)(=O)[C@@H](C)CNS(C)(=O)=O)CC1 HKSNTAGHEWZGSX-GGYWPGCISA-N 0.000 description 1
• UMNUHWFAONZIRM-FERBBOLQSA-N n-[1-[4-[[[(2s)-1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl]-ethylamino]methyl]piperidin-1-yl]-2-methyl-1-oxopropan-2-yl]methanesulfonamide;hydrochloride Chemical compound Cl.CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(C(=O)C(C)(C)NS(C)(=O)=O)CC1 UMNUHWFAONZIRM-FERBBOLQSA-N 0.000 description 1
• MOMIPMMNTINUJW-UHFFFAOYSA-N n-[1-[4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-3-methylsulfonyl-1-oxopropan-2-yl]methanesulfonamide;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC1CCN(C(=O)C(CS(C)(=O)=O)NS(C)(=O)=O)CC1 MOMIPMMNTINUJW-UHFFFAOYSA-N 0.000 description 1
• KGNBQZNFYLVZND-UHFFFAOYSA-N n-[1-[4-[[ethyl-[1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]methyl]piperidin-1-yl]-3-oxopropyl]-n-methylmethanesulfonamide;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC1CCN(C(CC=O)N(C)S(C)(=O)=O)CC1 KGNBQZNFYLVZND-UHFFFAOYSA-N 0.000 description 1
• MOYUGEJRUXGRTG-SFHVURJKSA-N n-[2-[4-[[[(2s)-1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl]-ethylamino]methyl]piperidin-1-yl]sulfonylethyl]methanesulfonamide Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(S(=O)(=O)CCNS(C)(=O)=O)CC1 MOYUGEJRUXGRTG-SFHVURJKSA-N 0.000 description 1
• PYFYCUQQXAEFCB-GJFSDDNBSA-N n-[3-[(2r)-2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]cyclohexanecarboxamide;hydrochloride Chemical compound Cl.CCCN([C@H](C)CC=1C=C(NC(=O)C2CCCCC2)C=CC=1)CC(CC1)CCN1C(=O)N1CCOCC1 PYFYCUQQXAEFCB-GJFSDDNBSA-N 0.000 description 1
• XJVRKVLAONOVTF-BOXHHOBZSA-N n-[3-[(2s)-2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]cyclohexanecarboxamide;hydrochloride Chemical compound Cl.CCCN([C@@H](C)CC=1C=C(NC(=O)C2CCCCC2)C=CC=1)CC1CCN(S(C)(=O)=O)CC1 XJVRKVLAONOVTF-BOXHHOBZSA-N 0.000 description 1
• PYFYCUQQXAEFCB-JIDHJSLPSA-N n-[3-[(2s)-2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]cyclohexanecarboxamide;hydrochloride Chemical compound Cl.CCCN([C@@H](C)CC=1C=C(NC(=O)C2CCCCC2)C=CC=1)CC(CC1)CCN1C(=O)N1CCOCC1 PYFYCUQQXAEFCB-JIDHJSLPSA-N 0.000 description 1
• MBMNQJUXQDWCQP-UHFFFAOYSA-N n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]-3-phenylpropanamide Chemical compound C=1C=CC(NC(=O)CCC=2C=CC=CC=2)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 MBMNQJUXQDWCQP-UHFFFAOYSA-N 0.000 description 1
• NDMFTLVMNWWSRY-UHFFFAOYSA-N n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]furan-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2OC=CC=2)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 NDMFTLVMNWWSRY-UHFFFAOYSA-N 0.000 description 1
• URNUXSCQMVEAES-UHFFFAOYSA-N n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]furan-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2OC=CC=2)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 URNUXSCQMVEAES-UHFFFAOYSA-N 0.000 description 1
• LVBXRIFWTAICPW-UHFFFAOYSA-N n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]methanesulfonamide;hydrochloride Chemical compound Cl.C=1C=CC(NS(C)(=O)=O)=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 LVBXRIFWTAICPW-UHFFFAOYSA-N 0.000 description 1
• CWPPUPCLOPYVBL-UHFFFAOYSA-N n-[3-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]pentanamide Chemical compound CCCCC(=O)NC1=CC=CC(CC(C)N(CCC)CC2CCN(CC2)S(C)(=O)=O)=C1 CWPPUPCLOPYVBL-UHFFFAOYSA-N 0.000 description 1
• YFMWWVWPKKDGFC-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]-1h-1,2,4-triazole-5-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2NN=CN=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 YFMWWVWPKKDGFC-UHFFFAOYSA-N 0.000 description 1
• ZTLFJYBGQDKSRS-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]-1h-pyrazole-4-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C2=CNN=C2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 ZTLFJYBGQDKSRS-UHFFFAOYSA-N 0.000 description 1
