US20070060563A1 - Quinuclidine derivatives binding to mucarinic m3 receptors - Google Patents
Quinuclidine derivatives binding to mucarinic m3 receptors Download PDFInfo
- Publication number
- US20070060563A1 US20070060563A1 US10/554,558 US55455804A US2007060563A1 US 20070060563 A1 US20070060563 A1 US 20070060563A1 US 55455804 A US55455804 A US 55455804A US 2007060563 A1 US2007060563 A1 US 2007060563A1
- Authority
- US
- United States
- Prior art keywords
- alkyl
- carbocyclic group
- sulphur
- nitrogen
- oxygen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000027455 binding Effects 0.000 title description 3
- 150000008584 quinuclidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 189
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 102000007202 Muscarinic M3 Receptor Human genes 0.000 claims abstract description 3
- 108010008405 Muscarinic M3 Receptor Proteins 0.000 claims abstract description 3
- 230000001404 mediated effect Effects 0.000 claims abstract description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 116
- 125000000623 heterocyclic group Chemical group 0.000 claims description 113
- 229910052757 nitrogen Inorganic materials 0.000 claims description 112
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 110
- 239000005864 Sulphur Chemical group 0.000 claims description 110
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 110
- 125000005842 heteroatom Chemical group 0.000 claims description 110
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 110
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 110
- 229910052760 oxygen Inorganic materials 0.000 claims description 110
- 239000001301 oxygen Chemical group 0.000 claims description 110
- -1 cyano, amino Chemical group 0.000 claims description 84
- 239000001257 hydrogen Substances 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 75
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 72
- 238000000034 method Methods 0.000 claims description 44
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 230000002757 inflammatory effect Effects 0.000 claims description 11
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 10
- 150000004820 halides Chemical class 0.000 claims description 9
- 239000007822 coupling agent Substances 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 229940088679 drug related substance Drugs 0.000 claims description 6
- 208000027771 Obstructive airways disease Diseases 0.000 claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 5
- 239000000739 antihistaminic agent Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 4
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 4
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 4
- 230000001387 anti-histamine Effects 0.000 claims description 4
- 239000003434 antitussive agent Substances 0.000 claims description 4
- 229940124584 antitussives Drugs 0.000 claims description 4
- 239000000850 decongestant Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 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 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 229940124630 bronchodilator Drugs 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 488
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 178
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 132
- 239000000243 solution Substances 0.000 description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 47
- 239000011541 reaction mixture Substances 0.000 description 46
- 239000000203 mixture Substances 0.000 description 45
- 238000000746 purification Methods 0.000 description 45
- XQQBUAPQHNYYRS-UHFFFAOYSA-N CC1=CC=CS1 Chemical compound CC1=CC=CS1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 43
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
- 0 [1*]C([2*])([3*])C(=O)OC1C[N+]2([4*])CCC1CC2 Chemical compound [1*]C([2*])([3*])C(=O)OC1C[N+]2([4*])CCC1CC2 0.000 description 37
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
- 239000007787 solid Substances 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 22
- HGMITUYOCPPQLE-IBGZPJMESA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 HGMITUYOCPPQLE-IBGZPJMESA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 21
- 238000002953 preparative HPLC Methods 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000000377 silicon dioxide Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 208000006673 asthma Diseases 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- GYDFTKNRHZMENP-ZDUSSCGKSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 GYDFTKNRHZMENP-ZDUSSCGKSA-N 0.000 description 13
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000007821 HATU Substances 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 229940093499 ethyl acetate Drugs 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000003960 organic solvent Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- XNVQHBNQPWFYSU-ODZKUHOFSA-N [(3r)-1-[2-(azetidine-3-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1CNC1 XNVQHBNQPWFYSU-ODZKUHOFSA-N 0.000 description 9
- RASHAQUEEZFVSX-UPGPKNOMSA-M [(3r)-1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)OC(C)(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 RASHAQUEEZFVSX-UPGPKNOMSA-M 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
- 201000010099 disease Diseases 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- ZWRNKZRCIVIYMO-SSVLGJNASA-M [(3r)-1-pent-4-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCCC#C)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 ZWRNKZRCIVIYMO-SSVLGJNASA-M 0.000 description 8
- KDKYADYSIPSCCQ-UHFFFAOYSA-N [H]C#CCC Chemical compound [H]C#CCC KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 8
- 239000000556 agonist Substances 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- VONWPEXRCLHKRJ-UHFFFAOYSA-N 2-chloro-n-phenylacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1 VONWPEXRCLHKRJ-UHFFFAOYSA-N 0.000 description 7
- OAZWKSFACASWNG-FPJVJKMXSA-M [(3r)-1-(2-aminoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide;hydrobromide Chemical compound Br.[Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCN)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 OAZWKSFACASWNG-FPJVJKMXSA-M 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000000414 obstructive effect Effects 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000012453 solvate Substances 0.000 description 7
- BTQDGUZAOOCURB-IUKYZBKLSA-N 2-[(3r)-3-(2-hydroxy-2,2-diphenylacetyl)oxy-1-azoniabicyclo[2.2.2]octan-1-yl]acetic acid;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)O)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 BTQDGUZAOOCURB-IUKYZBKLSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- NKOFPGOHUMCOLQ-UHFFFAOYSA-N CCCNC(=O)NC1=CC=CC=C1 Chemical compound CCCNC(=O)NC1=CC=CC=C1 NKOFPGOHUMCOLQ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- RFUNLGOHYSYQFY-TXBRGTRZSA-N [(3r)-1-(2-anilino-2-oxoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC(=O)NC1=CC=CC=C1 RFUNLGOHYSYQFY-TXBRGTRZSA-N 0.000 description 6
- HMTVZNQCGSLLLE-PBJIGMDXSA-N [(3r)-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCNC(=O)OC(C)(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 HMTVZNQCGSLLLE-PBJIGMDXSA-N 0.000 description 6
- 150000001350 alkyl halides Chemical class 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 229960004132 diethyl ether Drugs 0.000 description 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 description 5
- ZTHRQJQJODGZHV-UHFFFAOYSA-N CCC(=O)NC1=CC=CC=C1 Chemical compound CCC(=O)NC1=CC=CC=C1 ZTHRQJQJODGZHV-UHFFFAOYSA-N 0.000 description 5
- GRLSYRNKNDLBAO-UHFFFAOYSA-N CCCNC(=O)NC1CCCCC1 Chemical compound CCCNC(=O)NC1CCCCC1 GRLSYRNKNDLBAO-UHFFFAOYSA-N 0.000 description 5
- SBOLKCRPTBJXQW-UHFFFAOYSA-N CCCOC(=O)NC1CCCCC1 Chemical compound CCCOC(=O)NC1CCCCC1 SBOLKCRPTBJXQW-UHFFFAOYSA-N 0.000 description 5
- LZCOQTDXKCNBEE-XJMZPCNVSA-N N-methylscopolamine Chemical compound C1([C@@H](CO)C(=O)OC2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-XJMZPCNVSA-N 0.000 description 5
- SFCRJXJVNYFJGD-VAXCQOKESA-M [(3r)-1-(2-oxo-2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-fluoro-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(F)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)OC1=CC=CC=C1 SFCRJXJVNYFJGD-VAXCQOKESA-M 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- GIWMPTVSSKUNBX-UHFFFAOYSA-N 2-bromo-n-(1,2-oxazol-3-yl)acetamide Chemical compound BrCC(=O)NC=1C=CON=1 GIWMPTVSSKUNBX-UHFFFAOYSA-N 0.000 description 4
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 4
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 4
- HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- UXFIKVWAAMKFQE-UHFFFAOYSA-N 5-chloropent-1-yne Chemical compound ClCCCC#C UXFIKVWAAMKFQE-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- XYBFBXTUWDPXLK-UHFFFAOYSA-N CCC#CC(C)(C)C Chemical compound CCC#CC(C)(C)C XYBFBXTUWDPXLK-UHFFFAOYSA-N 0.000 description 4
- POBOUPFSQKXZFZ-UHFFFAOYSA-N CCC#CC(C)C Chemical compound CCC#CC(C)C POBOUPFSQKXZFZ-UHFFFAOYSA-N 0.000 description 4
- FFFMSANAQQVUJA-UHFFFAOYSA-N CCC#CC1=CC=CC=C1 Chemical compound CCC#CC1=CC=CC=C1 FFFMSANAQQVUJA-UHFFFAOYSA-N 0.000 description 4
- VIKQDCOIMZHWFA-UHFFFAOYSA-N CCC#CC1CC1 Chemical compound CCC#CC1CC1 VIKQDCOIMZHWFA-UHFFFAOYSA-N 0.000 description 4
- DQQNMIPXXNPGCV-UHFFFAOYSA-N CCC#CCC Chemical compound CCC#CCC DQQNMIPXXNPGCV-UHFFFAOYSA-N 0.000 description 4
- KLYHSJRCIZOUHE-UHFFFAOYSA-N CCC#CCCC Chemical compound CCC#CCCC KLYHSJRCIZOUHE-UHFFFAOYSA-N 0.000 description 4
- RCJKLZVMQBZTMP-UHFFFAOYSA-N CCC(=O)N/C1=N/C2=C(C=CC(F)=C2)S1 Chemical compound CCC(=O)N/C1=N/C2=C(C=CC(F)=C2)S1 RCJKLZVMQBZTMP-UHFFFAOYSA-N 0.000 description 4
- UCWQHVABVFGEJB-UHFFFAOYSA-N CCC(=O)NC1=NC=CN=C1 Chemical compound CCC(=O)NC1=NC=CN=C1 UCWQHVABVFGEJB-UHFFFAOYSA-N 0.000 description 4
- DXFTYLAKFSFIPH-UHFFFAOYSA-N CCC(=O)NC1=NC=NC=C1 Chemical compound CCC(=O)NC1=NC=NC=C1 DXFTYLAKFSFIPH-UHFFFAOYSA-N 0.000 description 4
- DGDMYRNZAMTVJQ-UHFFFAOYSA-N CCC(=O)NC1=NOC=C1 Chemical compound CCC(=O)NC1=NOC=C1 DGDMYRNZAMTVJQ-UHFFFAOYSA-N 0.000 description 4
- ZFNAETKJDHAQEN-UHFFFAOYSA-N CCC(=O)NCC1=CC=CC=C1 Chemical compound CCC(=O)NCC1=CC=CC=C1 ZFNAETKJDHAQEN-UHFFFAOYSA-N 0.000 description 4
- MXSNQMUVXLVDHI-UHFFFAOYSA-N CCCCNC(=O)OC(C)(C)C Chemical compound CCCCNC(=O)OC(C)(C)C MXSNQMUVXLVDHI-UHFFFAOYSA-N 0.000 description 4
- DYJASQCJAVAXFR-UHFFFAOYSA-N CCCNC(=O)C1=C(C)OC(S(=O)(=O)N(C)C)=C1 Chemical compound CCCNC(=O)C1=C(C)OC(S(=O)(=O)N(C)C)=C1 DYJASQCJAVAXFR-UHFFFAOYSA-N 0.000 description 4
- ABMDIECEEGFXNC-UHFFFAOYSA-N CCNC(=O)CC Chemical compound CCNC(=O)CC ABMDIECEEGFXNC-UHFFFAOYSA-N 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 229920001367 Merrifield resin Polymers 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- XIFPICWZWKKDRA-KBGMEFHRSA-N [(3r)-1-[2-(naphthalene-2-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCNC(=O)C=2C=C3C=CC=CC3=CC=2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 XIFPICWZWKKDRA-KBGMEFHRSA-N 0.000 description 4
- OSPFOMJEVHALEH-OWQBZFBLSA-M [(3r)-1-[2-[(4-methylphenyl)sulfonylamino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(C)=CC=C1S(=O)(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 OSPFOMJEVHALEH-OWQBZFBLSA-M 0.000 description 4
- PMRLLZYLVMJJEG-FKRVERSVSA-N [(3r)-1-[3-(phenylcarbamoylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)NC1=CC=CC=C1 PMRLLZYLVMJJEG-FKRVERSVSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
- WKCWELSTTLPNKW-UHFFFAOYSA-N 2-bromo-n-pyrazin-2-ylacetamide Chemical compound BrCC(=O)NC1=CN=CC=N1 WKCWELSTTLPNKW-UHFFFAOYSA-N 0.000 description 3
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 description 3
- VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 description 3
- ZOVIYWYFBOQKIA-UHFFFAOYSA-N 5,6-diethyl-2,3-dihydro-1h-inden-2-amine;hydrochloride Chemical compound Cl.C1=C(CC)C(CC)=CC2=C1CC(N)C2 ZOVIYWYFBOQKIA-UHFFFAOYSA-N 0.000 description 3
- WQEJTLRSBBMKOS-UHFFFAOYSA-N CCC(=O)NC1=NC=C(C)S1 Chemical compound CCC(=O)NC1=NC=C(C)S1 WQEJTLRSBBMKOS-UHFFFAOYSA-N 0.000 description 3
- DWTFNIVLILBVAQ-UHFFFAOYSA-N CCC(=O)NC1=NC=CC=N1 Chemical compound CCC(=O)NC1=NC=CC=N1 DWTFNIVLILBVAQ-UHFFFAOYSA-N 0.000 description 3
- FVNSFMILKBPVBY-UHFFFAOYSA-N CCC(=O)NC1CC2=C(C=CC=C2)C1 Chemical compound CCC(=O)NC1CC2=C(C=CC=C2)C1 FVNSFMILKBPVBY-UHFFFAOYSA-N 0.000 description 3
- YSSQDJGNEOEMHI-UHFFFAOYSA-N CCC(=O)NCC1=CC(Cl)=CC=C1 Chemical compound CCC(=O)NCC1=CC(Cl)=CC=C1 YSSQDJGNEOEMHI-UHFFFAOYSA-N 0.000 description 3
- VCSXMVPQDMMPIF-UHFFFAOYSA-N CCC(=O)NCCC#N Chemical compound CCC(=O)NCCC#N VCSXMVPQDMMPIF-UHFFFAOYSA-N 0.000 description 3
- IPFWLYJZTYYCPN-UHFFFAOYSA-N CCC(=O)NCCCOC(C)C Chemical compound CCC(=O)NCCCOC(C)C IPFWLYJZTYYCPN-UHFFFAOYSA-N 0.000 description 3
- VHOMAPWVLKRQAZ-UHFFFAOYSA-N CCC(=O)OCC1=CC=CC=C1 Chemical compound CCC(=O)OCC1=CC=CC=C1 VHOMAPWVLKRQAZ-UHFFFAOYSA-N 0.000 description 3
- JOLOYYRHPUVBJM-UHFFFAOYSA-N CCC(C)NC(=O)OC(C)(C)C Chemical compound CCC(C)NC(=O)OC(C)(C)C JOLOYYRHPUVBJM-UHFFFAOYSA-N 0.000 description 3
- PEFMXZJRCDFXFU-UHFFFAOYSA-N CCCCC(=O)NCC1=CC=CC=C1 Chemical compound CCCCC(=O)NCC1=CC=CC=C1 PEFMXZJRCDFXFU-UHFFFAOYSA-N 0.000 description 3
- KEBWOOMKEMSTRE-UHFFFAOYSA-N CCCCNC(=O)C1=CC(OC)=C(OC)C=C1 Chemical compound CCCCNC(=O)C1=CC(OC)=C(OC)C=C1 KEBWOOMKEMSTRE-UHFFFAOYSA-N 0.000 description 3
- ZZGQHICCVXGFTA-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC(S(C)(=O)=O)=C1 Chemical compound CCCCNC(=O)C1=CC=CC(S(C)(=O)=O)=C1 ZZGQHICCVXGFTA-UHFFFAOYSA-N 0.000 description 3
- LSQWYLYRHIIGND-UHFFFAOYSA-N CCCCNC(=O)C1CCCCCC1 Chemical compound CCCCNC(=O)C1CCCCCC1 LSQWYLYRHIIGND-UHFFFAOYSA-N 0.000 description 3
- LTVQBQWNOXXFQH-UHFFFAOYSA-N CCCCNC(=O)CC1=CC=CC=N1 Chemical compound CCCCNC(=O)CC1=CC=CC=N1 LTVQBQWNOXXFQH-UHFFFAOYSA-N 0.000 description 3
- KNABXILHUUESGV-UHFFFAOYSA-N CCCCNC(=O)NC1=C(C)C=C(CCCC)C=C1 Chemical compound CCCCNC(=O)NC1=C(C)C=C(CCCC)C=C1 KNABXILHUUESGV-UHFFFAOYSA-N 0.000 description 3
- DOUCJWNVCGEZRR-UHFFFAOYSA-N CCCCNC(=O)NC1=CC=CC=C1 Chemical compound CCCCNC(=O)NC1=CC=CC=C1 DOUCJWNVCGEZRR-UHFFFAOYSA-N 0.000 description 3
- MTTMAMTXCCOTIU-UHFFFAOYSA-N CCCNC(=O)C#CC1=CC=CC=C1 Chemical compound CCCNC(=O)C#CC1=CC=CC=C1 MTTMAMTXCCOTIU-UHFFFAOYSA-N 0.000 description 3
- MARWNCSRYSYKTR-UHFFFAOYSA-N CCCNC(=O)C1=C(C)C2=C(C=CC(Cl)=C2)S1 Chemical compound CCCNC(=O)C1=C(C)C2=C(C=CC(Cl)=C2)S1 MARWNCSRYSYKTR-UHFFFAOYSA-N 0.000 description 3
- GLLXKBGKVSOVAK-UHFFFAOYSA-N CCCNC(=O)C1=C(C)N=NS1 Chemical compound CCCNC(=O)C1=C(C)N=NS1 GLLXKBGKVSOVAK-UHFFFAOYSA-N 0.000 description 3
- PMRYKEPCZYJIMN-UHFFFAOYSA-N CCCNC(=O)C1=C(Cl)C(C)=CS1 Chemical compound CCCNC(=O)C1=C(Cl)C(C)=CS1 PMRYKEPCZYJIMN-UHFFFAOYSA-N 0.000 description 3
- NLLOIMOIOPQMOG-UHFFFAOYSA-N CCCNC(=O)C1=C(Cl)C=CS1 Chemical compound CCCNC(=O)C1=C(Cl)C=CS1 NLLOIMOIOPQMOG-UHFFFAOYSA-N 0.000 description 3
- APHNCTFMKZXGJY-UHFFFAOYSA-N CCCNC(=O)C1=C2CCCCC2=CS1 Chemical compound CCCNC(=O)C1=C2CCCCC2=CS1 APHNCTFMKZXGJY-UHFFFAOYSA-N 0.000 description 3
- RLFJQXGIIOLVKI-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(C#N)C=C1 Chemical compound CCCNC(=O)C1=CC=C(C#N)C=C1 RLFJQXGIIOLVKI-UHFFFAOYSA-N 0.000 description 3
- LNOMPWJHVMEYHM-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(C(C)=O)S1 Chemical compound CCCNC(=O)C1=CC=C(C(C)=O)S1 LNOMPWJHVMEYHM-UHFFFAOYSA-N 0.000 description 3
- IKEPZOWMJQLIJR-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 Chemical compound CCCNC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 IKEPZOWMJQLIJR-UHFFFAOYSA-N 0.000 description 3
- UIZMNZSBUBXXOG-UHFFFAOYSA-N CCCNC(=O)C1=CSC(Cl)=C1OC Chemical compound CCCNC(=O)C1=CSC(Cl)=C1OC UIZMNZSBUBXXOG-UHFFFAOYSA-N 0.000 description 3
- ZELDQXCYNWBBHM-UHFFFAOYSA-N CCCNC(=O)C1CCOCC1 Chemical compound CCCNC(=O)C1CCOCC1 ZELDQXCYNWBBHM-UHFFFAOYSA-N 0.000 description 3
- CUDKXVVKOCEJEY-QMMMGPOBSA-N CCCNC(=O)[C@@H]1CCCCN1 Chemical compound CCCNC(=O)[C@@H]1CCCCN1 CUDKXVVKOCEJEY-QMMMGPOBSA-N 0.000 description 3
- KNVGUBLHWBKVBV-ZCFIWIBFSA-N CCCNC(=O)[C@H]1CCN1 Chemical compound CCCNC(=O)[C@H]1CCN1 KNVGUBLHWBKVBV-ZCFIWIBFSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010047924 Wheezing Diseases 0.000 description 3
- RZVNETFQRBSXGB-JYSSDCQASA-M [(3r)-1-(3-aminopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride;hydrochloride Chemical compound Cl.[Cl-].O([C@@H]1C2CC[N+](CC2)(C1)CCCN)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 RZVNETFQRBSXGB-JYSSDCQASA-M 0.000 description 3
- XNPFOSZMEKWFRP-XZZGORAUSA-N [(3r)-1-[2-[(4-hydroxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C1=CC(O)=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 XNPFOSZMEKWFRP-XZZGORAUSA-N 0.000 description 3
- NQPFBZJRMCWKKR-BRKBLGTFSA-N [(3r)-1-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCCNC(=O)OC(C)(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 NQPFBZJRMCWKKR-BRKBLGTFSA-N 0.000 description 3
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- 229960004373 acetylcholine Drugs 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 3
- 102000014974 beta2-adrenergic receptor activity proteins Human genes 0.000 description 3
- 108040006828 beta2-adrenergic receptor activity proteins Proteins 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 230000003182 bronchodilatating effect Effects 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- DDRPCXLAQZKBJP-UHFFFAOYSA-N furfurylamine Chemical compound NCC1=CC=CO1 DDRPCXLAQZKBJP-UHFFFAOYSA-N 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 3
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 3
