AU2002222909B2 - Pharmaceutical compositions for treating neurological disorders - Google Patents
Pharmaceutical compositions for treating neurological disorders Download PDFInfo
- Publication number
- AU2002222909B2 AU2002222909B2 AU2002222909A AU2002222909A AU2002222909B2 AU 2002222909 B2 AU2002222909 B2 AU 2002222909B2 AU 2002222909 A AU2002222909 A AU 2002222909A AU 2002222909 A AU2002222909 A AU 2002222909A AU 2002222909 B2 AU2002222909 B2 AU 2002222909B2
- Authority
- AU
- Australia
- Prior art keywords
- tartaric acid
- substituted
- compound
- toluoyl
- alkyl
- 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.)
- Ceased
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 43
- 208000012902 Nervous system disease Diseases 0.000 title description 3
- 208000025966 Neurological disease Diseases 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 208
- 125000003118 aryl group Chemical group 0.000 claims abstract description 65
- 239000000203 mixture Substances 0.000 claims abstract description 60
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims description 94
- 125000000623 heterocyclic group Chemical group 0.000 claims description 61
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 229910052799 carbon Chemical group 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 37
- 241000894007 species Species 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 229960001270 d- tartaric acid Drugs 0.000 claims description 29
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 125000003107 substituted aryl group Chemical group 0.000 claims description 23
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 230000003957 neurotransmitter release Effects 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 10
- CMIBUZBMZCBCAT-HOTGVXAUSA-N (2s,3s)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@H](C(O)=O)[C@@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HOTGVXAUSA-N 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 230000004075 alteration Effects 0.000 claims description 8
- CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 claims description 7
- NNNQNUXYOQZVDB-ZIAGYGMSSA-N (2r,3r)-2,3-bis(2,2-dimethylpropanoyl)-2,3-dihydroxybutanedioic acid Chemical compound CC(C)(C)C(=O)[C@@](O)(C(O)=O)[C@](O)(C(O)=O)C(=O)C(C)(C)C NNNQNUXYOQZVDB-ZIAGYGMSSA-N 0.000 claims description 5
- OCQAXYHNMWVLRH-QZTJIDSGSA-N (2r,3r)-2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound O=C([C@@](O)(C(=O)O)[C@](O)(C(O)=O)C(=O)C=1C=CC=CC=1)C1=CC=CC=C1 OCQAXYHNMWVLRH-QZTJIDSGSA-N 0.000 claims description 5
- OCQAXYHNMWVLRH-ROUUACIJSA-N (2s,3s)-2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound O=C([C@](O)(C(=O)O)[C@@](O)(C(O)=O)C(=O)C=1C=CC=CC=1)C1=CC=CC=C1 OCQAXYHNMWVLRH-ROUUACIJSA-N 0.000 claims description 5
- PEOCCFXRLGYKBM-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(OCO2)C2=C1 PEOCCFXRLGYKBM-UHFFFAOYSA-N 0.000 claims description 5
- SNZMBGPVGUVXRP-UHFFFAOYSA-N 4,5-dichloroquinoline Chemical compound C1=CC(Cl)=C2C(Cl)=CC=CC2=N1 SNZMBGPVGUVXRP-UHFFFAOYSA-N 0.000 claims description 5
- DVMNOSBSAVUYEU-WOJBJXKFSA-N C1(=CC(=CC=C1)C(=O)[C@@]([C@@](C(=O)O)(O)C(=O)C=1C=C(C=CC1)C)(O)C(=O)O)C Chemical compound C1(=CC(=CC=C1)C(=O)[C@@]([C@@](C(=O)O)(O)C(=O)C=1C=C(C=CC1)C)(O)C(=O)O)C DVMNOSBSAVUYEU-WOJBJXKFSA-N 0.000 claims description 5
- BKLZIAYVINRQEJ-UHFFFAOYSA-K trifluoroalumane;trihydrate Chemical compound O.O.O.F[Al](F)F BKLZIAYVINRQEJ-UHFFFAOYSA-K 0.000 claims description 5
