CA2482312A1 - Thienyl compounds - Google Patents
Thienyl compounds Download PDFInfo
- Publication number
- CA2482312A1 CA2482312A1 CA002482312A CA2482312A CA2482312A1 CA 2482312 A1 CA2482312 A1 CA 2482312A1 CA 002482312 A CA002482312 A CA 002482312A CA 2482312 A CA2482312 A CA 2482312A CA 2482312 A1 CA2482312 A1 CA 2482312A1
- Authority
- CA
- Canada
- Prior art keywords
- azabicyclo
- octane
- spiro
- pyridine
- furo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 125000001544 thienyl group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
- 238000011282 treatment Methods 0.000 claims description 29
- 238000011321 prophylaxis Methods 0.000 claims description 26
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims description 23
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims description 23
- 230000006735 deficit Effects 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 22
- 125000003003 spiro group Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 208000028017 Psychotic disease Diseases 0.000 claims description 10
- 229960002715 nicotine Drugs 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 8
- 208000018737 Parkinson disease Diseases 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 8
- 208000016620 Tourette disease Diseases 0.000 claims description 8
- 230000036506 anxiety Effects 0.000 claims description 8
- 201000000980 schizophrenia Diseases 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 208000000044 Amnesia Diseases 0.000 claims description 7
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- 208000020925 Bipolar disease Diseases 0.000 claims description 7
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 7
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 7
- 206010026749 Mania Diseases 0.000 claims description 7
- 208000026139 Memory disease Diseases 0.000 claims description 7
- 206010057852 Nicotine dependence Diseases 0.000 claims description 7
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 7
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 7
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 7
- 230000003935 attention Effects 0.000 claims description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 7
- 208000028683 bipolar I disease Diseases 0.000 claims description 7
- 230000001713 cholinergic effect Effects 0.000 claims description 7
- 230000007278 cognition impairment Effects 0.000 claims description 7
- 235000019788 craving Nutrition 0.000 claims description 7
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000006984 memory degeneration Effects 0.000 claims description 7
- 208000023060 memory loss Diseases 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 230000036407 pain Effects 0.000 claims description 7
- 230000000391 smoking effect Effects 0.000 claims description 7
- 210000000225 synapse Anatomy 0.000 claims description 7
- 229910052722 tritium Inorganic materials 0.000 claims description 7
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 230000004913 activation Effects 0.000 claims description 6
- 230000009286 beneficial effect Effects 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- 230000008484 agonism Effects 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- LYTMVABTDYMBQK-UHFFFAOYSA-N 2-benzothiophene Chemical group C1=CC=CC2=CSC=C21 LYTMVABTDYMBQK-UHFFFAOYSA-N 0.000 claims description 2
