ZA200501226B - Birayl diazabicycloalkane amides as nicotinic acetylcholine agonists - Google Patents

Birayl diazabicycloalkane amides as nicotinic acetylcholine agonists Download PDF

Info

Publication number: ZA200501226B
Authority: ZA; South Africa
Prior art keywords: diazabicyclo; methanone; furan; thiophen; pyridyl
Prior art date: 2002-08-14

Application number

ZA200501226A

Other languages

English (en)

Inventor

Glen Ernst

Richard Schmiesing

Eifion Phillips

Original Assignee

Astrazeneca Ab

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.)

2002-08-14

Filing date

2005-02-10

Publication date

2006-07-26

2005-02-10 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2006-07-26 Publication of ZA200501226B publication Critical patent/ZA200501226B/en

Links

150000001408 amides Chemical class 0.000 title description 8
239000000064 cholinergic agonist Substances 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 30
150000003839 salts Chemical class 0.000 claims abstract description 19
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 abstract description 3
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 124
-1 3-(2-pyridyl)phenyl Chemical group 0.000 claims description 96
CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 73
FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 claims description 57
229910052760 oxygen Inorganic materials 0.000 claims description 50
239000001301 oxygen Substances 0.000 claims description 50
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 49
229910052717 sulfur Inorganic materials 0.000 claims description 39
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 38
239000011593 sulfur Substances 0.000 claims description 38
239000002904 solvent Substances 0.000 claims description 33
229910052736 halogen Inorganic materials 0.000 claims description 32
150000002367 halogens Chemical class 0.000 claims description 32
125000005842 heteroatom Chemical group 0.000 claims description 29
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
239000003054 catalyst Substances 0.000 claims description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
229910052757 nitrogen Inorganic materials 0.000 claims description 20
125000002524 organometallic group Chemical group 0.000 claims description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 13
230000006735 deficit Effects 0.000 claims description 12
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims description 9
108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims description 9
208000035475 disorder Diseases 0.000 claims description 8
125000001072 heteroaryl group Chemical group 0.000 claims description 8
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
208000024827 Alzheimer disease Diseases 0.000 claims description 5
208000019901 Anxiety disease Diseases 0.000 claims description 5
208000000323 Tourette Syndrome Diseases 0.000 claims description 5
208000016620 Tourette disease Diseases 0.000 claims description 5
230000036506 anxiety Effects 0.000 claims description 5
150000002902 organometallic compounds Chemical class 0.000 claims description 5
238000011321 prophylaxis Methods 0.000 claims description 5
201000000980 schizophrenia Diseases 0.000 claims description 5
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 4
208000000044 Amnesia Diseases 0.000 claims description 4
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
208000020925 Bipolar disease Diseases 0.000 claims description 4
208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 4
206010009900 Colitis ulcerative Diseases 0.000 claims description 4
208000023105 Huntington disease Diseases 0.000 claims description 4
208000001456 Jet Lag Syndrome Diseases 0.000 claims description 4
206010026749 Mania Diseases 0.000 claims description 4
208000026139 Memory disease Diseases 0.000 claims description 4
208000002193 Pain Diseases 0.000 claims description 4
208000018737 Parkinson disease Diseases 0.000 claims description 4
208000028017 Psychotic disease Diseases 0.000 claims description 4
201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
230000004913 activation Effects 0.000 claims description 4
230000003935 attention Effects 0.000 claims description 4
208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
230000009286 beneficial effect Effects 0.000 claims description 4
208000028683 bipolar I disease Diseases 0.000 claims description 4
230000001713 cholinergic effect Effects 0.000 claims description 4
230000007278 cognition impairment Effects 0.000 claims description 4
208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 4
230000006984 memory degeneration Effects 0.000 claims description 4
208000023060 memory loss Diseases 0.000 claims description 4
208000015122 neurodegenerative disease Diseases 0.000 claims description 4
229960002715 nicotine Drugs 0.000 claims description 4
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 4
230000036407 pain Effects 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
230000000391 smoking effect Effects 0.000 claims description 4