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
- TZRQZPMQUXEZMC-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCBr TZRQZPMQUXEZMC-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 3
- RHFWLPWDOYJEAL-UHFFFAOYSA-N 1,2-oxazol-3-amine Chemical compound NC=1C=CON=1 RHFWLPWDOYJEAL-UHFFFAOYSA-N 0.000 description 2
- NCADHSLPNSTDMJ-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]azetidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CC(C(O)=O)C1 NCADHSLPNSTDMJ-UHFFFAOYSA-N 0.000 description 2
- QTWRCKAEEXUAGN-FPJVJKMXSA-M 1-[(3r)-1-(2-aminoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2,2-diphenylethanone;chloride;hydrochloride Chemical compound Cl.[Cl-].O=C([C@@H]1C2CC[N+](CC2)(C1)CCN)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 QTWRCKAEEXUAGN-FPJVJKMXSA-M 0.000 description 2
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 2
- DCYGAPKNVCQNOE-UHFFFAOYSA-N 2,2,2-triphenylacetic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)O)C1=CC=CC=C1 DCYGAPKNVCQNOE-UHFFFAOYSA-N 0.000 description 2
- HFHNLWNFYUFJJS-UHFFFAOYSA-N 2-bromo-n-pyrimidin-4-ylacetamide Chemical compound BrCC(=O)NC1=CC=NC=N1 HFHNLWNFYUFJJS-UHFFFAOYSA-N 0.000 description 2
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 description 2
- YNWWOFMLRVRLAW-QBJDRERVSA-N 4-[(3r)-3-(2-hydroxy-2,2-diphenylacetyl)oxy-1-azoniabicyclo[2.2.2]octan-1-yl]butanoic acid;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCCC(=O)O)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 YNWWOFMLRVRLAW-QBJDRERVSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- AQSCHALQLXXKKC-UHFFFAOYSA-N 4-phenylmethoxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCC1=CC=CC=C1 AQSCHALQLXXKKC-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- XRFWKHVQMACVTA-UHFFFAOYSA-N C=CCOC(=O)CC Chemical compound C=CCOC(=O)CC XRFWKHVQMACVTA-UHFFFAOYSA-N 0.000 description 2
- TZKRMYSHIZVEKJ-UHFFFAOYSA-N CC#CC(=O)NCCC Chemical compound CC#CC(=O)NCCC TZKRMYSHIZVEKJ-UHFFFAOYSA-N 0.000 description 2
- NKTDTMONXHODTI-UHFFFAOYSA-N CC#CCC Chemical compound CC#CCC NKTDTMONXHODTI-UHFFFAOYSA-N 0.000 description 2
- MELUCTCJOARQQG-UHFFFAOYSA-N CC#CCCC Chemical compound CC#CCCC MELUCTCJOARQQG-UHFFFAOYSA-N 0.000 description 2
- YGFAGDNPORPFTC-UHFFFAOYSA-N CCC#CCN1C(=O)C2=C(C=CC=C2)C1=O Chemical compound CCC#CCN1C(=O)C2=C(C=CC=C2)C1=O YGFAGDNPORPFTC-UHFFFAOYSA-N 0.000 description 2
- HNCDGGUYKIJTLE-UHFFFAOYSA-N CCC(=O)N(C)C1=CC=CC=C1 Chemical compound CCC(=O)N(C)C1=CC=CC=C1 HNCDGGUYKIJTLE-UHFFFAOYSA-N 0.000 description 2
- KYKDOARTYFGHPC-UHFFFAOYSA-N CCC(=O)NC(C)C Chemical compound CCC(=O)NC(C)C KYKDOARTYFGHPC-UHFFFAOYSA-N 0.000 description 2
- IYGONUQBIMIRHJ-UHFFFAOYSA-N CCC(=O)NC1=C(C)C(C)=C(Br)C=N1 Chemical compound CCC(=O)NC1=C(C)C(C)=C(Br)C=N1 IYGONUQBIMIRHJ-UHFFFAOYSA-N 0.000 description 2
- MTRUXNRENSVOCE-UHFFFAOYSA-N CCC(=O)NC1=C(C)C(C)=NO1 Chemical compound CCC(=O)NC1=C(C)C(C)=NO1 MTRUXNRENSVOCE-UHFFFAOYSA-N 0.000 description 2
- VEANOUHGYWVFBZ-UHFFFAOYSA-N CCC(=O)NC1=C(O)C=CC=N1 Chemical compound CCC(=O)NC1=C(O)C=CC=N1 VEANOUHGYWVFBZ-UHFFFAOYSA-N 0.000 description 2
- HEIVMRKEARFNNK-UHFFFAOYSA-N CCC(=O)NC1=CC(C)=NN1C Chemical compound CCC(=O)NC1=CC(C)=NN1C HEIVMRKEARFNNK-UHFFFAOYSA-N 0.000 description 2
- LFULEKSKNZEWOE-UHFFFAOYSA-N CCC(=O)NC1=CC=C(Cl)C(Cl)=C1 Chemical compound CCC(=O)NC1=CC=C(Cl)C(Cl)=C1 LFULEKSKNZEWOE-UHFFFAOYSA-N 0.000 description 2
- FFHGCIYKPNISDY-UHFFFAOYSA-N CCC(=O)NC1=CC=C(Cl)C=C1 Chemical compound CCC(=O)NC1=CC=C(Cl)C=C1 FFHGCIYKPNISDY-UHFFFAOYSA-N 0.000 description 2
- SSMYTAQHMUHRSK-UHFFFAOYSA-N CCC(=O)NC1=CC=C(O)C=C1 Chemical compound CCC(=O)NC1=CC=C(O)C=C1 SSMYTAQHMUHRSK-UHFFFAOYSA-N 0.000 description 2
- JGOOIQJTIVEDES-UHFFFAOYSA-N CCC(=O)NC1=CC=C(OC)C=C1 Chemical compound CCC(=O)NC1=CC=C(OC)C=C1 JGOOIQJTIVEDES-UHFFFAOYSA-N 0.000 description 2
- XHHRFANWCYGWQW-UHFFFAOYSA-N CCC(=O)NC1=CC=C([N+](=O)[O-])C=C1 Chemical compound CCC(=O)NC1=CC=C([N+](=O)[O-])C=C1 XHHRFANWCYGWQW-UHFFFAOYSA-N 0.000 description 2
- ROPADTYAXYLKKQ-UHFFFAOYSA-N CCC(=O)NC1=CC=CC(CC)=N1 Chemical compound CCC(=O)NC1=CC=CC(CC)=N1 ROPADTYAXYLKKQ-UHFFFAOYSA-N 0.000 description 2
- LNXSTOYGBVLUGY-UHFFFAOYSA-N CCC(=O)NC1=CC=CC(Cl)=C1 Chemical compound CCC(=O)NC1=CC=CC(Cl)=C1 LNXSTOYGBVLUGY-UHFFFAOYSA-N 0.000 description 2
- YXSKGOCVSTWEJU-UHFFFAOYSA-N CCC(=O)NC1=CC=CC(O)=C1 Chemical compound CCC(=O)NC1=CC=CC(O)=C1 YXSKGOCVSTWEJU-UHFFFAOYSA-N 0.000 description 2
- GCLTULYRNJFGNC-UHFFFAOYSA-N CCC(=O)NC1=CC=CC=C1Br Chemical compound CCC(=O)NC1=CC=CC=C1Br GCLTULYRNJFGNC-UHFFFAOYSA-N 0.000 description 2
- OOZZQDJPLCJMML-UHFFFAOYSA-N CCC(=O)NC1=CC=CC=C1C Chemical compound CCC(=O)NC1=CC=CC=C1C OOZZQDJPLCJMML-UHFFFAOYSA-N 0.000 description 2
- VCVUMBWLSGNGFA-UHFFFAOYSA-N CCC(=O)NC1=CC=CC=C1Cl Chemical compound CCC(=O)NC1=CC=CC=C1Cl VCVUMBWLSGNGFA-UHFFFAOYSA-N 0.000 description 2
- DCGZZKDVNPMJHZ-UHFFFAOYSA-N CCC(=O)NC1=CC=CC=N1 Chemical compound CCC(=O)NC1=CC=CC=N1 DCGZZKDVNPMJHZ-UHFFFAOYSA-N 0.000 description 2
- QQASUXQGFWJISL-UHFFFAOYSA-N CCC(=O)NC1=CC=CN=C1 Chemical compound CCC(=O)NC1=CC=CN=C1 QQASUXQGFWJISL-UHFFFAOYSA-N 0.000 description 2
- XVWRQKKRVAHDMU-UHFFFAOYSA-N CCC(=O)NC1=CC=NC=C1 Chemical compound CCC(=O)NC1=CC=NC=C1 XVWRQKKRVAHDMU-UHFFFAOYSA-N 0.000 description 2
- VFDCDIBHMVGRKT-UHFFFAOYSA-N CCC(=O)NC1=CC=NC=C1C(F)(F)F Chemical compound CCC(=O)NC1=CC=NC=C1C(F)(F)F VFDCDIBHMVGRKT-UHFFFAOYSA-N 0.000 description 2
- QQVCTMKMNIWRJK-UHFFFAOYSA-N CCC(=O)NC1=CC=NN1CC Chemical compound CCC(=O)NC1=CC=NN1CC QQVCTMKMNIWRJK-UHFFFAOYSA-N 0.000 description 2
- JAGYCRPGTCYSMZ-UHFFFAOYSA-N CCC(=O)NC1=NC(C)=CC=N1 Chemical compound CCC(=O)NC1=NC(C)=CC=N1 JAGYCRPGTCYSMZ-UHFFFAOYSA-N 0.000 description 2
- MFPMIGRMKUOXNL-UHFFFAOYSA-N CCC(=O)NC1=NC(C)=CO1 Chemical compound CCC(=O)NC1=NC(C)=CO1 MFPMIGRMKUOXNL-UHFFFAOYSA-N 0.000 description 2
- AIOZNYOAFODHNA-UHFFFAOYSA-N CCC(=O)NC1=NC(C)=CS1 Chemical compound CCC(=O)NC1=NC(C)=CS1 AIOZNYOAFODHNA-UHFFFAOYSA-N 0.000 description 2
- LDJUPXNORPVNKE-UHFFFAOYSA-N CCC(=O)NC1=NC(C)=NS1 Chemical compound CCC(=O)NC1=NC(C)=NS1 LDJUPXNORPVNKE-UHFFFAOYSA-N 0.000 description 2
- MOROBGYKYCOMJB-UHFFFAOYSA-N CCC(=O)NC1CC2=C(C=C(CC)C(CC)=C2)C1 Chemical compound CCC(=O)NC1CC2=C(C=C(CC)C(CC)=C2)C1 MOROBGYKYCOMJB-UHFFFAOYSA-N 0.000 description 2
- OSLMDZTZEPAYCP-UHFFFAOYSA-N CCC(=O)NC1CCCCC1 Chemical compound CCC(=O)NC1CCCCC1 OSLMDZTZEPAYCP-UHFFFAOYSA-N 0.000 description 2
- DIAQLYQNZGJGSG-UHFFFAOYSA-N CCC(=O)NCC1=CC(Cl)=C(Cl)C=C1 Chemical compound CCC(=O)NCC1=CC(Cl)=C(Cl)C=C1 DIAQLYQNZGJGSG-UHFFFAOYSA-N 0.000 description 2
- NXEHUVBLMTVJGJ-UHFFFAOYSA-N CCC(=O)NCC1=CC=C(C)C=C1 Chemical compound CCC(=O)NCC1=CC=C(C)C=C1 NXEHUVBLMTVJGJ-UHFFFAOYSA-N 0.000 description 2
- PWBNDMWSJOLKMW-UHFFFAOYSA-N CCC(=O)NCC1=CC=C(Cl)C=C1 Chemical compound CCC(=O)NCC1=CC=C(Cl)C=C1 PWBNDMWSJOLKMW-UHFFFAOYSA-N 0.000 description 2
- FHOUWLZBMAEMHM-UHFFFAOYSA-N CCC(=O)NCC1=CC=CC2=CC=CC=C21 Chemical compound CCC(=O)NCC1=CC=CC2=CC=CC=C21 FHOUWLZBMAEMHM-UHFFFAOYSA-N 0.000 description 2
- WJPQWWMWVNNVOG-UHFFFAOYSA-N CCC(=O)NCC1=CC=CC=C1Cl Chemical compound CCC(=O)NCC1=CC=CC=C1Cl WJPQWWMWVNNVOG-UHFFFAOYSA-N 0.000 description 2
- WGSUSGRCTBVQMS-UHFFFAOYSA-N CCC(=O)NCC1=CC=CO1 Chemical compound CCC(=O)NCC1=CC=CO1 WGSUSGRCTBVQMS-UHFFFAOYSA-N 0.000 description 2
- GKEWNISANMMAMX-UHFFFAOYSA-N CCC(=O)NCC1=CC=CS1 Chemical compound CCC(=O)NCC1=CC=CS1 GKEWNISANMMAMX-UHFFFAOYSA-N 0.000 description 2
- PCOUSFYVLFMDCP-UHFFFAOYSA-N CCC(=O)NCC1CC1 Chemical compound CCC(=O)NCC1CC1 PCOUSFYVLFMDCP-UHFFFAOYSA-N 0.000 description 2
- SOGZMDYBQZTXIJ-UHFFFAOYSA-N CCC(=O)NCC1CCCCC1 Chemical compound CCC(=O)NCC1CCCCC1 SOGZMDYBQZTXIJ-UHFFFAOYSA-N 0.000 description 2
- ZXNZKPHZMIMFGR-UHFFFAOYSA-N CCC(=O)NCCC1=CC=C(S(N)(=O)=O)C=C1 Chemical compound CCC(=O)NCCC1=CC=C(S(N)(=O)=O)C=C1 ZXNZKPHZMIMFGR-UHFFFAOYSA-N 0.000 description 2
- IABUULYQQIHCIL-UHFFFAOYSA-N CCC(=O)NCCC1=CC=CC=C1 Chemical compound CCC(=O)NCCC1=CC=CC=C1 IABUULYQQIHCIL-UHFFFAOYSA-N 0.000 description 2
- GQMRZIWAPUVJJD-UHFFFAOYSA-N CCC(=O)NCCC1=CC=CS1 Chemical compound CCC(=O)NCCC1=CC=CS1 GQMRZIWAPUVJJD-UHFFFAOYSA-N 0.000 description 2
- QVVOHYJKTAVJDX-UHFFFAOYSA-N CCC(=O)NCCCN1CCCC1=O Chemical compound CCC(=O)NCCCN1CCCC1=O QVVOHYJKTAVJDX-UHFFFAOYSA-N 0.000 description 2
- CVKMCTKUFWPCBY-UHFFFAOYSA-N CCC(=O)NCCOC Chemical compound CCC(=O)NCCOC CVKMCTKUFWPCBY-UHFFFAOYSA-N 0.000 description 2
- JAELLLITIZHOGQ-UHFFFAOYSA-N CCC(=O)OC(C)(C)C Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 2
- DYUMLJSJISTVPV-UHFFFAOYSA-N CCC(=O)OC1=CC=CC=C1 Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 2
- BHRZNVHARXXAHW-UHFFFAOYSA-N CCC(C)N Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 0.000 description 2
- WSCVMXQGRHTYEP-UHFFFAOYSA-N CCC(C)NC(=O)C1=CC=CC=C1 Chemical compound CCC(C)NC(=O)C1=CC=CC=C1 WSCVMXQGRHTYEP-UHFFFAOYSA-N 0.000 description 2
- QZZUEBNBZAPZLX-QFIPXVFZSA-N CCC1=CC2=C(C=C1CC)CC(NC[C@H](O)C1=C3C=CC(=O)NC3=C(O)C=C1)C2 Chemical compound CCC1=CC2=C(C=C1CC)CC(NC[C@H](O)C1=C3C=CC(=O)NC3=C(O)C=C1)C2 QZZUEBNBZAPZLX-QFIPXVFZSA-N 0.000 description 2
- BFGORQVKKUDFKQ-UHFFFAOYSA-N CCCCC(=O)N(C)C1=CC=CC=C1 Chemical compound CCCCC(=O)N(C)C1=CC=CC=C1 BFGORQVKKUDFKQ-UHFFFAOYSA-N 0.000 description 2
- PGMBORLSOHYBFJ-UHFFFAOYSA-N CCCCC(=O)NC1=CC=CC=C1 Chemical compound CCCCC(=O)NC1=CC=CC=C1 PGMBORLSOHYBFJ-UHFFFAOYSA-N 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N CCCCC(=O)O Chemical compound CCCCC(=O)O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- SCSLUABEVMLYEA-UHFFFAOYSA-N CCCCC(=O)OC(C)(C)C Chemical compound CCCCC(=O)OC(C)(C)C SCSLUABEVMLYEA-UHFFFAOYSA-N 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N CCCCN Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- CWLSNKCMKWFVHV-UHFFFAOYSA-N CCCCN(C)C(=O)OC(C)(C)C Chemical compound CCCCN(C)C(=O)OC(C)(C)C CWLSNKCMKWFVHV-UHFFFAOYSA-N 0.000 description 2
- GZAROOOHRGKEPC-UHFFFAOYSA-N CCCCNC(=O)C(C)C Chemical compound CCCCNC(=O)C(C)C GZAROOOHRGKEPC-UHFFFAOYSA-N 0.000 description 2
- SFCPQTHFUJOUGH-UHFFFAOYSA-N CCCCNC(=O)C1=C(C#N)C=CC=C1 Chemical compound CCCCNC(=O)C1=C(C#N)C=CC=C1 SFCPQTHFUJOUGH-UHFFFAOYSA-N 0.000 description 2
- FPEGZHZPRMWZJR-UHFFFAOYSA-N CCCCNC(=O)C1=C(C)C=CC=C1C Chemical compound CCCCNC(=O)C1=C(C)C=CC=C1C FPEGZHZPRMWZJR-UHFFFAOYSA-N 0.000 description 2
- IJUQKMXTGSUKLP-UHFFFAOYSA-N CCCCNC(=O)C1=C(OC)C(OC)=CC=C1 Chemical compound CCCCNC(=O)C1=C(OC)C(OC)=CC=C1 IJUQKMXTGSUKLP-UHFFFAOYSA-N 0.000 description 2
- KCHRXUYOOLSMST-UHFFFAOYSA-N CCCCNC(=O)C1=C(OC)C=C(OC)C=C1 Chemical compound CCCCNC(=O)C1=C(OC)C=C(OC)C=C1 KCHRXUYOOLSMST-UHFFFAOYSA-N 0.000 description 2
- VNKGKMPGQVYXMM-UHFFFAOYSA-N CCCCNC(=O)C1=C(OC)C=CC=C1 Chemical compound CCCCNC(=O)C1=C(OC)C=CC=C1 VNKGKMPGQVYXMM-UHFFFAOYSA-N 0.000 description 2
- BCMPZFUMPIOQSO-UHFFFAOYSA-N CCCCNC(=O)C1=CC(C#N)=CC=C1 Chemical compound CCCCNC(=O)C1=CC(C#N)=CC=C1 BCMPZFUMPIOQSO-UHFFFAOYSA-N 0.000 description 2
- SFBUGRSGACNSHS-UHFFFAOYSA-N CCCCNC(=O)C1=CC(C)=CC(C)=C1 Chemical compound CCCCNC(=O)C1=CC(C)=CC(C)=C1 SFBUGRSGACNSHS-UHFFFAOYSA-N 0.000 description 2
- RTYMOQRHVZDYQI-UHFFFAOYSA-N CCCCNC(=O)C1=CC(F)=C(OC)C=C1 Chemical compound CCCCNC(=O)C1=CC(F)=C(OC)C=C1 RTYMOQRHVZDYQI-UHFFFAOYSA-N 0.000 description 2
- AMVFIDNKEHIPPE-UHFFFAOYSA-N CCCCNC(=O)C1=CC(OC)=CC(OC)=C1 Chemical compound CCCCNC(=O)C1=CC(OC)=CC(OC)=C1 AMVFIDNKEHIPPE-UHFFFAOYSA-N 0.000 description 2
- MAWFHMSYICLJIM-UHFFFAOYSA-N CCCCNC(=O)C1=CC(OC)=CC=C1 Chemical compound CCCCNC(=O)C1=CC(OC)=CC=C1 MAWFHMSYICLJIM-UHFFFAOYSA-N 0.000 description 2
- IKCJNZVSLPKXLB-UHFFFAOYSA-N CCCCNC(=O)C1=CC2=C(C=CC=C2)C=C1 Chemical compound CCCCNC(=O)C1=CC2=C(C=CC=C2)C=C1 IKCJNZVSLPKXLB-UHFFFAOYSA-N 0.000 description 2
- BLFXAAJEVQDEPW-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(C#N)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(C#N)C=C1 BLFXAAJEVQDEPW-UHFFFAOYSA-N 0.000 description 2
- YSXNZUCHDLXTRZ-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(C(F)(F)F)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(C(F)(F)F)C=C1 YSXNZUCHDLXTRZ-UHFFFAOYSA-N 0.000 description 2
- WGSJUYGDRVTDJJ-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(C2=CC=CC=C2)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(C2=CC=CC=C2)C=C1 WGSJUYGDRVTDJJ-UHFFFAOYSA-N 0.000 description 2
- KAFBLXVBYGBBKH-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(CC)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(CC)C=C1 KAFBLXVBYGBBKH-UHFFFAOYSA-N 0.000 description 2
- WBKMAVFQCXJDDT-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(Cl)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(Cl)C=C1 WBKMAVFQCXJDDT-UHFFFAOYSA-N 0.000 description 2
- SMFXKURBPKLMMC-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(N2C=CC=C2)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(N2C=CC=C2)C=C1 SMFXKURBPKLMMC-UHFFFAOYSA-N 0.000 description 2
- OMTDEZKSEMZLHO-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(OC(C)C)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(OC(C)C)C=C1 OMTDEZKSEMZLHO-UHFFFAOYSA-N 0.000 description 2
- PCJWVQUPHYPGIE-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(OC)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(OC)C=C1 PCJWVQUPHYPGIE-UHFFFAOYSA-N 0.000 description 2
- CQSSXBUAUOOYFP-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC(C(F)(F)F)=C1 Chemical compound CCCCNC(=O)C1=CC=CC(C(F)(F)F)=C1 CQSSXBUAUOOYFP-UHFFFAOYSA-N 0.000 description 2
- NKQOQWJDLCYELT-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC(Cl)=C1 Chemical compound CCCCNC(=O)C1=CC=CC(Cl)=C1 NKQOQWJDLCYELT-UHFFFAOYSA-N 0.000 description 2
- BAULSHLTGVOYKM-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC=C1 Chemical compound CCCCNC(=O)C1=CC=CC=C1 BAULSHLTGVOYKM-UHFFFAOYSA-N 0.000 description 2
- FMQDDICEJGNHTL-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC=C1C(F)(F)F Chemical compound CCCCNC(=O)C1=CC=CC=C1C(F)(F)F FMQDDICEJGNHTL-UHFFFAOYSA-N 0.000 description 2
- PERRBGDAOVSLIV-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC=C1Cl Chemical compound CCCCNC(=O)C1=CC=CC=C1Cl PERRBGDAOVSLIV-UHFFFAOYSA-N 0.000 description 2
- YMVFINNWXDYUKB-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC=C1S(C)(=O)=O Chemical compound CCCCNC(=O)C1=CC=CC=C1S(C)(=O)=O YMVFINNWXDYUKB-UHFFFAOYSA-N 0.000 description 2
- YRNIXNMRAQAEON-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CC=C1[N+](=O)[O-] Chemical compound CCCCNC(=O)C1=CC=CC=C1[N+](=O)[O-] YRNIXNMRAQAEON-UHFFFAOYSA-N 0.000 description 2
- IIYYDBVPDWCIFL-UHFFFAOYSA-N CCCCNC(=O)C1=CC=CN=C1C Chemical compound CCCCNC(=O)C1=CC=CN=C1C IIYYDBVPDWCIFL-UHFFFAOYSA-N 0.000 description 2
- IDNGPRYAMMACEI-UHFFFAOYSA-N CCCCNC(=O)C1=CC=NC=C1 Chemical compound CCCCNC(=O)C1=CC=NC=C1 IDNGPRYAMMACEI-UHFFFAOYSA-N 0.000 description 2
- ZGJYDNSUCSSKMU-UHFFFAOYSA-N CCCCNC(=O)C1=CN=CC=C1 Chemical compound CCCCNC(=O)C1=CN=CC=C1 ZGJYDNSUCSSKMU-UHFFFAOYSA-N 0.000 description 2
- WIKJTTMIIUENIR-UHFFFAOYSA-N CCCCNC(=O)C1=CN=CC=N1 Chemical compound CCCCNC(=O)C1=CN=CC=N1 WIKJTTMIIUENIR-UHFFFAOYSA-N 0.000 description 2
- QZPUBZPFCZHUMI-UHFFFAOYSA-N CCCCNC(=O)C1=NC=CC=C1 Chemical compound CCCCNC(=O)C1=NC=CC=C1 QZPUBZPFCZHUMI-UHFFFAOYSA-N 0.000 description 2
- WSCVIFLDAWYBMW-UHFFFAOYSA-N CCCCNC(=O)C1=NOC(C)=C1 Chemical compound CCCCNC(=O)C1=NOC(C)=C1 WSCVIFLDAWYBMW-UHFFFAOYSA-N 0.000 description 2
- SVCHLPOCRNNCNA-UHFFFAOYSA-N CCCCNC(=O)C1CC2=C(C=CC=C2)C1 Chemical compound CCCCNC(=O)C1CC2=C(C=CC=C2)C1 SVCHLPOCRNNCNA-UHFFFAOYSA-N 0.000 description 2
- ZDYDDKTZZLZSGO-UHFFFAOYSA-N CCCCNC(=O)C1CCCC1 Chemical compound CCCCNC(=O)C1CCCC1 ZDYDDKTZZLZSGO-UHFFFAOYSA-N 0.000 description 2
- WHJBSNFKYDXSDN-UHFFFAOYSA-N CCCCNC(=O)C1CCCCC1 Chemical compound CCCCNC(=O)C1CCCCC1 WHJBSNFKYDXSDN-UHFFFAOYSA-N 0.000 description 2
- VMYAYGQHSOVGHM-UHFFFAOYSA-N CCCCNC(=O)C1CCN(C(C)=O)CC1 Chemical compound CCCCNC(=O)C1CCN(C(C)=O)CC1 VMYAYGQHSOVGHM-UHFFFAOYSA-N 0.000 description 2
- GBKLGIAEHPXBIT-UHFFFAOYSA-N CCCCNC(=O)CC(C)(C)C Chemical compound CCCCNC(=O)CC(C)(C)C GBKLGIAEHPXBIT-UHFFFAOYSA-N 0.000 description 2
- JQZKYZUXIWDPAD-UHFFFAOYSA-N CCCCNC(=O)CC1=CC=CC=C1 Chemical compound CCCCNC(=O)CC1=CC=CC=C1 JQZKYZUXIWDPAD-UHFFFAOYSA-N 0.000 description 2
- XLRYJQPBOZDPRE-UHFFFAOYSA-N CCCCNC(=O)CC1CCCC1 Chemical compound CCCCNC(=O)CC1CCCC1 XLRYJQPBOZDPRE-UHFFFAOYSA-N 0.000 description 2
- UZTVEZLZUTUCBJ-UHFFFAOYSA-N CCCCNC(=O)CCC1=CC=CC=C1 Chemical compound CCCCNC(=O)CCC1=CC=CC=C1 UZTVEZLZUTUCBJ-UHFFFAOYSA-N 0.000 description 2
- IPRJXAGUEGOFGG-UHFFFAOYSA-N CCCCNS(=O)(=O)C1=CC=CC=C1 Chemical compound CCCCNS(=O)(=O)C1=CC=CC=C1 IPRJXAGUEGOFGG-UHFFFAOYSA-N 0.000 description 2
- AEYBXFRYLBPSBB-UHFFFAOYSA-N CCCN(C)C(=O)C1=CC=CC=C1 Chemical compound CCCN(C)C(=O)C1=CC=CC=C1 AEYBXFRYLBPSBB-UHFFFAOYSA-N 0.000 description 2
- GVWISOJSERXQBM-UHFFFAOYSA-N CCCNC Chemical compound CCCNC GVWISOJSERXQBM-UHFFFAOYSA-N 0.000 description 2
- PAJCXILGGZEVFP-UHFFFAOYSA-N CCCNC(=O)C1(O)CC1 Chemical compound CCCNC(=O)C1(O)CC1 PAJCXILGGZEVFP-UHFFFAOYSA-N 0.000 description 2
- RVAMEMQMIYPLGW-UHFFFAOYSA-N CCCNC(=O)C1=C(Br)C=CS1 Chemical compound CCCNC(=O)C1=C(Br)C=CS1 RVAMEMQMIYPLGW-UHFFFAOYSA-N 0.000 description 2
- MAAYBWDOVAXVRM-UHFFFAOYSA-N CCCNC(=O)C1=C(C#N)C=CC=C1 Chemical compound CCCNC(=O)C1=C(C#N)C=CC=C1 MAAYBWDOVAXVRM-UHFFFAOYSA-N 0.000 description 2
- VLLYUSXCJYKKAB-UHFFFAOYSA-N CCCNC(=O)C1=C(C(F)(F)F)C=CC=C1 Chemical compound CCCNC(=O)C1=C(C(F)(F)F)C=CC=C1 VLLYUSXCJYKKAB-UHFFFAOYSA-N 0.000 description 2
- GVOPBWSGBHIQQX-UHFFFAOYSA-N CCCNC(=O)C1=C(C(F)(F)F)N=C2N=CC=CC2=C1 Chemical compound CCCNC(=O)C1=C(C(F)(F)F)N=C2N=CC=CC2=C1 GVOPBWSGBHIQQX-UHFFFAOYSA-N 0.000 description 2
- KUBOCROYARJLEU-UHFFFAOYSA-N CCCNC(=O)C1=C(C(F)(F)F)ON=C1C Chemical compound CCCNC(=O)C1=C(C(F)(F)F)ON=C1C KUBOCROYARJLEU-UHFFFAOYSA-N 0.000 description 2