- 230000008485 antagonism Effects 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- RGRFTIUNUVXJFV-NRFANRHFSA-N (3r)-5'-(1-benzothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound C1=CC=C2SC(C=3C=C4C[C@]5(C6CCN(CC6)C5)OC4=NC=3)=CC2=C1 RGRFTIUNUVXJFV-NRFANRHFSA-N 0.000 claims 1
- MKMCCVGYQLOGJN-NRFANRHFSA-N (3r)-5'-(1-benzothiophen-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound C1=CC=C2C(C=3C=C4C[C@]5(C6CCN(CC6)C5)OC4=NC=3)=CSC2=C1 MKMCCVGYQLOGJN-NRFANRHFSA-N 0.000 claims 1
- XMYKXOCVJKLGSH-SFHVURJKSA-N (3r)-5'-(4-methylthiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound CC1=CSC(C=2C=C3C[C@@]4(OC3=NC=2)C2CCN(CC2)C4)=C1 XMYKXOCVJKLGSH-SFHVURJKSA-N 0.000 claims 1
- CABQJIZQLLQXQI-KRWDZBQOSA-N (3r)-5'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound S1C(Br)=CC=C1C1=CN=C(O[C@]2(C3)C4CCN(CC4)C2)C3=C1 CABQJIZQLLQXQI-KRWDZBQOSA-N 0.000 claims 1
- DBGIZTGPWQNSSJ-KRWDZBQOSA-N (3r)-5'-(5-bromothiophen-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound S1C(Br)=CC(C=2C=C3C[C@@]4(OC3=NC=2)C2CCN(CC2)C4)=C1 DBGIZTGPWQNSSJ-KRWDZBQOSA-N 0.000 claims 1
- CJYZUXDETNGQMM-KRWDZBQOSA-N (3r)-5'-(5-chlorothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound S1C(Cl)=CC=C1C1=CN=C(O[C@]2(C3)C4CCN(CC4)C2)C3=C1 CJYZUXDETNGQMM-KRWDZBQOSA-N 0.000 claims 1
- RQFPIXLGXRQAPI-KRWDZBQOSA-N (3r)-5'-(5-chlorothiophen-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound S1C(Cl)=CC(C=2C=C3C[C@@]4(OC3=NC=2)C2CCN(CC2)C4)=C1 RQFPIXLGXRQAPI-KRWDZBQOSA-N 0.000 claims 1
- OMSGRSKTHWPJNV-KRWDZBQOSA-N (3r)-5'-(5-fluorothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound S1C(F)=CC=C1C1=CN=C(O[C@]2(C3)C4CCN(CC4)C2)C3=C1 OMSGRSKTHWPJNV-KRWDZBQOSA-N 0.000 claims 1
- DYLBIMKJVBZUNA-KRWDZBQOSA-N (3r)-5'-(5-fluorothiophen-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound S1C(F)=CC(C=2C=C3C[C@@]4(OC3=NC=2)C2CCN(CC2)C4)=C1 DYLBIMKJVBZUNA-KRWDZBQOSA-N 0.000 claims 1
- PVCRUOGAHDRKGZ-SFHVURJKSA-N (3r)-5'-(5-methylthiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound S1C(C)=CC=C1C1=CN=C(O[C@]2(C3)C4CCN(CC4)C2)C3=C1 PVCRUOGAHDRKGZ-SFHVURJKSA-N 0.000 claims 1
- AHRUHWJGGHPBCA-KRWDZBQOSA-N (3r)-5'-thiophen-2-ylspiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound C([C@]1(C2CCN(CC2)C1)OC1=NC=2)C1=CC=2C1=CC=CS1 AHRUHWJGGHPBCA-KRWDZBQOSA-N 0.000 claims 1
- PKEIGGSVAYHOQK-KRWDZBQOSA-N (3r)-5'-thiophen-3-ylspiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound C([C@]1(C2CCN(CC2)C1)OC1=NC=2)C1=CC=2C=1C=CSC=1 PKEIGGSVAYHOQK-KRWDZBQOSA-N 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 101100149678 Caenorhabditis elegans snr-3 gene Proteins 0.000 claims 1
- 125000001626 borono group Chemical group [H]OB([*])O[H] 0.000 claims 1
- ACJGOCAFNPOHJE-AHJYMZSGSA-N trimethyl-[(3r)-spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine]-5'-yl]stannane Chemical compound C1N(CC2)CCC2[C@@]11OC2=NC=C([Sn](C)(C)C)C=C2C1 ACJGOCAFNPOHJE-AHJYMZSGSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 18
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 34
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 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 11