210000000225 synapse Anatomy 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
GENNWRVZHQPVBO-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(3-pyridin-4-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CC=CC=1C1=CC=NC=C1 GENNWRVZHQPVBO-UHFFFAOYSA-N 0.000 claims description 2
LFQXLDRICKOWGM-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(3-thiophen-2-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CC=CC=1C1=CC=CS1 LFQXLDRICKOWGM-UHFFFAOYSA-N 0.000 claims description 2
DHJJHUMTVYKNTK-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-pyridin-3-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C1=CC=CN=C1 DHJJHUMTVYKNTK-UHFFFAOYSA-N 0.000 claims description 2
IRIRSSBNMMWXKV-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-pyridin-4-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C1=CC=NC=C1 IRIRSSBNMMWXKV-UHFFFAOYSA-N 0.000 claims description 2
HSLQOYKHBCLWOB-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-thiophen-3-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C=1C=CSC=1 HSLQOYKHBCLWOB-UHFFFAOYSA-N 0.000 claims description 2
LHGVLQATESRNBH-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-phenylthiophen-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CSC=1C1=CC=CC=C1 LHGVLQATESRNBH-UHFFFAOYSA-N 0.000 claims description 2
MKBBUDXINIFDPX-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-3-ylthiophen-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CSC=1C1=CC=CN=C1 MKBBUDXINIFDPX-UHFFFAOYSA-N 0.000 claims description 2
DLASHEKCTDFEAZ-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[3-(furan-3-yl)phenyl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CC=CC=1C=1C=COC=1 DLASHEKCTDFEAZ-UHFFFAOYSA-N 0.000 claims description 2
CHLWYKCXPSNISN-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(furan-2-yl)furan-3-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=COC=1C1=CC=CO1 CHLWYKCXPSNISN-UHFFFAOYSA-N 0.000 claims description 2
KPDXQGPZVDOPAC-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(furan-3-yl)thiophen-3-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CSC=1C=1C=COC=1 KPDXQGPZVDOPAC-UHFFFAOYSA-N 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
239000000126 substance Substances 0.000 claims 7
GNPQLYUSJOCBMA-UHFFFAOYSA-N (5-bromofuran-2-yl)-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone Chemical compound O1C(Br)=CC=C1C(=O)N1C(CC2)CCN2CC1 GNPQLYUSJOCBMA-UHFFFAOYSA-N 0.000 claims 3
208000009829 Lewy Body Disease Diseases 0.000 claims 3
201000002832 Lewy body dementia Diseases 0.000 claims 3
206010057852 Nicotine dependence Diseases 0.000 claims 3
208000025569 Tobacco Use disease Diseases 0.000 claims 3
230000002265 prevention Effects 0.000 claims 3
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 2
CLENPZXNGSLLJQ-UHFFFAOYSA-N (4-bromophenyl)methanone Chemical compound BrC1=CC=C([C+]=O)C=C1 CLENPZXNGSLLJQ-UHFFFAOYSA-N 0.000 claims 1
PFOHKMLFVACSFW-UHFFFAOYSA-N (5-bromothiophen-2-yl)-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone Chemical compound S1C(Br)=CC=C1C(=O)N1C(CC2)CCN2CC1 PFOHKMLFVACSFW-UHFFFAOYSA-N 0.000 claims 1
CDSCDKTXQWLABR-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(3-pyridin-3-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CC=CC=1C1=CC=CN=C1 CDSCDKTXQWLABR-UHFFFAOYSA-N 0.000 claims 1
HAXPXNGBJPFDGV-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-iodophenyl)methanone Chemical compound C1=CC(I)=CC=C1C(=O)N1C(CC2)CCN2CC1 HAXPXNGBJPFDGV-UHFFFAOYSA-N 0.000 claims 1
ITPFUCDKDQZSAY-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-phenylfuran-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(OC=1)=CC=1C1=CC=CC=C1 ITPFUCDKDQZSAY-UHFFFAOYSA-N 0.000 claims 1
WTSKNUGIAJZTMU-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-phenylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 WTSKNUGIAJZTMU-UHFFFAOYSA-N 0.000 claims 1
YFNUMKDCWUSIRV-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-phenylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(SC=1)=CC=1C1=CC=CC=C1 YFNUMKDCWUSIRV-UHFFFAOYSA-N 0.000 claims 1
RJJNRYMNCLCVOG-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-pyridin-2-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C1=CC=CC=N1 RJJNRYMNCLCVOG-UHFFFAOYSA-N 0.000 claims 1
ZNVCOLOEINQRSA-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-pyridin-2-ylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(SC=1)=CC=1C1=CC=CC=N1 ZNVCOLOEINQRSA-UHFFFAOYSA-N 0.000 claims 1
QOXDDTRJHUWFSC-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-pyridin-3-ylfuran-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(OC=1)=CC=1C1=CC=CN=C1 QOXDDTRJHUWFSC-UHFFFAOYSA-N 0.000 claims 1
SFCOAMGARZGOFF-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-pyridin-4-ylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(SC=1)=CC=1C1=CC=NC=C1 SFCOAMGARZGOFF-UHFFFAOYSA-N 0.000 claims 1
IQQWZDQMXJJYNM-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-thiophen-2-ylphenyl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C1=CC=CS1 IQQWZDQMXJJYNM-UHFFFAOYSA-N 0.000 claims 1