• QAHYKIUTCDBXKL-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=C3OCCOC3=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 QAHYKIUTCDBXKL-UHFFFAOYSA-N 0.000 description 1
• CJWRYWWEGPMQPW-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]-2,3-dihydro-1-benzofuran-5-carboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=C3CCOC3=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 CJWRYWWEGPMQPW-UHFFFAOYSA-N 0.000 description 1
• CMVFPVPRYPZVDC-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]-4-propylbenzamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=CC(CCC)=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 CMVFPVPRYPZVDC-UHFFFAOYSA-N 0.000 description 1
• RLTGYZBSWKGVKL-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC(NC(=O)C=2C=CC=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 RLTGYZBSWKGVKL-UHFFFAOYSA-N 0.000 description 1
• PYFYCUQQXAEFCB-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]cyclohexanecarboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C2CCCCC2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 PYFYCUQQXAEFCB-UHFFFAOYSA-N 0.000 description 1
• CARQKQIWOXSMHM-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]methanesulfonamide;hydrochloride Chemical compound Cl.C=1C=CC(NS(C)(=O)=O)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 CARQKQIWOXSMHM-UHFFFAOYSA-N 0.000 description 1
• UHKOYSLPJMBDNZ-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]naphthalene-1-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C3=CC=CC=C3C=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 UHKOYSLPJMBDNZ-UHFFFAOYSA-N 0.000 description 1
• RDKJUKOHMRRQDZ-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]naphthalene-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C=C3C=CC=CC3=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 RDKJUKOHMRRQDZ-UHFFFAOYSA-N 0.000 description 1
• YJTZHBFMLSUQRN-UHFFFAOYSA-N n-[3-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]thiophene-2-carboxamide Chemical compound C=1C=CC(NC(=O)C=2SC=CC=2)=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 YJTZHBFMLSUQRN-UHFFFAOYSA-N 0.000 description 1
• SHIMDVQVGHAUAQ-UHFFFAOYSA-N n-[3-[2-[butyl-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl]amino]propyl]phenyl]-4-methoxybenzamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=CC(OC)=CC=2)=CC=1CC(C)N(CCCC)CC(CC1)CCN1C(=O)N1CCOCC1 SHIMDVQVGHAUAQ-UHFFFAOYSA-N 0.000 description 1
• HMMIAIHARORIFV-UHFFFAOYSA-N n-[3-[2-[butyl-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl]amino]propyl]phenyl]cyclohexanecarboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C2CCCCC2)=CC=1CC(C)N(CCCC)CC(CC1)CCN1C(=O)N1CCOCC1 HMMIAIHARORIFV-UHFFFAOYSA-N 0.000 description 1
• ODXAINGNJSVGTH-UHFFFAOYSA-N n-[3-[2-[ethyl-[(1-methylsulfonylpiperidin-4-yl)methyl]amino]propyl]phenyl]cyclohexanecarboxamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C2CCCCC2)=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 ODXAINGNJSVGTH-UHFFFAOYSA-N 0.000 description 1
• IMKRPQTURXWPIM-UHFFFAOYSA-N n-[3-[2-[ethyl-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl]amino]propyl]phenyl]-4-methylbenzamide;hydrochloride Chemical compound Cl.C=1C=CC(NC(=O)C=2C=CC(C)=CC=2)=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCOCC1 IMKRPQTURXWPIM-UHFFFAOYSA-N 0.000 description 1
• JTMMHOGIESGUCL-UHFFFAOYSA-N n-[4-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]cyclohexanecarboxamide Chemical compound C=1C=C(NC(=O)C2CCCCC2)C=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 JTMMHOGIESGUCL-UHFFFAOYSA-N 0.000 description 1
• YNHIJQUUTNVDQU-UHFFFAOYSA-N n-[4-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]furan-2-carboxamide;hydrochloride Chemical compound Cl.C=1C=C(NC(=O)C=2OC=CC=2)C=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 YNHIJQUUTNVDQU-UHFFFAOYSA-N 0.000 description 1
• WCDPOBNXPKQVTJ-UHFFFAOYSA-N n-[4-[2-[(1-methylsulfonylpiperidin-4-yl)methyl-propylamino]propyl]phenyl]methanesulfonamide;hydrochloride Chemical compound Cl.C=1C=C(NS(C)(=O)=O)C=CC=1CC(C)N(CCC)CC1CCN(S(C)(=O)=O)CC1 WCDPOBNXPKQVTJ-UHFFFAOYSA-N 0.000 description 1
• DTMPANIQABLNCY-UHFFFAOYSA-N n-[4-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]cyclohexanecarboxamide;hydrochloride Chemical compound Cl.C=1C=C(NC(=O)C2CCCCC2)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 DTMPANIQABLNCY-UHFFFAOYSA-N 0.000 description 1
• QZTXQZZCNAWRBV-UHFFFAOYSA-N n-[4-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]methanesulfonamide;hydrochloride Chemical compound Cl.C=1C=C(NS(C)(=O)=O)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 QZTXQZZCNAWRBV-UHFFFAOYSA-N 0.000 description 1
• CIXIPXFATMQVSC-UHFFFAOYSA-N n-[4-[2-[[1-(morpholine-4-carbonyl)piperidin-4-yl]methyl-propylamino]propyl]phenyl]morpholine-4-carboxamide;hydrochloride Chemical compound Cl.C=1C=C(NC(=O)N2CCOCC2)C=CC=1CC(C)N(CCC)CC(CC1)CCN1C(=O)N1CCOCC1 CIXIPXFATMQVSC-UHFFFAOYSA-N 0.000 description 1
• KQNXTDCWRSPKCL-UHFFFAOYSA-N n-ethyl-1-(2-fluorophenyl)propan-2-amine;hydrochloride Chemical compound Cl.CCNC(C)CC1=CC=CC=C1F KQNXTDCWRSPKCL-UHFFFAOYSA-N 0.000 description 1
• PUJNOWQUPWZVER-UHFFFAOYSA-N n-ethyl-1-(4-fluorophenyl)propan-2-amine Chemical compound CCNC(C)CC1=CC=C(F)C=C1 PUJNOWQUPWZVER-UHFFFAOYSA-N 0.000 description 1
• BQNMPRLHGWUENJ-UHFFFAOYSA-N n-ethyl-1-(4-methoxyphenyl)-n-[(1-propan-2-ylsulfonylpiperidin-4-yl)methyl]propan-2-amine Chemical compound C=1C=C(OC)C=CC=1CC(C)N(CC)CC1CCN(S(=O)(=O)C(C)C)CC1 BQNMPRLHGWUENJ-UHFFFAOYSA-N 0.000 description 1
• KWQLOEWGKCQLPR-UHFFFAOYSA-N n-ethyl-1-(4-methoxyphenyl)propan-2-amine;hydrochloride Chemical compound Cl.CCNC(C)CC1=CC=C(OC)C=C1 KWQLOEWGKCQLPR-UHFFFAOYSA-N 0.000 description 1
• NQGSMZJOIGOEPQ-UHFFFAOYSA-N n-ethyl-1-(4-methylsulfanylphenyl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C(SC)C=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 NQGSMZJOIGOEPQ-UHFFFAOYSA-N 0.000 description 1
• FQKWCUPXTBWNQR-UHFFFAOYSA-N n-ethyl-1-(4-methylsulfonylphenyl)-n-[(1-methylsulfonylpiperidin-4-yl)methyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=C(S(C)(=O)=O)C=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 FQKWCUPXTBWNQR-UHFFFAOYSA-N 0.000 description 1
• SLUSSZKUMPDXJI-UHFFFAOYSA-N n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-1-(3-nitrophenyl)propan-2-amine Chemical compound C=1C=CC([N+]([O-])=O)=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 SLUSSZKUMPDXJI-UHFFFAOYSA-N 0.000 description 1
• FHYLLQHPCSYJDM-UHFFFAOYSA-N n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-1-[3-(trifluoromethyl)phenyl]propan-2-amine;hydrochloride Chemical compound Cl.C=1C=CC(C(F)(F)F)=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 FHYLLQHPCSYJDM-UHFFFAOYSA-N 0.000 description 1
• HAQVGBIALKYXCC-UHFFFAOYSA-N n-ethyl-n-[(1-methylsulfonylpiperidin-4-yl)methyl]-1-naphthalen-2-ylpropan-2-amine;hydrochloride Chemical compound Cl.C=1C=C2C=CC=CC2=CC=1CC(C)N(CC)CC1CCN(S(C)(=O)=O)CC1 HAQVGBIALKYXCC-UHFFFAOYSA-N 0.000 description 1
• AGARDWQCKAGZNV-UHFFFAOYSA-N n-tert-butyl-4-[[1-[3-[(4-tert-butylbenzoyl)amino]phenyl]propan-2-yl-propylamino]methyl]piperidine-1-carboxamide Chemical compound C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC1CCN(C(=O)NC(C)(C)C)CC1 AGARDWQCKAGZNV-UHFFFAOYSA-N 0.000 description 1
• OAXXBELWLDLMRC-UHFFFAOYSA-N n-tert-butyl-4-[[1-[3-[(4-tert-butylbenzoyl)amino]phenyl]propan-2-yl-propylamino]methyl]piperidine-1-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC(NC(=O)C=2C=CC(=CC=2)C(C)(C)C)=CC=1CC(C)N(CCC)CC1CCN(C(=O)NC(C)(C)C)CC1 OAXXBELWLDLMRC-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 235000021096 natural sweeteners Nutrition 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000004971 nitroalkyl group Chemical group 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• 150000002902 organometallic compounds Chemical class 0.000 description 1
• 125000002524 organometallic group Chemical group 0.000 description 1
