JP2002509918A - ムスカリン性レセプタに活性を有する化合物 - Google Patents
ムスカリン性レセプタに活性を有する化合物Info
- Publication number
- JP2002509918A JP2002509918A JP2000541152A JP2000541152A JP2002509918A JP 2002509918 A JP2002509918 A JP 2002509918A JP 2000541152 A JP2000541152 A JP 2000541152A JP 2000541152 A JP2000541152 A JP 2000541152A JP 2002509918 A JP2002509918 A JP 2002509918A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- alkoxy
- compound according
- butyl
- compound
- 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.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 161
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 title claims description 26
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 title claims description 26
- 230000000694 effects Effects 0.000 title abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 60
- 201000010099 disease Diseases 0.000 claims abstract description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 81
- 239000000203 mixture Substances 0.000 claims description 65
- 125000003545 alkoxy group Chemical group 0.000 claims description 56
- 229910052760 oxygen Inorganic materials 0.000 claims description 42
- 229910052717 sulfur Inorganic materials 0.000 claims description 40
- 102000005962 receptors Human genes 0.000 claims description 33
- 108020003175 receptors Proteins 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- 125000005842 heteroatom Chemical group 0.000 claims description 26
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 25
- -1 amino, hydroxyl Chemical group 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 239000000651 prodrug Substances 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 208000024891 symptom Diseases 0.000 claims description 10
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- 208000010877 cognitive disease Diseases 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims description 8
- 229960004373 acetylcholine Drugs 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- 208000028698 Cognitive impairment Diseases 0.000 claims description 6
- 208000010412 Glaucoma Diseases 0.000 claims description 6
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 6
- 230000004410 intraocular pressure Effects 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 230000007000 age related cognitive decline Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 15
- 239000000556 agonist Substances 0.000 abstract description 11
- 230000003551 muscarinic effect Effects 0.000 abstract description 9
- 102000007207 Muscarinic M1 Receptor Human genes 0.000 abstract description 6
- 108010008406 Muscarinic M1 Receptor Proteins 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 239000011541 reaction mixture Substances 0.000 description 50
- 239000000460 chlorine Substances 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 239000012074 organic phase Substances 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 22
- 239000012043 crude product Substances 0.000 description 21
- 239000003480 eluent Substances 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 239000012298 atmosphere Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- 235000002639 sodium chloride Nutrition 0.000 description 15
- 125000001475 halogen functional group Chemical group 0.000 description 13
- 239000011777 magnesium Substances 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 208000024827 Alzheimer disease Diseases 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 10
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- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 10
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- KKYBXEIOWOSNHO-UHFFFAOYSA-N 4-(4-butylpiperidin-1-yl)butanenitrile Chemical compound CCCCC1CCN(CCCC#N)CC1 KKYBXEIOWOSNHO-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- MBSMLILTBZYTAZ-UHFFFAOYSA-N 4-(4-butylpiperazin-1-yl)-1-(2-methylphenyl)butan-1-one Chemical compound C1CN(CCCC)CCN1CCCC(=O)C1=CC=CC=C1C MBSMLILTBZYTAZ-UHFFFAOYSA-N 0.000 description 7
- XIQSPCJCAJVNJL-UHFFFAOYSA-N 4-butylpiperidine Chemical compound CCCCC1CCNCC1 XIQSPCJCAJVNJL-UHFFFAOYSA-N 0.000 description 7
- 125000000304 alkynyl group Chemical group 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000003920 cognitive function Effects 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 7
- 229940126062 Compound A Drugs 0.000 description 6
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 6
- 244000309466 calf Species 0.000 description 6
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 6
- 238000012937 correction Methods 0.000 description 6
- 239000000472 muscarinic agonist Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 229960001685 tacrine Drugs 0.000 description 6
- HDPXEBDNEDLBGZ-UHFFFAOYSA-N 1-(2-methylphenyl)-4-(2-propylpiperidin-1-yl)butan-1-one Chemical compound CCCC1CCCCN1CCCC(=O)C1=CC=CC=C1C HDPXEBDNEDLBGZ-UHFFFAOYSA-N 0.000 description 5
- BBVKMUIEPLHMRV-UHFFFAOYSA-N 1-(2-methylphenyl)-4-(4-methylpiperazin-1-yl)butan-1-one Chemical compound C1CN(C)CCN1CCCC(=O)C1=CC=CC=C1C BBVKMUIEPLHMRV-UHFFFAOYSA-N 0.000 description 5
- RINOYHWVBUKAQE-UHFFFAOYSA-N 1-iodo-2-methylbenzene Chemical compound CC1=CC=CC=C1I RINOYHWVBUKAQE-UHFFFAOYSA-N 0.000 description 5
- HBIKLKXKMSHWDH-UHFFFAOYSA-N 4-(4-butylpiperidin-1-yl)-1-(2,4-dimethylphenyl)butan-1-one Chemical compound C1CC(CCCC)CCN1CCCC(=O)C1=CC=C(C)C=C1C HBIKLKXKMSHWDH-UHFFFAOYSA-N 0.000 description 5
- RZQQFTJRGWURNW-UHFFFAOYSA-N 4-(4-butylpiperidin-1-yl)-1-(2-hydroxyphenyl)butan-1-one Chemical compound C1CC(CCCC)CCN1CCCC(=O)C1=CC=CC=C1O RZQQFTJRGWURNW-UHFFFAOYSA-N 0.000 description 5
- ANTKBACNWQHQJE-UHFFFAOYSA-N 4-(4-butylpiperidin-1-yl)-1-(2-methylphenyl)butan-1-one Chemical compound C1CC(CCCC)CCN1CCCC(=O)C1=CC=CC=C1C ANTKBACNWQHQJE-UHFFFAOYSA-N 0.000 description 5
- HQDNDPUCYICAHZ-UHFFFAOYSA-N 4-(4-butylpiperidin-1-yl)-1-(2-phenylmethoxyphenyl)butan-1-one Chemical compound C1CC(CCCC)CCN1CCCC(=O)C1=CC=CC=C1OCC1=CC=CC=C1 HQDNDPUCYICAHZ-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 229930182555 Penicillin Natural products 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
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- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 4
- LAPWDCHUQSJIRB-UHFFFAOYSA-N 1-iodo-2-phenylmethoxybenzene Chemical compound IC1=CC=CC=C1OCC1=CC=CC=C1 LAPWDCHUQSJIRB-UHFFFAOYSA-N 0.000 description 4
- GSNZLQKOEZWAFU-UHFFFAOYSA-N 4-(2-propylpiperidin-1-yl)butanenitrile Chemical compound CCCC1CCCCN1CCCC#N GSNZLQKOEZWAFU-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/104—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/108—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8013398P | 1998-03-31 | 1998-03-31 | |
| US60/080,133 | 1998-03-31 | ||
| PCT/US1999/007057 WO1999050247A1 (en) | 1998-03-31 | 1999-03-31 | Compounds with activity on muscarinic receptors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002509918A true JP2002509918A (ja) | 2002-04-02 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000541152A Withdrawn JP2002509918A (ja) | 1998-03-31 | 1999-03-31 | ムスカリン性レセプタに活性を有する化合物 |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP1068185A1 (es) |
| JP (1) | JP2002509918A (es) |
| KR (2) | KR20060120715A (es) |
| CN (1) | CN1303376A (es) |
| AR (1) | AR014974A1 (es) |