- ISRAHYXZPAHWIU-UHFFFAOYSA-N CCCNC(=O)C1=C(C)C2=C(C=CC=C2)S1 Chemical compound CCCNC(=O)C1=C(C)C2=C(C=CC=C2)S1 ISRAHYXZPAHWIU-UHFFFAOYSA-N 0.000 description 2
- OXTIAHCZDBXCTO-UHFFFAOYSA-N CCCNC(=O)C1=C(C)C=CC=C1C Chemical compound CCCNC(=O)C1=C(C)C=CC=C1C OXTIAHCZDBXCTO-UHFFFAOYSA-N 0.000 description 2
- XUCRFPTYZRDMTD-UHFFFAOYSA-N CCCNC(=O)C1=C(C)C=CO1 Chemical compound CCCNC(=O)C1=C(C)C=CO1 XUCRFPTYZRDMTD-UHFFFAOYSA-N 0.000 description 2
- ITVFATCTWAPRAL-UHFFFAOYSA-N CCCNC(=O)C1=C(C)C=CS1 Chemical compound CCCNC(=O)C1=C(C)C=CS1 ITVFATCTWAPRAL-UHFFFAOYSA-N 0.000 description 2
- KNHDWNRGGOIQFG-UHFFFAOYSA-N CCCNC(=O)C1=C(C)N=C2C=C(C)C=CN21 Chemical compound CCCNC(=O)C1=C(C)N=C2C=C(C)C=CN21 KNHDWNRGGOIQFG-UHFFFAOYSA-N 0.000 description 2
- YNVNHNOPVIZVCZ-UHFFFAOYSA-N CCCNC(=O)C1=C(C)OC(C)=C1 Chemical compound CCCNC(=O)C1=C(C)OC(C)=C1 YNVNHNOPVIZVCZ-UHFFFAOYSA-N 0.000 description 2
- GUJGEKHMVZXVTI-UHFFFAOYSA-N CCCNC(=O)C1=C(C)ON=C1C Chemical compound CCCNC(=O)C1=C(C)ON=C1C GUJGEKHMVZXVTI-UHFFFAOYSA-N 0.000 description 2
- WTBAHJPARTVJQR-UHFFFAOYSA-N CCCNC(=O)C1=C(Cl)C(S(C)(=O)=O)=CS1 Chemical compound CCCNC(=O)C1=C(Cl)C(S(C)(=O)=O)=CS1 WTBAHJPARTVJQR-UHFFFAOYSA-N 0.000 description 2
- PYRRKMSJTDHWNG-UHFFFAOYSA-N CCCNC(=O)C1=C(OC)C=C(OC)C=C1 Chemical compound CCCNC(=O)C1=C(OC)C=C(OC)C=C1 PYRRKMSJTDHWNG-UHFFFAOYSA-N 0.000 description 2
- UFTFPZFKCRNLBM-UHFFFAOYSA-N CCCNC(=O)C1=C(OC)C=CC(Cl)=C1 Chemical compound CCCNC(=O)C1=C(OC)C=CC(Cl)=C1 UFTFPZFKCRNLBM-UHFFFAOYSA-N 0.000 description 2
- DQBXKRNGBFVBLY-UHFFFAOYSA-N CCCNC(=O)C1=C(OC)C=CC=C1 Chemical compound CCCNC(=O)C1=C(OC)C=CC=C1 DQBXKRNGBFVBLY-UHFFFAOYSA-N 0.000 description 2
- JRUHCRDZYOGRLJ-UHFFFAOYSA-N CCCNC(=O)C1=C(OC)C=CC=C1OC Chemical compound CCCNC(=O)C1=C(OC)C=CC=C1OC JRUHCRDZYOGRLJ-UHFFFAOYSA-N 0.000 description 2
- HNCGYLMBTWIRQW-UHFFFAOYSA-N CCCNC(=O)C1=C(OC)C=CS1 Chemical compound CCCNC(=O)C1=C(OC)C=CS1 HNCGYLMBTWIRQW-UHFFFAOYSA-N 0.000 description 2
- CVWDDPHPIIUXGH-UHFFFAOYSA-N CCCNC(=O)C1=C(OC)N=CC=C1 Chemical compound CCCNC(=O)C1=C(OC)N=CC=C1 CVWDDPHPIIUXGH-UHFFFAOYSA-N 0.000 description 2
- FLBLWPRJLLKAOV-UHFFFAOYSA-N CCCNC(=O)C1=C(OCC)C=CS1 Chemical compound CCCNC(=O)C1=C(OCC)C=CS1 FLBLWPRJLLKAOV-UHFFFAOYSA-N 0.000 description 2
- OPQNVKBIBGFOCD-UHFFFAOYSA-N CCCNC(=O)C1=CC(C(F)(F)F)=CC=C1 Chemical compound CCCNC(=O)C1=CC(C(F)(F)F)=CC=C1 OPQNVKBIBGFOCD-UHFFFAOYSA-N 0.000 description 2
- SMTKIXBQEUFZDD-UHFFFAOYSA-N CCCNC(=O)C1=CC(C)=NN1C Chemical compound CCCNC(=O)C1=CC(C)=NN1C SMTKIXBQEUFZDD-UHFFFAOYSA-N 0.000 description 2
- AJMSRHNEAANECG-UHFFFAOYSA-N CCCNC(=O)C1=CC(Cl)=CC=C1 Chemical compound CCCNC(=O)C1=CC(Cl)=CC=C1 AJMSRHNEAANECG-UHFFFAOYSA-N 0.000 description 2
- HDWSLGBDYCXKCX-UHFFFAOYSA-N CCCNC(=O)C1=CC(F)=CC2=C1OCOC2 Chemical compound CCCNC(=O)C1=CC(F)=CC2=C1OCOC2 HDWSLGBDYCXKCX-UHFFFAOYSA-N 0.000 description 2
- MPYJKFQVOBQILB-UHFFFAOYSA-N CCCNC(=O)C1=CC(O)=NC(C)=C1 Chemical compound CCCNC(=O)C1=CC(O)=NC(C)=C1 MPYJKFQVOBQILB-UHFFFAOYSA-N 0.000 description 2
- IXLDZEGNMDSKHS-UHFFFAOYSA-N CCCNC(=O)C1=CC(OC)=C(OC)C=C1 Chemical compound CCCNC(=O)C1=CC(OC)=C(OC)C=C1 IXLDZEGNMDSKHS-UHFFFAOYSA-N 0.000 description 2
- UPMKYKHVFQTXJY-UHFFFAOYSA-N CCCNC(=O)C1=CC(OC)=CC(OC)=C1 Chemical compound CCCNC(=O)C1=CC(OC)=CC(OC)=C1 UPMKYKHVFQTXJY-UHFFFAOYSA-N 0.000 description 2
- XOKXCBFLSDEEIB-UHFFFAOYSA-N CCCNC(=O)C1=CC(OC)=CC=C1 Chemical compound CCCNC(=O)C1=CC(OC)=CC=C1 XOKXCBFLSDEEIB-UHFFFAOYSA-N 0.000 description 2
- VMICKIUUWVRQDJ-UHFFFAOYSA-N CCCNC(=O)C1=CC(S(C)(=O)=O)=CC=C1 Chemical compound CCCNC(=O)C1=CC(S(C)(=O)=O)=CC=C1 VMICKIUUWVRQDJ-UHFFFAOYSA-N 0.000 description 2
- AYDBSODEUKDWOU-UHFFFAOYSA-N CCCNC(=O)C1=CC2=C(C=CC=C2)C=C1 Chemical compound CCCNC(=O)C1=CC2=C(C=CC=C2)C=C1 AYDBSODEUKDWOU-UHFFFAOYSA-N 0.000 description 2
- WVKBROSRSRMKLV-UHFFFAOYSA-N CCCNC(=O)C1=CC2=C(C=CS2)S1 Chemical compound CCCNC(=O)C1=CC2=C(C=CS2)S1 WVKBROSRSRMKLV-UHFFFAOYSA-N 0.000 description 2
- NYRGYNRETDYFOW-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(Br)O1 Chemical compound CCCNC(=O)C1=CC=C(Br)O1 NYRGYNRETDYFOW-UHFFFAOYSA-N 0.000 description 2
- YRLNOXHJFHHLRC-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(Br)S1 Chemical compound CCCNC(=O)C1=CC=C(Br)S1 YRLNOXHJFHHLRC-UHFFFAOYSA-N 0.000 description 2
- SLODDXKEKAZOIL-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(C(F)(F)F)C=C1 Chemical compound CCCNC(=O)C1=CC=C(C(F)(F)F)C=C1 SLODDXKEKAZOIL-UHFFFAOYSA-N 0.000 description 2
- NJFWTSPUTLPZLL-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(C2=CC=CC=C2)C=C1 Chemical compound CCCNC(=O)C1=CC=C(C2=CC=CC=C2)C=C1 NJFWTSPUTLPZLL-UHFFFAOYSA-N 0.000 description 2
- KTOSFDDONGKMID-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(CC)C=C1 Chemical compound CCCNC(=O)C1=CC=C(CC)C=C1 KTOSFDDONGKMID-UHFFFAOYSA-N 0.000 description 2
- AZCPRUGQAUVUGG-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(Cl)C=C1 Chemical compound CCCNC(=O)C1=CC=C(Cl)C=C1 AZCPRUGQAUVUGG-UHFFFAOYSA-N 0.000 description 2
- HGZNCKODYKCUMS-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(Cl)S1 Chemical compound CCCNC(=O)C1=CC=C(Cl)S1 HGZNCKODYKCUMS-UHFFFAOYSA-N 0.000 description 2
- GIWBANLWMRHDQZ-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(F)C(Cl)=C1 Chemical compound CCCNC(=O)C1=CC=C(F)C(Cl)=C1 GIWBANLWMRHDQZ-UHFFFAOYSA-N 0.000 description 2
- FANUXYVEDSVSIW-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(N2C=CC=C2)C=C1 Chemical compound CCCNC(=O)C1=CC=C(N2C=CC=C2)C=C1 FANUXYVEDSVSIW-UHFFFAOYSA-N 0.000 description 2
- FOHAXXVIYAVXST-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(O)C=C1 Chemical compound CCCNC(=O)C1=CC=C(O)C=C1 FOHAXXVIYAVXST-UHFFFAOYSA-N 0.000 description 2
- SAKGWTFXSHCZGU-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(OC(C)C)C=C1 Chemical compound CCCNC(=O)C1=CC=C(OC(C)C)C=C1 SAKGWTFXSHCZGU-UHFFFAOYSA-N 0.000 description 2
- DCTXOCAIFUZKRH-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(OC)C=C1 Chemical compound CCCNC(=O)C1=CC=C(OC)C=C1 DCTXOCAIFUZKRH-UHFFFAOYSA-N 0.000 description 2
- IPPOWFRBKCNPGB-UHFFFAOYSA-N CCCNC(=O)C1=CC=C(OC)S1 Chemical compound CCCNC(=O)C1=CC=C(OC)S1 IPPOWFRBKCNPGB-UHFFFAOYSA-N 0.000 description 2
- FGLJTRFNCUWYNO-UHFFFAOYSA-N CCCNC(=O)C1=CC=C([N+](=O)[O-])O1 Chemical compound CCCNC(=O)C1=CC=C([N+](=O)[O-])O1 FGLJTRFNCUWYNO-UHFFFAOYSA-N 0.000 description 2
- BGOKXRSVSLGTAT-UHFFFAOYSA-N CCCNC(=O)C1=CC=CC(O)=C1 Chemical compound CCCNC(=O)C1=CC=CC(O)=C1 BGOKXRSVSLGTAT-UHFFFAOYSA-N 0.000 description 2
- DYZWXBMTHNHXML-UHFFFAOYSA-N CCCNC(=O)C1=CC=CC=C1 Chemical compound CCCNC(=O)C1=CC=CC=C1 DYZWXBMTHNHXML-UHFFFAOYSA-N 0.000 description 2
- BMWAABRBTKIPAR-UHFFFAOYSA-N CCCNC(=O)C1=CC=CC=C1OCCC Chemical compound CCCNC(=O)C1=CC=CC=C1OCCC BMWAABRBTKIPAR-UHFFFAOYSA-N 0.000 description 2
- ZKJYUBHTDYLCQE-UHFFFAOYSA-N CCCNC(=O)C1=CC=CN1C Chemical compound CCCNC(=O)C1=CC=CN1C ZKJYUBHTDYLCQE-UHFFFAOYSA-N 0.000 description 2
- CGOIKKOEFBUPMP-UHFFFAOYSA-N CCCNC(=O)C1=CC=CO1 Chemical compound CCCNC(=O)C1=CC=CO1 CGOIKKOEFBUPMP-UHFFFAOYSA-N 0.000 description 2
- ZJJYCXCPUAOXFI-UHFFFAOYSA-N CCCNC(=O)C1=CC=CS1 Chemical compound CCCNC(=O)C1=CC=CS1 ZJJYCXCPUAOXFI-UHFFFAOYSA-N 0.000 description 2
- MQXQZWVASGXWEW-UHFFFAOYSA-N CCCNC(=O)C1=CC=NC=C1 Chemical compound CCCNC(=O)C1=CC=NC=C1 MQXQZWVASGXWEW-UHFFFAOYSA-N 0.000 description 2
- QXPHVVHPNAHPGZ-UHFFFAOYSA-N CCCNC(=O)C1=CN=C(C)C=C1 Chemical compound CCCNC(=O)C1=CN=C(C)C=C1 QXPHVVHPNAHPGZ-UHFFFAOYSA-N 0.000 description 2
- RBMGZXJPSYXVGD-UHFFFAOYSA-N CCCNC(=O)C1=CN=CC(Br)=C1 Chemical compound CCCNC(=O)C1=CN=CC(Br)=C1 RBMGZXJPSYXVGD-UHFFFAOYSA-N 0.000 description 2
- YIEIQMFWAGTFCB-UHFFFAOYSA-N CCCNC(=O)C1=CN=CC=C1 Chemical compound CCCNC(=O)C1=CN=CC=C1 YIEIQMFWAGTFCB-UHFFFAOYSA-N 0.000 description 2
- JPJFDPHYBWUZLG-UHFFFAOYSA-N CCCNC(=O)C1=COC=C1 Chemical compound CCCNC(=O)C1=COC=C1 JPJFDPHYBWUZLG-UHFFFAOYSA-N 0.000 description 2
- YHBMQZZMGAMNIU-UHFFFAOYSA-N CCCNC(=O)C1=CSC=C1 Chemical compound CCCNC(=O)C1=CSC=C1 YHBMQZZMGAMNIU-UHFFFAOYSA-N 0.000 description 2
- UHLKYWONQWEUIP-UHFFFAOYSA-N CCCNC(=O)C1=CSC=C1OC Chemical compound CCCNC(=O)C1=CSC=C1OC UHLKYWONQWEUIP-UHFFFAOYSA-N 0.000 description 2
- LYSGHVSIBCITIS-UHFFFAOYSA-N CCCNC(=O)C1=NC=CN=C1 Chemical compound CCCNC(=O)C1=NC=CN=C1 LYSGHVSIBCITIS-UHFFFAOYSA-N 0.000 description 2
- GUMUXPNAFFPIDN-UHFFFAOYSA-N CCCNC(=O)C1=NN(C)C(C)=C1 Chemical compound CCCNC(=O)C1=NN(C)C(C)=C1 GUMUXPNAFFPIDN-UHFFFAOYSA-N 0.000 description 2
- ZWUGZXVTHBPREY-UHFFFAOYSA-N CCCNC(=O)C1=NN(C2=CC=CC=C2)N=C1C Chemical compound CCCNC(=O)C1=NN(C2=CC=CC=C2)N=C1C ZWUGZXVTHBPREY-UHFFFAOYSA-N 0.000 description 2
- GDMWNGKRPHLZET-UHFFFAOYSA-N CCCNC(=O)C1=NNC2=C1C=CC=C2 Chemical compound CCCNC(=O)C1=NNC2=C1C=CC=C2 GDMWNGKRPHLZET-UHFFFAOYSA-N 0.000 description 2
- WXBPTLSYPVVNFU-UHFFFAOYSA-N CCCNC(=O)C1=NOC(C)=C1 Chemical compound CCCNC(=O)C1=NOC(C)=C1 WXBPTLSYPVVNFU-UHFFFAOYSA-N 0.000 description 2
- ATADNMCXCXUSOW-UHFFFAOYSA-N CCCNC(=O)C1CC1 Chemical compound CCCNC(=O)C1CC1 ATADNMCXCXUSOW-UHFFFAOYSA-N 0.000 description 2
- IBPFHMBIICBYIS-UHFFFAOYSA-N CCCNC(=O)C1CC2=C(C=CC=C2)C1 Chemical compound CCCNC(=O)C1CC2=C(C=CC=C2)C1 IBPFHMBIICBYIS-UHFFFAOYSA-N 0.000 description 2
- MBMJCPLNNKJRCT-UHFFFAOYSA-N CCCNC(=O)C1CNC1 Chemical compound CCCNC(=O)C1CNC1 MBMJCPLNNKJRCT-UHFFFAOYSA-N 0.000 description 2
- YUMCRXLLWKQDJY-UHFFFAOYSA-N CCCNC(=O)CC Chemical compound CCCNC(=O)CC YUMCRXLLWKQDJY-UHFFFAOYSA-N 0.000 description 2
- ICZKPBRVSMRXHY-UHFFFAOYSA-N CCCNC(=O)CC1CCCC1 Chemical compound CCCNC(=O)CC1CCCC1 ICZKPBRVSMRXHY-UHFFFAOYSA-N 0.000 description 2
- IYWLQMRIMWEQQC-UHFFFAOYSA-N CCCNC(=O)CCC1=CC=CC=C1 Chemical compound CCCNC(=O)CCC1=CC=CC=C1 IYWLQMRIMWEQQC-UHFFFAOYSA-N 0.000 description 2
- VBUWHAJDOUIJMV-UHFFFAOYSA-N CCCNC(=O)OC(C)(C)C Chemical compound CCCNC(=O)OC(C)(C)C VBUWHAJDOUIJMV-UHFFFAOYSA-N 0.000 description 2
- ITPBGPDKSKEXEA-ZETCQYMHSA-N CCCNC(=O)[C@@H]1CCCN1 Chemical compound CCCNC(=O)[C@@H]1CCCN1 ITPBGPDKSKEXEA-ZETCQYMHSA-N 0.000 description 2
- CUDKXVVKOCEJEY-MRVPVSSYSA-N CCCNC(=O)[C@H]1CCCCN1 Chemical compound CCCNC(=O)[C@H]1CCCCN1 CUDKXVVKOCEJEY-MRVPVSSYSA-N 0.000 description 2
- OGCKAWAZXMMQRG-SSDOTTSWSA-N CCCNC(=O)[C@H]1CCCO1 Chemical compound CCCNC(=O)[C@H]1CCCO1 OGCKAWAZXMMQRG-SSDOTTSWSA-N 0.000 description 2
- FGTLUYQJKVPUHM-UHFFFAOYSA-N CCCNS(=O)(=O)C1=CC=C(C)C=C1 Chemical compound CCCNS(=O)(=O)C1=CC=C(C)C=C1 FGTLUYQJKVPUHM-UHFFFAOYSA-N 0.000 description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N CCCOC(C)=O Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
- 102000017925 CHRM3 Human genes 0.000 description 2
- 101150060249 CHRM3 gene Proteins 0.000 description 2
- 101150015280 Cel gene Proteins 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 206010020853 Hypertonic bladder Diseases 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
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- KGCNHGGJKGWCSG-OTFBLGHHSA-M [(3r)-1-(2-aminopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride;hydrochloride Chemical compound Cl.[Cl-].O([C@@H]1C2CC[N+](CC2)(C1)CC(N)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 KGCNHGGJKGWCSG-OTFBLGHHSA-M 0.000 description 2
- SWKOWYPFFMOBGV-XAEROCQYSA-N [(3r)-1-(2-benzamidoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=CC=C1 SWKOWYPFFMOBGV-XAEROCQYSA-N 0.000 description 2
- FULPWIZKGOHREM-QBJDRERVSA-M [(3r)-1-(3-aminopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].O([C@@H]1C2CC[N+](CC2)(C1)CCCN)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 FULPWIZKGOHREM-QBJDRERVSA-M 0.000 description 2
- UKPJFZOCZXCVGV-RKZALIOASA-N [(3r)-1-(3-benzamidopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC=C1 UKPJFZOCZXCVGV-RKZALIOASA-N 0.000 description 2
- BDOZRVOIIAVPMG-GXVQUIFISA-N [(3r)-1-[2-(1,2-oxazol-3-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC=1C=CON=1 BDOZRVOIIAVPMG-GXVQUIFISA-N 0.000 description 2
- CPAXWPVFZURKJC-ZFUWMPTASA-N [(3r)-1-[2-(phenylcarbamoylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)NC1=CC=CC=C1 CPAXWPVFZURKJC-ZFUWMPTASA-N 0.000 description 2
- DRPSSCMONVBVJP-XZZGORAUSA-N [(3r)-1-[2-[(3-hydroxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].OC1=CC=CC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 DRPSSCMONVBVJP-XZZGORAUSA-N 0.000 description 2
- IZZPXYPMIJLKNY-CJBXXQLDSA-N [(3r)-1-[2-[(4-phenylmethoxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 IZZPXYPMIJLKNY-CJBXXQLDSA-N 0.000 description 2
- FQXQDKZAPVIZLN-GQZBUVINSA-N [(3r)-1-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)NC1CC=2C=C(C(=CC=2C1)CC)CC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 FQXQDKZAPVIZLN-GQZBUVINSA-N 0.000 description 2
- KVYFPKJRJWDXCT-LWOCSEGBSA-O [(3r)-1-[2-oxo-2-(pyrazin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC(=O)NC1=CN=CC=N1 KVYFPKJRJWDXCT-LWOCSEGBSA-O 0.000 description 2
- KJRYOXYCFNYCKD-XTBFPHCZSA-N [(3r)-1-[2-oxo-2-(pyrazin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;chloride Chemical compound [Cl-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC(=O)NC1=CN=CC=N1 KJRYOXYCFNYCKD-XTBFPHCZSA-N 0.000 description 2
- ZPFCXHFVCOFWOZ-XTBFPHCZSA-N [(3r)-1-[2-oxo-2-(pyrimidin-4-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC(=O)NC1=CC=NC=N1 ZPFCXHFVCOFWOZ-XTBFPHCZSA-N 0.000 description 2
- RVRHMFZGZGFYIO-XWVWEEIQSA-N [(3r)-1-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCCNC(=O)OC(C)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 RVRHMFZGZGFYIO-XWVWEEIQSA-N 0.000 description 2
- JYTMGTTUIXPUMR-IBGZPJMESA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 2-fluoro-2,2-diphenylacetate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)C(F)(C=1C=CC=CC=1)C1=CC=CC=C1 JYTMGTTUIXPUMR-IBGZPJMESA-N 0.000 description 2
- CGHIBGNXEGJPQZ-UHFFFAOYSA-N [H]C#CCCCC Chemical compound [H]C#CCCCC CGHIBGNXEGJPQZ-UHFFFAOYSA-N 0.000 description 2
- WXIONIWNXBAHRU-UHFFFAOYSA-N [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylidene]-dimethylazanium Chemical compound C1=CN=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 WXIONIWNXBAHRU-UHFFFAOYSA-N 0.000 description 2
- ZULJYVVAYGFYKU-UHFFFAOYSA-N acetonitrile;chloroform Chemical compound CC#N.ClC(Cl)Cl ZULJYVVAYGFYKU-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000006242 amine protecting group Chemical group 0.000 description 2
- 230000001022 anti-muscarinic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- AQIHMSVIAGNIDM-UHFFFAOYSA-N benzoyl bromide Chemical compound BrC(=O)C1=CC=CC=C1 AQIHMSVIAGNIDM-UHFFFAOYSA-N 0.000 description 2
- 150000003842 bromide salts Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 230000007885 bronchoconstriction Effects 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 description 2
- 150000003841 chloride salts Chemical class 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 238000007598 dipping method Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 150000005828 hydrofluoroalkanes Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000035874 hyperreactivity Effects 0.000 description 2
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 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
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- SYHWYWHVEQQDMO-UHFFFAOYSA-N methyl 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical compound C=1C=CSC=1C(O)(C(=O)OC)C1=CC=CS1 SYHWYWHVEQQDMO-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- FHWXHTWOJWDSAR-UHFFFAOYSA-N n-(2-bromophenyl)-2-chloroacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1Br FHWXHTWOJWDSAR-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- UEWYUCGVQMZMGY-UHFFFAOYSA-N phenyl 2-bromoacetate Chemical compound BrCC(=O)OC1=CC=CC=C1 UEWYUCGVQMZMGY-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 206010035653 pneumoconiosis Diseases 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- QOFDEXBKGJKMGL-JINVOGFWSA-M tert-butyl 4-[(3r)-3-(2-hydroxy-2,2-diphenylacetyl)oxy-1-azoniabicyclo[2.2.2]octan-1-yl]butanoate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCCC(=O)OC(C)(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 QOFDEXBKGJKMGL-JINVOGFWSA-M 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 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
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- IVLICPVPXWEGCA-ZETCQYMHSA-N (3r)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@@H](O)CN1CC2 IVLICPVPXWEGCA-ZETCQYMHSA-N 0.000 description 1
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-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
- PMGQWSIVQFOFOQ-BDUVBVHRSA-N (e)-but-2-enedioic acid;(2r)-2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.CN1CCC[C@@H]1CCOC(C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 PMGQWSIVQFOFOQ-BDUVBVHRSA-N 0.000 description 1
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- UNWKVSDABPCZMK-UHFFFAOYSA-N 1,2-dithiophen-2-ylethane-1,2-dione Chemical compound C=1C=CSC=1C(=O)C(=O)C1=CC=CS1 UNWKVSDABPCZMK-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- PEOKRJBEMJAYRG-QNHHWSGXSA-M 1-[(3r)-1-(2-aminoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2,2-diphenylethanone;bromide Chemical compound [Br-].O=C([C@@H]1C2CC[N+](CC2)(C1)CCN)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 PEOKRJBEMJAYRG-QNHHWSGXSA-M 0.000 description 1
- 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 1
- VIXOOIRHFJMNBT-UHFFFAOYSA-N 1-bromohex-2-yne Chemical compound CCCC#CCBr VIXOOIRHFJMNBT-UHFFFAOYSA-N 0.000 description 1