• 208000020629 overactive bladder Diseases 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 238000005949 ozonolysis reaction Methods 0.000 description 1
• 230000036407 pain Effects 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical group OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• NEGYEDYHPHMHGK-UHFFFAOYSA-N para-methoxyamphetamine Chemical compound COC1=CC=C(CC(C)N)C=C1 NEGYEDYHPHMHGK-UHFFFAOYSA-N 0.000 description 1
• 230000001734 parasympathetic effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 239000012026 peptide coupling reagents‎ Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical class NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
• XPANMBKYWOIIMT-UHFFFAOYSA-N piperidin-3-ylidenemethanone Chemical compound O=C=C1CCCNC1 XPANMBKYWOIIMT-UHFFFAOYSA-N 0.000 description 1
• XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
• IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• PYNUOAIJIQGACY-UHFFFAOYSA-N propylazanium;chloride Chemical compound Cl.CCCN PYNUOAIJIQGACY-UHFFFAOYSA-N 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000001525 receptor binding assay Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006485 reductive methylation reaction Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 230000033764 rhythmic process Effects 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000002295 serotoninergic effect Effects 0.000 description 1
• 230000016160 smooth muscle contraction Effects 0.000 description 1
• 229910052708 sodium Inorganic materials 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
• 239000011780 sodium chloride Substances 0.000 description 1
• ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000001593 sorbitan monooleate Substances 0.000 description 1
• 235000011069 sorbitan monooleate Nutrition 0.000 description 1
• 229940035049 sorbitan monooleate Drugs 0.000 description 1
• 208000018198 spasticity Diseases 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 238000013223 sprague-dawley female rat Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008117 stearic acid Chemical group 0.000 description 1
• 208000022170 stress incontinence Diseases 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000003890 substance P antagonist Substances 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 230000000153 supplemental effect Effects 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000005062 synaptic transmission Effects 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 239000007885 tablet disintegrant Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• KLKBCNDBOVRQIJ-UHFFFAOYSA-N tert-butyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CN)CC1 KLKBCNDBOVRQIJ-UHFFFAOYSA-N 0.000 description 1
• RQYFRNGJIJDXQP-UHFFFAOYSA-N tert-butyl 4-[4-[[ethyl-[1-(4-methoxyphenyl)propan-2-yl]amino]methyl]piperidine-1-carbonyl]piperazine-1-carboxylate Chemical compound C=1C=C(OC)C=CC=1CC(C)N(CC)CC(CC1)CCN1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1 RQYFRNGJIJDXQP-UHFFFAOYSA-N 0.000 description 1
• KKNCBCCEMQCKST-UHFFFAOYSA-N tert-butyl 4-[[1-(4-nitrophenyl)propan-2-yl-propylamino]methyl]piperidine-1-carboxylate;hydrochloride Chemical compound Cl.C=1C=C([N+]([O-])=O)C=CC=1CC(C)N(CCC)CC1CCN(C(=O)OC(C)(C)C)CC1 KKNCBCCEMQCKST-UHFFFAOYSA-N 0.000 description 1
• QKXUITNZXUMWDP-FQEVSTJZSA-N tert-butyl n-[3-[4-[[[(2s)-1-(2,3-dihydro-1-benzofuran-5-yl)propan-2-yl]-ethylamino]methyl]piperidin-1-yl]-3-oxopropyl]carbamate Chemical compound CCN([C@@H](C)CC=1C=C2CCOC2=CC=1)CC1CCN(C(=O)CCNC(=O)OC(C)(C)C)CC1 QKXUITNZXUMWDP-FQEVSTJZSA-N 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 206010046494 urge incontinence Diseases 0.000 description 1
• 210000001635 urinary tract Anatomy 0.000 description 1
• 230000006442 vascular tone Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000011345 viscous material Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 150000003738 xylenes Chemical class 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1