- 239000003054 catalyst Substances 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- -1 heterocyclic amines Chemical class 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 125000002524 organometallic group Chemical group 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical class [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 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 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical group O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 150000001491 aromatic compounds Chemical class 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ABMUSXPGSSMPLK-UHFFFAOYSA-N 4-bromo-2-methylthiophene Chemical compound CC1=CC(Br)=CS1 ABMUSXPGSSMPLK-UHFFFAOYSA-N 0.000 description 2
- DJYVXBJLHPKUKS-UHFFFAOYSA-N 4-bromothiophene-2-carbonitrile Chemical compound BrC1=CSC(C#N)=C1 DJYVXBJLHPKUKS-UHFFFAOYSA-N 0.000 description 2
- YVVHCBNJWHPMCQ-UHFFFAOYSA-N 5-bromothiophene-2-carbonitrile Chemical compound BrC1=CC=C(C#N)S1 YVVHCBNJWHPMCQ-UHFFFAOYSA-N 0.000 description 2
- UHTBNRHIZVPITN-UHFFFAOYSA-N 5-tributylstannylthiophene-2-carbonitrile Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C#N)S1 UHTBNRHIZVPITN-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- LAWUZBKFMNSOGG-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=[C]S1 LAWUZBKFMNSOGG-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- MOOOGTOEKZWEJA-UHFFFAOYSA-N (3-methylthiophen-2-yl)boronic acid Chemical compound CC=1C=CSC=1B(O)O MOOOGTOEKZWEJA-UHFFFAOYSA-N 0.000 description 1
- YGFFDFKDCIJMIG-ZDUSSCGKSA-N (3r)-5'-bromospiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound C1N(CC2)CCC2[C@@]11OC2=NC=C(Br)C=C2C1 YGFFDFKDCIJMIG-ZDUSSCGKSA-N 0.000 description 1
- DFUMIZDUIJNUJU-UHFFFAOYSA-N (4-methylthiophen-2-yl)boronic acid Chemical compound CC1=CSC(B(O)O)=C1 DFUMIZDUIJNUJU-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
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- 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
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- A61P25/16—Anti-Parkinson drugs
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201187A SE0201187D0 (sv) | 2002-04-18 | 2002-04-18 | Thienyl compounds |
| SE0201187-2 | 2002-04-18 | ||
| SE0203608A SE0203608D0 (sv) | 2002-12-04 | 2002-12-04 | Thienyl compounds |
| SE0203608-5 | 2002-12-04 | ||
| PCT/SE2003/000614 WO2003087103A1 (en) | 2002-04-18 | 2003-04-15 | Thienyl compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2482312A1 true CA2482312A1 (en) | 2003-10-23 |
Family
ID=29253789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002482312A Abandoned CA2482312A1 (en) | 2002-04-18 | 2003-04-15 | Thienyl compounds |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US7186836B2 (enExample) |
| EP (1) | EP1499615B1 (enExample) |
| JP (1) | JP4511196B2 (enExample) |
| KR (1) | KR20040099448A (enExample) |
| CN (1) | CN1325499C (enExample) |
| AT (1) | ATE477256T1 (enExample) |
| AU (1) | AU2003224545B2 (enExample) |
| BR (1) | BR0309342A (enExample) |
| CA (1) | CA2482312A1 (enExample) |
| DE (1) | DE60333746D1 (enExample) |
| ES (1) | ES2348282T3 (enExample) |
| IL (1) | IL164613A0 (enExample) |
| MX (1) | MXPA04010193A (enExample) |
| NO (1) | NO20044997L (enExample) |
| NZ (1) | NZ535978A (enExample) |
| WO (1) | WO2003087103A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| CZ2004408A3 (cs) | 2001-10-02 | 2005-03-16 | Pharmacia & Upjohn Company | Azabicyklicky substituované kondenzované heteroarylsloučeniny |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| BR0309343A (pt) * | 2002-04-18 | 2005-02-15 | Astrazeneca Ab | Composto, composição farmacêutica, uso de um composto, e, método de tratamento ou profilaxia de doenças ou condições humanas |
| BR0309342A (pt) * | 2002-04-18 | 2005-02-15 | Astrazeneca Ab | Composto, composição farmacêutica, uso de um composto, e, método de tratamento ou profilaxia de doenças ou condições humanas |
| JP4855264B2 (ja) * | 2003-10-21 | 2012-01-18 | アストラゼネカ・アクチエボラーグ | スピロフロピリジンアリール誘導体 |
| US7045530B2 (en) | 2003-12-22 | 2006-05-16 | Abbott Laboratories | Spirocyclic quinuclidinic ether derivatives |
| TW200813067A (en) * | 2006-05-17 | 2008-03-16 | Astrazeneca Ab | Nicotinic acetylcholine receptor ligands |
| SA08290475B1 (ar) * | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| CA2728675A1 (en) | 2008-06-20 | 2009-12-23 | Astrazeneca Ab | Dibenzothiazepine derivatives and use thereof |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| TWI519532B (zh) | 2010-05-17 | 2016-02-01 | 艾維沃製藥公司 | （Ｒ）－７－氯－Ｎ－（啶－３－基）苯並［b］噻吩－２－羧醯胺鹽酸鹽單水合物之結晶形體 |
| GB201111704D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Novel compounds |
| GB201111705D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Compounds and their use |
| JO3115B1 (ar) | 2011-08-22 | 2017-09-20 | Takeda Pharmaceuticals Co | مركبات بيريدازينون واستخدامها كمثبطات daao |
| RU2017136693A (ru) | 2012-05-08 | 2019-02-08 | Форум Фармасьютикалз, Инк. | Способы поддержания, лечения или улучшения когнитивной функции |
| GB201209587D0 (en) | 2012-05-30 | 2012-07-11 | Takeda Pharmaceutical | Therapeutic compounds |
| US9593106B2 (en) | 2013-02-07 | 2017-03-14 | Heptares Therapeutics Limited | Piperidin-1-yl and azepin-1-yl carboxylates as muscarinic M4 receptor agonists |
| JP6401254B2 (ja) | 2013-06-21 | 2018-10-10 | 武田薬品工業株式会社 | プロキネシチン受容体のモジュレータとしての１−スルホニルピペリジン誘導体 |
| GB201314286D0 (en) | 2013-08-08 | 2013-09-25 | Takeda Pharmaceutical | Therapeutic Compounds |
| GB201318222D0 (en) | 2013-10-15 | 2013-11-27 | Takeda Pharmaceutical | Novel compounds |
| GB201320905D0 (en) | 2013-11-27 | 2014-01-08 | Takeda Pharmaceutical | Therapeutic compounds |
| TW201613864A (en) | 2014-02-20 | 2016-04-16 | Takeda Pharmaceutical | Novel compounds |
| GB201616839D0 (en) | 2016-10-04 | 2016-11-16 | Takeda Pharmaceutical Company Limited | Therapeutic compounds |
| GB201619514D0 (en) | 2016-11-18 | 2017-01-04 | Takeda Pharmaceuticals Co | Novel compounds |
| JP2021138648A (ja) | 2020-03-04 | 2021-09-16 | 武田薬品工業株式会社 | 経口固形製剤 |
| CN112898312B (zh) * | 2021-01-29 | 2021-11-12 | 湖南南新制药股份有限公司 | 一种稠合多环吡啶酮衍生物及其用途 |
| GB202414193D0 (en) | 2024-09-27 | 2024-11-13 | Addex Pharmaceuticals Sa | Novel compounds |
| GB202414197D0 (en) | 2024-09-27 | 2024-11-13 | Addex Pharmaceuticals Sa | Novel compounds |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR013184A1 (es) * | 1997-07-18 | 2000-12-13 | Astrazeneca Ab | Aminas heterociclicas espiroazobiciclicas, composicion farmaceutica, uso de dichas aminas para preparar medicamentos y metodo de tratamiento o profilaxis |