YBRYSLNAJMICEX-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-phenylfuran-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=COC=1C1=CC=CC=C1 YBRYSLNAJMICEX-UHFFFAOYSA-N 0.000 claims 1
DLHCGZZYPGPVCR-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-2-ylfuran-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=COC=1C1=CC=CC=N1 DLHCGZZYPGPVCR-UHFFFAOYSA-N 0.000 claims 1
QPPBIBLFYOSNPS-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-2-ylthiophen-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CSC=1C1=CC=CC=N1 QPPBIBLFYOSNPS-UHFFFAOYSA-N 0.000 claims 1
MBWNIKDPLGYNBF-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-3-ylfuran-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=COC=1C1=CC=CN=C1 MBWNIKDPLGYNBF-UHFFFAOYSA-N 0.000 claims 1
ZXSSSLLUZQKGDV-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-3-ylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(S1)=CC=C1C1=CC=CN=C1 ZXSSSLLUZQKGDV-UHFFFAOYSA-N 0.000 claims 1
MWXBVPSLVKVWBA-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-4-ylfuran-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(O1)=CC=C1C1=CC=NC=C1 MWXBVPSLVKVWBA-UHFFFAOYSA-N 0.000 claims 1
KEJSEMWXIQEIDY-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-4-ylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(S1)=CC=C1C1=CC=NC=C1 KEJSEMWXIQEIDY-UHFFFAOYSA-N 0.000 claims 1
HYMMMRPPFFEINN-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-thiophen-2-ylfuran-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=COC=1C1=CC=CS1 HYMMMRPPFFEINN-UHFFFAOYSA-N 0.000 claims 1
JYSBTOLWQZATNJ-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-thiophen-3-ylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(S1)=CC=C1C=1C=CSC=1 JYSBTOLWQZATNJ-UHFFFAOYSA-N 0.000 claims 1
UYXQTYKMPHONOO-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[3-(furan-2-yl)phenyl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CC=CC=1C1=CC=CO1 UYXQTYKMPHONOO-UHFFFAOYSA-N 0.000 claims 1
ZZMOMAZUUAPGBY-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[4-(furan-2-yl)furan-2-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(OC=1)=CC=1C1=CC=CO1 ZZMOMAZUUAPGBY-UHFFFAOYSA-N 0.000 claims 1
DHQSIENQTWLGCD-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[4-(furan-2-yl)phenyl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C1=CC=CO1 DHQSIENQTWLGCD-UHFFFAOYSA-N 0.000 claims 1
CEHAHHKXNFJLFU-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[4-(furan-2-yl)thiophen-2-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(SC=1)=CC=1C1=CC=CO1 CEHAHHKXNFJLFU-UHFFFAOYSA-N 0.000 claims 1
AUDBITKNIDHJPP-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[4-(furan-3-yl)furan-2-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(OC=1)=CC=1C=1C=COC=1 AUDBITKNIDHJPP-UHFFFAOYSA-N 0.000 claims 1
CVFFPZUTOZEQBY-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[4-(furan-3-yl)phenyl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=C1)=CC=C1C=1C=COC=1 CVFFPZUTOZEQBY-UHFFFAOYSA-N 0.000 claims 1
GZLLLTUIOLORTQ-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(furan-3-yl)furan-2-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(O1)=CC=C1C=1C=COC=1 GZLLLTUIOLORTQ-UHFFFAOYSA-N 0.000 claims 1
MIJYHLLUFJGZPR-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(furan-3-yl)thiophen-2-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(S1)=CC=C1C=1C=COC=1 MIJYHLLUFJGZPR-UHFFFAOYSA-N 0.000 claims 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims 1
BRVKMWXEKXINNU-UHFFFAOYSA-N 5-pyridin-4-ylfuran-3-carbaldehyde Chemical compound O=CC1=COC(C=2C=CN=CC=2)=C1 BRVKMWXEKXINNU-UHFFFAOYSA-N 0.000 claims 1
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239000003085 diluting agent Substances 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
239000003446 ligand Substances 0.000 abstract description 18
108010009685 Cholinergic Receptors Proteins 0.000 abstract description 2
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
239000002585 base Substances 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical class [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
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239000003153 chemical reaction reagent Substances 0.000 description 10
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 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000007822 coupling agent Substances 0.000 description 9
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 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
239000012442 inert solvent Substances 0.000 description 8
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
239000004210 ether based solvent Substances 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
230000010933 acylation Effects 0.000 description 6
238000005917 acylation reaction Methods 0.000 description 6
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
125000005620 boronic acid group Chemical class 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 4
229910001863 barium hydroxide Inorganic materials 0.000 description 4
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
229910000024 caesium carbonate Inorganic materials 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