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims 9
- 230000000052 comparative effect Effects 0.000 claims 3
- 229960003753 nitric oxide Drugs 0.000 claims 3
- 235000019391 nitrogen oxide Nutrition 0.000 claims 3
- JUOSGGQXEBBCJB-UHFFFAOYSA-N Metanicotine Natural products CNCCC=CC1=CC=CN=C1 JUOSGGQXEBBCJB-UHFFFAOYSA-N 0.000 claims 1
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims 1
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 229960001367 tartaric acid Drugs 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 42
- 239000002253 acid Substances 0.000 abstract description 32
- 150000001412 amines Chemical class 0.000 abstract description 26
- 208000015114 central nervous system disease Diseases 0.000 abstract description 21
- -1 nicotinic compounds Chemical class 0.000 description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- 208000035475 disorder Diseases 0.000 description 40
- 230000000694 effects Effects 0.000 description 33
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 31
- 238000005859 coupling reaction Methods 0.000 description 31
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 29
- 239000000126 substance Substances 0.000 description 28
- 230000008878 coupling Effects 0.000 description 27
- 238000010168 coupling process Methods 0.000 description 27
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 19
- 210000003169 central nervous system Anatomy 0.000 description 18
- 238000007341 Heck reaction Methods 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 16
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 150000001336 alkenes Chemical group 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 229910052763 palladium Inorganic materials 0.000 description 14
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 13
- 230000002265 prevention Effects 0.000 description 13
- MGFRWLSGAABYES-UHFFFAOYSA-N tert-butyl n-methyl-n-pent-4-en-2-ylcarbamate Chemical compound C=CCC(C)N(C)C(=O)OC(C)(C)C MGFRWLSGAABYES-UHFFFAOYSA-N 0.000 description 13
- 238000010438 heat treatment Methods 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 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 12
- 125000003277 amino group Chemical group 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 10
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 150000007513 acids Chemical class 0.000 description 10
- 229960002715 nicotine Drugs 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 229960003638 dopamine Drugs 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 6
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 230000016396 cytokine production Effects 0.000 description 6
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000002858 neurotransmitter agent Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 150000003222 pyridines Chemical class 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
- NTOIKDYVJIWVSU-WOJBJXKFSA-N (2r,3r)-2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical group C1=CC(C)=CC=C1C(=O)[C@@](O)(C(O)=O)[C@](O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-WOJBJXKFSA-N 0.000 description 5
- SOSPMXMEOFGPIM-UHFFFAOYSA-N 3,5-dibromopyridine Chemical compound BrC1=CN=CC(Br)=C1 SOSPMXMEOFGPIM-UHFFFAOYSA-N 0.000 description 5
- ASEHPOZWQJRWAD-UHFFFAOYSA-N 3-bromo-5-propan-2-yloxypyridine Chemical class CC(C)OC1=CN=CC(Br)=C1 ASEHPOZWQJRWAD-UHFFFAOYSA-N 0.000 description 5
- KXBXUHWCODHRHK-UHFFFAOYSA-N 5-bromo-3-hydroxy-1h-pyridin-2-one Chemical compound OC1=CC(Br)=CNC1=O KXBXUHWCODHRHK-UHFFFAOYSA-N 0.000 description 5
- YRGMYJUKFJPNPD-UHFFFAOYSA-N 5-bromopyridine-2,3-diamine Chemical compound NC1=CC(Br)=CN=C1N YRGMYJUKFJPNPD-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- JUOSGGQXEBBCJB-GORDUTHDSA-N rivanicline Chemical compound CNCC\C=C\C1=CC=CN=C1 JUOSGGQXEBBCJB-GORDUTHDSA-N 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZHZCYWWNFQUZOR-RXMQYKEDSA-N (2r)-pent-4-en-2-ol Chemical compound C[C@@H](O)CC=C ZHZCYWWNFQUZOR-RXMQYKEDSA-N 0.000 description 4
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 4
- KQSQZCCLUXPANQ-UHFFFAOYSA-N 2,3-dihydropyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2[N]CCC2=C1 KQSQZCCLUXPANQ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical compound C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- LCKIPSGLXMCAOF-UHFFFAOYSA-N dibenzyl 2,3-dihydroxybutanedioate Chemical compound C=1C=CC=CC=1COC(=O)C(O)C(O)C(=O)OCC1=CC=CC=C1 LCKIPSGLXMCAOF-UHFFFAOYSA-N 0.000 description 4
- 208000037765 diseases and disorders Diseases 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- CAWHJQAVHZEVTJ-UHFFFAOYSA-N methylpyrazine Chemical compound CC1=CN=CC=N1 CAWHJQAVHZEVTJ-UHFFFAOYSA-N 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- ZHZCYWWNFQUZOR-UHFFFAOYSA-N pent-4-en-2-ol Chemical compound CC(O)CC=C ZHZCYWWNFQUZOR-UHFFFAOYSA-N 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZUBFDFTWPBWMPD-UHFFFAOYSA-N tert-butyl n-methyl-n-(5-oxopentan-2-yl)carbamate Chemical compound O=CCCC(C)N(C)C(=O)OC(C)(C)C ZUBFDFTWPBWMPD-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- FILVIKOEJGORQS-UHFFFAOYSA-N 1,5-dimethylpyrrolidin-2-one Chemical compound CC1CCC(=O)N1C FILVIKOEJGORQS-UHFFFAOYSA-N 0.000 description 3
- IFMHNXABCSMTFF-UHFFFAOYSA-N 2,3-dihydrofuro[2,3-b]pyridine Chemical compound C1=CN=C2OCCC2=C1 IFMHNXABCSMTFF-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- FZWUIWQMJFAWJW-UHFFFAOYSA-N 3-bromo-5-methoxypyridine Chemical class COC1=CN=CC(Br)=C1 FZWUIWQMJFAWJW-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- KTXDLMQWUZXRPA-UHFFFAOYSA-N 5-bromo-2-methylpyridin-3-ol Chemical compound CC1=NC=C(Br)C=C1O KTXDLMQWUZXRPA-UHFFFAOYSA-N 0.000 description 3
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- 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
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/22—Anxiolytics
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Medicinal Preparation (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2006202005A AU2006202005B2 (en) | 2000-07-14 | 2006-05-12 | Pharmaceutical compositions for treating neurological disorders |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/616,743 US6432954B1 (en) | 2000-07-14 | 2000-07-14 | Pharmaceutical compositions and methods for use |
| US09/616,743 | 2000-07-14 | ||
| PCT/US2001/021872 WO2002005798A2 (en) | 2000-07-14 | 2001-07-11 | Pharmaceutical compositions for treating neurological disorders |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2006202005A Division AU2006202005B2 (en) | 2000-07-14 | 2006-05-12 | Pharmaceutical compositions for treating neurological disorders |
Publications (2)
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| AU2002222909A1 AU2002222909A1 (en) | 2002-05-02 |
| AU2002222909B2 true AU2002222909B2 (en) | 2005-12-15 |
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|---|---|---|---|
| AU2290902A Pending AU2290902A (en) | 2000-07-14 | 2001-07-11 | Pharmaceutical compositions and methods for use |
| AU2002222909A Ceased AU2002222909B2 (en) | 2000-07-14 | 2001-07-11 | Pharmaceutical compositions for treating neurological disorders |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2290902A Pending AU2290902A (en) | 2000-07-14 | 2001-07-11 | Pharmaceutical compositions and methods for use |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6432954B1 (enExample) |
| EP (1) | EP1311265B1 (enExample) |
| JP (1) | JP2004509851A (enExample) |
| CN (2) | CN1468100A (enExample) |
| AT (1) | ATE285773T1 (enExample) |
| AU (2) | AU2290902A (enExample) |
| BR (1) | BR0112130A (enExample) |
| CA (1) | CA2415901A1 (enExample) |
| DE (1) | DE60108130T2 (enExample) |
| HU (1) | HUP0301553A3 (enExample) |
| IL (3) | IL153577A0 (enExample) |
| NO (1) | NO20030155L (enExample) |
| NZ (1) | NZ523606A (enExample) |
| PL (1) | PL360532A1 (enExample) |
| WO (1) | WO2002005798A2 (enExample) |
| ZA (1) | ZA200300135B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6979695B2 (en) * | 1996-04-23 | 2005-12-27 | Targacept, Inc. | Compounds capable of activating cholinergic receptors |
| AU2005235414A1 (en) * | 2004-04-21 | 2005-11-03 | Basf Aktiengesellschaft | Fungicidal mixtures |
| UA88792C2 (ru) * | 2004-11-10 | 2009-11-25 | Таргасепт, Інк. | Гидроксибензоатные соли метаникотиновых соединений |
| US7459469B2 (en) | 2004-11-10 | 2008-12-02 | Targacept, Inc. | Hydroxybenzoate salts of metanicotine compounds |
| TWI389889B (zh) * | 2006-05-09 | 2013-03-21 | Targacept Inc | （２ｓ）-（４ｅ）-ｎ-甲基-５-〔３-（５-異丙氧基吡啶）基〕-４-戊烯-２-胺之新穎多晶型 |
| WO2007134038A2 (en) * | 2006-05-09 | 2007-11-22 | Astrazeneca Ab | Salt forms of (2s)-(4e)-n-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine |
| WO2008034041A2 (en) * | 2006-09-15 | 2008-03-20 | Astrazeneca Ab | Therapeutic combinations |
| US20100028447A1 (en) * | 2007-01-22 | 2010-02-04 | Targacept, Inc. | Intranasal, Buccal, And Sublingual Administration Of Metanicotine Analogs |
| KR20100052490A (ko) * | 2007-07-31 | 2010-05-19 | 타가셉트 인코포레이티드 | (2ｓ)-(4ｅ)-ｎ-메틸-5-(3-(5-이소프로폭시피리딘)일)-4-펜텐-2-아민의 경피투여 |
| JP2013528601A (ja) | 2010-05-20 | 2013-07-11 | アストラゼネカ・アクチエボラーグ | アリール置換オレフィン系アミンの新規な製造方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1409551A (en) | 1972-04-14 | 1975-10-08 | Allen & Hanburys Ltd | Cyclopent a indene derivatives |
| US4528290A (en) | 1984-01-30 | 1985-07-09 | Eli Lilly And Company | Stimulating dopamine D-1 receptors |
| GB8606254D0 (en) | 1986-03-13 | 1986-04-16 | Wyeth John & Brother Ltd | Substituted pyrimidoindoles |
| FR2664600B1 (fr) | 1990-07-16 | 1994-09-02 | Rhone Poulenc Sante | Nouveau sel derive de la dialcoylaminoalcoyl-sulfonyl-26 pristinamycine iib. |
| US5278176A (en) * | 1992-08-21 | 1994-01-11 | Abbott Laboratories | Nicotine derivatives that enhance cognitive function |
| AU3470495A (en) * | 1994-09-14 | 1996-03-29 | H. Lundbeck A/S | Carbamoyloxy amine compounds |
| US5597919A (en) * | 1995-01-06 | 1997-01-28 | Dull; Gary M. | Pyrimidinyl or Pyridinyl alkenyl amine compounds |
| US5616716A (en) * | 1996-01-06 | 1997-04-01 | Dull; Gary M. | (3-(5-ethoxypyridin)yl)-alkenyl 1 amine compounds |
| US5663356A (en) * | 1996-04-23 | 1997-09-02 | Ruecroft; Graham | Method for preparation of aryl substituted alefinic secondary amino compounds |
| JP3603177B2 (ja) * | 1998-03-26 | 2004-12-22 | 参天製薬株式会社 | 新規ウレア誘導体 |
| ES2150353B1 (es) * | 1998-04-15 | 2001-07-01 | Esteve Labor Dr | Tienilazolilalcoxietanaminas, su preparacion y su aplicacion como medicamentos. |
| DE69919537T2 (de) * | 1998-06-16 | 2005-09-08 | Targacept, Inc. | Arylsubstituierte olefinische amine und ihre verwendung als cholinergische rezeptoragonisten |
| DE10032456A1 (de) * | 2000-07-04 | 2002-01-31 | Lohmann Therapie Syst Lts | Schnell zerfallende Darreichungsform zur Freisetzung von Wirkstoffen im Mundraum oder in Körperhöhlen |
| US6743812B1 (en) * | 2000-07-14 | 2004-06-01 | Targacept, Inc. | Pharmaceutical compositions and methods for use |
-
2000
- 2000-07-14 US US09/616,743 patent/US6432954B1/en not_active Expired - Fee Related
-
2001
- 2001-07-11 WO PCT/US2001/021872 patent/WO2002005798A2/en not_active Ceased
- 2001-07-11 PL PL01360532A patent/PL360532A1/xx not_active Application Discontinuation
- 2001-07-11 DE DE60108130T patent/DE60108130T2/de not_active Expired - Fee Related
- 2001-07-11 CA CA002415901A patent/CA2415901A1/en not_active Abandoned
- 2001-07-11 JP JP2002511731A patent/JP2004509851A/ja active Pending
- 2001-07-11 HU HU0301553A patent/HUP0301553A3/hu unknown
- 2001-07-11 AU AU2290902A patent/AU2290902A/xx active Pending
- 2001-07-11 AT AT01984212T patent/ATE285773T1/de not_active IP Right Cessation
- 2001-07-11 CN CNA018127924A patent/CN1468100A/zh active Pending
- 2001-07-11 NZ NZ523606A patent/NZ523606A/xx unknown
- 2001-07-11 IL IL15357701A patent/IL153577A0/xx unknown
- 2001-07-11 BR BR0112130-8A patent/BR0112130A/pt not_active Application Discontinuation
- 2001-07-11 AU AU2002222909A patent/AU2002222909B2/en not_active Ceased
- 2001-07-11 EP EP01984212A patent/EP1311265B1/en not_active Expired - Lifetime
- 2001-07-11 CN CNA2005100541592A patent/CN1680326A/zh active Pending
-
2002
- 2002-12-22 IL IL153577A patent/IL153577A/en not_active IP Right Cessation
-
2003
- 2003-01-06 ZA ZA200300135A patent/ZA200300135B/en unknown
- 2003-01-13 NO NO20030155A patent/NO20030155L/no not_active Application Discontinuation
-
2008
- 2008-06-18 IL IL192287A patent/IL192287A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1468100A (zh) | 2004-01-14 |
| NO20030155D0 (no) | 2003-01-13 |
| DE60108130D1 (de) | 2005-02-03 |
| IL192287A0 (en) | 2008-12-29 |
| EP1311265A2 (en) | 2003-05-21 |
| BR0112130A (pt) | 2003-09-02 |
| WO2002005798A3 (en) | 2003-03-13 |
| WO2002005798A2 (en) | 2002-01-24 |
| ZA200300135B (en) | 2004-04-06 |
| ATE285773T1 (de) | 2005-01-15 |
| EP1311265B1 (en) | 2004-12-29 |
| PL360532A1 (en) | 2004-09-06 |
| IL153577A (en) | 2009-07-20 |
| US6432954B1 (en) | 2002-08-13 |
| IL153577A0 (en) | 2003-07-06 |
| NZ523606A (en) | 2004-12-24 |
| CA2415901A1 (en) | 2002-01-24 |
| JP2004509851A (ja) | 2004-04-02 |
| CN1680326A (zh) | 2005-10-12 |
| NO20030155L (no) | 2003-03-13 |
| HUP0301553A2 (hu) | 2003-08-28 |
| AU2290902A (en) | 2002-01-30 |
| HUP0301553A3 (en) | 2005-05-30 |
| DE60108130T2 (de) | 2006-02-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PC1 | Assignment before grant (sect. 113) |
Owner name: TARGACEPT, INC. Free format text: FORMER APPLICANT(S): TARGACEPT, INC.; AVENTIS PHARMA S.A. |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |