IL94763A - R) - (Quinuclidinol esters of converted azacycloalkanoic acids in position 1, their preparation and pharmaceutical preparations containing them - Google Patents

R) - (Quinuclidinol esters of converted azacycloalkanoic acids in position 1, their preparation and pharmaceutical preparations containing them

Info

Publication number: IL94763A
Authority: IL; Israel
Prior art keywords: carboxylate; oxo; compounds; absent; compound
Prior art date: 1989-06-20

Application number

IL9476390A

Other languages

English (en)

Hebrew (he)

Other versions

IL94763A0 (en

Original Assignee

Boehringer Ingelheim Italia

Priority date (The priority date 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 date listed.)

1989-06-20

Filing date

1990-06-18

Publication date

1994-08-26

1990-06-18 Application filed by Boehringer Ingelheim Italia filed Critical Boehringer Ingelheim Italia

1991-04-15 Publication of IL94763A0 publication Critical patent/IL94763A0/xx

1994-08-26 Publication of IL94763A publication Critical patent/IL94763A/en

Links

IVLICPVPXWEGCA-ZETCQYMHSA-N (3r)-1-azabicyclo[2.2.2]octan-3-ol Chemical class C1CC2[C@@H](O)CN1CC2 IVLICPVPXWEGCA-ZETCQYMHSA-N 0.000 title claims abstract description 12
238000002360 preparation method Methods 0.000 title claims abstract description 12
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
239000002253 acid Substances 0.000 title claims description 14
150000007513 acids Chemical class 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 77
229910052799 carbon Inorganic materials 0.000 claims abstract description 42
238000000034 method Methods 0.000 claims abstract description 29
-1 3-quinuclidinyl Chemical group 0.000 claims abstract description 28
125000000217 alkyl group Chemical group 0.000 claims abstract description 16
230000008569 process Effects 0.000 claims abstract description 16
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
150000007522 mineralic acids Chemical class 0.000 claims abstract description 5
150000007524 organic acids Chemical class 0.000 claims abstract description 5
125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 4
125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
125000002252 acyl group Chemical group 0.000 claims abstract description 4
150000001450 anions Chemical class 0.000 claims abstract description 4
125000003118 aryl group Chemical group 0.000 claims abstract description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
239000001301 oxygen Substances 0.000 claims abstract description 4
239000005864 Sulphur Substances 0.000 claims abstract description 3
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 3
239000000203 mixture Substances 0.000 claims description 27
239000004480 active ingredient Substances 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 16
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical group BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
229940102396 methyl bromide Drugs 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
208000035475 disorder Diseases 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 5
230000001148 spastic effect Effects 0.000 claims description 5
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
206010006482 Bronchospasm Diseases 0.000 claims description 3
239000002168 alkylating agent Substances 0.000 claims description 3
229940100198 alkylating agent Drugs 0.000 claims description 3
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 claims description 3
230000007885 bronchoconstriction Effects 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
239000002798 polar solvent Substances 0.000 claims description 3
230000002485 urinary effect Effects 0.000 claims description 3
229910052727 yttrium Inorganic materials 0.000 claims description 3
206010006458 Bronchitis chronic Diseases 0.000 claims description 2
206010007645 Cardiospasm Diseases 0.000 claims description 2
206010010774 Constipation Diseases 0.000 claims description 2
206010014561 Emphysema Diseases 0.000 claims description 2
208000000289 Esophageal Achalasia Diseases 0.000 claims description 2
208000008469 Peptic Ulcer Diseases 0.000 claims description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
206010046543 Urinary incontinence Diseases 0.000 claims description 2
201000000621 achalasia Diseases 0.000 claims description 2
230000001154 acute effect Effects 0.000 claims description 2
208000006673 asthma Diseases 0.000 claims description 2
210000003445 biliary tract Anatomy 0.000 claims description 2
230000015572 biosynthetic process Effects 0.000 claims description 2
206010006451 bronchitis Diseases 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
208000007451 chronic bronchitis Diseases 0.000 claims description 2
230000001684 chronic effect Effects 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
230000000414 obstructive effect Effects 0.000 claims description 2
208000011906 peptic ulcer disease Diseases 0.000 claims description 2
206010037628 pylorospasm Diseases 0.000 claims description 2
210000002345 respiratory system Anatomy 0.000 claims description 2
235000002906 tartaric acid Nutrition 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
210000001635 urinary tract Anatomy 0.000 claims description 2
239000003814 drug Substances 0.000 claims 1
239000003149 muscarinic antagonist Substances 0.000 abstract description 4
208000018522 Gastrointestinal disease Diseases 0.000 abstract description 3
208000018569 Respiratory Tract disease Diseases 0.000 abstract description 3
230000002496 gastric effect Effects 0.000 abstract description 3
125000004185 ester group Chemical group 0.000 abstract description 2
238000006467 substitution reaction Methods 0.000 abstract description 2
150000001721 carbon Chemical group 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 46
229910001868 water Inorganic materials 0.000 description 44
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 41
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
239000003480 eluent Substances 0.000 description 28
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
238000004128 high performance liquid chromatography Methods 0.000 description 20
238000004458 analytical method Methods 0.000 description 19
239000000543 intermediate Substances 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
229960004132 diethyl ether Drugs 0.000 description 16
239000000725 suspension Substances 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000007787 solid Substances 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
238000003756 stirring Methods 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000011734 sodium Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
229960004633 pirenzepine Drugs 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
CELPHAGZKFMOMR-UHFFFAOYSA-N azanium;dichloromethane;methanol;hydroxide Chemical compound [NH4+].[OH-].OC.ClCCl CELPHAGZKFMOMR-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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 4
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 4
102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 4
108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
230000027455 binding Effects 0.000 description 4
210000003710 cerebral cortex Anatomy 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
239000008101 lactose Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
239000000829 suppository Substances 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
238000004821 distillation Methods 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
150000004665 fatty acids Chemical class 0.000 description 3
238000004108 freeze drying Methods 0.000 description 3
125000005456 glyceride group Chemical group 0.000 description 3
230000003551 muscarinic effect Effects 0.000 description 3
239000008188 pellet Substances 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000001509 sodium citrate Substances 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
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 2
XTWASPQZSASCGU-UHFFFAOYSA-N CCOC(C(CCCN1C)(C2=CC=CC=C2)C1=O)=O Chemical compound CCOC(C(CCCN1C)(C2=CC=CC=C2)C1=O)=O XTWASPQZSASCGU-UHFFFAOYSA-N 0.000 description 2
MAZXAQJHGDHACF-UHFFFAOYSA-N CCOC(CCC(C(OCC)=O)(C1=CC=CC=C1)C#N)=O Chemical compound CCOC(CCC(C(OCC)=O)(C1=CC=CC=C1)C#N)=O MAZXAQJHGDHACF-UHFFFAOYSA-N 0.000 description 2
102000017926 CHRM2 Human genes 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
239000001828 Gelatine Substances 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
FZBCOCPXJJBHEG-UHFFFAOYSA-N O=C1NCC(CC1)(C(=O)OC(CC)CCCCC)C1=CC=CC=C1 Chemical compound O=C1NCC(CC1)(C(=O)OC(CC)CCCCC)C1=CC=CC=C1 FZBCOCPXJJBHEG-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
230000009858 acid secretion Effects 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
230000001022 anti-muscarinic effect Effects 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
LWZBDTQYCJMNPJ-UHFFFAOYSA-N ethyl 2-cyano-2-pyridin-2-ylacetate Chemical compound CCOC(=O)C(C#N)C1=CC=CC=N1 LWZBDTQYCJMNPJ-UHFFFAOYSA-N 0.000 description 2
YMBBAZTUKIDXBV-UHFFFAOYSA-N ethyl 2-oxo-3-phenylpiperidine-3-carboxylate Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCCNC1=O YMBBAZTUKIDXBV-UHFFFAOYSA-N 0.000 description 2
SXIRJEDGTAKGKU-UHFFFAOYSA-N ethyl phenylcyanoacetate Chemical compound CCOC(=O)C(C#N)C1=CC=CC=C1 SXIRJEDGTAKGKU-UHFFFAOYSA-N 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000000605 extraction Methods 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000003446 ligand Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
238000006386 neutralization reaction Methods 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
229940098462 oral drops Drugs 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
230000002265 prevention Effects 0.000 description 2
210000002460 smooth muscle Anatomy 0.000 description 2
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
239000000126 substance Substances 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
238000005303 weighing Methods 0.000 description 2
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239000011975 tartaric acid Substances 0.000 description 1
150000003512 tertiary amines Chemical group 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
208000014001 urinary system disease Diseases 0.000 description 1
239000008215 water for injection Substances 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Pulmonology (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyrrole Compounds (AREA)

IL9476390A 1989-06-20 1990-06-18 R) - (Quinuclidinol esters of converted azacycloalkanoic acids in position 1, their preparation and pharmaceutical preparations containing them IL94763A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
IT8920929A IT1230881B (it)	1989-06-20	1989-06-20	Derivati del r(-) 3-chinuclidinolo

Publications (2)

Publication Number	Publication Date
IL94763A0 IL94763A0 (en)	1991-04-15
IL94763A true IL94763A (en)	1994-08-26

Family

ID=11174223

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9476390A IL94763A (en)	1989-06-20	1990-06-18	R) - (Quinuclidinol esters of converted azacycloalkanoic acids in position 1, their preparation and pharmaceutical preparations containing them

Country Status (19)

Country	Link
US (1)	US5164386A (de)
EP (1)	EP0404737A3 (de)
JP (1)	JPH0331279A (de)
KR (1)	KR910000720A (de)
AU (1)	AU634787B2 (de)
CA (1)	CA2019251A1 (de)
DD (1)	DD300105A5 (de)
FI (1)	FI94131C (de)
HU (1)	HUT54151A (de)
IE (1)	IE902208A1 (de)
IL (1)	IL94763A (de)
IT (1)	IT1230881B (de)
NO (1)	NO174053C (de)
NZ (1)	NZ234157A (de)
PL (1)	PL164218B1 (de)
PT (1)	PT94408A (de)
RU (1)	RU2034843C1 (de)
YU (1)	YU47356B (de)
ZA (1)	ZA904736B (de)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9106571D0 (en) *	1991-03-27	1991-05-15	Erba Carlo Spa	Derivatives of substituted imidazol-2-one and process for their preparation
US5202318A (en) *	1990-05-14	1993-04-13	Syntex (U.S.A.) Inc.	Tricyclic compounds acting at serotonin receptor subtypes
AU7618991A (en) *	1990-05-14	1991-11-14	Syntex (U.S.A.) Inc.	Novel tricyclic compounds
EP0566589A1 (de) *	1991-01-10	1993-10-27	Pfizer Inc.	N-alkyl chinuclidiniumsalze als substanz-p-antagoniste
US5340826A (en) *	1993-02-04	1994-08-23	Pfizer Inc.	Pharmaceutical agents for treatment of urinary incontinence
NO2005012I1 (no) *	1994-12-28	2005-06-06	Debio Rech Pharma Sa	Triptorelin og farmasoytisk akseptable salter derav
US7214686B2 (en) *	1997-06-30	2007-05-08	Targacept, Inc.	Pharmaceutical compositions and methods for effecting dopamine release
DE60121813T2 (de)	2000-12-28	2007-09-20	Almirall Ag	Neue chinuclidinderivate und medizinische zusammensetzungen, die diese verbindungen enthalten
ES2206021B1 (es) *	2002-04-16	2005-08-01	Almirall Prodesfarma, S.A.	Nuevos derivados de pirrolidinio.
AR044134A1 (es) *	2003-05-02	2005-08-24	Novartis Ag	Derivados de quinuclidina, metodo de preparacion y composiciones farmaceuticas.
CA3178035A1 (en)	2012-12-24	2014-07-03	Neurogastrx, Inc.	Methods for treating gi tract disorders
US9844554B2 (en)	2014-06-24	2017-12-19	Neurogastrx, Inc.	Prodrugs of metopimazine
KR102423577B1 (ko)	2017-04-07	2022-07-21	삼성전자주식회사	가전기기
US10836757B1 (en)	2020-04-02	2020-11-17	Neurogastrx, Inc.	Polymorphic forms of metopimazine

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3290316A (en) *	1962-08-03	1966-12-06	Hoffmann La Roche	Alpha-3-pyridylmandelic acid and derivatives thereof
WO1985001048A1 (en) *	1983-08-26	1985-03-14	Sandoz Ag	Aromatic esters or amides of carboxylic acid and sulfonic acid
CA1307790C (en) *	1987-08-04	1992-09-22	Ian Anthony Cliffe	Ethers
US4921982A (en) *	1988-07-21	1990-05-01	Eli Lilly And Company	5-halo-2,3-dihydro-2,2-dimethylbenzofuran-7-carboxylic acids useful as intermediates for 5-HT3 antagonists
IL87674A (en) *	1987-09-08	1993-08-18	Lilly Co Eli	Azabicycloalkyl esters and amides of heterocyclic acids, their preparation and pharmaceutical compositions containing them
IT1231413B (it) *	1987-09-23	1991-12-04	Angeli Inst Spa	Derivati dell'acido benzimidazolin-2-osso-1-carbossilico utili come antagonisti dei recettori 5-ht
US4975437A (en) *	1989-12-14	1990-12-04	Marion Laboratories, Inc.	Isomers of 1-azabicyclo(2.2.2)oct-3-yl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-5-nitropyridine-3-carboxylate

1989
- 1989-06-20 IT IT8920929A patent/IT1230881B/it active
1990
- 1990-06-18 IL IL9476390A patent/IL94763A/en not_active IP Right Cessation
- 1990-06-18 DD DD341777A patent/DD300105A5/de unknown
- 1990-06-18 PL PL90285669A patent/PL164218B1/pl unknown
- 1990-06-19 JP JP2161192A patent/JPH0331279A/ja active Pending
- 1990-06-19 FI FI903077A patent/FI94131C/fi not_active IP Right Cessation
- 1990-06-19 KR KR1019900008991A patent/KR910000720A/ko not_active Withdrawn
- 1990-06-19 HU HU903908A patent/HUT54151A/hu unknown
- 1990-06-19 YU YU120290A patent/YU47356B/sh unknown
- 1990-06-19 EP EP19900830281 patent/EP0404737A3/de not_active Withdrawn
- 1990-06-19 IE IE220890A patent/IE902208A1/en unknown
- 1990-06-19 CA CA002019251A patent/CA2019251A1/en not_active Abandoned
- 1990-06-19 ZA ZA904736A patent/ZA904736B/xx unknown
- 1990-06-19 PT PT94408A patent/PT94408A/pt not_active Application Discontinuation
- 1990-06-19 NO NO902710A patent/NO174053C/no unknown
- 1990-06-20 AU AU57649/90A patent/AU634787B2/en not_active Ceased
- 1990-06-20 US US07/541,106 patent/US5164386A/en not_active Expired - Fee Related
- 1990-06-20 NZ NZ234157A patent/NZ234157A/xx unknown
1992
- 1992-03-10 RU SU925011061A patent/RU2034843C1/ru active

Also Published As

Publication number	Publication date
YU120290A (sh)	1992-12-21
PL164218B1 (pl)	1994-07-29
FI903077A0 (fi)	1990-06-19
EP0404737A3 (de)	1992-03-11
CA2019251A1 (en)	1990-12-20
HU903908D0 (en)	1990-11-28
PT94408A (pt)	1991-02-08
YU47356B (sh)	1995-01-31
IE902208A1 (en)	1991-01-02
NO174053B (no)	1993-11-29
IT8920929A0 (it)	1989-06-20
EP0404737A2 (de)	1990-12-27
PL285669A1 (en)	1991-03-11
AU5764990A (en)	1991-01-03
IL94763A0 (en)	1991-04-15
RU2034843C1 (ru)	1995-05-10
HUT54151A (en)	1991-01-28
NO902710D0 (no)	1990-06-19
DD300105A5 (de)	1992-05-21
NZ234157A (en)	1992-09-25
IT1230881B (it)	1991-11-08
JPH0331279A (ja)	1991-02-12
FI94131B (fi)	1995-04-13
US5164386A (en)	1992-11-17
FI94131C (fi)	1995-07-25
IE902208L (en)	1990-12-20
NO174053C (no)	1994-03-16
NO902710L (no)	1990-12-21
ZA904736B (en)	1992-02-26
AU634787B2 (en)	1993-03-04
KR910000720A (ko)	1991-01-30

Legal Events

Date	Code	Title	Description
1997-03-18	RH	Patent void

Publication	Publication Date	Title
KR100869721B1 (ko)	2008-11-21	신규한 퀴누클리딘 유도체 및 그를 함유한 의약 조성물
US7192978B2 (en)	2007-03-20	Pyrrolidinium derivatives
JP5014121B2 (ja)	2012-08-29	ムスカリン性アセチルコリン受容体アンタゴニスト
US5073560A (en)	1991-12-17	Spiro-isoxazolidine derivatives as cholinergic agents
US5106851A (en)	1992-04-21	Benzofused-n-containing heterocycle derivatives
US5591755A (en)	1997-01-07	Pyridinyl thiadiazolyl compounds for treating glaucoma
IE68434B1 (en)	1996-06-12	New tricyclic compounds
US5164386A (en)	1992-11-17	R(-)3-quinuclidinol derivatives
EP1725552B1 (de)	2008-06-25	Neue quaternisierte chinuclidinester
US20070232599A1 (en)	2007-10-04	Muscarinic Acetylcholine Receptor Antagonists
CA1321996C (en)	1993-09-07	Condensed diazepinones, processes for preparing them and pharmaceutical compositions containing these compounds
US5637596A (en)	1997-06-10	Azabicycloalkyl derivatives of imidazo[1,5-a]indol-3-one and process for their preparation
US5227394A (en)	1993-07-13	Pyrazole derivatives, compositions and use
AU4325793A (en)	1994-01-04	Derivatives of imidazo (5,1-C)(1, 4)benzoxazin-1-one as 5 HT3 antagonists
HK1101855B (en)	2009-04-30	New quaternized quinuclidine esters
KR20050024450A (ko)	2005-03-10	신규한 퀴누클리딘 아미드 유도체