- VDHGRVFJBGRHMD-UHFFFAOYSA-N 1-bromopent-2-yne Chemical compound CCC#CCBr VDHGRVFJBGRHMD-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- QOHWRKQTLQNUFN-UPDNOBPNSA-N 2,2,2-trifluoroacetate;[(3r)-1-[2-[[3-(trifluoromethyl)benzoyl]amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=CC(C(F)(F)F)=C1 QOHWRKQTLQNUFN-UPDNOBPNSA-N 0.000 description 1
- OQAXVEHRWIJZLJ-UPDNOBPNSA-N 2,2,2-trifluoroacetate;[(3r)-1-[2-[[4-(trifluoromethyl)benzoyl]amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=C(C(F)(F)F)C=C1 OQAXVEHRWIJZLJ-UPDNOBPNSA-N 0.000 description 1
- DFFMWQSIYSJMFO-WGYOFOBQSA-N 2,2,2-trifluoroacetate;[(3r)-1-[3-[[2-(trifluoromethyl)benzoyl]amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC=C1C(F)(F)F DFFMWQSIYSJMFO-WGYOFOBQSA-N 0.000 description 1
- SZGYZCVOMSXFNH-WGYOFOBQSA-N 2,2,2-trifluoroacetate;[(3r)-1-[3-[[3-(trifluoromethyl)benzoyl]amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC(C(F)(F)F)=C1 SZGYZCVOMSXFNH-WGYOFOBQSA-N 0.000 description 1
- OHXZQFDLPFVGRS-WGYOFOBQSA-N 2,2,2-trifluoroacetate;[(3r)-1-[3-[[4-(trifluoromethyl)benzoyl]amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=C(C(F)(F)F)C=C1 OHXZQFDLPFVGRS-WGYOFOBQSA-N 0.000 description 1
- PYHXGXCGESYPCW-UHFFFAOYSA-M 2,2-diphenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)[O-])C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-M 0.000 description 1
- WVBNZZHGECFCSH-UHFFFAOYSA-N 2,4-dichloro-1-isothiocyanatobenzene Chemical compound ClC1=CC=C(N=C=S)C(Cl)=C1 WVBNZZHGECFCSH-UHFFFAOYSA-N 0.000 description 1
- QMRZNGGAEXWZST-UHFFFAOYSA-N 2-(3-chloroprop-1-ynyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(C#CCCl)C(=O)C2=C1 QMRZNGGAEXWZST-UHFFFAOYSA-N 0.000 description 1
- GHCFWKFREBNSPC-UHFFFAOYSA-N 2-Amino-4-methylpyrimidine Chemical compound CC1=CC=NC(N)=N1 GHCFWKFREBNSPC-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- IITXJRHHQHZFNO-UHFFFAOYSA-N 2-bromo-n-(5-fluoro-1,3-benzothiazol-2-yl)acetamide Chemical compound FC1=CC=C2SC(NC(=O)CBr)=NC2=C1 IITXJRHHQHZFNO-UHFFFAOYSA-N 0.000 description 1
- VUOFGWLJEBESHL-UHFFFAOYSA-N 2-chloro-n-methyl-n-phenylacetamide Chemical compound ClCC(=O)N(C)C1=CC=CC=C1 VUOFGWLJEBESHL-UHFFFAOYSA-N 0.000 description 1
- FBVYTVCSQYVRES-UHFFFAOYSA-N 2-chloro-n-pyrazin-2-ylacetamide Chemical compound ClCC(=O)NC1=CN=CC=N1 FBVYTVCSQYVRES-UHFFFAOYSA-N 0.000 description 1
- WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- DDYUBCCTNHWSQM-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(1,3-dioxoisoindol-2-yl)propanamide Chemical compound COC1=CC=C(C(CC(N)=O)N2C(C3=CC=CC=C3C2=O)=O)C=C1OC1CCCC1 DDYUBCCTNHWSQM-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- ZTGQZSKPSJUEBU-UHFFFAOYSA-N 3-bromopropan-1-amine Chemical compound NCCCBr ZTGQZSKPSJUEBU-UHFFFAOYSA-N 0.000 description 1
- PQIYSSSTRHVOBW-UHFFFAOYSA-N 3-bromopropan-1-amine;hydron;bromide Chemical compound Br.NCCCBr PQIYSSSTRHVOBW-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- FRXJYUFHAXXSAL-UHFFFAOYSA-N 3-chloro-n-phenylpropanamide Chemical compound ClCCC(=O)NC1=CC=CC=C1 FRXJYUFHAXXSAL-UHFFFAOYSA-N 0.000 description 1
- CISXCTKEQYOZAM-UHFFFAOYSA-N 3-phenylmethoxybenzoic acid Chemical compound OC(=O)C1=CC=CC(OCC=2C=CC=CC=2)=C1 CISXCTKEQYOZAM-UHFFFAOYSA-N 0.000 description 1
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical class C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZIDVZMFYBGXIBH-UHFFFAOYSA-N 4-butyl-1-isocyanato-2-methylbenzene Chemical compound CCCCC1=CC=C(N=C=O)C(C)=C1 ZIDVZMFYBGXIBH-UHFFFAOYSA-N 0.000 description 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-M 4-chlorobenzoate Chemical compound [O-]C(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-M 0.000 description 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 208000033116 Asbestos intoxication Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- 208000007596 Byssinosis Diseases 0.000 description 1
- OTHIZHVVFOPCRK-DFIQVTRPSA-M C[3H]C(=O)O[W] Chemical compound C[3H]C(=O)O[W] OTHIZHVVFOPCRK-DFIQVTRPSA-M 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- 229940122444 Chemokine receptor antagonist Drugs 0.000 description 1
- LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 206010063057 Cystitis noninfective Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical group COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- RRJFVPUCXDGFJB-UHFFFAOYSA-N Fexofenadine hydrochloride Chemical compound Cl.C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RRJFVPUCXDGFJB-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 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
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
- 229940122694 Muscarinic M3 receptor antagonist Drugs 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 206010036018 Pollakiuria Diseases 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036600 Premature labour Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- RUOGJYKOQBFJIG-UHFFFAOYSA-N SCH-351591 Chemical compound C12=CC=C(C(F)(F)F)N=C2C(OC)=CC=C1C(=O)NC1=C(Cl)C=[N+]([O-])C=C1Cl RUOGJYKOQBFJIG-UHFFFAOYSA-N 0.000 description 1
- 229910006074 SO2NH2 Inorganic materials 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 206010040741 Sinus bradycardia Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000001871 Tachycardia Diseases 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
- 206010044565 Tremor Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010052568 Urticaria chronic Diseases 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- YAKAELJGPNDCCP-PUQCJQIMSA-N [(3R)-1-[2-[(2-chlorophenyl)methylamino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate 2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1=CC=CC=C1Cl YAKAELJGPNDCCP-PUQCJQIMSA-N 0.000 description 1
- UBSKLLAXUJYCBB-LQLGBDKGSA-M [(3r)-1-(2-acetyloxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-fluoro-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCOC(=O)C)C(=O)C(F)(C=1C=CC=CC=1)C1=CC=CC=C1 UBSKLLAXUJYCBB-LQLGBDKGSA-M 0.000 description 1
- DDKRTQBNMXWMFI-FPJVJKMXSA-M [(3r)-1-(2-aminoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride;hydrochloride Chemical group Cl.[Cl-].O([C@@H]1C2CC[N+](CC2)(C1)CCN)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 DDKRTQBNMXWMFI-FPJVJKMXSA-M 0.000 description 1
- FWIZKZTUMMTZQJ-IMYXDSERSA-O [(3r)-1-(2-anilino-2-oxoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=CC=C1 FWIZKZTUMMTZQJ-IMYXDSERSA-O 0.000 description 1
- DSVHANKTRVCEJH-VAXCQOKESA-N [(3r)-1-(2-anilino-2-oxoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=CC=C1 DSVHANKTRVCEJH-VAXCQOKESA-N 0.000 description 1
- VCHOQRRTIMZCOW-VAXCQOKESA-N [(3r)-1-(2-anilino-2-oxoethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=CC=C1 VCHOQRRTIMZCOW-VAXCQOKESA-N 0.000 description 1
- SUMGTXQQMSAWJP-HHPIWPOQSA-M [(3r)-1-(2-oxo-2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)OCC1=CC=CC=C1 SUMGTXQQMSAWJP-HHPIWPOQSA-M 0.000 description 1
- VTBFRMIRSOVUCT-NTPQTCQESA-M [(3r)-1-(3-amino-5-methyl-4-oxohexyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCC(N)C(=O)C(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 VTBFRMIRSOVUCT-NTPQTCQESA-M 0.000 description 1
- YUVRDYIMYFBJIC-YVLJNVBMSA-N [(3r)-1-(3-aminopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CCCN)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 YUVRDYIMYFBJIC-YVLJNVBMSA-N 0.000 description 1
- OLSSHHTYWYQDBI-ZZNGFPBBSA-M [(3r)-1-(3-cyclopropylprop-2-ynyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC#CC1CC1 OLSSHHTYWYQDBI-ZZNGFPBBSA-M 0.000 description 1
- AEVPTDRPCKHFMY-ZMDRYIOLSA-M [(3r)-1-(3-cyclopropylprop-2-ynyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC#CC1CC1 AEVPTDRPCKHFMY-ZMDRYIOLSA-M 0.000 description 1
- GFAFSNLFRKSDQF-LWCCLMHTSA-M [(3r)-1-(3-phenylprop-2-ynyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC#CC1=CC=CC=C1 GFAFSNLFRKSDQF-LWCCLMHTSA-M 0.000 description 1
- MMWCNXPCNCEIQX-NNQSNFSGSA-M [(3r)-1-(4,4-dimethylpent-2-ynyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CC#CC(C)(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 MMWCNXPCNCEIQX-NNQSNFSGSA-M 0.000 description 1
- KADJQOZJGHYAKT-WZSPKAJJSA-M [(3r)-1-(4,4-dimethylpent-2-ynyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CC#CC(C)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 KADJQOZJGHYAKT-WZSPKAJJSA-M 0.000 description 1
- SGXWLNSBYRXUFT-RKZALIOASA-N [(3r)-1-(4-anilino-4-oxobutyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCC(=O)NC1=CC=CC=C1 SGXWLNSBYRXUFT-RKZALIOASA-N 0.000 description 1
- VOQNSMXKIIAKGU-ZZNGFPBBSA-M [(3r)-1-(4-methylpent-2-ynyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CC#CC(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 VOQNSMXKIIAKGU-ZZNGFPBBSA-M 0.000 description 1
- MNTIMKNHYASQNC-ZMDRYIOLSA-M [(3r)-1-(4-methylpent-2-ynyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CC#CC(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 MNTIMKNHYASQNC-ZMDRYIOLSA-M 0.000 description 1
- PTHNRUQVXLGKKT-WTHDWRSPSA-N [(3r)-1-[2-(1,2-oxazol-3-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC(=O)NC=1C=CON=1 PTHNRUQVXLGKKT-WTHDWRSPSA-N 0.000 description 1
- VBODKZFRMVWQTQ-STNBFCITSA-N [(3r)-1-[2-(2,3-dihydro-1h-inden-2-ylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CC(=O)NC2CC3=CC=CC=C3C2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 VBODKZFRMVWQTQ-STNBFCITSA-N 0.000 description 1
- SFUGEGCJTAETQF-WWMRKDEFSA-N [(3r)-1-[2-(2,3-dihydro-1h-indene-2-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCNC(=O)C2CC3=CC=CC=C3C2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 SFUGEGCJTAETQF-WWMRKDEFSA-N 0.000 description 1
- RKJQVEPMMVSVIX-SVMFROAESA-N [(3r)-1-[2-(2-chloroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=CC=C1Cl RKJQVEPMMVSVIX-SVMFROAESA-N 0.000 description 1
- ZXTCKMAALPICBS-WVSVAZAGSA-N [(3r)-1-[2-(2-cyanoethylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CC(=O)NCCC#N)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 ZXTCKMAALPICBS-WVSVAZAGSA-N 0.000 description 1
- ZFDBOEDDJPEGDX-UPGPKNOMSA-N [(3r)-1-[2-(2-methoxyethylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)NCCOC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 ZFDBOEDDJPEGDX-UPGPKNOMSA-N 0.000 description 1
- SWBPKGYTIVLHGV-XAEROCQYSA-N [(3r)-1-[2-(2-methylanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=CC=CC=C1NC(=O)C[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 SWBPKGYTIVLHGV-XAEROCQYSA-N 0.000 description 1
- XUPMAHBLBVVSJQ-XEMMLLNASA-N [(3r)-1-[2-(3,4-dichloroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=C(Cl)C(Cl)=C1 XUPMAHBLBVVSJQ-XEMMLLNASA-N 0.000 description 1
- RMNRWXHQGCUKFH-SVMFROAESA-N [(3r)-1-[2-(3-chloroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=CC(Cl)=C1 RMNRWXHQGCUKFH-SVMFROAESA-N 0.000 description 1
- YDPUOJKEEGEHTE-VGXFIXORSA-N [(3r)-1-[2-(3-hydroxyanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].OC1=CC=CC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 YDPUOJKEEGEHTE-VGXFIXORSA-N 0.000 description 1
- XALSCQWPYCJUFM-AFRGNJIESA-N [(3r)-1-[2-(3-phenylpropanoylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)CCC1=CC=CC=C1 XALSCQWPYCJUFM-AFRGNJIESA-N 0.000 description 1
- LEHWIAIAVRLITR-SVMFROAESA-N [(3r)-1-[2-(4-chloroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=C(Cl)C=C1 LEHWIAIAVRLITR-SVMFROAESA-N 0.000 description 1
- XEQHBXFUSGKNSL-VGXFIXORSA-N [(3r)-1-[2-(4-hydroxyanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C1=CC(O)=CC=C1NC(=O)C[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 XEQHBXFUSGKNSL-VGXFIXORSA-N 0.000 description 1
- YHLVZNJTUKJSNN-XZZGORAUSA-N [(3r)-1-[2-(4-methoxyanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(OC)=CC=C1NC(=O)C[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 YHLVZNJTUKJSNN-XZZGORAUSA-N 0.000 description 1
- MXMSBAATBOFQCO-SVMFROAESA-N [(3r)-1-[2-(4-nitroanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=C([N+]([O-])=O)C=C1 MXMSBAATBOFQCO-SVMFROAESA-N 0.000 description 1
- GJJFYZIVLACTBT-GLSBDXMNSA-N [(3r)-1-[2-(benzylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1=CC=CC=C1 GJJFYZIVLACTBT-GLSBDXMNSA-N 0.000 description 1
- LAGANMMMAQLPPR-OXBIGKRVSA-N [(3r)-1-[2-(benzylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC(=O)NCC1=CC=CC=C1 LAGANMMMAQLPPR-OXBIGKRVSA-N 0.000 description 1
- AOYQTBUCTWRFAR-VAXCQOKESA-N [(3r)-1-[2-(cyclohexylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1CCCCC1 AOYQTBUCTWRFAR-VAXCQOKESA-N 0.000 description 1
- ILBCVAATKBSBKZ-ZFUWMPTASA-N [(3r)-1-[2-(cyclohexylcarbamoylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)NC1CCCCC1 ILBCVAATKBSBKZ-ZFUWMPTASA-N 0.000 description 1
- DEAQXIJPJHNQRZ-IBOVTGBGSA-N [(3r)-1-[2-(cyclohexylcarbamoylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCNC(=O)NC1CCCCC1 DEAQXIJPJHNQRZ-IBOVTGBGSA-N 0.000 description 1
- KCNRGBCYULAKQQ-XAEROCQYSA-N [(3r)-1-[2-(cyclohexylcarbamoyloxy)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCOC(=O)NC1CCCCC1 KCNRGBCYULAKQQ-XAEROCQYSA-N 0.000 description 1
- HIYCGICJAQWXRT-QGVPIXNJSA-N [(3r)-1-[2-(cyclohexylcarbamoyloxy)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCOC(=O)NC1CCCCC1 HIYCGICJAQWXRT-QGVPIXNJSA-N 0.000 description 1
- QQFSWVHLLRLXPM-GLSBDXMNSA-N [(3r)-1-[2-(cyclohexylmethylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1CCCCC1 QQFSWVHLLRLXPM-GLSBDXMNSA-N 0.000 description 1
- RNNJHYKXHZNZLS-KEIYDZBTSA-N [(3r)-1-[2-(cyclopropylmethylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1CC1 RNNJHYKXHZNZLS-KEIYDZBTSA-N 0.000 description 1
- KNYBWAZMXBVDKB-VYSUVQMHSA-N [(3r)-1-[2-(ethylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)NCC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 KNYBWAZMXBVDKB-VYSUVQMHSA-N 0.000 description 1
- NQJBQMPDWBDCHK-AYIBHJBZSA-N [(3r)-1-[2-(furan-2-ylmethylamino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1=CC=CO1 NQJBQMPDWBDCHK-AYIBHJBZSA-N 0.000 description 1
- FCFNUDDCVWRDRR-AYIBHJBZSA-N [(3r)-1-[2-(furan-3-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C=1C=COC=1 FCFNUDDCVWRDRR-AYIBHJBZSA-N 0.000 description 1
- QMRUIIYEUVEPON-JYSSDCQASA-M [(3r)-1-[2-(methylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide;hydrobromide Chemical compound Br.[Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCNC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 QMRUIIYEUVEPON-JYSSDCQASA-M 0.000 description 1
- JHTRTDHTLYFUGK-BRFPSQFKSA-N [(3r)-1-[2-(n-methylanilino)-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)N(C)C=1C=CC=CC=1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 JHTRTDHTLYFUGK-BRFPSQFKSA-N 0.000 description 1
- NCWIPOVVRPBKID-IMYXDSERSA-O [(3r)-1-[2-(oxane-4-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1CCOCC1 NCWIPOVVRPBKID-IMYXDSERSA-O 0.000 description 1
- LRGFRKBXGAHXNQ-IBOVTGBGSA-N [(3r)-1-[2-(phenylcarbamoylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCNC(=O)NC1=CC=CC=C1 LRGFRKBXGAHXNQ-IBOVTGBGSA-N 0.000 description 1
- LBTCPHIIAQOGQI-QGQACGQESA-N [(3r)-1-[2-(pyrazine-2-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CN=CC=N1 LBTCPHIIAQOGQI-QGQACGQESA-N 0.000 description 1
- UHURTTIUOCAPTA-XDVWKIBCSA-N [(3r)-1-[2-(pyridine-3-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=CN=C1 UHURTTIUOCAPTA-XDVWKIBCSA-N 0.000 description 1
- ICXZGDBARYYIHN-AYIBHJBZSA-N [(3r)-1-[2-(thiophene-3-carbonylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C=1C=CSC=1 ICXZGDBARYYIHN-AYIBHJBZSA-N 0.000 description 1
- YSTKLIVZPJJYGD-WWAPZXQFSA-N [(3r)-1-[2-[(1,5-dimethylpyrazole-3-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CN1C(C)=CC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 YSTKLIVZPJJYGD-WWAPZXQFSA-N 0.000 description 1
- DDBDZSHLEJKDJR-XDVWKIBCSA-N [(3r)-1-[2-[(1-methylpyrrole-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CN1C=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 DDBDZSHLEJKDJR-XDVWKIBCSA-N 0.000 description 1
- IUDZPAMLFVINKS-STNBFCITSA-N [(3r)-1-[2-[(2,4-dimethoxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC(OC)=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 IUDZPAMLFVINKS-STNBFCITSA-N 0.000 description 1
- SAQXACJHIOQSMM-XAEROCQYSA-N [(3r)-1-[2-[(2,5-dimethylfuran-3-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O1C(C)=CC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C SAQXACJHIOQSMM-XAEROCQYSA-N 0.000 description 1
- DIOGWSVQRDZDKL-WWAPZXQFSA-N [(3r)-1-[2-[(2,5-dimethylpyrazole-3-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CN1N=C(C)C=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 DIOGWSVQRDZDKL-WWAPZXQFSA-N 0.000 description 1
- LRKISOTWVBKKNN-VDQWJEDOSA-N [(3r)-1-[2-[(2,6-dimethylbenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=CC=CC(C)=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 LRKISOTWVBKKNN-VDQWJEDOSA-N 0.000 description 1
- WFJFLAFQCUVXES-KYSMUZRFSA-N [(3r)-1-[2-[(2-carbamoylbenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.NC(=O)C1=CC=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 WFJFLAFQCUVXES-KYSMUZRFSA-N 0.000 description 1
- IOYSGKLJTRJGEG-SGNXQQFXSA-N [(3r)-1-[2-[(2-cyanobenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=CC=C1C#N IOYSGKLJTRJGEG-SGNXQQFXSA-N 0.000 description 1
- OBAKKRNLLVDNPC-GLSBDXMNSA-N [(3r)-1-[2-[(2-cyclopentylacetyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)CC1CCCC1 OBAKKRNLLVDNPC-GLSBDXMNSA-N 0.000 description 1
- PZAKJAYQAMCRMH-ADFHNETRSA-N [(3r)-1-[2-[(2-ethylpyrazol-3-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CCN1N=CC=C1NC(=O)C[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 PZAKJAYQAMCRMH-ADFHNETRSA-N 0.000 description 1
- SWVTUQPDKWONRO-VRCWUQCGSA-N [(3r)-1-[2-[(2-methoxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 SWVTUQPDKWONRO-VRCWUQCGSA-N 0.000 description 1
