SK75999A3 - 3-pyridyl enantiomers and their use as analgesics - Google Patents
3-pyridyl enantiomers and their use as analgesics Download PDFInfo
- Publication number
- SK75999A3 SK75999A3 SK759-99A SK75999A SK75999A3 SK 75999 A3 SK75999 A3 SK 75999A3 SK 75999 A SK75999 A SK 75999A SK 75999 A3 SK75999 A3 SK 75999A3
- Authority
- SK
- Slovakia
- Prior art keywords
- compound
- group
- ethenyl
- azetidine
- mmol
- Prior art date
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- 239000000730 antalgic agent Substances 0.000 title abstract description 17
- 229940035676 analgesics Drugs 0.000 title abstract description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 396
- 238000000034 method Methods 0.000 claims abstract description 128
- 208000002193 Pain Diseases 0.000 claims abstract description 64
- 230000036407 pain Effects 0.000 claims abstract description 59
- 238000011282 treatment Methods 0.000 claims abstract description 52
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 241000124008 Mammalia Species 0.000 claims abstract description 9
- 230000016273 neuron death Effects 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 297
- 239000000203 mixture Substances 0.000 claims description 135
- 229910052799 carbon Inorganic materials 0.000 claims description 131
- 229910052757 nitrogen Inorganic materials 0.000 claims description 131
- -1 azetidinylmethoxy Chemical group 0.000 claims description 92
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 80
- 229910052801 chlorine Inorganic materials 0.000 claims description 76
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 68
- 239000002243 precursor Substances 0.000 claims description 57
- 229910052731 fluorine Inorganic materials 0.000 claims description 53
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 50
- 229910052794 bromium Inorganic materials 0.000 claims description 49
- 230000000694 effects Effects 0.000 claims description 46
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 40
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- 229960005181 morphine Drugs 0.000 claims description 20
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 19
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 16
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 15
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 230000004054 inflammatory process Effects 0.000 claims description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- UOWHCAKKYIRMSX-UHFFFAOYSA-N [N].C1CNC1 Chemical compound [N].C1CNC1 UOWHCAKKYIRMSX-UHFFFAOYSA-N 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- 229910052727 yttrium Inorganic materials 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 239000012442 inert solvent Substances 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000000129 anionic group Chemical group 0.000 claims description 3
- 229960005261 aspartic acid Drugs 0.000 claims description 3
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 150000004678 hydrides Chemical class 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 239000012038 nucleophile Substances 0.000 claims description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 claims description 2
- MKTAGSRKQIGEBH-SSDOTTSWSA-N tebanicline Chemical compound C1=NC(Cl)=CC=C1OC[C@@H]1NCC1 MKTAGSRKQIGEBH-SSDOTTSWSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000005490 tosylate group Chemical group 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims 6
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 claims 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 4
- 229910010082 LiAlH Inorganic materials 0.000 claims 3
- SPRIOUNJHPCKPV-UHFFFAOYSA-N hydridoaluminium Chemical compound [AlH] SPRIOUNJHPCKPV-UHFFFAOYSA-N 0.000 claims 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 2
- 150000001539 azetidines Chemical class 0.000 claims 2
- 239000004202 carbamide Substances 0.000 claims 2
- 150000002081 enamines Chemical class 0.000 claims 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 150000003571 thiolactams Chemical class 0.000 claims 2
- 238000006477 desulfuration reaction Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000005978 reductive desulfurization reaction Methods 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 371
- 238000005481 NMR spectroscopy Methods 0.000 description 202
- 239000000460 chlorine Substances 0.000 description 197
- 239000000243 solution Substances 0.000 description 186
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 181
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 169
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 152
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 103
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 102
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 101
- 238000004458 analytical method Methods 0.000 description 94
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 85
- 239000007787 solid Substances 0.000 description 84
- 239000000741 silica gel Substances 0.000 description 83
- 229910002027 silica gel Inorganic materials 0.000 description 83
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 78
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- 239000000047 product Substances 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- 239000002904 solvent Substances 0.000 description 71
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 67
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 67
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
- 239000003921 oil Substances 0.000 description 55
- 235000019198 oils Nutrition 0.000 description 55
- 238000006243 chemical reaction Methods 0.000 description 50
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 41
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- 239000000284 extract Substances 0.000 description 37
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 30
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 29
- 235000019441 ethanol Nutrition 0.000 description 28
- 230000004044 response Effects 0.000 description 28
- 229920006395 saturated elastomer Polymers 0.000 description 28
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 28
- 239000012458 free base Substances 0.000 description 27
- 238000012360 testing method Methods 0.000 description 26
- 239000012267 brine Substances 0.000 description 24
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 239000012043 crude product Substances 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
- 239000012230 colorless oil Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 18
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- 239000000543 intermediate Substances 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- 229920002554 vinyl polymer Polymers 0.000 description 17
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 230000000875 corresponding effect Effects 0.000 description 16
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000003446 ligand Substances 0.000 description 15
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 15
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
- 239000012298 atmosphere Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
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- 238000002347 injection Methods 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 13
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
- 230000000202 analgesic effect Effects 0.000 description 13
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- 229940002612 prodrug Drugs 0.000 description 13
- 239000000651 prodrug Substances 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
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- 229930040373 Paraformaldehyde Natural products 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 12
- 230000027455 binding Effects 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
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- 229910052763 palladium Inorganic materials 0.000 description 12
- 229920002866 paraformaldehyde Polymers 0.000 description 12
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 12
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 11
- 239000008346 aqueous phase Substances 0.000 description 11
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 208000004296 neuralgia Diseases 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 239000003039 volatile agent Substances 0.000 description 11
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 208000021722 neuropathic pain Diseases 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
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- 239000003054 catalyst Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 210000002683 foot Anatomy 0.000 description 9
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 9
- 239000012414 tert-butyl nitrite Substances 0.000 description 9
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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- XFTSTOZKKGXMQV-CQSZACIVSA-N tert-butyl (2r)-2-(benzylsulfonyloxymethyl)azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H]1COS(=O)(=O)CC1=CC=CC=C1 XFTSTOZKKGXMQV-CQSZACIVSA-N 0.000 description 1
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- QULNGGSZUGCITL-SNVBAGLBSA-N tert-butyl (2r)-2-[(6-fluoropyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H]1COC1=CC=C(F)N=C1 QULNGGSZUGCITL-SNVBAGLBSA-N 0.000 description 1
- IFXAZQPIZYEAAE-ZETCQYMHSA-N tert-butyl (2s)-1-(hydroxymethyl)azetidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCN1CO IFXAZQPIZYEAAE-ZETCQYMHSA-N 0.000 description 1
- GGWIDFJKKFDHCP-NSHDSACASA-N tert-butyl (2s)-2-[(5-bromo-6-methylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound C1=C(Br)C(C)=NC=C1OC[C@H]1N(C(=O)OC(C)(C)C)CC1 GGWIDFJKKFDHCP-NSHDSACASA-N 0.000 description 1
- UEOMZNZJGRNZHA-AWEZNQCLSA-N tert-butyl (2s)-2-[(5-ethyl-6-methylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound N1=C(C)C(CC)=CC(OC[C@H]2N(CC2)C(=O)OC(C)(C)C)=C1 UEOMZNZJGRNZHA-AWEZNQCLSA-N 0.000 description 1
- YWTOOYWRVNGCSV-NSHDSACASA-N tert-butyl (2s)-2-[(5-fluoropyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1COC1=CN=CC(F)=C1 YWTOOYWRVNGCSV-NSHDSACASA-N 0.000 description 1
- JTOWMVURJWKYCL-LBPRGKRZSA-N tert-butyl (2s)-2-[(6-chloro-5-ethylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound N1=C(Cl)C(CC)=CC(OC[C@H]2N(CC2)C(=O)OC(C)(C)C)=C1 JTOWMVURJWKYCL-LBPRGKRZSA-N 0.000 description 1
- HEYKCIOFPMUUCY-LBPRGKRZSA-N tert-butyl (2s)-2-[[6-(hydroxymethyl)pyridin-3-yl]oxymethyl]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1COC1=CC=C(CO)N=C1 HEYKCIOFPMUUCY-LBPRGKRZSA-N 0.000 description 1
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- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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- YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical class Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CHQOEHPMXSHGCL-UHFFFAOYSA-N trimethaphan Chemical compound C12C[S+]3CCCC3C2N(CC=2C=CC=CC=2)C(=O)N1CC1=CC=CC=C1 CHQOEHPMXSHGCL-UHFFFAOYSA-N 0.000 description 1
- 229940035742 trimethaphan Drugs 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3232196P | 1996-12-10 | 1996-12-10 | |
US76327896A | 1996-12-10 | 1996-12-10 | |
PCT/US1997/022811 WO1998025920A1 (en) | 1996-12-10 | 1997-12-10 | 3-pyridyl enantiomers and their use as analgesics |
Publications (1)
Publication Number | Publication Date |
---|---|
SK75999A3 true SK75999A3 (en) | 2000-05-16 |
Family
ID=26708255
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK759-99A SK75999A3 (en) | 1996-12-10 | 1997-12-10 | 3-pyridyl enantiomers and their use as analgesics |
Country Status (21)
Country | Link |
---|---|
EP (1) | EP0950057B1 (tr) |
JP (2) | JP4272261B2 (tr) |
KR (2) | KR100472154B1 (tr) |
CN (1) | CN1125064C (tr) |
AT (1) | ATE227717T1 (tr) |
AU (1) | AU733881B2 (tr) |
BG (1) | BG64196B1 (tr) |
BR (1) | BR9714677A (tr) |
CA (2) | CA2273917C (tr) |
DE (1) | DE69717148T2 (tr) |
DK (1) | DK0950057T3 (tr) |
ES (1) | ES2189003T3 (tr) |
HU (1) | HUP0001110A3 (tr) |
IL (1) | IL130083A0 (tr) |
NO (1) | NO992705L (tr) |
NZ (1) | NZ335810A (tr) |
PL (1) | PL333920A1 (tr) |
PT (1) | PT950057E (tr) |
SK (1) | SK75999A3 (tr) |
TR (1) | TR199901904T2 (tr) |
WO (1) | WO1998025920A1 (tr) |
Families Citing this family (26)
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AU2880699A (en) | 1998-04-02 | 1999-10-25 | R.J. Reynolds Tobacco Company | Pharmaceutical compositions and methods for use |
US6054451A (en) * | 1998-04-21 | 2000-04-25 | Algos Pharmaceutical Corporation | Analgesic composition and method for alleviating pain |
US6362371B1 (en) | 1998-06-08 | 2002-03-26 | Advanced Medicine, Inc. | β2- adrenergic receptor agonists |
US20010031771A1 (en) | 1999-05-24 | 2001-10-18 | Gary Maurice Dull | Pharmaceutical compositions and methods for use |
US6103911A (en) * | 1999-06-15 | 2000-08-15 | Abbott Laboratories | Process for reduction of (2R)-4-oxoazetidinone-2-carboxylic acid |
US6818787B2 (en) | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
US8048917B2 (en) | 2005-04-06 | 2011-11-01 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
US7186855B2 (en) | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
WO2003097043A1 (en) * | 2002-05-15 | 2003-11-27 | Abbott Laboratories | Treatment of neuropathic pain |
EP1741709A1 (en) | 2005-06-28 | 2007-01-10 | Sanofi-Aventis Deutschland GmbH | Heteroaryl-substituted amides comprising a saturated linker group, and their use as pharmaceuticals |
KR20080085014A (ko) | 2005-12-09 | 2008-09-22 | 에프. 호프만-라 로슈 아게 | 비만 치료에 유용한 트라이사이클릭 아마이드 유도체 |
TW200800020A (en) * | 2006-01-26 | 2008-01-01 | Basf Ag | Methods to use 3-pyridyl derivatives as pesticides |
WO2008028903A2 (en) | 2006-09-04 | 2008-03-13 | Neurosearch A/S | Pharmaceutical combinations of a nicotine receptor modulator and a cognitive enhancer |
JP4939192B2 (ja) * | 2006-12-05 | 2012-05-23 | ユニ・チャーム株式会社 | 不織布、不織布の製造方法及び吸収性物品 |
DE102007058504A1 (de) | 2007-12-05 | 2009-07-09 | Acino Ag | Transdermales therapeutisches System mit einem Gehalt an einem Modulator für nikotinische Acetylcholinrezeptoren (nAChR) |
AU2009303545A1 (en) | 2008-10-14 | 2010-04-22 | Psychogenics, Inc | Nicotinic acetylcholine receptor ligands and the uses thereof |
US8474529B2 (en) * | 2009-04-09 | 2013-07-02 | Regency Technologies Llc | Control of concentric tubing direction |
AR075988A1 (es) * | 2009-04-09 | 2011-05-11 | Lilly Co Eli | Compuesto de piridiloxi - pirrolidina inhibidor de recaptacion de serotonina y norepinefrina, composicion farmaceutica que lo comprende y su uso para la manufactura de un medicamento util para el tratamiento de dolor cronico |
MX2013013326A (es) | 2011-06-30 | 2014-02-27 | Toray Industries | Agente antipruritico. |
WO2014160783A1 (en) | 2013-03-27 | 2014-10-02 | Georgetown University | 2-halo-5-alkynyl-pyridyl nicotinic ligands |
CA3066361A1 (en) | 2017-06-07 | 2018-12-13 | Shifamed Holdings, Llc | Intravascular fluid movement devices, systems, and methods of use |
US11511103B2 (en) | 2017-11-13 | 2022-11-29 | Shifamed Holdings, Llc | Intravascular fluid movement devices, systems, and methods of use |
EP3746149A4 (en) | 2018-02-01 | 2021-10-27 | Shifamed Holdings, LLC | INTRAVASCULAR BLOOD PUMPS AND METHODS OF USE AND METHODS OF MANUFACTURING |
EP3996797A4 (en) | 2019-07-12 | 2023-08-02 | Shifamed Holdings, LLC | INTRAVASCULAR BLOOD PUMPS AND METHOD OF USE AND METHOD OF MAKING |
US11654275B2 (en) | 2019-07-22 | 2023-05-23 | Shifamed Holdings, Llc | Intravascular blood pumps with struts and methods of use and manufacture |
WO2021062265A1 (en) | 2019-09-25 | 2021-04-01 | Shifamed Holdings, Llc | Intravascular blood pump systems and methods of use and control thereof |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
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GB8301702D0 (en) * | 1983-01-21 | 1983-02-23 | Shell Int Research | Azetidine compounds |
US4902684A (en) * | 1988-06-20 | 1990-02-20 | E. R. Squibb & Sons, Inc. | Benzazepine and benzothiazepine derivatives |
US5068234A (en) * | 1990-02-26 | 1991-11-26 | Sterling Drug Inc. | 3-arylcarbonyl-1-(c-attached-n-heteryl)-1h-indoles |
IL107184A (en) * | 1992-10-09 | 1997-08-14 | Abbott Lab | Heterocyclic ether compounds that enhance cognitive function |
US5585388A (en) * | 1995-04-07 | 1996-12-17 | Sibia Neurosciences, Inc. | Substituted pyridines useful as modulators of acetylcholine receptors |
IL118279A (en) * | 1995-06-07 | 2006-10-05 | Abbott Lab | Compounds 3 - Pyridyloxy (or Thio) Alkyl Heterocyclic Pharmaceutical Compositions Containing Them and Their Uses for Preparing Drugs to Control Synaptic Chemical Transmission |
US5629325A (en) * | 1996-06-06 | 1997-05-13 | Abbott Laboratories | 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission |
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1997
- 1997-12-10 DE DE69717148T patent/DE69717148T2/de not_active Expired - Lifetime
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- 1997-12-10 TR TR1999/01904T patent/TR199901904T2/tr unknown
- 1997-12-10 SK SK759-99A patent/SK75999A3/sk unknown
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- 1997-12-10 JP JP52698398A patent/JP4272261B2/ja not_active Expired - Fee Related
- 1997-12-10 DK DK97952392T patent/DK0950057T3/da active
- 1997-12-10 WO PCT/US1997/022811 patent/WO1998025920A1/en not_active Application Discontinuation
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- 1997-12-10 AU AU56010/98A patent/AU733881B2/en not_active Ceased
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- 1997-12-10 AT AT97952392T patent/ATE227717T1/de active
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1999
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