HRP970451A2 - Quaternary ammonium compounds - Google Patents
Quaternary ammonium compoundsInfo
- Publication number
- HRP970451A2 HRP970451A2 HR9617730.8A HRP970451A HRP970451A2 HR P970451 A2 HRP970451 A2 HR P970451A2 HR P970451 A HRP970451 A HR P970451A HR P970451 A2 HRP970451 A2 HR P970451A2
- Authority
- HR
- Croatia
- Prior art keywords
- dichlorophenyl
- cyclohexyl
- compound
- alkyl
- quinuclidinium
- Prior art date
Links
- 150000003856 quaternary ammonium compounds Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 228
- 239000002904 solvent Substances 0.000 claims description 92
- 239000000203 mixture Substances 0.000 claims description 78
- -1 benzo[b]thienyl Chemical group 0.000 claims description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 43
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 27
- 208000035475 disorder Diseases 0.000 claims description 25
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 22
- 125000001153 fluoro group Chemical group F* 0.000 claims description 20
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 150000001450 anions Chemical class 0.000 claims description 17
- 206010020751 Hypersensitivity Diseases 0.000 claims description 15
- 208000026935 allergic disease Diseases 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 14
- SBYHFKPVCBCYGV-UHFFFAOYSA-O 1-azoniabicyclo[2.2.2]octane Chemical compound C1CC2CC[NH+]1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-O 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 108010072901 Tachykinin Receptors Proteins 0.000 claims description 12
- 102000007124 Tachykinin Receptors Human genes 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 208000002193 Pain Diseases 0.000 claims description 10
- 208000010668 atopic eczema Diseases 0.000 claims description 10
- 210000003169 central nervous system Anatomy 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 230000002496 gastric effect Effects 0.000 claims description 10
- 230000009610 hypersensitivity Effects 0.000 claims description 10
- 208000004296 neuralgia Diseases 0.000 claims description 10
- 230000003042 antagnostic effect Effects 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- BZLBBZLOMXKMTA-UHFFFAOYSA-N 1-azoniabicyclo[2.2.2]octane;chloride Chemical compound Cl.C1CC2CCN1CC2 BZLBBZLOMXKMTA-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 208000000187 Abnormal Reflex Diseases 0.000 claims description 5
- 241000894006 Bacteria Species 0.000 claims description 5
- 208000001387 Causalgia Diseases 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 5
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 5
- 206010011224 Cough Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 5
- 201000004624 Dermatitis Diseases 0.000 claims description 5
- 206010012434 Dermatitis allergic Diseases 0.000 claims description 5
- 206010012442 Dermatitis contact Diseases 0.000 claims description 5
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 5
- 241000590002 Helicobacter pylori Species 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 208000019693 Lung disease Diseases 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 5
- 241000159243 Toxicodendron radicans Species 0.000 claims description 5
- 108010046334 Urease Proteins 0.000 claims description 5
- 206010047700 Vomiting Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 208000005298 acute pain Diseases 0.000 claims description 5
- 201000010105 allergic rhinitis Diseases 0.000 claims description 5
- 230000007815 allergy Effects 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 206010009887 colitis Diseases 0.000 claims description 5
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 claims description 5
- 208000010247 contact dermatitis Diseases 0.000 claims description 5
- 201000003146 cystitis Diseases 0.000 claims description 5
- 208000028659 discharge Diseases 0.000 claims description 5
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 5
- 229940037467 helicobacter pylori Drugs 0.000 claims description 5
- 206010020745 hyperreflexia Diseases 0.000 claims description 5
- 230000035859 hyperreflexia Effects 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 208000005877 painful neuropathy Diseases 0.000 claims description 5
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 230000008673 vomiting Effects 0.000 claims description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- JEJYYKZPVIEEAS-MWLZSUMNSA-M n-[(2s)-4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-n-methyl-3,5-bis(trifluoromethyl)benzamide;methanesulfonate Chemical compound CS([O-])(=O)=O.C([C@H](CN(C)C(=O)C=1C=C(C=C(C=1)C(F)(F)F)C(F)(F)F)C=1C=C(Cl)C(Cl)=CC=1)C[N+](CC1)(CC2)CCC12C1CCCCC1 JEJYYKZPVIEEAS-MWLZSUMNSA-M 0.000 claims description 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 3
- KLDZWUGMONAXRQ-UHFFFAOYSA-M 1-[3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-2-(3,5-dimethylphenyl)ethanone;methanesulfonate Chemical compound CS([O-])(=O)=O.CC1=CC(C)=CC(CC(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 KLDZWUGMONAXRQ-UHFFFAOYSA-M 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- LNYNEARZUZEACV-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(3,4,5-trimethoxyphenyl)methanone;methanesulfonate Chemical compound CS([O-])(=O)=O.COC1=C(OC)C(OC)=CC(C(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 LNYNEARZUZEACV-UHFFFAOYSA-M 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- VSMZWLOPAIUBBT-UHFFFAOYSA-M 2-[3,5-bis(trifluoromethyl)phenyl]-1-[3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)piperidin-1-yl]ethanone;methanesulfonate Chemical compound CS([O-])(=O)=O.FC(F)(F)C1=CC(C(F)(F)F)=CC(CC(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CCC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 VSMZWLOPAIUBBT-UHFFFAOYSA-M 0.000 claims description 2
- NXKYPBPYSFRTTI-UHFFFAOYSA-M 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-n-methylacetamide;chloride Chemical compound [Cl-].C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1CC(=O)N(C)CC(C=1C=C(Cl)C(Cl)=CC=1)CC[N+](CC1)(CC2)CCC12C1CCCCC1 NXKYPBPYSFRTTI-UHFFFAOYSA-M 0.000 claims description 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- OJWWTQVGHQDKST-UHFFFAOYSA-M [3,5-bis(trifluoromethyl)phenyl]-[3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]methanone;chloride Chemical compound [Cl-].FC(F)(F)C1=CC(C(F)(F)F)=CC(C(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 OJWWTQVGHQDKST-UHFFFAOYSA-M 0.000 claims description 2
- RDNPWRJVRSFLKP-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(2,3-dihydro-1-benzofuran-7-yl)methanone;chloride Chemical compound [Cl-].C1=C(Cl)C(Cl)=CC=C1C1(CC[N+]23CCC(CC2)(CC3)C2CCCCC2)CN(C(=O)C=2C=3OCCC=3C=CC=2)CC1 RDNPWRJVRSFLKP-UHFFFAOYSA-M 0.000 claims description 2
- NCQUCDMVISVUJK-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(2,3-dimethylphenyl)methanone;chloride Chemical compound [Cl-].CC1=CC=CC(C(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1C NCQUCDMVISVUJK-UHFFFAOYSA-M 0.000 claims description 2
- MRMSEMWDTZLSGC-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(3,4,5-triethoxyphenyl)methanone;chloride Chemical compound [Cl-].CCOC1=C(OCC)C(OCC)=CC(C(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 MRMSEMWDTZLSGC-UHFFFAOYSA-M 0.000 claims description 2
- QINMLOBUXZEJFY-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(3,4-dimethoxyphenyl)methanone;chloride Chemical compound [Cl-].C1=C(OC)C(OC)=CC=C1C(=O)N1CC(CC[N+]23CCC(CC2)(CC3)C2CCCCC2)(C=2C=C(Cl)C(Cl)=CC=2)CC1 QINMLOBUXZEJFY-UHFFFAOYSA-M 0.000 claims description 2
- CCRRWCZNLWGASF-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(3,5-dimethoxy-4-methylphenyl)methanone;chloride Chemical compound [Cl-].COC1=C(C)C(OC)=CC(C(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 CCRRWCZNLWGASF-UHFFFAOYSA-M 0.000 claims description 2
- SEDMCKUZCUIQIO-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(3,5-dimethoxyphenyl)methanone;chloride Chemical compound [Cl-].COC1=CC(OC)=CC(C(=O)N2CC(CC[N+]34CCC(CC3)(CC4)C3CCCCC3)(CC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 SEDMCKUZCUIQIO-UHFFFAOYSA-M 0.000 claims description 2
- BDSLFYJIBKQZQQ-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-(4-methoxy-3,5-dimethylphenyl)methanone;chloride Chemical compound [Cl-].C1=C(C)C(OC)=C(C)C=C1C(=O)N1CC(CC[N+]23CCC(CC2)(CC3)C2CCCCC2)(C=2C=C(Cl)C(Cl)=CC=2)CC1 BDSLFYJIBKQZQQ-UHFFFAOYSA-M 0.000 claims description 2
- AFMLFCDYNQCDGO-UHFFFAOYSA-M [3-[2-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)ethyl]-3-(3,4-dichlorophenyl)pyrrolidin-1-yl]-[4-fluoro-3-(trifluoromethyl)phenyl]methanone;chloride Chemical compound [Cl-].C1=C(C(F)(F)F)C(F)=CC=C1C(=O)N1CC(CC[N+]23CCC(CC2)(CC3)C2CCCCC2)(C=2C=C(Cl)C(Cl)=CC=2)CC1 AFMLFCDYNQCDGO-UHFFFAOYSA-M 0.000 claims description 2
- 125000003118 aryl group Chemical class 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- NWFDFBZDCBTXGB-UHFFFAOYSA-M n-[4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-2-(3,5-dimethylphenyl)-n-methylacetamide;methanesulfonate Chemical compound CS([O-])(=O)=O.C=1C(C)=CC(C)=CC=1CC(=O)N(C)CC(C=1C=C(Cl)C(Cl)=CC=1)CC[N+](CC1)(CC2)CCC12C1CCCCC1 NWFDFBZDCBTXGB-UHFFFAOYSA-M 0.000 claims description 2
- REUCYWLAFJTNID-UHFFFAOYSA-M n-[4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-4-fluoro-n-methyl-3-(trifluoromethyl)benzamide;methanesulfonate Chemical compound CS([O-])(=O)=O.C=1C=C(F)C(C(F)(F)F)=CC=1C(=O)N(C)CC(C=1C=C(Cl)C(Cl)=CC=1)CC[N+](CC1)(CC2)CCC12C1CCCCC1 REUCYWLAFJTNID-UHFFFAOYSA-M 0.000 claims description 2
- LQUZEEXGXITRFV-UHFFFAOYSA-M n-[4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-n,3,5-trimethylbenzamide;methanesulfonate Chemical compound CS([O-])(=O)=O.C=1C(C)=CC(C)=CC=1C(=O)N(C)CC(C=1C=C(Cl)C(Cl)=CC=1)CC[N+](CC1)(CC2)CCC12C1CCCCC1 LQUZEEXGXITRFV-UHFFFAOYSA-M 0.000 claims description 2
- KLELVRFDVCCGKO-UHFFFAOYSA-M n-[4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-n-methyl-2-phenylacetamide;chloride Chemical compound [Cl-].C=1C=CC=CC=1CC(=O)N(C)CC(C=1C=C(Cl)C(Cl)=CC=1)CC[N+](CC1)(CC2)CCC12C1CCCCC1 KLELVRFDVCCGKO-UHFFFAOYSA-M 0.000 claims description 2
- JEJYYKZPVIEEAS-UHFFFAOYSA-M n-[4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-n-methyl-3,5-bis(trifluoromethyl)benzamide;methanesulfonate Chemical compound CS([O-])(=O)=O.C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1C(=O)N(C)CC(C=1C=C(Cl)C(Cl)=CC=1)CC[N+](CC1)(CC2)CCC12C1CCCCC1 JEJYYKZPVIEEAS-UHFFFAOYSA-M 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- JFSPBVWPKOEZCB-UHFFFAOYSA-N fenfuram Chemical compound O1C=CC(C(=O)NC=2C=CC=CC=2)=C1C JFSPBVWPKOEZCB-UHFFFAOYSA-N 0.000 claims 2
- XMWLUUIDVVWLMW-MWLZSUMNSA-M n-[(2s)-4-(4-cyclohexyl-1-azoniabicyclo[2.2.2]octan-1-yl)-2-(3,4-dichlorophenyl)butyl]-n-methyl-3,5-bis(trifluoromethyl)benzamide;chloride Chemical compound [Cl-].C([C@H](CN(C)C(=O)C=1C=C(C=C(C=1)C(F)(F)F)C(F)(F)F)C=1C=C(Cl)C(Cl)=CC=1)C[N+](CC1)(CC2)CCC12C1CCCCC1 XMWLUUIDVVWLMW-MWLZSUMNSA-M 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 216
- 238000002360 preparation method Methods 0.000 description 112
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 230000002829 reductive effect Effects 0.000 description 88
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 82