- UTDHDOCVJRGKEX-UPDBXMIASA-N [(3r)-1-[2-[(2-pyridin-3-ylacetyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)CC1=CC=CN=C1 UTDHDOCVJRGKEX-UPDBXMIASA-N 0.000 description 1
- VYFCQZPJJPAGKV-KYSMUZRFSA-N [(3r)-1-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1=CC=C(Cl)C(Cl)=C1 VYFCQZPJJPAGKV-KYSMUZRFSA-N 0.000 description 1
- DJXZPTKQWIPPQA-STNBFCITSA-N [(3r)-1-[2-[(3,4-dimethoxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=C(OC)C(OC)=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 DJXZPTKQWIPPQA-STNBFCITSA-N 0.000 description 1
- ZWRAGTJECUITLZ-DMWRAEOSSA-N [(3r)-1-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=NOC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C ZWRAGTJECUITLZ-DMWRAEOSSA-N 0.000 description 1
- QTGVAXZCQNHRDJ-STNBFCITSA-N [(3r)-1-[2-[(3,5-dimethoxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC(OC)=CC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 QTGVAXZCQNHRDJ-STNBFCITSA-N 0.000 description 1
- ZGLWVGMJQXIRIU-LAAOYOPBSA-O [(3r)-1-[2-[(3,5-dimethyl-1,2-oxazole-4-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound CC1=NOC(C)=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 ZGLWVGMJQXIRIU-LAAOYOPBSA-O 0.000 description 1
- OFKNMQUOPPFTOI-MUAISIBCSA-N [(3r)-1-[2-[(3-bromothiophene-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C=1SC=CC=1Br OFKNMQUOPPFTOI-MUAISIBCSA-N 0.000 description 1
- JRYQGGMNKJCAIH-FZCUKYEHSA-O [(3r)-1-[2-[(3-chloro-4-methylthiophene-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound CC1=CSC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1Cl JRYQGGMNKJCAIH-FZCUKYEHSA-O 0.000 description 1
- TZGNAAWMIURZDD-PUQCJQIMSA-N [(3r)-1-[2-[(3-chlorobenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=CC(Cl)=C1 TZGNAAWMIURZDD-PUQCJQIMSA-N 0.000 description 1
- SHISNIWXYYAVDA-ZFUWMPTASA-N [(3r)-1-[2-[(3-chlorophenyl)methylamino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1=CC=CC(Cl)=C1 SHISNIWXYYAVDA-ZFUWMPTASA-N 0.000 description 1
- OEGDEHLXIHIGLA-MUAISIBCSA-N [(3r)-1-[2-[(3-chlorothiophene-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C=1SC=CC=1Cl OEGDEHLXIHIGLA-MUAISIBCSA-N 0.000 description 1
- OWBGQEKIPSKAEC-XDVWKIBCSA-N [(3r)-1-[2-[(3-ethoxythiophene-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CSC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1OCC OWBGQEKIPSKAEC-XDVWKIBCSA-N 0.000 description 1
- SNDVRHLCANHYPM-VRCWUQCGSA-N [(3r)-1-[2-[(3-methoxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC=CC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNDVRHLCANHYPM-VRCWUQCGSA-N 0.000 description 1
- ZJHQUGSJYKRDFB-VIWWJSOESA-N [(3r)-1-[2-[(3-methyl-1,2,4-thiadiazol-5-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=NSC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 ZJHQUGSJYKRDFB-VIWWJSOESA-N 0.000 description 1
- ARNGABDYKFTMQG-BRKBLGTFSA-N [(3r)-1-[2-[(3-methylfuran-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=COC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C ARNGABDYKFTMQG-BRKBLGTFSA-N 0.000 description 1
- WZQKDCGMAQAINY-VRCWUQCGSA-N [(3r)-1-[2-[(3-methylsulfonylbenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CS(=O)(=O)C1=CC=CC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 WZQKDCGMAQAINY-VRCWUQCGSA-N 0.000 description 1
- HBWPYZRKBCAWJN-ZFUWMPTASA-N [(3r)-1-[2-[(4-chlorophenyl)methylamino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1=CC=C(Cl)C=C1 HBWPYZRKBCAWJN-ZFUWMPTASA-N 0.000 description 1
- OJLXKVPMJICRQO-FKRVERSVSA-N [(3r)-1-[2-[(4-cyanobenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=C(C#N)C=C1 OJLXKVPMJICRQO-FKRVERSVSA-N 0.000 description 1
- DMOJJQFVMPLVFV-OCCBKRFISA-N [(3r)-1-[2-[(4-ethylbenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(CC)=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 DMOJJQFVMPLVFV-OCCBKRFISA-N 0.000 description 1
- OBMYJOCLLKNTFU-VRCWUQCGSA-N [(3r)-1-[2-[(4-methoxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(OC)=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 OBMYJOCLLKNTFU-VRCWUQCGSA-N 0.000 description 1
- MOYMIVYGCSOYQQ-KINHEAOASA-N [(3r)-1-[2-[(4-methoxythiophene-3-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CSC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 MOYMIVYGCSOYQQ-KINHEAOASA-N 0.000 description 1
- AASWBDJHOFNMQI-WULMZJJMSA-N [(3r)-1-[2-[(4-methyl-1,3-oxazol-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].CC1=COC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 AASWBDJHOFNMQI-WULMZJJMSA-N 0.000 description 1
- IJICUMCYNUTWGY-WULMZJJMSA-N [(3r)-1-[2-[(4-methyl-1,3-thiazol-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].CC1=CSC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 IJICUMCYNUTWGY-WULMZJJMSA-N 0.000 description 1
- MXALBWDKMNPMHG-YDQMMYGOSA-N [(3r)-1-[2-[(4-methylphenyl)methylamino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(C)=CC=C1CNC(=O)C[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 MXALBWDKMNPMHG-YDQMMYGOSA-N 0.000 description 1
- ZEUQPAMZOJHNSK-ADFHNETRSA-N [(3r)-1-[2-[(4-methylpyrimidin-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].CC1=CC=NC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 ZEUQPAMZOJHNSK-ADFHNETRSA-N 0.000 description 1
- KPAVWRQKCUOUKM-HQWOFFSHSA-N [(3r)-1-[2-[(4-methylthiadiazole-5-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N1=NSC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C KPAVWRQKCUOUKM-HQWOFFSHSA-N 0.000 description 1
- MWRCLQHIXITPHR-XEQSUQAISA-N [(3r)-1-[2-[(4-phenylbenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C(C=C1)=CC=C1C1=CC=CC=C1 MWRCLQHIXITPHR-XEQSUQAISA-N 0.000 description 1
- KQBKGNJBAOHYRR-KHLAQOCXSA-N [(3r)-1-[2-[(4-propan-2-yloxybenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(OC(C)C)=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 KQBKGNJBAOHYRR-KHLAQOCXSA-N 0.000 description 1
- CDGLWWAREMULBU-NSWSQUBZSA-N [(3r)-1-[2-[(4-pyrrol-1-ylbenzoyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C(C=C1)=CC=C1N1C=CC=C1 CDGLWWAREMULBU-NSWSQUBZSA-N 0.000 description 1
- OFNWGVZPOGMBHB-LAAOYOPBSA-O [(3r)-1-[2-[(5-acetylthiophene-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound S1C(C(=O)C)=CC=C1C(=O)NCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 OFNWGVZPOGMBHB-LAAOYOPBSA-O 0.000 description 1
- OTCQDIDZQFWKEH-XELXMEPDSA-N [(3r)-1-[2-[(5-bromo-3,4-dimethylpyridin-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=C(Br)C=NC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C OTCQDIDZQFWKEH-XELXMEPDSA-N 0.000 description 1
- CBCCIDFKTLCTHV-MUAISIBCSA-N [(3r)-1-[2-[(5-bromofuran-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=C(Br)O1 CBCCIDFKTLCTHV-MUAISIBCSA-N 0.000 description 1
- IDVIJCRBXJRCEI-BOTALQKVSA-N [(3r)-1-[2-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2SC3=CC=C(F)C=C3N=2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 IDVIJCRBXJRCEI-BOTALQKVSA-N 0.000 description 1
- WQZACDOQKDTFAA-MEXRWQJUSA-N [(3r)-1-[2-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CC(=O)NC=2SC3=CC=C(F)C=C3N=2)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 WQZACDOQKDTFAA-MEXRWQJUSA-N 0.000 description 1
- KKVXERHUCSHEQI-KINHEAOASA-N [(3r)-1-[2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O1C(C)=CC(C(=O)NCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 KKVXERHUCSHEQI-KINHEAOASA-N 0.000 description 1
- OZSJSCXVSUDVGD-WULMZJJMSA-N [(3r)-1-[2-[(5-methyl-1,3-thiazol-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].S1C(C)=CN=C1NC(=O)C[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 OZSJSCXVSUDVGD-WULMZJJMSA-N 0.000 description 1
- LTDMQBYVUJZCNO-MUAISIBCSA-N [(3r)-1-[2-[(5-nitrofuran-2-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)C1=CC=C([N+]([O-])=O)O1 LTDMQBYVUJZCNO-MUAISIBCSA-N 0.000 description 1
- SGDRNQHFZHEBDG-WWAPZXQFSA-N [(3r)-1-[2-[(6-ethylpyridin-2-yl)amino]-2-oxoethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CCC1=CC=CC(NC(=O)C[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 SGDRNQHFZHEBDG-WWAPZXQFSA-N 0.000 description 1
- NNSNCVRBZHLLEA-KWGAIPKDSA-O [(3r)-1-[2-[(6-fluoro-4h-1,3-benzodioxine-8-carbonyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound O([C@@H]1C2CC[N+](CC2)(CCNC(=O)C=2C=3OCOCC=3C=C(F)C=2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 NNSNCVRBZHLLEA-KWGAIPKDSA-O 0.000 description 1
- KTNVRTMWNTWKSW-GUZXURRKSA-N [(3r)-1-[2-[[(2r)-piperidine-2-carbonyl]amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)[C@H]1CCCCN1 KTNVRTMWNTWKSW-GUZXURRKSA-N 0.000 description 1
- YBYFVCGOKDSMOG-SZHZOLEGSA-N [(3r)-1-[2-[[(2s)-azetidine-2-carbonyl]amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)[C@@H]1CCN1 YBYFVCGOKDSMOG-SZHZOLEGSA-N 0.000 description 1
- KTNVRTMWNTWKSW-CPORYGAYSA-N [(3r)-1-[2-[[(2s)-piperidine-2-carbonyl]amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)[C@@H]1CCCCN1 KTNVRTMWNTWKSW-CPORYGAYSA-N 0.000 description 1
- HINUYZVFPREBHV-JYASWXMCSA-N [(3r)-1-[2-[[(2s)-pyrrolidine-2-carbonyl]amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCNC(=O)[C@@H]1CCCN1 HINUYZVFPREBHV-JYASWXMCSA-N 0.000 description 1
- RKOGJBFPDQGNFV-RKZALIOASA-M [(3r)-1-[2-[benzoyl(methyl)amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCN(C)C(=O)C=1C=CC=CC=1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 RKOGJBFPDQGNFV-RKZALIOASA-M 0.000 description 1
- LPLYKBHXYMRPMU-AQELMELHSA-O [(3r)-1-[2-oxo-2-(2-phenylethylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCCC1=CC=CC=C1 LPLYKBHXYMRPMU-AQELMELHSA-O 0.000 description 1
- XBRCNHJXRXNKHQ-VAXCQOKESA-N [(3r)-1-[2-oxo-2-(2-thiophen-2-ylethylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCCC1=CC=CS1 XBRCNHJXRXNKHQ-VAXCQOKESA-N 0.000 description 1
- FADSUTPRLVYRDR-AOOWOONRSA-N [(3r)-1-[2-oxo-2-(3-propan-2-yloxypropylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)NCCCOC(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 FADSUTPRLVYRDR-AOOWOONRSA-N 0.000 description 1
- OLNWCKMINVGOSU-UPGPKNOMSA-N [(3r)-1-[2-oxo-2-(propan-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)NC(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 OLNWCKMINVGOSU-UPGPKNOMSA-N 0.000 description 1
- PNUPQZSNVOAQCV-UPGPKNOMSA-N [(3r)-1-[2-oxo-2-(propylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC(=O)NCCC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 PNUPQZSNVOAQCV-UPGPKNOMSA-N 0.000 description 1
- DWSOYLYYUKBWKD-ZITBFLLYSA-O [(3r)-1-[2-oxo-2-(pyrazin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate Chemical compound C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CN=CC=N1 DWSOYLYYUKBWKD-ZITBFLLYSA-O 0.000 description 1
- QJARDZBQNQIKKZ-XTBFPHCZSA-N [(3r)-1-[2-oxo-2-(pyrazin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CC(=O)NC1=CN=CC=N1 QJARDZBQNQIKKZ-XTBFPHCZSA-N 0.000 description 1
- UBKYCBQAGHIVIA-DMWRAEOSSA-N [(3r)-1-[2-oxo-2-(pyridin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=CC=N1 UBKYCBQAGHIVIA-DMWRAEOSSA-N 0.000 description 1
- LWKLWVBLWLJVCR-KINHEAOASA-N [(3r)-1-[2-oxo-2-(pyridin-3-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=CN=C1 LWKLWVBLWLJVCR-KINHEAOASA-N 0.000 description 1
- LEBYPNULUOVHIM-KINHEAOASA-N [(3r)-1-[2-oxo-2-(pyridin-4-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=NC=C1 LEBYPNULUOVHIM-KINHEAOASA-N 0.000 description 1
- XTKUWTCMWDYPOI-HQWOFFSHSA-N [(3r)-1-[2-oxo-2-(pyrimidin-2-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=NC=CC=N1 XTKUWTCMWDYPOI-HQWOFFSHSA-N 0.000 description 1
- OVLMYQSXUOVHGZ-HQWOFFSHSA-N [(3r)-1-[2-oxo-2-(pyrimidin-4-ylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=NC=N1 OVLMYQSXUOVHGZ-HQWOFFSHSA-N 0.000 description 1
- HWDXWMHLXUUTCX-AYIBHJBZSA-N [(3r)-1-[2-oxo-2-(thiophen-2-ylmethylamino)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCC1=CC=CS1 HWDXWMHLXUUTCX-AYIBHJBZSA-N 0.000 description 1
- PMYXCXGDSHPJCL-FKRVERSVSA-N [(3r)-1-[2-oxo-2-[2-(4-sulfamoylphenyl)ethylamino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)C[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 PMYXCXGDSHPJCL-FKRVERSVSA-N 0.000 description 1
- WKMNMIZXZFVNDB-XLKOHVDKSA-N [(3r)-1-[2-oxo-2-[3-(2-oxopyrrolidin-1-yl)propylamino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NCCCN1CCCC1=O WKMNMIZXZFVNDB-XLKOHVDKSA-N 0.000 description 1
- BWXBYADMVSKBMS-CXQAAXLGSA-N [(3r)-1-[2-oxo-2-[[3-(trifluoromethyl)pyridin-4-yl]amino]ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CC(=O)NC1=CC=NC=C1C(F)(F)F BWXBYADMVSKBMS-CXQAAXLGSA-N 0.000 description 1
- ZQANQEJELDOMSM-SGNXQQFXSA-M [(3r)-1-[3-(1,3-dioxoisoindol-2-yl)prop-2-ynyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CC#CN2C(C3=CC=CC=C3C2=O)=O)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 ZQANQEJELDOMSM-SGNXQQFXSA-M 0.000 description 1
- AHPXSSOAIDPVGY-LUVSZFQPSA-N [(3r)-1-[3-(2,3-dihydro-1h-indene-2-carbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCCNC(=O)C2CC3=CC=CC=C3C2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 AHPXSSOAIDPVGY-LUVSZFQPSA-N 0.000 description 1
- VYJDKYNXBXNCQW-MVIHUCQCSA-N [(3r)-1-[3-(3,3-dimethylbutanoylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCNC(=O)CC(C)(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 VYJDKYNXBXNCQW-MVIHUCQCSA-N 0.000 description 1
- QKBALMVCRCTBKA-RBCCZXILSA-N [(3r)-1-[3-(3-phenylpropanoylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)CCC1=CC=CC=C1 QKBALMVCRCTBKA-RBCCZXILSA-N 0.000 description 1
- PZLGNZQOVNBQAQ-OWQBZFBLSA-M [(3r)-1-[3-(benzenesulfonamido)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNS(=O)(=O)C1=CC=CC=C1 PZLGNZQOVNBQAQ-OWQBZFBLSA-M 0.000 description 1
- LXZAIORANPELQY-OCCBKRFISA-N [(3r)-1-[3-(cycloheptanecarbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1CCCCCC1 LXZAIORANPELQY-OCCBKRFISA-N 0.000 description 1
- OICBPVDJXHFVNP-RKZALIOASA-N [(3r)-1-[3-(cyclohexanecarbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1CCCCC1 OICBPVDJXHFVNP-RKZALIOASA-N 0.000 description 1
- KWPUALZYYBSCTR-XAEROCQYSA-N [(3r)-1-[3-(cyclopentanecarbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1CCCC1 KWPUALZYYBSCTR-XAEROCQYSA-N 0.000 description 1
- JLYYMDKXQQNXBQ-AXPNMRJASA-N [(3r)-1-[3-(naphthalene-2-carbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CCCNC(=O)C=2C=C3C=CC=CC3=CC=2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 JLYYMDKXQQNXBQ-AXPNMRJASA-N 0.000 description 1
- ZQVOTFKHEVHKDJ-WWAPZXQFSA-N [(3r)-1-[3-(pyrazine-2-carbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CN=CC=N1 ZQVOTFKHEVHKDJ-WWAPZXQFSA-N 0.000 description 1
- RLOLIVGIQWJUQQ-ZFUWMPTASA-N [(3r)-1-[3-(pyridine-2-carbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC=N1 RLOLIVGIQWJUQQ-ZFUWMPTASA-N 0.000 description 1
- BFCGJWXUGGWIKX-ZFUWMPTASA-N [(3r)-1-[3-(pyridine-3-carbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CN=C1 BFCGJWXUGGWIKX-ZFUWMPTASA-N 0.000 description 1
- CXRIVWVEHDIRHR-ZFUWMPTASA-N [(3r)-1-[3-(pyridine-4-carbonylamino)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=NC=C1 CXRIVWVEHDIRHR-ZFUWMPTASA-N 0.000 description 1
- PFWUVWIZTDYXLE-LYKCHTKKSA-N [(3r)-1-[3-[(2,3-dimethoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC=CC(C(=O)NCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1OC PFWUVWIZTDYXLE-LYKCHTKKSA-N 0.000 description 1
- SVTUDSMHPGYRIG-WWMRKDEFSA-N [(3r)-1-[3-[(2,4-dimethoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC(OC)=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 SVTUDSMHPGYRIG-WWMRKDEFSA-N 0.000 description 1
- HVJGIDBIBOWZBG-KUYIIIHJSA-N [(3r)-1-[3-[(2,6-dimethylbenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=CC=CC(C)=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 HVJGIDBIBOWZBG-KUYIIIHJSA-N 0.000 description 1
- AASIRVBXERSVSK-SGNXQQFXSA-N [(3r)-1-[3-[(2-chlorobenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC=C1Cl AASIRVBXERSVSK-SGNXQQFXSA-N 0.000 description 1
- ASRAORYYTNXDID-LYKCHTKKSA-N [(3r)-1-[3-[(2-cyanobenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC=C1C#N ASRAORYYTNXDID-LYKCHTKKSA-N 0.000 description 1
- NULDGVVFPHIWBK-YDQMMYGOSA-N [(3r)-1-[3-[(2-cyclopentylacetyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)CC1CCCC1 NULDGVVFPHIWBK-YDQMMYGOSA-N 0.000 description 1
- NIQVLHNLMBMUQD-CYFCJVRHSA-N [(3r)-1-[3-[(2-methoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 NIQVLHNLMBMUQD-CYFCJVRHSA-N 0.000 description 1
- UUOUXQPMDGWIRV-FKRVERSVSA-N [(3r)-1-[3-[(2-methylpyridine-3-carbonyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=NC=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 UUOUXQPMDGWIRV-FKRVERSVSA-N 0.000 description 1
- OOQWVNBCBFQTFY-FKRVERSVSA-N [(3r)-1-[3-[(2-methylsulfonylbenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CS(=O)(=O)C1=CC=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 OOQWVNBCBFQTFY-FKRVERSVSA-N 0.000 description 1
- YGDIRMSXHILKDR-SGNXQQFXSA-N [(3r)-1-[3-[(2-nitrobenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC=C1[N+]([O-])=O YGDIRMSXHILKDR-SGNXQQFXSA-N 0.000 description 1
- INAZWEBTRYSNJT-AFRGNJIESA-N [(3r)-1-[3-[(2-phenylacetyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)CC1=CC=CC=C1 INAZWEBTRYSNJT-AFRGNJIESA-N 0.000 description 1
- JVSJQLQKJFYFIF-FKRVERSVSA-N [(3r)-1-[3-[(2-pyridin-2-ylacetyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)CC1=CC=CC=N1 JVSJQLQKJFYFIF-FKRVERSVSA-N 0.000 description 1
- IYWYHSCHXJEVJF-WWMRKDEFSA-N [(3r)-1-[3-[(3,4-dimethoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=C(OC)C(OC)=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 IYWYHSCHXJEVJF-WWMRKDEFSA-N 0.000 description 1
- UWVSMEHWMFTZNS-WWMRKDEFSA-N [(3r)-1-[3-[(3,5-dimethoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC(OC)=CC(C(=O)NCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 UWVSMEHWMFTZNS-WWMRKDEFSA-N 0.000 description 1