| SE9900100D0 (sv) | 1999-01-15 | 1999-01-15 | Astra Ab | New compounds |
| FR2788982B1 (fr) * | 1999-02-02 | 2002-08-02 | Synthelabo | Compositions pharmaceutiques contenant de la nicotine et leur application dans le sevrage tabagique |
| US20010016677A1 (en) * | 1999-02-16 | 2001-08-23 | Dan Russell Poole | Incubator with thermoelectric cooler |
| US6569865B2 (en) * | 2001-06-01 | 2003-05-27 | Astrazeneca Ab | Spiro 1-azabicyclo[2.2.2]octane-3,2′(3′h)-furo[2,3-b]pyridine |
| WO2002096912A1 (en) * | 2001-06-01 | 2002-12-05 | Astrazeneca Ab | Novel ligand for nicotinic acetylcholine receptors useful in therapy |
| BR0309343A (pt) * | 2002-04-18 | 2005-02-15 | Astrazeneca Ab | Composto, composição farmacêutica, uso de um composto, e, método de tratamento ou profilaxia de doenças ou condições humanas |
| BR0309342A (pt) * | 2002-04-18 | 2005-02-15 | Astrazeneca Ab | Composto, composição farmacêutica, uso de um composto, e, método de tratamento ou profilaxia de doenças ou condições humanas |
-
2003
- 2003-04-15 BR BR0309342-5A patent/BR0309342A/pt not_active IP Right Cessation
- 2003-04-15 AU AU2003224545A patent/AU2003224545B2/en not_active Expired - Fee Related
- 2003-04-15 DE DE60333746T patent/DE60333746D1/de not_active Expired - Lifetime
- 2003-04-15 EP EP03721208A patent/EP1499615B1/en not_active Expired - Lifetime
- 2003-04-15 US US10/511,522 patent/US7186836B2/en not_active Expired - Fee Related
- 2003-04-15 CN CNB038137828A patent/CN1325499C/zh not_active Expired - Fee Related
- 2003-04-15 NZ NZ535978A patent/NZ535978A/en unknown
- 2003-04-15 KR KR10-2004-7016548A patent/KR20040099448A/ko not_active Ceased
- 2003-04-15 WO PCT/SE2003/000614 patent/WO2003087103A1/en not_active Ceased
- 2003-04-15 JP JP2003584059A patent/JP4511196B2/ja not_active Expired - Fee Related
- 2003-04-15 ES ES03721208T patent/ES2348282T3/es not_active Expired - Lifetime
- 2003-04-15 AT AT03721208T patent/ATE477256T1/de not_active IP Right Cessation
- 2003-04-15 CA CA002482312A patent/CA2482312A1/en not_active Abandoned
- 2003-04-15 MX MXPA04010193A patent/MXPA04010193A/es active IP Right Grant
-
2004
- 2004-10-14 IL IL16461304A patent/IL164613A0/xx unknown
- 2004-11-17 NO NO20044997A patent/NO20044997L/no not_active Application Discontinuation
-
2007
- 2007-01-29 US US11/668,099 patent/US20070142419A1/en not_active Abandoned
-
2010
- 2010-10-27 US US12/912,840 patent/US20110124672A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE60333746D1 (de) | 2010-09-23 |
| MXPA04010193A (es) | 2005-02-03 |
| BR0309342A (pt) | 2005-02-15 |
| AU2003224545A1 (en) | 2003-10-27 |
| NZ535978A (en) | 2007-10-26 |
| US20050171106A1 (en) | 2005-08-04 |
| ATE477256T1 (de) | 2010-08-15 |
| US20070142419A1 (en) | 2007-06-21 |
| IL164613A0 (en) | 2005-12-18 |
| WO2003087103A1 (en) | 2003-10-23 |
| HK1079522A1 (en) | 2006-04-07 |
| JP2005527588A (ja) | 2005-09-15 |
| KR20040099448A (ko) | 2004-11-26 |
| JP4511196B2 (ja) | 2010-07-28 |
| US7186836B2 (en) | 2007-03-06 |
| EP1499615A1 (en) | 2005-01-26 |
| CN1659170A (zh) | 2005-08-24 |
| US20110124672A1 (en) | 2011-05-26 |
| ES2348282T3 (es) | 2010-12-02 |
| CN1325499C (zh) | 2007-07-11 |
| AU2003224545B2 (en) | 2009-08-13 |
| EP1499615B1 (en) | 2010-08-11 |
| NO20044997L (no) | 2005-01-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20101201 |