- 239000000243 solution Substances 0.000 description 70
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000007858 starting material Substances 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 21
- 239000007787 solid Substances 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000012043 crude product Substances 0.000 description 17
- 239000000377 silicon dioxide Substances 0.000 description 15
- 239000003921 oil Substances 0.000 description 13
- NZFGRMZVCZOLHP-UHFFFAOYSA-N 4-cyclohexyl-1-azabicyclo[2.2.2]octane Chemical compound C1CCCCC1C1(CC2)CCN2CC1 NZFGRMZVCZOLHP-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9617730.8A GB9617730D0 (en) | 1996-08-23 | 1996-08-23 | Quarternary ammonium compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP970451A2 true HRP970451A2 (en) | 1998-08-31 |
Family
ID=10798878
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR9617730.8A HRP970451A2 (en) | 1996-08-23 | 1997-08-22 | Quaternary ammonium compounds |
Country Status (11)
| Country | Link |
|---|---|
| AP (1) | AP9701074A0 (fr) |
| AR (1) | AR009293A1 (fr) |
| AU (1) | AU4015397A (fr) |
| CO (1) | CO4560548A1 (fr) |
| GB (1) | GB9617730D0 (fr) |
| HR (1) | HRP970451A2 (fr) |
| ID (1) | ID18069A (fr) |
| MA (1) | MA26436A1 (fr) |
| PA (1) | PA8436301A1 (fr) |
| TN (1) | TNSN97140A1 (fr) |
| WO (1) | WO1998007722A1 (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002520316A (ja) * | 1998-07-10 | 2002-07-09 | アストラゼネカ・アクチエボラーグ | ニューロキニン受容体アンタゴニストとしてのｎ−置換ナフタレンカルボキサミド |
| GB9826941D0 (en) | 1998-12-09 | 1999-02-03 | Zeneca Pharmaceuticals | Compounds |
| DE19938736A1 (de) | 1999-08-16 | 2001-02-22 | Bayer Ag | Verfahren zur Herstellung von [Bis-(trifluormethyl)-phenyl]-essigsäuren und deren Alkylestern sowie [Bis-(trifluormethyl)-phenyl]-malonsäure-dialkylester |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| US8093268B2 (en) | 2007-01-24 | 2012-01-10 | Glaxo Group Limited | Pharmaceutical compositions comprising 2-methoxy-5-(5-trifluoromethyl-tetrazol-1-yl-benzyl)-(2S-phenylpiperidin-3S-yl-) |
| RU2722720C1 (ru) * | 2016-12-14 | 2020-06-03 | Бейджинг Шоубай Фармасьютикэл Ко., Лтд. | Класс бифункциональных соединений со структурой соли четвертичного аммония |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2696178B1 (fr) * | 1992-09-30 | 1994-12-30 | Sanofi Elf | Amides basiques quaternaires, procédé pour leur préparation et compositions pharmaceutiques en contenant. |
| CA2162786A1 (fr) * | 1994-11-22 | 1996-05-23 | Philip Arthur Hipskind | Antagonistes heterocycliques des recepteurs des tachykinines |
-
1996
- 1996-08-23 GB GBGB9617730.8A patent/GB9617730D0/en active Pending
-
1997
- 1997-08-11 WO PCT/EP1997/004414 patent/WO1998007722A1/fr active Application Filing
- 1997-08-11 AU AU40153/97A patent/AU4015397A/en not_active Abandoned
- 1997-08-14 PA PA19978436301A patent/PA8436301A1/es unknown
- 1997-08-20 TN TNTNSN97140A patent/TNSN97140A1/fr unknown
- 1997-08-21 AR ARP970103804A patent/AR009293A1/es unknown
- 1997-08-21 MA MA24773A patent/MA26436A1/fr unknown
- 1997-08-21 AP APAP/P/1997/001074A patent/AP9701074A0/en unknown
- 1997-08-22 HR HR9617730.8A patent/HRP970451A2/hr not_active Application Discontinuation
- 1997-08-22 ID IDP972936A patent/ID18069A/id unknown
- 1997-08-22 CO CO97048580A patent/CO4560548A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998007722A1 (fr) | 1998-02-26 |
| MA26436A1 (fr) | 2004-12-20 |
| PA8436301A1 (es) | 2000-05-24 |
| CO4560548A1 (es) | 1998-02-10 |
| AR009293A1 (es) | 2000-04-12 |
| GB9617730D0 (en) | 1996-10-02 |
| AP9701074A0 (en) | 1997-10-31 |
| ID18069A (id) | 1998-02-26 |
| AU4015397A (en) | 1998-03-06 |
| TNSN97140A1 (fr) | 2005-03-15 |
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