| AU (1) | AU762726B2 (es) |
| BR (1) | BR9909277A (es) |
| CA (1) | CA2326804C (es) |
| MX (1) | MXPA00009569A (es) |
| NO (1) | NO319835B1 (es) |
| NZ (2) | NZ525108A (es) |
| RU (2) | RU2230740C2 (es) |
| WO (1) | WO1999050247A1 (es) |
| ZA (1) | ZA200005149B (es) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007501254A (ja) * | 2003-08-05 | 2007-01-25 | サマリタン,ファーマスーティカルス,インク. | アセチルコリンエステラーゼ阻害特性を有する、シグマ‐1受容体配位子 |
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| US6528529B1 (en) | 1998-03-31 | 2003-03-04 | Acadia Pharmaceuticals Inc. | Compounds with activity on muscarinic receptors |
| US6624162B2 (en) | 2001-10-22 | 2003-09-23 | Pfizer Inc. | Imidazopyridine compounds as 5-HT4 receptor modulators |
| US7550459B2 (en) | 2001-12-28 | 2009-06-23 | Acadia Pharmaceuticals, Inc. | Tetrahydroquinoline analogues as muscarinic agonists |
| DE60206198T2 (de) | 2001-12-28 | 2006-06-14 | Acadia Pharm Inc | Tetrahydrochinolinderivate als muscarinische agonisten |
| MXPA03000145A (es) | 2002-01-07 | 2003-07-15 | Pfizer | Compuestos de oxo u oxi-piridina como moduladores de receptores 5-ht4. |
| GB0211230D0 (en) | 2002-05-16 | 2002-06-26 | Medinnova Sf | Treatment of heart failure |
| CA2499494A1 (en) | 2002-09-20 | 2004-04-01 | Pfizer Inc. | N-substituted piperidinyl-imidazopyridine compounds as 5-ht4 receptor modulators |
| DOP2003000703A (es) | 2002-09-20 | 2004-03-31 | Pfizer | Compuestos de imidazopiradina como agonistas del receptor 5-ht4 |
| HU227534B1 (en) | 2003-08-04 | 2011-08-29 | Richter Gedeon Nyrt | (thio)carbamoyl-cyclohexane derivatives, process for producing them and pharmaceutical compositions containing them |
| EP1669348A4 (en) | 2003-09-30 | 2009-03-11 | Eisai R&D Man Co Ltd | NEW ANTIPILIC AGENT CONTAINING A HETEROCYCLIC COMPOUND |
| CA2550735A1 (en) | 2003-12-22 | 2005-07-14 | Acadia Pharmaceuticals Inc. | Amino substituted diaryl[a,d]cycloheptene analogs as muscarinic agonists and methods of treatment of neuropsychiatric disorders |
| AP2006003771A0 (en) | 2004-04-30 | 2006-10-31 | Warner Lambert Co | Substituted morpholine compounds for the treatmentof central nervous system disorders |
| EP1758891A2 (en) | 2004-06-15 | 2007-03-07 | Pfizer Japan Inc. | Benzimidazolone carboxylic acid derivatives |
| US7737163B2 (en) | 2004-06-15 | 2010-06-15 | Pfizer Inc. | Benzimidazolone carboxylic acid derivatives |
| US20080275028A1 (en) * | 2004-07-20 | 2008-11-06 | Giovanni Gaviraghi | Modulators or Alpha7 Nicotinic Acetylcholine Receptors and Therapeutic Uses Thereof |
| EP1833819A1 (en) | 2004-12-30 | 2007-09-19 | Astex Therapeutics Limited | Pyrazole compounds that modulate the activity of cdk, gsk and aurora kinases |
| EA012589B1 (ru) | 2004-12-30 | 2009-10-30 | Янссен Фармацевтика Н.В. | Производные фениламида 4-(бензил)пиперазин-1-карбоновой кислоты и родственные соединения в качестве модуляторов амида жирной кислоты гидролазы для лечения страхов, боли и других состояний |
| WO2006106711A1 (ja) | 2005-03-30 | 2006-10-12 | Eisai R & D Management Co., Ltd. | ピリジン誘導体を含有する抗真菌剤 |
| JP4324221B2 (ja) | 2005-08-26 | 2009-09-02 | 株式会社医薬分子設計研究所 | Pparアゴニスト活性を有する誘導体 |
| EP1928437A2 (en) | 2005-08-26 | 2008-06-11 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| TWI385169B (zh) | 2005-10-31 | 2013-02-11 | Eisai R&D Man Co Ltd | 經雜環取代之吡啶衍生物及含有彼之抗真菌劑 |
| US8399442B2 (en) | 2005-12-30 | 2013-03-19 | Astex Therapeutics Limited | Pharmaceutical compounds |
| US8435970B2 (en) | 2006-06-29 | 2013-05-07 | Astex Therapeutics Limited | Pharmaceutical combinations of 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea |
| TW200901974A (en) | 2007-01-16 | 2009-01-16 | Wyeth Corp | Compounds, compositions, and methods of making and using them |
| HUP0700353A2 (en) | 2007-05-18 | 2008-12-29 | Richter Gedeon Nyrt | Metabolites of (thio)carbamoyl-cyclohexane derivatives |
| US7875610B2 (en) | 2007-12-03 | 2011-01-25 | Richter Gedeon Nyrt. | Pyrimidinyl-piperazines useful as D3/D2 receptor ligands |
| US8513287B2 (en) | 2007-12-27 | 2013-08-20 | Eisai R&D Management Co., Ltd. | Heterocyclic ring and phosphonoxymethyl group substituted pyridine derivatives and antifungal agent containing same |
| RS53866B1 (sr) | 2008-07-16 | 2015-08-31 | Richter Gedeon Nyrt. | Farmaceutske formulacije koje sadrže ligande dopaminskih receptora |
| HU230067B1 (hu) | 2008-12-17 | 2015-06-29 | Richter Gedeon Nyrt | Új piperazin só és eljárás előállítására |
| HUP0800765A2 (en) | 2008-12-18 | 2010-11-29 | Richter Gedeon Nyrt | A new process for the preparation of piperazine derivatives and their hydrochloric salts |
| HUP0800766A2 (en) | 2008-12-18 | 2010-11-29 | Richter Gedeon Vegyeszet | Process for the preparation of piperazine derivatives |
| UA108233C2 (uk) | 2010-05-03 | 2015-04-10 | Модулятори активності гідролази амідів жирних кислот | |
| GB201106817D0 (en) | 2011-04-21 | 2011-06-01 | Astex Therapeutics Ltd | New compound |
| CN102558026A (zh) * | 2011-12-27 | 2012-07-11 | 盛世泰科生物医药技术(苏州)有限公司 | 关于4-n-丁基-1-[4-(2-甲基苯基)-4-酮-1-丁基]哌啶的合成及工艺优化 |
| US8912197B2 (en) | 2012-08-20 | 2014-12-16 | Forest Laboratories Holdings Ltd. | Crystalline form of carbamoyl-cyclohexane derivatives |
| CN102997438A (zh) * | 2012-10-16 | 2013-03-27 | 李誊 | 改善热量利用率的电热水器控制方法 |
| US9980973B2 (en) | 2012-10-19 | 2018-05-29 | Astex Therapeutics Limited | Bicyclic heterocycle compounds and their uses in therapy |
| GB201218864D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
| GB201218862D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
| GB201218850D0 (en) | 2012-10-19 | 2012-12-05 | Astex Therapeutics Ltd | Bicyclic heterocycle compounds and their uses in therapy |
| BR112015021985B1 (pt) | 2013-03-15 | 2022-12-13 | Global Blood Therapeutics, Inc | Compostos ou sais farmaceuticamente aceitáveis dos mesmos, respectivos usos e composição |
| EA202092627A1 (ru) | 2013-11-18 | 2021-09-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| PL3083616T3 (pl) | 2013-12-20 | 2021-12-06 | Astex Therapeutics Limited | Bicykliczne związki heterocykliczne i ich zastosowania w terapii |
| US11274087B2 (en) | 2016-07-08 | 2022-03-15 | Richter Gedeon Nyrt. | Industrial process for the preparation of cariprazine |
| EP4092013A1 (en) | 2017-06-20 | 2022-11-23 | Imbria Pharmaceuticals, Inc. | Compositions and methods for increasing efficiency of cardiac metabolism |
| EP3866794B1 (en) | 2018-10-17 | 2024-12-04 | Imbria Pharmaceuticals, Inc. | Methods of treating rheumatic diseases using trimetazidine-based compounds |
| US11547707B2 (en) | 2019-04-10 | 2023-01-10 | Richter Gedeon Nyrt. | Carbamoyl cyclohexane derivatives for treating autism spectrum disorder |
| US11530184B2 (en) | 2020-06-30 | 2022-12-20 | Imbria Pharmaceuticals, Inc. | Crystal forms of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11780811B2 (en) | 2020-06-30 | 2023-10-10 | Imbria Pharmaceuticals, Inc. | Methods of synthesizing 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11883396B2 (en) | 2021-05-03 | 2024-01-30 | Imbria Pharmaceuticals, Inc. | Methods of treating kidney conditions using modified forms of trimetazidine |
| CN117224508A (zh) * | 2023-10-17 | 2023-12-15 | 中国农业科学院农产品加工研究所 | 一种多层包埋槟榔碱缓释系统及其制备方法和应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US2695295A (en) * | 1952-12-19 | 1954-11-23 | Mcneilab Inc | Unsymmetrical n, n'-substituted ethylenediamine and piperazine compounds |
| GB874206A (en) * | 1956-09-05 | 1961-08-02 | Knoll Ag | Basic derivatives of salicylamide |
| BE610830A (es) * | 1960-12-01 | |||
| GB1053301A (es) * | 1963-01-14 | |||
| FR1382425A (fr) * | 1963-01-14 | 1964-12-18 | Ciba Geigy | Procédé de préparation de diaza-cyclo-alcanes, entre autres de la 3-méthyl-4-phényl-1-(2-phénylmercapto-éthyl)-pipérazine |
| US3488352A (en) * | 1966-10-11 | 1970-01-06 | Shulton Inc | Basically substituted alkoxy anthranilamides,their corresponding 2-nitro compounds and derivatives thereof |
| FR1543944A (fr) * | 1967-03-10 | 1968-10-31 | Bruneau & Cie Lab | Dérivés amidés de l'acide salicylique et leur préparation |
| DE2335432A1 (de) * | 1973-07-12 | 1975-01-30 | Boehringer Mannheim Gmbh | 3,4-dihydro-2h-naphthalinon-(1)5-oxy-propyl-piperazin-derivate und verfahren zu ihrer herstellung |
| BE792187A (fr) * | 1971-12-03 | 1973-03-30 | Sumitomo Chemical Co | Nouveaux derives d'alkylamines |
| GB1459506A (en) * | 1974-02-18 | 1976-12-22 | Wyeth John & Brother Ltd | Piperidine derivatives |
| GB1498884A (en) * | 1975-04-15 | 1978-01-25 | Wyeth John & Brother Ltd | Aminoacetamide-pyridyl-tetrahydropyridyl and-piperidyl derivatives |
| US5889006A (en) * | 1995-02-23 | 1999-03-30 | Schering Corporation | Muscarinic antagonists |
| IL117149A0 (en) * | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| HUP9904363A3 (en) * | 1996-08-15 | 2000-12-28 | Schering Corp | Piperidine ether muscarinic antagonists and pharmaceutical compositions containing them |
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1999
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- 1999-03-31 EP EP99914306A patent/EP1068185A1/en not_active Withdrawn
- 1999-03-31 JP JP2000541152A patent/JP2002509918A/ja not_active Withdrawn
- 1999-03-31 AU AU32187/99A patent/AU762726B2/en not_active Ceased
- 1999-03-31 RU RU2000127105/04A patent/RU2230740C2/ru active
- 1999-03-31 NZ NZ525108A patent/NZ525108A/en unknown
- 1999-03-31 WO PCT/US1999/007057 patent/WO1999050247A1/en not_active Ceased
- 1999-03-31 BR BR9909277-8A patent/BR9909277A/pt not_active Application Discontinuation
- 1999-03-31 CA CA002326804A patent/CA2326804C/en not_active Expired - Fee Related
- 1999-03-31 KR KR1020067023572A patent/KR20060120715A/ko not_active Ceased
- 1999-03-31 CN CN99806618A patent/CN1303376A/zh active Pending
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2000
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- 2000-09-29 NO NO20004912A patent/NO319835B1/no unknown
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2004
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007501254A (ja) * | 2003-08-05 | 2007-01-25 | サマリタン,ファーマスーティカルス,インク. | アセチルコリンエステラーゼ阻害特性を有する、シグマ‐1受容体配位子 |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ507204A (en) | 2003-12-19 |
| CA2326804A1 (en) | 1999-10-07 |
| AU762726B2 (en) | 2003-07-03 |
| KR100672186B1 (ko) | 2007-01-19 |
| WO1999050247A1 (en) | 1999-10-07 |
| EP1068185A1 (en) | 2001-01-17 |
| KR20060120715A (ko) | 2006-11-27 |
| KR20010042248A (ko) | 2001-05-25 |
| BR9909277A (pt) | 2001-10-16 |
| CA2326804C (en) | 2006-05-02 |
| AU3218799A (en) | 1999-10-18 |
| MXPA00009569A (es) | 2002-08-06 |
| RU2004107218A (ru) | 2005-08-20 |
| RU2230740C2 (ru) | 2004-06-20 |
| NO20004912D0 (no) | 2000-09-29 |
| NO20004912L (no) | 2000-11-23 |
| CN1303376A (zh) | 2001-07-11 |
| RU2278111C2 (ru) | 2006-06-20 |
| NO319835B1 (no) | 2005-09-19 |
| AR014974A1 (es) | 2001-04-11 |
| ZA200005149B (en) | 2002-01-08 |
| NZ525108A (en) | 2005-02-25 |
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