229910000073 phosphorus hydride Inorganic materials 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-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 3
239000004215 Carbon black (E152) Substances 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 3
150000001718 carbodiimides Chemical class 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
150000002430 hydrocarbons Chemical class 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 3
125000005500 uronium group Chemical group 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
150000001412 amines Chemical class 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
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000003786 synthesis reaction Methods 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
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 2
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
MZMRVHKSQCNPKT-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-pyridin-2-ylfuran-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(OC=1)=CC=1C1=CC=CC=N1 MZMRVHKSQCNPKT-UHFFFAOYSA-N 0.000 description 1
JLQSEOZBGVGQAI-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(4-thiophen-3-ylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(SC=1)=CC=1C=1C=CSC=1 JLQSEOZBGVGQAI-UHFFFAOYSA-N 0.000 description 1
RQPHTSNRBQUGSU-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-phenylfuran-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(O1)=CC=C1C1=CC=CC=C1 RQPHTSNRBQUGSU-UHFFFAOYSA-N 0.000 description 1
SODJXZKVCLJFEE-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-phenylthiophen-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(S1)=CC=C1C1=CC=CC=C1 SODJXZKVCLJFEE-UHFFFAOYSA-N 0.000 description 1
RLJRNTDELRCHII-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-pyridin-4-ylthiophen-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CSC=1C1=CC=NC=C1 RLJRNTDELRCHII-UHFFFAOYSA-N 0.000 description 1
CFSYVLPMJBCKBT-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-thiophen-2-ylfuran-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(O1)=CC=C1C1=CC=CS1 CFSYVLPMJBCKBT-UHFFFAOYSA-N 0.000 description 1
ADRZDHXTXVMBOR-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-thiophen-3-ylfuran-2-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(O1)=CC=C1C=1C=CSC=1 ADRZDHXTXVMBOR-UHFFFAOYSA-N 0.000 description 1
YYSWQOGFUOIEAW-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-(5-thiophen-3-ylthiophen-3-yl)methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CSC=1C=1C=CSC=1 YYSWQOGFUOIEAW-UHFFFAOYSA-N 0.000 description 1
BIAAPEZXONIEPI-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(furan-2-yl)furan-2-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(O1)=CC=C1C1=CC=CO1 BIAAPEZXONIEPI-UHFFFAOYSA-N 0.000 description 1
VBGJVKGJWKENNB-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-(furan-2-yl)thiophen-3-yl]methanone Chemical compound C1CN(CC2)CCC2N1C(=O)C(C=1)=CSC=1C1=CC=CO1 VBGJVKGJWKENNB-UHFFFAOYSA-N 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
NSXWVWBHCINPIG-UHFFFAOYSA-N 4-methoxyphenylthionophosphine sulfide Chemical class COC1=CC=C(P(=S)=S)C=C1 NSXWVWBHCINPIG-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
VKCLPVFDVVKEKU-UHFFFAOYSA-N S=[P] Chemical class S=[P] VKCLPVFDVVKEKU-UHFFFAOYSA-N 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
230000036592 analgesia Effects 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
150000001502 aryl halides Chemical class 0.000 description 1
WGNZRLMOMHJUSP-UHFFFAOYSA-N benzotriazol-1-yloxy(tripyrrolidin-1-yl)phosphanium Chemical compound C1CCCN1[P+](N1CCCC1)(N1CCCC1)ON1C2=CC=CC=C2N=N1 WGNZRLMOMHJUSP-UHFFFAOYSA-N 0.000 description 1
150000005347 biaryls Chemical class 0.000 description 1
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
230000006949 cholinergic function Effects 0.000 description 1
230000001149 cognitive effect Effects 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
229940079593 drug Drugs 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
DOTMOQHOJINYBL-UHFFFAOYSA-N molecular nitrogen;molecular oxygen Chemical group N#N.O=O DOTMOQHOJINYBL-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
230000004112 neuroprotection Effects 0.000 description 1
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
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230000005586 smoking cessation Effects 0.000 description 1
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150000004763 sulfides Chemical class 0.000 description 1
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- 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
- A61P25/00—Drugs for disorders of the nervous system
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/24—Antidepressants
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Animal Behavior & Ethology (AREA)
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Chemical Kinetics & Catalysis (AREA)
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ZA200501226A 2002-08-14 2005-02-10 Birayl diazabicycloalkane amides as nicotinic acetylcholine agonists ZA200501226B (en)

Applications Claiming Priority (1)

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SE0202430A SE0202430D0 (sv)	2002-08-14	2002-08-14	New Compounds

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US (1)	US20050239774A1 (de)
EP (1)	EP1539765B1 (de)
JP (1)	JP2006507241A (de)
KR (1)	KR20060002727A (de)
CN (1)	CN100343256C (de)
AT (1)	ATE417049T1 (de)
AU (1)	AU2003248592B2 (de)
BR (1)	BR0313234A (de)
CA (1)	CA2493920A1 (de)
DE (1)	DE60325234D1 (de)
ES (1)	ES2316848T3 (de)
IL (1)	IL166416A0 (de)
MX (1)	MXPA05001583A (de)
NO (1)	NO20051259L (de)
NZ (1)	NZ537882A (de)
SE (1)	SE0202430D0 (de)
WO (1)	WO2004016617A1 (de)
ZA (1)	ZA200501226B (de)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE521512C2 (sv)	2001-06-25	2003-11-11	Niconovum Ab	Anordning för administrering av en substans till främre delen av en individs munhåla
DE10164139A1 (de)	2001-12-27	2003-07-10	Bayer Ag	2-Heteroarylcarbonsäureamide
SE0202465D0 (sv) *	2002-08-14	2002-08-14	Astrazeneca Ab	New compounds
AU2003276919B2 (en)	2002-09-25	2013-05-16	Memory Pharmaceuticals Corporation	Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
DK1803443T3 (en)	2002-12-20	2019-02-25	Niconovum Ab	Nicotine-containing particulate material with a crystalline cellulose
EP1599476B1 (de) *	2003-02-27	2009-10-14	Neurosearch A/S	Neue diazabicyclische arylderivate
TW200529860A (en) *	2003-12-22	2005-09-16	Astrazeneca Ab	Nicotinic acetylcholine receptor ligands
DE602004010299T2 (de)	2003-12-22	2008-09-18	Memory Pharmaceuticals Corp.	Indole, 1h-indazole, 1,2-benzisoxazole und 1,2-benzisothiazole und deren herstellung und anwendungen
CN100445285C (zh) *	2003-12-22	2008-12-24	阿斯利康(瑞典)有限公司	烟碱性乙酰胆碱受体配体
CA2555311A1 (en) *	2004-02-04	2005-08-18	Neurosearch A/S	Diazabicyclic aryl derivatives as nicotinic acetylcholine receptor ligands
RU2417225C2 (ru)	2004-03-25	2011-04-27	Мемори Фармасьютиклз Корпорейшн	Индазолы, бензотиазолы, бензоизотиазолы, бензизоксазолы и их получение и применение
JP2007534692A (ja)	2004-04-22	2007-11-29	メモリー・ファーマシューティカルズ・コーポレイション	インドール、１ｈ−インダゾール、１，２−ベンズイソキサゾール、１，２−ベンゾイソチアゾール、ならびにその調製および使用
JP2007538011A (ja)	2004-05-07	2007-12-27	メモリー・ファーマシューティカルズ・コーポレイション	１ｈ−インダゾール、ベンゾチアゾール、１，２−ベンゾイソキサゾール、１，２−ベンゾイソチアゾール、およびクロモン、ならびにそれらの調製および使用
US7652010B2 (en)	2004-10-15	2010-01-26	Neurosearch A/S	Azabicyclic aryl derivatives and their medical use
BRPI0517494A (pt)	2004-12-22	2008-10-14	Memory Pharm Corp	composto, composição farmacêutica, método de ativação/estimulação seletiva de receptores nicotìnicos de a-7 em um paciente em que tal ativação/estimulação tem um efeito terapêutico, método de tratamento de um paciente que sofre de uma doença psicótica, uma doença neurodegenerativa que envolve uma disfunção do sistema colinérgico, e/ou uma condição de debilitação da memória e/ou da cognição, método de tratamento de um paciente que sofre de demência e/ou uma outra condição com perda da memória, método de tratamento de um paciente que sofre de debilitação da memória devido à debilitação cognitiva suave devido ao envelhecimento, mal de alzheimer, esquizofrenia, mal de parkinson, mal de huntington, mal de pick, mal de creutzfeldt-jakob, depressão, envelhecimento, trauma na cabeça, acidente vascular cerebral, hipoxia do snc, senilidade cerebral, demência de multiinfarto, hiv e/ou doença cardiovascular, método de tratamento e/ou prevenção da demência em um paciente com o mal de alzheimer, método de tratamento de um paciente para cortar o vìcio do álcool ou o tratamento de um paciente com a terapia anti-intoxicação, método de tratamento de um paciente para propiciar neuroproteção contra os danos associados com acidentes vasculares cerebrais e isquemia e excitotoxicidade induzida por glutamatos, método de tratamento de um paciente que sofre do vìcio da nicotina, dor, tontura do fuso horário, obesidade e/ou diabetes, método de indução do ato de parar fumar em um paciente, método de tratamento de um paciente que sofre de debilitação cognitiva suave (mci), demência vascular (vad), declìnio cognitivo associado com a idade (aacd), amnésia associada com a cirurgia com o coração aberto, parada cardìaca, anestesia geral, deficiências da memória devido à exposição a agentes anestésicos, debilitação cognitiva induzida pela privação do sono, sìndrome de fadiga crÈnica, narcolepsia, demência relacionada com a aids, debilitação cognitiva relacionada com a epilepsia, sìndrome de down, demência relacionada ao alcoolismo, debilitações da memória induzidas por drogas/substáncias, demência pugilìstica (sìndrome do boxeador), ou demência animal, método para o tratamento da perda da memória, método para o tratamento de um paciente que sofre de debilitação da memória, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da disfunção da transmissão do receptor nicotìnico de acetilcolina em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante de receptores nicotìnicos de acetilcolina defeituosos ou funcionando mal em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da transmissão suprimida do receptor nicotìnico de acetilcolina em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da perda de sinapses colinérgicas em um paciente, método para a proteção dos neurÈnios em um paciente com neurotoxicidade induzi
JP2009526777A (ja)	2006-02-14	2009-07-23	ノイロサーチアクティーゼルスカブ	ニコチン性アセチルコリン受容体作用薬としての３，９−ジアザビシクロ（３．３．１）ノナ−３−イル−アリールメタノン誘導体
CA2646942C (en)	2006-03-16	2014-07-29	Modoral Brands Inc.	Improved snuff composition
MX2008014890A (es)	2006-05-30	2008-12-05	Neurosearch As	Nuevos derivados de 1,4-diaza-biciclo[3.2.2]nonil pirimidinilo y su uso medico.
TWI454262B (zh) *	2006-11-02	2014-10-01	Targacept Inc	菸鹼乙醯膽鹼受體亞型選擇性之二氮雜雙環烷類醯胺
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
JP2011500728A (ja) *	2007-10-22	2011-01-06	メモリーファーマシューティカルスコーポレーション	疾患の処置に有用なニコチン性アセチルコリン受容体の（１，４−ジアザ−ビシクロ［３．２．２］ノン−６−エン−４−イル）−ヘテロシクリル−メタノンリガンド
GB0724251D0 (en)	2007-12-12	2008-02-06	Univ Edinburgh	Therapeutic compounds and their use
GB0804685D0 (en) *	2008-03-13	2008-04-16	Univ Edinburgh	Therapeutic compounds and their use
ME01516B (me)	2008-06-20	2014-04-20	Astrazeneca Ab	DERIVAT DIBENZOTIAZEPINA l NJEGOVA UPOTREBA
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
EP2443113A1 (de)	2009-06-15	2012-04-25	The University Of Edinburgh	Amidoisothiazolverbindungen und ihre verwendung als 11beta-hsd1-hemmer zur behandlung von stoffwechselsyndrom und assoziierten erkrankungen
KR101702159B1 (ko)	2009-09-16	2017-02-02	더 유니버시티 오브 에든버러	（４―페닐―피페리딘―1―일）―［５―（1ｈ―피라졸―４―일）―티오펜―３―일］―메탄온 화합물 및 그의 용도
CA2826623A1 (en) *	2010-02-03	2011-08-11	Meh Associates, Inc	Multiple substituted fluoromethanes as selective and bioactive isosteres
ES2543692T3 (es)	2010-04-29	2015-08-21	The University Of Edinburgh	(8-aza-biciclo[3.2.1biciclo[oct-8-il)-[5-(1H-pirazol-4-il)-tiofeno-3-il]-metanonas 3,3-disustituidas como inhibidores de 11beta-HSD1
MX357676B (es)	2010-05-17	2018-07-18	Forum Pharmaceuticals Inc	Una forma cristalina de clorhidrato de (r)-7-cloro-n-(quinuclidin- 3-il)benzo[b]tiofeno-2-carboxamida monohidratado.
BR112013000925A2 (pt) *	2010-07-15	2020-12-01	Bayer Intellectual Property Gmbh	compostos heterocíclicos como pesticidas
GB201111705D0 (en)	2011-07-07	2011-08-24	Takeda Pharmaceutical	Compounds and their use
GB201111704D0 (en)	2011-07-07	2011-08-24	Takeda Pharmaceutical	Novel compounds
JO3115B1 (ar)	2011-08-22	2017-09-20	Takeda Pharmaceuticals Co	مركبات بيريدازينون واستخدامها كمثبطات daao
EP3666272A1 (de)	2012-05-08	2020-06-17	Forum Pharmaceuticals Inc.	Verwendung von encenicline bei der behandlung von kognitiver behinderung, alzheimer-krankheit, speicherdefizit
GB201209587D0 (en)	2012-05-30	2012-07-11	Takeda Pharmaceutical	Therapeutic compounds
MA37975B2 (fr)	2012-09-11	2021-03-31	Genzyme Corp	Inhibiteurs de synthase de glucosylcéramide
CN105189482A (zh)	2013-02-07	2015-12-23	武田药品工业株式会社	作为毒蕈碱m4受体激动剂的哌啶-1-基羧酸酯和氮杂卓-1-基羧酸酯
US10208016B2 (en)	2013-06-21	2019-02-19	Takeda Pharmaceutical Company Limited	1-sulfonyl piperidine derivatives as modulators of prokineticin receptors
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
US12527776B2 (en)	2019-02-04	2026-01-20	Genzyme Corporation	Treatment of ciliopathies using inhibitors of glucosylceramide synthase (GCS)
EP4100009A1 (de)	2020-02-03	2022-12-14	Genzyme Corporation	Verfahren zur behandlung neurologischer symptome im zusammenhang mit lysosomalen speicherkrankheiten
JP2021138648A (ja)	2020-03-04	2021-09-16	武田薬品工業株式会社	経口固形製剤
KR20230043024A (ko)	2020-07-24	2023-03-30	젠자임 코포레이션	벤글루스타트를 포함하는 제약 조성물
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 (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3281423A (en) *	1964-02-03	1966-10-25	Merck & Co Inc	1, 3-ethanopiperazines and process
US4895943A (en) *	1988-10-25	1990-01-23	Pfizer Inc.	Preparation of 1,4-diazabicyclo(3.2.2)nonane
US5679673A (en) *	1992-09-24	1997-10-21	The United States Of America, Represented By The Department Of Health And Human Services	Aralkyl bridged diazabicycloalkane derivatives for CNS disorders
FR2791678B1 (fr) *	1999-03-30	2001-05-04	Synthelabo	Derives de 1,4-diazabicyclo [3.2.2] nonane-4-carboxylates et -carboxamides, leur preparation et leur application en therapeutique
FR2809732B1 (fr) *	2000-05-31	2002-07-19	Sanofi Synthelabo	DERIVES DE 4(-2-PHENYLTHIAZOL-5-yl)-1,4-DIAZABICYCLO-[3.2.2] NONANE, LEUR PREPARATION ET LEUR APPLICATION ENTHERAPEUTIQUE
FR2809731B1 (fr) *	2000-05-31	2002-07-19	Sanofi Synthelabo	Derives de 1,4-diazabicyclo-[3.2.2] nonane-pheylisoxazole, leur preparation et leur application en therapeutique
SE0202465D0 (sv) *	2002-08-14	2002-08-14	Astrazeneca Ab	New compounds
EP1599476B1 (de) *	2003-02-27	2009-10-14	Neurosearch A/S	Neue diazabicyclische arylderivate
TW200529860A (en) *	2003-12-22	2005-09-16	Astrazeneca Ab	Nicotinic acetylcholine receptor ligands
CN100445285C (zh) *	2003-12-22	2008-12-24	阿斯利康(瑞典)有限公司	烟碱性乙酰胆碱受体配体

2002
- 2002-08-14 SE SE0202430A patent/SE0202430D0/xx unknown
2003
- 2003-08-13 ES ES03788214T patent/ES2316848T3/es not_active Expired - Lifetime
- 2003-08-13 AT AT03788214T patent/ATE417049T1/de not_active IP Right Cessation
- 2003-08-13 CN CNB038194791A patent/CN100343256C/zh not_active Expired - Fee Related
- 2003-08-13 NZ NZ537882A patent/NZ537882A/en unknown
- 2003-08-13 AU AU2003248592A patent/AU2003248592B2/en not_active Expired - Fee Related
- 2003-08-13 WO PCT/SE2003/001277 patent/WO2004016617A1/en not_active Ceased
- 2003-08-13 DE DE60325234T patent/DE60325234D1/de not_active Expired - Fee Related
- 2003-08-13 JP JP2004529002A patent/JP2006507241A/ja active Pending
- 2003-08-13 EP EP03788214A patent/EP1539765B1/de not_active Expired - Lifetime
- 2003-08-13 KR KR1020057002265A patent/KR20060002727A/ko not_active Ceased
- 2003-08-13 MX MXPA05001583A patent/MXPA05001583A/es unknown
- 2003-08-13 BR BR0313234-0A patent/BR0313234A/pt not_active IP Right Cessation
- 2003-08-13 CA CA002493920A patent/CA2493920A1/en not_active Abandoned
- 2003-08-13 US US10/524,484 patent/US20050239774A1/en not_active Abandoned
2005
- 2005-01-20 IL IL16641605A patent/IL166416A0/xx unknown
- 2005-02-10 ZA ZA200501226A patent/ZA200501226B/en unknown
- 2005-03-11 NO NO20051259A patent/NO20051259L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
IL166416A0 (en)	2006-01-15
US20050239774A1 (en)	2005-10-27
SE0202430D0 (sv)	2002-08-14
HK1077571A1 (en)	2006-02-17
CN1678615A (zh)	2005-10-05
NO20051259L (no)	2005-05-12
CA2493920A1 (en)	2004-02-26
DE60325234D1 (de)	2009-01-22
CN100343256C (zh)	2007-10-17
EP1539765A1 (de)	2005-06-15
AU2003248592A1 (en)	2004-03-03
JP2006507241A (ja)	2006-03-02
WO2004016617A1 (en)	2004-02-26
BR0313234A (pt)	2005-06-14
KR20060002727A (ko)	2006-01-09
AU2003248592B2 (en)	2008-04-03
NZ537882A (en)	2008-02-29
MXPA05001583A (es)	2005-04-25
EP1539765B1 (de)	2008-12-10
ES2316848T3 (es)	2009-04-16
ATE417049T1 (de)	2008-12-15

Publication	Publication Date	Title
AU2003248592B2 (en)	2008-04-03	Biaryl diazabicycloalkane amides as nicotinic acetylcholine agonists
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US20050043346A1 (en)	2005-02-24	Pyridylpyrrole derivatives active as kinase inhibitors
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TW200536849A (en)	2005-11-16	Substituted heterocycles and the uses thereof
CN114007691A (zh)	2022-02-01	吡啶氨基甲酸酯及其作为GluN2B受体调节剂的用途
JP2010502651A5 (de)	2010-07-29
WO2014145004A1 (en)	2014-09-18	Pyridone amides and analogs exhibiting anti-cancer and anti-proliferative activities
JP2012506381A5 (de)	2012-11-29
ZA200600154B (en)	2007-04-25	Spiro[1-azabicyclo[2.2.2]octan-3,5'-oxazolidin-2'-one] derivatives with affinity to the alpha 7 nicotinic acetylcholine receptor
JP2013516393A5 (de)	2013-08-01
JP6123097B2 (ja)	2017-05-10	チエノピリミジン化合物を製造するための方法
WO2017066193A1 (en)	2017-04-20	Novel inhibitors of protein kinases
CA2960477A1 (en)	2016-03-17	Fused bicyclic (hetero)aromatic compounds useful for the treatment of cancers
MX2013009551A (es)	2013-09-06	Compuestos que contienen fosforo como inhibidores de proteina cinasa.
AU2020246317A1 (en)	2021-11-18	Small-molecule inhibitor of PD-1/PD-L1, pharmaceutical composition thereof with PD-L1 antibody, and application of same
CA2756152A1 (fr)	2010-09-30	Derives d'azacarbolines 9h-pyrrolo[2,3-b:5,4-c']dipyridine, leur preparation et leur utilisation therapeutique
Arbuzova et al.	2018	Regio-and stereoselective reaction of 3-fluoropyridine, electron-deficient alkynes and bis (fluoroalkyl) phosphites: Catalyst-and solvent-free synthesis of polyfluoroalkylphosphonylated 3-fluoro-1, 2-dihydropyridines
Schnürch	2011	Recent progress on the halogen dance reaction on heterocycles
Emberson et al.	2017	Diastereoselective Lithiation of N-Benzyl Pyrroloimidazolones Derived from l-Proline Hydantoin
RU2010132230A (ru)	2012-02-10	Производные 2-гетероароилимидазо[1,2-а] пиридина, способ их получения и применение их в терапии
WO2014043895A1 (zh)	2014-03-27	光学活性的2-羟基四氢噻吩并吡啶衍生物及其制备方法和用途
Verma	2023	Hydroamination to access N-silylamines and imines, valuable reactive intermediates for unsaturated and saturated N-heterocycle synthesis