- DGNMIHCHPIFVIK-FGCKQQAGSA-N [(3r)-1-[3-[(3,5-dimethylbenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=CC(C)=CC(C(=O)NCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 DGNMIHCHPIFVIK-FGCKQQAGSA-N 0.000 description 1
- KETHOOCDXWTJIX-SGNXQQFXSA-N [(3r)-1-[3-[(3-chlorobenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC(Cl)=C1 KETHOOCDXWTJIX-SGNXQQFXSA-N 0.000 description 1
- SERGHQSERNSILZ-YJZUVJCESA-N [(3r)-1-[3-[(3-cyanobenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=CC(C#N)=C1 SERGHQSERNSILZ-YJZUVJCESA-N 0.000 description 1
- PRBOCIFWEOLABT-UTZSPFMWSA-N [(3r)-1-[3-[(3-fluoro-4-methoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=C(F)C(OC)=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 PRBOCIFWEOLABT-UTZSPFMWSA-N 0.000 description 1
- QIYVGJXLOCGAJV-CYFCJVRHSA-N [(3r)-1-[3-[(3-methoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.COC1=CC=CC(C(=O)NCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 QIYVGJXLOCGAJV-CYFCJVRHSA-N 0.000 description 1
- AQKXWZBEKIDZAF-CYFCJVRHSA-N [(3r)-1-[3-[(3-methylsulfonylbenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CS(=O)(=O)C1=CC=CC(C(=O)NCCC[N+]23CCC(CC2)[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 AQKXWZBEKIDZAF-CYFCJVRHSA-N 0.000 description 1
- TYYPNBRNIIMTCE-ODDGICHGSA-N [(3r)-1-[3-[(4-butyl-2-methylphenyl)carbamoylamino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=CC(CCCC)=CC=C1NC(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 TYYPNBRNIIMTCE-ODDGICHGSA-N 0.000 description 1
- SDSYZBKMHPYMNY-SGNXQQFXSA-N [(3r)-1-[3-[(4-chlorobenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=C(Cl)C=C1 SDSYZBKMHPYMNY-SGNXQQFXSA-N 0.000 description 1
- NTGVJRDDLLQOAB-YJZUVJCESA-N [(3r)-1-[3-[(4-cyanobenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C1=CC=C(C#N)C=C1 NTGVJRDDLLQOAB-YJZUVJCESA-N 0.000 description 1
- DOWZCCDIQBHZBT-FGCKQQAGSA-N [(3r)-1-[3-[(4-ethylbenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(CC)=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 DOWZCCDIQBHZBT-FGCKQQAGSA-N 0.000 description 1
- AIBBEPCULKFSSA-CYFCJVRHSA-N [(3r)-1-[3-[(4-methoxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(OC)=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 AIBBEPCULKFSSA-CYFCJVRHSA-N 0.000 description 1
- DXFATGATASMSOI-KBGMEFHRSA-N [(3r)-1-[3-[(4-propan-2-yloxybenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1=CC(OC(C)C)=CC=C1C(=O)NCCC[N+]1(C[C@@H]2OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)CCC2CC1 DXFATGATASMSOI-KBGMEFHRSA-N 0.000 description 1
- OOVPCIYIJQRQCR-MOGMCNDHSA-N [(3r)-1-[3-[(4-pyrrol-1-ylbenzoyl)amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)OC(=O)C(O)(C=3C=CC=CC=3)C=3C=CC=CC=3)[N+]21CCCNC(=O)C(C=C1)=CC=C1N1C=CC=C1 OOVPCIYIJQRQCR-MOGMCNDHSA-N 0.000 description 1
- BIVLBNXKFDFUBR-MVIHUCQCSA-M [(3r)-1-[3-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;chloride Chemical compound [Cl-].O([C@@H]1C2CC[N+](CC2)(C1)CCCN(C)C(=O)OC(C)(C)C)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 BIVLBNXKFDFUBR-MVIHUCQCSA-M 0.000 description 1
- UONCMHCTOMGXOL-OCCBKRFISA-M [(3r)-1-[4-(n-methylanilino)-4-oxobutyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CCCC(=O)N(C)C=1C=CC=CC=1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 UONCMHCTOMGXOL-OCCBKRFISA-M 0.000 description 1
- JRZQQXAPEBDSIO-PKMIAXOUSA-M [(3r)-1-but-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC#CC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 JRZQQXAPEBDSIO-PKMIAXOUSA-M 0.000 description 1
- DWZOGFBSDRHNJJ-ZZNGFPBBSA-M [(3r)-1-hex-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC#CCCC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 DWZOGFBSDRHNJJ-ZZNGFPBBSA-M 0.000 description 1
- FJHCIUGFYGCQFT-ZMDRYIOLSA-M [(3r)-1-hex-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC#CCCC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 FJHCIUGFYGCQFT-ZMDRYIOLSA-M 0.000 description 1
- JBBYNDCMKODEMV-SSVLGJNASA-M [(3r)-1-pent-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC#CCC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 JBBYNDCMKODEMV-SSVLGJNASA-M 0.000 description 1
- HVHVRWKGNDETMJ-DCNLQBDOSA-M [(3r)-1-pent-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(C1)CC#CCC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 HVHVRWKGNDETMJ-DCNLQBDOSA-M 0.000 description 1
- FADYMROAIKHOMP-DCNLQBDOSA-M [(3r)-1-pent-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CC#CCC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 FADYMROAIKHOMP-DCNLQBDOSA-M 0.000 description 1
- UWQBXQZELWPMNJ-SSVLGJNASA-M [(3r)-1-pent-3-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(C1)CCC#CC)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 UWQBXQZELWPMNJ-SSVLGJNASA-M 0.000 description 1
- WEJLKRQCQIRIKT-QBJDRERVSA-M [(3r)-1-prop-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-fluoro-2,2-diphenylacetate;bromide Chemical compound [Br-].O([C@@H]1C2CC[N+](CC2)(CC#C)C1)C(=O)C(F)(C=1C=CC=CC=1)C1=CC=CC=C1 WEJLKRQCQIRIKT-QBJDRERVSA-M 0.000 description 1
- UVPGZQWXNCFSKP-BSUYUKDKSA-M [(3r)-1-prop-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CC#C)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 UVPGZQWXNCFSKP-BSUYUKDKSA-M 0.000 description 1
- GJXSUGFSAARCFS-DMEOCDBTSA-M [(3r)-1-prop-2-ynyl-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.O([C@@H]1C2CC[N+](CC2)(CC#C)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 GJXSUGFSAARCFS-DMEOCDBTSA-M 0.000 description 1
- YPFLFUJKZDAXRA-UHFFFAOYSA-N [3-(carbamoylamino)-2-(2,4-dichlorobenzoyl)-1-benzofuran-6-yl] methanesulfonate Chemical compound O1C2=CC(OS(=O)(=O)C)=CC=C2C(NC(N)=O)=C1C(=O)C1=CC=C(Cl)C=C1Cl YPFLFUJKZDAXRA-UHFFFAOYSA-N 0.000 description 1
- ZNVZNTIJAFGESZ-UHFFFAOYSA-N [O-]C(C[N+]1(CCC2CC1)CC2OC(C(C1=CC=CS1)(C1=CC=CS1)O)=O)=O Chemical compound [O-]C(C[N+]1(CCC2CC1)CC2OC(C(C1=CC=CS1)(C1=CC=CS1)O)=O)=O ZNVZNTIJAFGESZ-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- WBDLSXCAFVEULB-UHFFFAOYSA-N acetonitrile;methylsulfinylmethane Chemical compound CC#N.CS(C)=O WBDLSXCAFVEULB-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 102000015007 alpha-adrenergic receptor activity proteins Human genes 0.000 description 1
- 108040006816 alpha-adrenergic receptor activity proteins Proteins 0.000 description 1
- PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 208000028462 aluminosis Diseases 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 208000010123 anthracosis Diseases 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940124623 antihistamine drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- GVTLDPJNRVMCAL-UHFFFAOYSA-N arofylline Chemical compound C1=2N=CNC=2C(=O)N(CCC)C(=O)N1C1=CC=C(Cl)C=C1 GVTLDPJNRVMCAL-UHFFFAOYSA-N 0.000 description 1
- 229950009746 arofylline Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 206010003441 asbestosis Diseases 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 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
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 150000005350 bicyclononyls Chemical group 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960004342 cetirizine hydrochloride Drugs 0.000 description 1
- 239000002559 chemokine receptor antagonist Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 201000003139 chronic cystitis Diseases 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- 229960003728 ciclesonide Drugs 0.000 description 1
- 229950001653 cilomilast Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960002689 clemastine fumarate Drugs 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical group C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 208000007784 diverticulitis Diseases 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 229960000354 fexofenadine hydrochloride Drugs 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- ZYCMDWDFIQDPLP-UHFFFAOYSA-N hbr bromine Chemical compound Br.Br ZYCMDWDFIQDPLP-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 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
- 208000008585 mastocytosis Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
- 229960001664 mometasone Drugs 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000003681 muscarinic M3 receptor antagonist Substances 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- DPHDSIQHVGSITN-UHFFFAOYSA-N n-(3,5-dichloropyridin-4-yl)-2-[1-[(4-fluorophenyl)methyl]-5-hydroxyindol-3-yl]-2-oxoacetamide Chemical compound C1=C(C(=O)C(=O)NC=2C(=CN=CC=2Cl)Cl)C2=CC(O)=CC=C2N1CC1=CC=C(F)C=C1 DPHDSIQHVGSITN-UHFFFAOYSA-N 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 208000020629 overactive bladder Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000001734 parasympathetic effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- MUWVIMJPXKIXJK-UHFFFAOYSA-N prop-2-enyl 2-bromoacetate Chemical compound BrCC(=O)OCC=C MUWVIMJPXKIXJK-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 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
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical group C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 1
- 229960002586 roflumilast Drugs 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 208000004003 siderosis Diseases 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000003890 substance P antagonist Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- CWCFCGSAAZGWCE-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)-n-methylcarbamate Chemical compound BrCCN(C)C(=O)OC(C)(C)C CWCFCGSAAZGWCE-UHFFFAOYSA-N 0.000 description 1
- RUHJCVPNOYXWLC-PBJIGMDXSA-N tert-butyl n-[2-[(3r)-3-(2-hydroxy-2,2-diphenylacetyl)-1-azoniabicyclo[2.2.2]octan-1-yl]ethyl]carbamate;bromide Chemical compound [Br-].O=C([C@@H]1C2CC[N+](CC2)(C1)CCNC(=O)OC(C)(C)C)C(O)(C=1C=CC=CC=1)C1=CC=CC=C1 RUHJCVPNOYXWLC-PBJIGMDXSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This invention relates to organic compounds, their preparation and use as pharmaceuticals.
- the invention provides compounds of formula I in salt or zwitterionic form wherein R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or —CR 1 R 2 R 3 together form a group of formula where R is a bond, —O—, —S—, —CH 2 —, —CH ⁇ CH—, —CH 2 —CH 2 —, amino or —N(CH 3 )—; R 2 is hydrogen, halo, hydroxy, C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl optionally substituted by hydroxy; R 4 is C 3 -C 10 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NRS—SO 2 —R 8 , ——R
- Optionally substituted means the group referred to can be substituted at one or more positions, e.g. 1, 2 or 3 positions, by any one or any combination of the radicals described.
- C 1 -C 8 -alkyl denotes straight chain or branched alkyl having 1 to 8 carbon atoms.
- C 1 -C 8 -alkyl is C 1 -C 4 -alkyl.
- C 1 -C 8 -alkylene denotes straight chain or branched alkylene that contains 1 to 8 carbon atoms.
- C 1 -C 8 -alkylene is C 1 -C 4 -alkylene.
- C 2 -C 8 -alkenyl denotes straight chain or branched hydrocarbon chains that contain two to eight carbon atoms and one or more carbon-carbon double bonds.
- C 2 -C 8 -alkenyl is “C 2 -C 4 -alkenyl”.
- C 2 -C 10 -alkynyl denotes straight chain or branched hydrocarbon chains that contain two to ten carbon atoms and one or more carbon-carbon triple bonds.
- C 2 -C 10 -alkynyl is “C 3 -C 8 -alkynyl”.
- C 3 -C 15 -carbocyclic group denotes a carbocyclic group having 3 to 15 ring carbon atoms, for example a monocyclic group, either cycloaliphatic, such as a C 3 -C 8 -cycloalkyl, or aromatic such as phenyl, which can be substituted by one or more, usually one or two, C 1 -C 4 -alkyl groups, or a bicyclic group such as bicyclooctyl, bicyclononyl including indanyl and indenyl, and bicyclodecyl including naphthyl, again any of which can be substituted by one or more, usually one or two, C 1 -C 4 -alkyl groups.
- the C 3 -C 15 -carbocyclic group is a C 3 -C 10 -carbocyclic group, for example cyclopropyl, cyclopentyl, cyclohexyl, cyclohepcyl, phenyl, indanyl or naphthyl.
- the C 3 -C 15 -carbocyclic group can be substituted or unsubstituted.
- Preferred substituents include halo (e.g. fluoro, chloro or bromo), cyano, hydroxy, amino, nitro, carboxy, C 1 -C 8 -alkyl (e.g.
- halo-C 1 -C 8 -alkyl C 1 -C 8 -alkoxy, C 1 -C 8 -alkylcarbonyl, C 1 -C 8 -alkylsulfonyl, —SO 2 NH 2 , a C 3 -C 15 -carbocyclic group and a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur.
- C 3 -C 8 -cycloalkyl denotes cycloalkyl having 3 to 8 carbon atoms.
- C 3 -C 8 -cycloalkyl is “C 3 -C 6 -cycloalkyl”.
- C 1 -C 8 -haloalkyl denotes C 1 -C 8 -alkyl as hereinbefore defined substituted by one or more halogen atoms, preferably one, two or three halogen atoms.
- C 1 -C 8 -haloalkyl is “C 1 -C 4 -haloalkyl”.
- C 1 -C 8 -alkylcarbonyl denotes C 1 -C 8 -alkyl as hereinbefore defined linked to a carbonyl group.
- C 1 -C 8 -alkylcarbonyl is “C 1 -C 4 -alkylcarbonyl”.
- C 1 -C 8 -alkylthio denotes C 1 -C 8 -alkyl as hereinbefore defined linked to —S—.
- C 1 -C 8 -alkylthio is “C 1 -C 4 -alkylthio”.
- C 1 -C 8 -alkylsulfonyl denotes C 1 -C 8 -alkyl as hereinbefore defined linked to —SO 2 —.
- C 1 -C 8 -alkylsulfonyl is “C 1 -C 4 -alkylsulfonyl”.
- C 1 -C 8 -alkoxy denotes straight chain or branched alkoxy having 1 to 8 carbon atoms.
- C 1 -C 8 -alkoxy is C 1 -C 4 -alkoxy.
- C 1 -C 8 -haloalkoxy denotes C 1 -C 8 -alkoxy as hereinbefore defined substituted by one or more halogen atoms, preferably one, two or three halogen atoms.
- C 1 -C 8 -haloalkoxy is “C 1 -C 4 -haloalkoxy”.
- di(C 1 -C 8 -alkyl)sulfamoyl denotes —SO 2 —NH 2 where the nitrogen atom is substituted at two positions by C 1 -C 8 -alkyl as hereinbefore defined, which may be the same or different.
- di(C 1 -C 8 -alkyl)sulfamoyl is —SO 2 —N(CH 3 ) 2 .
- Halo or halogen denotes a element belonging to group 17 (formerly group VII) of the Periodic Table of Elements, which may be, for example, fluorine, chlorine, bromine or iodine. Preferably halo or halogen is fluorine, chlorine or bromine.
- Aminocarbonyl as used herein denotes amino attached through the nitrogen atom to a carbonyl group.
- Monoheterocyclic groups include azetidinyl, tetrahydrofuranyl, furyl, pyrrolyl, pyrrolidinyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thienyl, thiazolyl, thiadiazolyl, isothiazolyl, oxadiazolyl, pyridinyl, oxazolyl, isoxazolyl, piperidinyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, piperazinyl, morpholinyl, triazinyl, oxazinyl, thiazolyl or tetrahydropyranyl.
- Biheterocyclic groups include thienothienyl, benzazolyl, benzothienyl, benzimidazolyl, benzodioxinyl, indazolyl, benzothiazolyl, imidazopyridinyl and naphthyridinyl.
- Preferred 4- to 12-membered heterocyclic groups include azetidinyl, tetrahydrofuranyl, furyl, pyrrolyl, pyrazolyl, triazolyl, thienyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, tetrahydropyranyl, piperidinyl, pyridinyl, pyrazinyl, pyrimidinyl, thienothienyl, benzazolyl, benzothienyl, benzimidazolyl, benzodioxinyl, indazolyl and benzothiazolyl, imidazopyridinyl, naphthyridinyl.
- the 4- to 12-membered heterocyclic group can be unsubstituted or substituted at one or more positions, e.g. 1, 2 or 3 positions, by any one or any combination of substituents.
- Preferred substituents include halo (e.g. fluoro, chloro or bromo), cyano, oxo, hydroxy, carboxy, nitro, C 1 -C 8 -alkyl (e.g. methyl or ethyl), halo-C 1 -C 8 -alkyl (e.g.
- C 1 -C 8 -alkylcarbonyl di(C 1 -C 8 -alkyl)sulfamoyl and C 1 -C 8 -alkoxy optionally substituted by aminocarbonyl.
- substituents include halo, oxo, C 1 -C 4 -alkyl and C 1 -C 4 -alkylcarbonyl.
- the invention provides compounds of formula I in salt or zwitterionic form wherein R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or —CR 1 R 2 R 3 together form a group of formula where R is a bond, —O—, —S—, —CH 2 —, —CH ⁇ CH—, —CH 2 —CH 2 —, amino or —N(CH 3 )—; R 2 is hydrogen, halo, hydroxy, C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl optionally substituted by hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8
- the invention provides compounds of formula I in salt or zwitterionic form wherein R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or —CR 1 R 2 R 3 together form a group of formula where R is a bond, —O—, —S—, —CH 2 —, —CH ⁇ CH—, —CH 2 —CH 2 —, amino or —N(CH 3 )—; R 2 is hydrogen, halo, hydroxy, C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl optionally substituted by hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NRS—SO 2 —R 8 ,
- Preferred compounds include those of formula I in salt or zwitterionic form, where R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 2 is halo or hydroxy
- R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 12 , —O—CO—R 13 or —CO—O—R 14 ,
- R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 5 is hydrogen or C 1 -C 8 -alkyl
- R 6 is C 1 -C 8 -alkyl, C 2 -C 10 -alkynyl or C 1 -C 8 -alkoxy in each case optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 6 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 7 is a C 3 -C 15 -carbocyclic group
- R 8 is a C 3 -C 15 -carbocyclic group
- R 9 is hydrogen or C 1 -C 8 -alkyl
- R 10 is C 1 -C 8 -alkyl optionally substituted by cyano, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group or by a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 10 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 12 is a C 3 -C 15 -carbocyclic group
- R 13 is C 1 -C 8 -alkyl
- R 14 is hydrogen, a C 3 -C 15 -carbocyclic group, C 1 -C 8 -alkenyl, or C 1 -C 8 -alkyl optionally substituted by a C 3 -C 15 -carbocyclic group.
- Preferred compounds include those of formula I in salt or zwitterionic form, where R 1 and R 3 are each independently a C 3 -C 1-5 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 2 is halo or hydroxy
- R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NRS—CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 12 , —O—CO—R 13 or —CO—O—R 14 ,
- R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 5 is hydrogen or C 1 -C 8 -alkyl
- R 6 is C 1 -C 8 -alkyl, C 2 -C 10 -alkynyl or C 1 -C 8 -alkoxy in each case optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 6 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 7 is a C 3 -C 15 -carbocyclic group
- R 8 is a C 3 -C 15 -carbocyclic group
- R 9 is hydrogen or C 1 -C 8 -alkyl
- R 10 is C 1 -C 8 -alkyl optionally substituted by cyano, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group or by a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 10 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 12 is a C 3 -C 15 -carbocyclic group
- R 13 is C 1 -C 8 -alkyl
- R 14 is hydrogen, a C 3 -C 15 -carbocyclic group or C 1 -C 8 -alkyl optionally substituted by a C 3 -C 15 -carbocyclic group.
- Preferred compounds also include those of formula I in salt or zwitterionic form, where R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 2 is halo or hydroxy
- R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 7 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 12 , —O—CO—R 13 or —CO—O—R 14 ,
- R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 5 is hydrogen
- R 6 is C 1 -C 8 -alkyl or C 1 -C 8 -alkoxy in either case optionally substituted by a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 6 is a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 7 is a C 3 -C 15 -carbocyclic group
- R 8 is a C 3 -C 15 -carbocyclic group
- R 9 is hydrogen or C 1 -C 8 -alkyl
- R 10 is C 1 -C 8 -alkyl optionally substituted by cyano, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group or by a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 10 is a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 12 is a C 3 -C 15 -carbocyclic group
- R 13 is C 1 -C 8 -alkyl
- R 14 is hydrogen, C 1 -C 8 -alkyl or a C 3 -C 15 -carbocyclic group.
- Especially preferred compounds include those of formula I in salt or zwitterionic form where R 1 and R 3 are each independently a C 6 -C 10 -carbocyclic aromatic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 2 is halo or hydroxy
- R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 12 , —O—CO—R 13 or —CO—O—R 14 ,
- R 4 is C 3 -C 8 -alkynyl optionally substituted by a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 5 is hydrogen or C 1 -C 4 -alkyl
- R 6 is C 1 -C 4 -alkyl, C 2 -C 8 -alkynyl or C 1 -C 4 -alkoxy in each case optionally substituted by a C 3 -C 10 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 6 is a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 7 is a C 3 -C 10 -carbocyclic group
- R 8 is a C 3 -C 10 -carbocyclic group
- R 9 is hydrogen or C 1 -C 4 -alkyl
- R 10 is C 1 -C 4 -alkyl optionally substituted by cyano, C 1 -C 4 -alkoxy, a C 3 -C 10 -carbocyclic group or by a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 10 is a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 12 is a C 3 -C 10 -carbocyclic group
- R 13 is C 1 -C 4 -alkyl
- R 14 is hydrogen, a C 3 -C 10 -carbocyclic group, C 1 -C 4 -alkenyl, or C 1 -C 4 -alkyl optionally substituted by a C 3 -C 10 -carbocyclic group.
- Especially preferred compounds include those of formula I in salt or zwitterionic form where R 1 and R 3 are each independently a C 6 -C 10 -carbocyclic aromatic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 2 is halo or hydroxy
- R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 12 , —O—CO—R 13 or —CO—O—R 14 ,
- R 4 is C 3 -C 8 -alkynyl optionally substituted by a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- Especially preferred compounds also include those of formula I in salt or zwitterionic form where
- R 1 and R 3 are each independently a C 6 -C 10 -carbocyclic aromatic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 2 is halo or hydroxy
- R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 12 , —O—CO—R 13 or —CO—O—R 14 ,
- R 4 is C 3 -C 8 -alkynyl optionally substituted by a C 3 -C 10 -carbocyclic group or a 5- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 5 is hydrogen
- R 6 is C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy in either case optionally substituted by a C 3 -C 10 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 6 is a C 3 -C 10 -carbocyclic group or a S— to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 7 is a C 3 -C 10 -carbocyclic group
- R 8 is a C 3 -C 10 -carbocyclic group
- R 9 is hydrogen or C 1 -C 4 -alkyl
- R 10 is C 1 -C 4 -alkyl optionally substituted by cyano, C 1 -C 4 -alkoxy, a C 3 -C 10 -carbocyclic group or by a 5- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
- R 10 is a C 3 -C 10 -carbocyclic group or a 5- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
- R 12 is a C 3 -C 10 -carbocyclic group
- R 13 is C 1 -C 4 -alkyl
- R 14 is hydrogen, C 1 -C 4 -alkyl or a C 3 -C 10 -carbocyclic group.
- the compounds of formula I are quaternary ammonium salts.
- Suitable counter ions are pharmaceutically acceptable counter ions including, for example, fluoride, chloride, bromide, iodide, nitrate, sulfate, phosphate, formate, acetate, trifluoroacetate, propionate, butyrate, lactate, citrate, tartrate, malate, maleate, succinate, benzoate, p-chlorobenzoate, diphenylacetate or triphenylacetate, o-hydroxybenzoate, p-hydroxybenzoate, 1-hydroxynaphthalene-2-carboxylate, 3-hydroxynaphthalene-2-carboxylate, methanesulfonate and benzenesulfonate.
- compositions of formula I that contain a basic centre are capable of forming acid addition salts, particularly pharmaceutically acceptable acid addition salts.
- Pharmaceutically acceptable acid addition salts of the compound of formula I include those of inorganic acids, for example, hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid; and organic acids, for example aliphatic monocarboxylic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid and butyric acid, aliphatic hydroxy acids such as lactic acid, citric acid, tartaric acid or malic acid, dicarboxylic acids such as maleic acid or succinic acid, aromatic carboxylic acids such as benzoic acid, p-chlorobenzoic acid, diphenylacetic acid or triphenylacetic acid, aromatic hydroxy acids such as o-hydroxybenzoic acid, p-hydroxybenzoic acid, 1-hydroxynaphthal
- Compounds of formula I which contain acidic, e.g. carboxyl, groups are also capable of forming salts with bases, in particular pharmaceutically acceptable bases such as those well known in the art; suitable such salts include metal salts, particularly alkali metal or alkaline earth metal salts such as sodium, potassium, magnesium or calcium salts, or salts with ammonia or pharmaceutically acceptable organic amines or heterocyclic bases such as ethanolamines, benzylamines or pyridine. These salts may be prepared from compounds of formula I by known salt-forming procedures.
- Compounds of formula I that contain acidic, e.g. carboxyl, groups may also exist as zwitterions with the quaternary ammonium centre.
- the compounds of the invention contain at least one asymmetric carbon atom and thus they exist in individual optically active isomeric forms or as mixtures thereof, e.g. as racemic mixtures. In cases where additional asymmetric centres exist the present invention also embraces both individual optically active isomers as well as mixtures, e.g. diastereomeric mixtures, thereof.
- the invention also provides a process for the preparation of compounds of formula I which comprises (i) (A) reacting a compound of compound of formula II
- Process variant (A) may be effected using known procedures for reacting quinuclidinol esters with halogenides or analogously as hereinafter described in the Examples.
- the reaction is conveniently carried out in water or an organic solvent, for example acetonitrile, dimethylformamide (DMF), dimethylsulphoxide (DMSO), ethyl acetate or chloroform.
- the reaction is carried out at a temperature between 20° C. to 120° C., conveniently between room temperature and 80° C.
- Process variant (B) may be effected using known procedures for reacting amines with carboxylic acids or amide-forming derivatives thereof such as acid halides to give amides or analogously as hereinafter described in the Examples.
- the reaction between the carboxylic acid and the amine is conveniently carried out in an organic solvent, for example dimethylformamide (DMF), optionally in the presence of a coupling agent, for example O-(7-azabenzotriazol-1-yl)-N,N,—N′,N′-tetramethyl-uronium hexafluorophate (HATU), and a base, for example diisopropyl-ethylamine (DIPEA) or triethylamine.
- Suitable reaction temperatures are from 0° C. to 50° C., conveniently room temperature.
- Process variant (C) may be effected using known procedures for reacting amines with isocyanates to give ureas or analogously as hereinafter described in the Examples.
- the reaction is conveniently carried out in an organic solvent, for example dimethylformamide (DMF), and preferably in the presence of a base, for example DIPEA.
- Suitable reaction temperatures are from ⁇ 78° C. to 40° C., conveniently room temperature.
- Process variant (D) may be effected using known procedures for reacting amines with sulfonylhalides to give sulfonamides or analogously as hereinafter described in the Examples.
- the reaction is conveniently carried out in an organic solvent, for example dimethylformamide (DMF), and preferably in the presence of a base, for example DIPEA.
- Suitable reaction temperatures are from 0° C. to 50° C., conveniently room temperature.
- Process variant (E) may be effected using known procedures for reacting carboxylic acids or amide-forming derivatives thereof such as acid halides with amines to give amides or analogously as hereinafter described in the Examples.
- the reaction between the carboxylic acid and the amine is conveniently carried out in an organic solvent, for example dimethylsulfoxide (DMSO) or dimethylformamide (DMF), optionally in the presence of a coupling agent, for example HATU, and preferably in the presence of a base, for example DIPEA.
- DMSO dimethylsulfoxide
- DMF dimethylformamide
- a coupling agent for example HATU
- a base for example DIPEA
- Compounds of formula IV may be prepared by deprotecting a compound of formula X where R 1 , R 2 , R 3 and R 5 are as hereinbefore defined, Q is an amine protecting group and T denotes C 1 -C 8 -alkylene, e.g. when Q is t-butyloxycarbonyl by treatment with a strong acid, e.g. hydrochloric acid or hydrobromic acid, which is conveniently carried out in an organic solvent, for example dioxan (1,4-dioxycyclohexane), and suitable reaction temperatures are from 0° C. to 60° C., conveniently room temperature.
- a strong acid e.g. hydrochloric acid or hydrobromic acid
- Compounds of formula VIII may be prepared by cleavage of a corresponding ester of formula XI where R 1 , R 2 , and R 3 are as hereinbefore defined, T denotes C 1 -C 8 -alkylene and W denotes a group that is readily replaceable by hydrogen.
- W is t-butyl the compound may be reacted with an anhydrous strong acid, e.g. hydrochloric acid, hydrobromic acid or trifluoroacetic acid, which is conveniently carried out in an organic solvent, for example dioxane, and suitable reaction temperatures are from ⁇ 20° C. to 40° C., conveniently room temperature.
- Compounds of formula X may be prepared by reacting a compound of formula II where R 1 , R 2 and R 3 are as hereinbefore defined, with a compound of formula XII where R 5 is as hereinbefore defined, Q is an amine protecting group e.g. t-butyloxycarbonyl, X 1 is chloro, bromo or iodo and T denotes C 1 -C 8 -alkylene.
- the reaction is conveniently carried out in an organic solvent, for example DMF. Suitable reaction temperatures are from 40° C. to 120° C., conveniently between room temperature and 80° C.
- Compounds of formula XI may be prepared by reacting a compound of formula II where R 1 , R 2 and R 3 are as hereinbefore defined, with a compound of formula XIII where T denotes C 1 -C 8 -alkylene, X 2 is chloro, bromo or iodo and W is a group that is readily replaceable by hydrogen.
- W is t-butyl the reaction is conveniently carried out in an organic solvent, for example DMF.
- Suitable reaction temperatures are from 0° C. to 120° C., conveniently between room temperature and 60° C.
- the protecting groups may be chosen in accordance with the nature of the functional group, for example as described in Protective Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, John Wiley & Sons Inc, Third Edition, 1999, which reference also describes procedures suitable for replacement of the protecting groups by hydrogen.
- Compounds of formula I are quaternary ammonium salts and may be converted between different salt forms using ion exchange chromatography.
- the compounds can be obtained in the form of hydrates or solvates containing a solvent used for crystallization.
- Compounds of formula I can be recovered from reaction mixtures and purified using known methods.
- Isomers, such as enantiomers, may be obtained in a conventional manner, e.g. by fractional crystallization, chiral phase chromatography or asymmetric synthesis from correspondingly asymmetrically substituted, e.g. optically active, starting materials.
- agents of the invention are useful as pharmaceuticals. Accordingly the invention also provides a compound of formula I in pharmaceutically acceptable salt or zwitterionic form for use as a pharmaceutical.
- the agents of the invention act as muscarinic antagonists, particularly muscarinic M3 receptor antagonists, thereby inhibiting acetylcholine-induced contraction of smooth muscle in e.g. respiratory tract, digestive tract and urinary systems.
- the affinity (Ki) of agents of the invention at the human muscarinic acetylcholine M3 receptor can be determined in a competitive filtration binding assay with the radio-labelled antagonist [ 3 H] n-methyl scopolamine methyl chloride (NMS):
- Membranes prepared from CHO cells stably transfected with human M3 receptor at 10 ⁇ g protein/well are incubated with serial dilutions of the agents of the invention, [ 3 H]NMS (0.25 nM) and assay buffer (20 mM HEPES, 1 mM MgCl 2 at pH 7.4) for 17 hours at room temperature.
- the assay is carried out in a 250 ⁇ L final volume, in the presence of a final dimethyl sulfoxide concentration of 1%.
- Total binding of [ 3 H]NMS is determined in the absence of the agents of the invention with a corresponding substituted volume of assay buffer.
- Non-specific binding of [ 3 H] NMS is determined in the presence of 300 nM ipratropium bromide.
- the membranes are harvested onto a UnifilterTM GF/B filter plate containing 0.05% polyethyleneimine, using a BrandelTM filtration harvester 9600. Filter plates are dried for two hours at 35° C. before the addition of MicroscintTM ‘O’ cocktail, and read on a Packard TopcountTM scintillator using a 3 H-Scintillation protocol. All IC50s are calculated with the aid of XL-Fit graph package and K i values derived using the Cheng-Prusoff correction (Cheng Y., Prusoff W. H. (1973) Biochem. Pharmacol 22 3099-3109).
- the compounds of the Examples herein below generally have Ki values below 1 ⁇ M in the above assay.
- the compounds of Examples 17, 34, 52, 54, 71, 76, 96, 114, 138, 159, 170, 190, 209, 221, 242 and 244 have M3 K i values of 0.0144, 0.0023, 0.0019, 0.0001, 0.0005, 0.0011, 0.0046, 0.0002, 0.0022. 0.0007, 0.0007, 0.0007, 0.0010, 0.0013, 0.0003 and 0.0003 ⁇ M respectively.
- agents of the invention are useful in the treatment of conditions mediated by the muscarinic M3 receptor, particularly those associated with increased parasympathetic tone leading to, for example, excessive glandular secretion or smooth muscle contraction.
- Treatment in accordance with the invention may be symptomatic or prophylactic.
- the agents of the invention are useful in the relaxation of bronchial smooth muscle and the relief of bronchoconstriction. Relief of bronchoconstriction can be measured in models such as the in vivo plethysmography models of Chong et al, J. Pharmacol. Toxicol. Methods 1998, 39, 163, Hammelmann et al, Am. J. Respir. Crit. Care Med., 1997, 156, 766 and analogous models.
- the agents of the invention are therefore useful in the treatment of obstructive or inflammatory airways diseases. In view of their long duration of action, it is possible to administer the agents of the invention once-a-day in the treatment of such diseases.
- agents of the invention commonly exhibit characteristics indicating a low incidence of side effects commonly encountered with ⁇ 2 agonists such as tachycardia, tremor and restlessness, such agents accordingly being suitable for use in on demand (rescue) treatment as well as prophylactic treatment of obstructive or inflammatory airways diseases.
- Inflammatory or obstructive airways diseases to which the present invention is applicable include asthma of whatever type or genesis including both intrinsic (non-allergic) asthma and extrinsic (allergic) asthma.
- Treatment of asthma is also to be understood as embracing treatment of subjects, e.g. of less than 4 or 5 years of age, exhibiting wheezing symptoms and diagnosed or diagnosable as “whez infants”, an established patient category of major medical concern and now often identified as incipient or early-phase asthmatics. (For convenience this particular asthmatic condition is referred to as “whez-infant syndrome”.)
- Prophylactic efficacy in the treatment of asthma will be evidenced by reduced frequency or severity of symptomatic attack, e.g. of acute asthmatic or bronchoconstrictor attack, improvement in lung function or improved airways hyperreactivity. It may further be evidenced by reduced requirement for other, symptomatic therapy, i.e. therapy for or intended to restrict or abort symptomatic attack when it occurs, for example anti-inflammatory (e.g. corticosteroid) or bronchodilatory.
- Prophylactic benefit in asthma may in particular be apparent in subjects prone to “morning dipping”. “Morning dipping” is a recognised asthmatic syndrome, common to a substantial percentage of asthmatics and characterised by asthma attack, e.g. between the hours of about 4 to 6 am, i.e. at a time normally substantially distant from any previously administered symptomatic asthma therapy.
- inflammatory or obstructive airways diseases and conditions to which the present invention is applicable include adult/acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary or airways disease (COPD or COAD), including chronic bronchitis, or dyspnea associated therewith, emphysema, as well as exacerbation of airways hyperreactivity consequent to other drug therapy, in particular other inhaled drug therapy.
- ARDS adult/acute respiratory distress syndrome
- COAD or COAD chronic obstructive pulmonary or airways disease
- chronic bronchitis or dyspnea associated therewith
- emphysema emphysema
- exacerbation of airways hyperreactivity consequent to other drug therapy in particular other inhaled drug therapy.
- the invention is also applicable to the treatment of bronchitis of whatever type or genesis including, e.g., acute, arachidic, catarrhal, croupus, chronic or phthinoid
- pneumoconiosis an inflammatory, commonly occupational, disease of the lungs, frequently accompanied by airways obstruction, whether chronic or acute, and occasioned by repeated inhalation of dusts
- pneumoconiosis an inflammatory, commonly occupational, disease of the lungs, frequently accompanied by airways obstruction, whether chronic or acute, and occasioned by repeated inhalation of dusts
- aluminosis an inflammatory, commonly occupational, disease of the lungs, frequently accompanied by airways obstruction, whether chronic or acute, and occasioned by repeated inhalation of dusts
- aluminosis anthracosis
- asbestosis chalicosis
- ptilosis ptilosis
- siderosis silicosis
- tabacosis tabacosis and byssinosis.
- the agents of the invention are also useful in the treatment of a condition requiring relaxation of smooth muscle of the uterus, bladder or vascular system. They are thus useful for the prevention or alleviation of premature labour pains in pregnancy.
- the agents of the invention are also useful as co-therapeutic agents for use in combination with other drug substances such as anti-inflammatory, bronchodilatory, antihistamine, decongestant or anti-tussive drug substances, particularly in the treatment of obstructive or inflammatory airways diseases such as those mentioned hereinbefore, for example as potentiators of therapeutic activity of such drugs or as a means of reducing required dosaging or potential side effects of such drugs.
- An agent of the invention may be mixed with one or more other drug substances in a fixed pharmaceutical composition or it may be administered separately, before, simultaneously with or after the other drug substance(s).
- the invention includes a combination of an agent of the invention as hereinbefore described with an anti-inflammatory, bronchodilatory, antihistamine, decongestant or anti-tussive drug substance, said agent of the invention and said drug substance being in the same or different pharmaceutical composition.
- Such anti-inflammatory drugs include steroids, for example glucocorticosteroids such as budesonide, beclamethasone, fluticasone, ciclesonide or mometasone, or steroids described in WO 02/88167, WO 02/12266, WO 02/100879 or WO 02/00679, especially those of Examples 3, 11, 14, 17, 19, 26, 34, 37, 39, 51, 60, 67, 72, 73, 90, 99 and 101, and non-steroidal steroid agonists such as those described in WO 00/00531, WO 02/10143, WO 03/082280, WO 03/082787, WO 03/104195, WO 04/005229; LTB4 antagonists such as those described in U.S.
- steroids for example glucocorticosteroids such as budesonide, beclamethasone, fluticasone, ciclesonide or mometasone
- agents of the invention are useful in combination therapy with chemokine receptor antagonists, calcium channel blockers, alpha-adrenoceptor antagonists, dopamine agonists, endothelin antagonists, substance-P antagonists, 5-LO inhibitors, VLA-4 antagonists and theophylline.
- the agents of the invention are also particularly useful as co-therapeutic agents for use in combination with beta-2 adrenoceptor agonists or corticosteroids.
- Suitable beta-2 adrenoceptor agonists include salbutamol, terbutaline, salmeterol and, especially, formoterol and pharmaceutically acceptable salts thereof, and compounds (in free or salt or solvate form) of formula I of WO 0075114, which document is incorporated herein by reference, preferably compounds of the Examples thereof, especially a compound of formula and pharmaceutically acceptable salts thereof, as well as compounds (in free or salt or solvate form) of formula I of WO 04/16601.
- Co-therapeutic antihistamine drug substances include cetirizine hydrochloride, acetaminophen, clemastine fumarate, promethazine, loratidine, desloratidine, diphenhydramine and fexofenadine hydrochloride.
- Combinations of agents of the invention and one or more of beta-2 adrenoceptor agonists, steroids, PDE4 inhibitors, A2a agonists, A2b agonists and LTD4 antagonists may be used, for example, in the treatment of asthma but particularly COPD.
- the present invention also provides a method for the treatment of an obstructive or inflammatory airways disease which comprises administering to a subject, particularly a human subject, in need thereof a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore described.
- the invention provides a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore described for use in the preparation of a medicament for the treatment of an obstructive or inflammatory airways disease.
- the agents of the invention may be administered by any appropriate route, e.g. orally, for example in the form of a tablet or capsule; parenterally, for example intravenously; topically to the skin, for example in the treatment of psoriasis; intranasally, for example in the treatment of hay fever; or, preferably, by inhalation, particularly in the treatment of obstructive or inflammatory airways diseases.
- the agents of the invention may be delivered as an inhalable formulation for the treatment of COPD and asthma.
- the invention also provides a pharmaceutical composition
- a pharmaceutical composition comprising a compound of formula I in free form or in the form of a pharmaceutically acceptable salt or solvate thereof, optionally together with a pharmaceutically acceptable diluent or carrier thereof.
- Such compositions may be prepared using conventional diluents or excipients and techniques known in the galenic art.
- oral dosage forms may include tablets and capsules.
- Formulations for topical administration may take the form of creams, ointments, gels or transdermal delivery systems, e.g. patches.
- Compositions for inhalation may comprise aerosol or other atomizable formulations or dry powder formulations.
- the composition comprises an aerosol formulation
- it preferably contains, for example, a hydro-fluoro-alkane (HFA) propellant such as HFA134a or HFA227 or a mixture of these, and may contain one or more co-solvents known in the art such as ethanol (up to 20% by weight), and/or one or more surfactants such as oleic acid or sorbitan trioleate, and/or one or more bulking agents such as lactose.
- HFA hydro-fluoro-alkane
- the composition comprises a dry powder formulation, it preferably contains, for example, the compound of formula I having a particle diameter up to 10 microns, optionally together with a diluent or carrier, such as lactose, of the desired particle size distribution and a compound that helps to protect against product performance deterioration due to moisture.
- a diluent or carrier such as lactose
- the composition comprises a nebulised formulation, it preferably contains, for example, the compound of formula I either dissolved, or suspended, in a vehicle containing water, a co-solvent such as ethanol or propylene glycol and a stabiliser, which may be a surfactant.
- the invention also includes (A) a compound of formula I as hereinbefore described in free form, or a pharmaceutically acceptable salt or solvate thereof, in inhalable form; (B) an inhalable medicament comprising such a compound in inhalable form together with a pharmaceutically acceptable carrier in inhalable form; (C) a pharmaceutical product comprising such a compound in inhalable form in association with an inhalation device; and (D) an inhalation device containing such a compound in inhalable form.
- Dosages of agents of the invention employed in practising the present invention will of course vary depending, for example, on the particular condition to be treated, the effect desired and the mode of administration.
- suitable daily dosages for administration by inhalation are of the order of 0.0001 to 30 mg/kg, typically 0.01 to 10 mg per patient, while for oral administration suitable daily doses are of the order of 0.01 to 100 mg/kg.
- Especially preferred compounds of formula I include compounds of formula XIV
- R 1 , R 2 , R 3 , and R 4 are as shown in Table 1 below, the method of preparation being described hereinafter. All compounds are quaternary ammonium salts. The table also shows mass spectrometry data. TABLE 1 M/s Ex.
- DAST is diethylaminosulfur trifluoride
- DCE is dichloroethane
- DCM is dichloromethane
- DIPEA is diisopropylethylamine
- DME is dimethoxyethane
- HATU is O-(7-azabenzotriazol-1-yl)-N,N, —N′,N′-tetramethyl-uronium hexafluorophophate
- HPLC High Performance Liquid Chromatography
- Isolute CBA is propylcarboxylic acid
- NBS is N-bromosuccinimide
- PyBOP is benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate
- THF is tetrahydrofuran.
- BEMP 2-tert-Butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine, polymer bound.
- the composition of the resulting counter ion was not confirmed spectroscopically, and may indeed be a variable mixture of trifluoroacetate and the halide resulting from the quaternarisation reaction.
- HATU is used as a coupling agent the counter ion may also be hexa fluorophosphate.
- This compound is made via an analogous procedure to (R)-3-(2-Hydroxy-2,2-diphenyl-acetoxy)-1-[3-(3-phenyl-ureido)-propyl)-1-azonia-bicyclo[2.2.2]octane trifluoroacetate (Example 47) by replacing phenyl isocyanate with 4-butyl-1-isocyanato-2-methyl-benzene.
- Potassium hydroxide (100 ml, 1.25 M solution) is added to 2,2′-thenil (Ubichem) at room temperature and the reaction mixture is heated to reflux for 4 hours and then cooled to room temperature.
- the solution is acidified to pH2 and extracted with ethyl acetate (3 ⁇ 100 ml). The combined organic portions are washed with water (100 ml), dried over Na 2 SO 4 and cooled to 0° C.
- TMS-diazomethane (20 ml of a 2M solution in hexanes) is added dropwise and the mixture is allowed to warm to room temperature.
- Acetic acid (4 ml) is added and the reaction mixture is left at room temperature overnight.
- the solvent is removed in vacuo and the crude product is dried and triturated with hexane to yield the titled compound as a brown amorphous solid.
- reaction mixture is diluted with DCM (10 ml) and the organic portion is separated.
- the aqueous layer is extracted with DCM (10 ml) and the organic portions are combined, dried over MgSO 4 and concentrated in vacuo.
- Purification of the crude residue is carried by chromatography on silica, eluting with DCM: methanol to yield the titled compound as a brown oil.
- This compound is made analogously to (R)-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-[2-(toluene-4-sulfonylamino)-ethyl]-1-azonia-bicyclo[2.2.2]octane trifluoroacetate (Example 49) by replacing p-toluenesulfonyl chloride with phenyl isocyanate.
- This compound is made analogously to (R)-3-(2-hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-phenylcarbamoylmethyl-1-azonia-bicyclo[2.2.2]octane trifluoroacetate (Example 76) by replacing 2-chloro-N-phenyl-acetamide with the appropriate alkyl halide.
- R 1 , R 2 , R 3 , and R 4 are as shown in Table 2 below, the method of preparation being described hereinafter. All compounds are quaternary ammonium salts. The table also shows mass spectrometry data. TABLE 2 M/s Ex.
- reaction mixture is filtered and PS-bromoacetic acid 1.2 mmol/g (0.2 g) is added to the filtrate and shaken at 30° C. for 1 hour.
- the reaction mixture is passed through a 1 g Isolute SPE (Al-B) cartridge.
- the solvent is removed in vacuo and purification of the crude residue by mass directed preparative HPLC eluting with water:acetonitrile:trifluoroacetic acid yield the compound as a yellow oil.
- the compounds are purified either by trituration with organic solvents, C18 chromatography (as for Example 60) or recrystalisation from acetonitrile, water or chloroform.
- the required halides for quaternarisation are either commercially available or readily synthesised by methods well known in the art.
- This compound is prepared analogously to (R)-1-(3-benzoylamino-propyl)-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-azonia-bicyclo[2.2.2]-octane trifluoroacetate [Example 2] but by replacing (R)-1-(3-amino-propyl)-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-azonia-bicyclo-[2.2.2]octane chloride hydrochloride [Example 1(ii)] with (R)-1-((R/S)-2-amino-propyl)-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-azoniabicyclo[2.2.2]octane chloride hydrochloride.
- Example 182 The crude product from Example 182 is dissolved in acetonitrile (10 ml) and filtered then cooled over an ice bath, under an argon atmosphere. To this cooled solution is added triethylamine (127 ⁇ l) followed by benzoyl bromide (64 ⁇ l) and the reaction stirred for 1 hour. Purification is carried out using mass directed preparative HPLC eluting with acetonitrile:water:trifluoroacetic acid to afford the titled compound.
- N-(2-Bromo-phenyl)-2-chloro-acetamide 155 mg, 0.622 mmol
- the reaction mixture is stirred at 0° C. for 2 hours.
- PS-Bromoacetamidomethyl-NovaGel 2.3 mmol/g (0.5 g) is added to the reaction mixture and shaken at room temperature for 4 hours.
- PS-Triphenylphosphine 3 mmol/g 0.5 g is added to the reaction mixture and shaken at room temperature overnight.
- reaction mixture is then passed through a 1 g Isolute SPE (Al-B) cartridge.
- the solvent is removed in vacuo and purification of the crude residue by mass directed preparative HPLC eluting with water:acetonitrile:trifluoroacetic acid yields the titled compound.
- reaction mixture is stirred at room temperature overnight.
- reaction mixture is passed through a 2 g Isolute SPE (Al-B) cartridge.
- the filtrate is concentrated in vacuo and purification of the crude residue by chromatography on C18 silica, eluting with water:acetonitrile affords the title compound as a white solid.
- This compound is prepared analogously to (R)-1- ⁇ 2-[(Furan-2-carbonyl)-amino]ethyl ⁇ -3-(2-hydroxy-2,2-diphenyl-acetyl)-1-azonia-bicyclo[2.2.2]octane hexafluorophosphate [Example 190] by replacing 2-furoic acid with 1-BOC-azetidine-3-carboxylic acid.
- This compound is prepared analogously to (R)-1-[(2-Bromo-phenylcarbamoyl)-methyl]-3-(2-hydroxy-2,2-diphenyl-acetoxy)]-1-azonia-bicyclo[2.2.2]octane trifluoroacetate [Example 184].
- BEMP 2.3 mmol/g (0.1 g, 1 eqv) is used with the PS-bromoacetamidomethyl-NovaGel 2.3 mmol/g (0.3 g, 1 eqv).
- This compound is prepared analogously to (R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-(pyrazin-2-ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane chloride [Example 159B] by substituting hydroxy-di-thiophen-2-yl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester and Pyrazin-2-yl-amine with hydroxy-diphenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester and 4-Methyl-pyrimidin-2-ylamine.
- reaction mixture is passed through a 1 g Isolute SPE (Al-B) cartridge and the filtrate concentrated in vacuo. Purification by mass directed preparative HPLC eluting with water:acetonitrile:trifluoracetic acid yields the titled compound.
- reaction mixture is filtered and the solution then washed with 1 M sodium carbonate solution, 1 M hydrochloric acid and brine. Concentration followed by purification by flash silica column chromatography (ethyl acetate/iso-hexane 3:7) gives the title compound as a white solid.
- R 1 , R 2 , R 3 , and R 4 are as shown in Table 3 below, the method of preparation being described hereinafter. All compounds are quaternary ammonium salts. The table also shows mass spectrometry data. TABLE 3 M/s Ex. R 1 and R 3 R 4 R 2 M+ 246 OH 448.3 247 OH 408.3 Preparation of Specific Examples
- the mixture is concentrated in vacuo and purified by gradient C18 column chromatography to give a pale yellow solid.
- the solid is then redissolved in a small volume of acetonitrile containing a few drops of water. After several hours a solid is formed which is filtered and dried to give the title compound as a pale yellow solid.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/582,291 US8168654B2 (en) | 2003-05-02 | 2009-10-20 | Quinuclidine derivatives binding to mucarinic M3 receptors |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0310232.4 | 2003-05-02 | ||
GB0310232 | 2003-05-02 | ||
GB0324887.9 | 2003-10-24 | ||
GB0324887A GB0324887D0 (en) | 2003-10-24 | 2003-10-24 | Organic compounds |
PCT/EP2004/004605 WO2004096800A2 (fr) | 2003-05-02 | 2004-04-30 | Composes organiques |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2004/004605 A-371-Of-International WO2004096800A2 (fr) | 2003-05-02 | 2004-04-30 | Composes organiques |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/582,291 Continuation US8168654B2 (en) | 2003-05-02 | 2009-10-20 | Quinuclidine derivatives binding to mucarinic M3 receptors |
Publications (1)
Publication Number | Publication Date |
---|---|
US20070060563A1 true US20070060563A1 (en) | 2007-03-15 |
Family
ID=33420896
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/554,558 Abandoned US20070060563A1 (en) | 2003-05-02 | 2004-04-30 | Quinuclidine derivatives binding to mucarinic m3 receptors |
US12/582,291 Expired - Fee Related US8168654B2 (en) | 2003-05-02 | 2009-10-20 | Quinuclidine derivatives binding to mucarinic M3 receptors |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/582,291 Expired - Fee Related US8168654B2 (en) | 2003-05-02 | 2009-10-20 | Quinuclidine derivatives binding to mucarinic M3 receptors |
Country Status (32)
Country | Link |
---|---|
US (2) | US20070060563A1 (fr) |
EP (1) | EP1631569B1 (fr) |
JP (1) | JP4416786B2 (fr) |
KR (1) | KR100896544B1 (fr) |
AR (1) | AR044134A1 (fr) |
AT (1) | ATE440840T1 (fr) |
AU (1) | AU2004234069B2 (fr) |
BR (1) | BRPI0410238A (fr) |
CA (1) | CA2523436C (fr) |
CL (1) | CL2004000918A1 (fr) |
CO (1) | CO5700782A2 (fr) |
CY (1) | CY1109655T1 (fr) |
DE (1) | DE602004022805D1 (fr) |
DK (1) | DK1631569T3 (fr) |
EC (1) | ECSP056134A (fr) |
ES (1) | ES2331185T3 (fr) |
HK (1) | HK1087704A1 (fr) |
HR (1) | HRP20050933A2 (fr) |
IL (1) | IL171591A (fr) |
IS (1) | IS2746B (fr) |
MA (1) | MA27775A1 (fr) |
MX (1) | MXPA05011739A (fr) |
MY (1) | MY142652A (fr) |
NO (1) | NO20055688L (fr) |
NZ (1) | NZ542995A (fr) |
PE (1) | PE20050465A1 (fr) |
PL (1) | PL1631569T3 (fr) |
PT (1) | PT1631569E (fr) |
RU (1) | RU2363700C2 (fr) |
SI (1) | SI1631569T1 (fr) |
TW (1) | TWI340139B (fr) |
WO (1) | WO2004096800A2 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090069335A1 (en) * | 2007-09-07 | 2009-03-12 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US20090170870A1 (en) * | 2007-12-14 | 2009-07-02 | Ji Yuhua | Amidine-containing compounds useful as muscarinic receptor antagonists |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2239546B1 (es) * | 2004-03-15 | 2006-12-01 | Almirall Prodesfarma, S.A. | Nuevos esteres de quinuclidina cuaternizados. |
GB0410712D0 (en) | 2004-05-13 | 2004-06-16 | Novartis Ag | Organic compounds |
GB0424284D0 (en) * | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
GB0428416D0 (en) | 2004-12-24 | 2005-02-02 | Novartis Ag | Organic compounds |
GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
EP1900737A1 (fr) * | 2006-08-31 | 2008-03-19 | Novartis AG | Polymorphe de (R)-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-(isoxazol-3-ylcarbamoyl-methyl)-1-azonia-bicyclo-[2.2.2]octane bromide |
EP1894568A1 (fr) * | 2006-08-31 | 2008-03-05 | Novartis AG | Composées pharmaceutiques destinées au traitement des maladies inflammatoires ou obstructives des bronches |
TW200825084A (en) | 2006-11-14 | 2008-06-16 | Astrazeneca Ab | New compounds 521 |
CN101610813A (zh) * | 2006-12-19 | 2009-12-23 | 阿斯利康(瑞典)有限公司 | 作为毒蕈碱受体拮抗剂的奎核醇衍生物 |
EP1950196A1 (fr) * | 2007-01-29 | 2008-07-30 | Boehringer Ingelheim Pharma GmbH & Co. KG | Procédé de fabrication d'hexafluorophosphates d'ammonium |
US8431578B2 (en) | 2008-01-11 | 2013-04-30 | Novartis Ag | Organic compounds |
CN102908624A (zh) * | 2008-05-13 | 2013-02-06 | 阿斯利康(瑞典)有限公司 | 包含毒蕈碱性受体拮抗剂和β2-肾上腺素受体激动剂的药物产品 |
GB0808709D0 (en) * | 2008-05-13 | 2008-06-18 | Astrazeneca Ab | New combination 295 |
WO2009138707A1 (fr) | 2008-05-13 | 2009-11-19 | Astrazeneca Ab | Dérivés de quinuclidine utilisés comme antagonistes des récepteurs muscariniques m3 |
US20090326004A1 (en) | 2008-06-03 | 2009-12-31 | Ranbaxy Laboratories Limited | Muscarinic receptor antagonists |
GB0811100D0 (en) * | 2008-06-17 | 2008-07-23 | Astrazeneca Ab | New combination |
WO2009153536A1 (fr) * | 2008-06-17 | 2009-12-23 | Argenta Discovery Limited | Dérivés de 1-aza-bicyclo [2.2.2] octane utiles en tant qu’antagonistes des récepteurs muscariniques |
KR20130087405A (ko) * | 2010-06-22 | 2013-08-06 | 키에시 파르마슈티시 엣스. 피. 에이. | 알칼로이드 아미노에스테르 유도체 및 이의 의약 조성물 |
WO2012034095A1 (fr) | 2010-09-09 | 2012-03-15 | Irm Llc | Composés et compositions comme inhibiteurs de trk |
US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
JP2011195593A (ja) * | 2011-06-30 | 2011-10-06 | Astrazeneca Ab | ムスカリンm3受容体アンタゴニストとしてのキヌクリジン誘導体 |
EP2797910B1 (fr) * | 2011-12-30 | 2015-09-16 | Chiesi Farmaceutici S.p.A. | Esters de quinuclidine et d'acide 1-azahétérocyclylacétique utilisés comme agents antimuscariniques, procédé pour leur préparation et compositions médicinales correspondantes |
CA2871926A1 (fr) | 2012-05-03 | 2013-11-07 | Saint Louis College Of Pharmacy | Compositions et procedes pour augmenter des peptides neurotrophiques |
TWI647227B (zh) | 2013-02-28 | 2019-01-11 | 日商安斯泰來製藥股份有限公司 | 2-醯胺噻唑衍生物或其鹽 |
CZ306791B6 (cs) | 2013-10-29 | 2017-07-12 | Zentiva, K.S. | Průmyslově využitelný způsob přípravy aklidinium bromidu o vysoké čistotě |
PT108370B (pt) * | 2015-03-30 | 2018-10-25 | Hovione Farm S A | Processo de preparação de brometo de aclidínio |
PL3111978T3 (pl) | 2015-07-03 | 2022-01-24 | Novartis Ag | Inhalator przystosowany do odczytu informacji przechowywanych w środkach przechowywania danych pojemnika |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3714357A (en) * | 1968-07-15 | 1973-01-30 | Rech D Applic Scient Sogeras S | Pharmaceutical compositions comprising quinuclidinol derivatives |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK534178A (da) * | 1977-12-16 | 1979-06-17 | Interx Research Corp | Anticholinerge midler med sektrtionshaemmende virkning |
ES2165768B1 (es) * | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
WO2002004402A1 (fr) * | 2000-07-11 | 2002-01-17 | Banyu Pharmaceutical Co., Ltd. | Derives d'ester |
EE05404B1 (et) * | 2000-12-28 | 2011-04-15 | Almirall Prodesfarma Ag | Kinuklidiini derivaat, selle saamine ja kasutamine ravimi valmistamiseks, mis on ette nhtud respiratoorsete, kuseelundite v?i mao-soolte haiguste ravimiseks, ning seda sisaldav ravimkompositsioon |
EA006505B1 (ru) * | 2001-12-20 | 2005-12-29 | Лабораториос С.А.Л.В.А.Т.,С.А. | Производные карбамата 1-алкил-1-азониабицикло[2.2.2]октана и их применение в качестве антагонистов мускаринового рецептора |
GB0424284D0 (en) * | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
EP1900737A1 (fr) * | 2006-08-31 | 2008-03-19 | Novartis AG | Polymorphe de (R)-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-(isoxazol-3-ylcarbamoyl-methyl)-1-azonia-bicyclo-[2.2.2]octane bromide |
-
2004
- 2004-04-29 AR ARP040101468A patent/AR044134A1/es not_active Application Discontinuation
- 2004-04-30 MX MXPA05011739A patent/MXPA05011739A/es active IP Right Grant
- 2004-04-30 KR KR1020057020776A patent/KR100896544B1/ko not_active IP Right Cessation
- 2004-04-30 DE DE602004022805T patent/DE602004022805D1/de not_active Expired - Lifetime
- 2004-04-30 EP EP04730519A patent/EP1631569B1/fr not_active Expired - Lifetime
- 2004-04-30 PT PT04730519T patent/PT1631569E/pt unknown
- 2004-04-30 BR BRPI0410238-0A patent/BRPI0410238A/pt not_active IP Right Cessation
- 2004-04-30 TW TW093112339A patent/TWI340139B/zh not_active IP Right Cessation
- 2004-04-30 JP JP2006505341A patent/JP4416786B2/ja not_active Expired - Fee Related
- 2004-04-30 US US10/554,558 patent/US20070060563A1/en not_active Abandoned
- 2004-04-30 AT AT04730519T patent/ATE440840T1/de active
- 2004-04-30 WO PCT/EP2004/004605 patent/WO2004096800A2/fr active Application Filing
- 2004-04-30 NZ NZ542995A patent/NZ542995A/en not_active IP Right Cessation
- 2004-04-30 RU RU2005137360/04A patent/RU2363700C2/ru not_active IP Right Cessation
- 2004-04-30 SI SI200431277T patent/SI1631569T1/sl unknown
- 2004-04-30 CA CA2523436A patent/CA2523436C/fr not_active Expired - Fee Related
- 2004-04-30 DK DK04730519T patent/DK1631569T3/da active
- 2004-04-30 PL PL04730519T patent/PL1631569T3/pl unknown
- 2004-04-30 MY MYPI20041637A patent/MY142652A/en unknown
- 2004-04-30 PE PE2004000435A patent/PE20050465A1/es not_active Application Discontinuation
- 2004-04-30 CL CL200400918A patent/CL2004000918A1/es unknown
- 2004-04-30 AU AU2004234069A patent/AU2004234069B2/en not_active Ceased
- 2004-04-30 ES ES04730519T patent/ES2331185T3/es not_active Expired - Lifetime
-
2005
- 2005-10-27 IL IL171591A patent/IL171591A/en not_active IP Right Cessation
- 2005-10-28 HR HR20050933A patent/HRP20050933A2/xx not_active Application Discontinuation
- 2005-11-01 EC EC2005006134A patent/ECSP056134A/es unknown
- 2005-11-03 CO CO05112195A patent/CO5700782A2/es not_active Application Discontinuation
- 2005-11-08 MA MA28583A patent/MA27775A1/fr unknown
- 2005-11-30 IS IS8158A patent/IS2746B/is unknown
- 2005-12-01 NO NO20055688A patent/NO20055688L/no not_active Application Discontinuation
-
2006
- 2006-07-17 HK HK06107974.9A patent/HK1087704A1/xx not_active IP Right Cessation
-
2009
- 2009-10-20 US US12/582,291 patent/US8168654B2/en not_active Expired - Fee Related
- 2009-11-25 CY CY20091101230T patent/CY1109655T1/el unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3714357A (en) * | 1968-07-15 | 1973-01-30 | Rech D Applic Scient Sogeras S | Pharmaceutical compositions comprising quinuclidinol derivatives |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090069335A1 (en) * | 2007-09-07 | 2009-03-12 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US7960385B2 (en) | 2007-09-07 | 2011-06-14 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US20110201583A1 (en) * | 2007-09-07 | 2011-08-18 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US8039489B2 (en) | 2007-09-07 | 2011-10-18 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US8198304B2 (en) | 2007-09-07 | 2012-06-12 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US8338424B2 (en) | 2007-09-07 | 2012-12-25 | Theravance, Inc. | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US8785633B2 (en) | 2007-09-07 | 2014-07-22 | Theravance Biopharma R&D Ip, Llc | Guanidine-containing compounds useful as muscarinic receptor antagonists |
US20090170870A1 (en) * | 2007-12-14 | 2009-07-02 | Ji Yuhua | Amidine-containing compounds useful as muscarinic receptor antagonists |
US8017617B2 (en) | 2007-12-14 | 2011-09-13 | Theravance, Inc. | Amidine-containing compounds useful as muscarinic receptor antagonists |
US8242138B2 (en) | 2007-12-14 | 2012-08-14 | Theravance, Inc. | Amidine-containing compounds useful as muscarinic receptor antagonists |
US8450362B2 (en) | 2007-12-14 | 2013-05-28 | Theravance, Inc. | Amidine-containing compounds useful as muscarinic receptor antagonists |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8168654B2 (en) | Quinuclidine derivatives binding to mucarinic M3 receptors | |
US8084463B2 (en) | Quinuclidine derivatives and their use as muscarinic M3 receptor antagonists | |
US8383625B2 (en) | Pyrrolidinium derivatives as M3 muscarnic receptor antagonists | |
US8153669B2 (en) | Quaternary ammonium salts as M3 antagonists | |
US20090311178A1 (en) | Pyrrolinidium derivatives as m3 muscarinic receptors | |
US7947730B2 (en) | Piperidinium and pyrrolidinium derivatives as ligands for the muscarinic M3 receptor | |
AU2008202203B2 (en) | Combinations of quinuclidine derivatives with antimuscarinic activity and beta-2 agonists and /or corticosteroids |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: NOVARTIS AG, SWITZERLAND Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:COLLINGWOOD, STEPHEN PAUL;COX, BRIAN;BAETTIG, URS;AND OTHERS;REEL/FRAME:023268/0877;SIGNING DATES FROM 20051110 TO 20051128 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |