TW200530222A - Quinazolinone and benzoxazinone derivatives and uses thereof - Google Patents

Info

Publication number

TW200530222A

TW200530222A TW094101029A TW94101029A TW200530222A TW 200530222 A TW200530222 A TW 200530222A TW 094101029 A TW094101029 A TW 094101029A TW 94101029 A TW94101029 A TW 94101029A TW 200530222 A TW200530222 A TW 200530222A

Authority

TW

Taiwan

Prior art keywords

compound

benzyl

dihydro

piperin

alkyl

Prior art date

2004-01-16

Links

• Espacenet
• Global Dossier
• Discuss

• AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title abstract description 7
• HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical class C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 210
• -1 amidoalkyl Chemical group 0.000 claims abstract description 184
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 94
• 239000001257 hydrogen Substances 0.000 claims abstract description 84
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 84
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 52
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 39
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 38
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 34
• 201000010099 disease Diseases 0.000 claims abstract description 28
• 150000003839 salts Chemical class 0.000 claims abstract description 27
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 21
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
• 229910052701 rubidium Inorganic materials 0.000 claims abstract description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
• 208000035475 disorder Diseases 0.000 claims abstract description 6
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
• 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 5
• 208000023105 Huntington disease Diseases 0.000 claims abstract description 4
• 208000018737 Parkinson disease Diseases 0.000 claims abstract description 4
• 208000026139 Memory disease Diseases 0.000 claims abstract description 3
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 3
• 208000012902 Nervous system disease Diseases 0.000 claims abstract 2
• 208000025966 Neurological disease Diseases 0.000 claims abstract 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract 2
• 238000000034 method Methods 0.000 claims description 45
• 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 27
• 125000005843 halogen group Chemical group 0.000 claims description 26
• 125000003545 alkoxy group Chemical group 0.000 claims description 25
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
• 239000007789 gas Substances 0.000 claims description 23
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 20
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 239000011737 fluorine Substances 0.000 claims description 15
• 229910052731 fluorine Inorganic materials 0.000 claims description 15
• 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 14
• 125000001188 haloalkyl group Chemical group 0.000 claims description 14
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• 239000000460 chlorine Substances 0.000 claims description 12
• 150000002576 ketones Chemical class 0.000 claims description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 11
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
• 125000004429 atom Chemical group 0.000 claims description 10
• BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 claims description 10
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
• 230000015572 biosynthetic process Effects 0.000 claims description 9
• 239000004305 biphenyl Substances 0.000 claims description 9
• 229910052801 chlorine Inorganic materials 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 239000000126 substance Substances 0.000 claims description 9
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000001153 fluoro group Chemical group F* 0.000 claims description 7
• CZPWVGJYEJSRLH-UHFFFAOYSA-O hydron;pyrimidine Chemical compound C1=CN=C[NH+]=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-O 0.000 claims description 7
• 125000001624 naphthyl group Chemical group 0.000 claims description 7
• 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 5
• 125000000304 alkynyl group Chemical group 0.000 claims description 5
• 125000005605 benzo group Chemical group 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 claims description 5
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 5
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 5
• 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 4
• 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 125000002947 alkylene group Chemical group 0.000 claims description 4
• 235000010290 biphenyl Nutrition 0.000 claims description 4
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
• 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 3
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
• 239000010949 copper Substances 0.000 claims description 3
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 3
• 125000004175 fluorobenzyl group Chemical group 0.000 claims description 3
• 125000000524 functional group Chemical group 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 101100074846 Caenorhabditis elegans lin-2 gene Proteins 0.000 claims description 2
• 101100497386 Mus musculus Cask gene Proteins 0.000 claims description 2
• 208000034189 Sclerosis Diseases 0.000 claims description 2
• 229910052802 copper Inorganic materials 0.000 claims description 2
• 229910052698 phosphorus Inorganic materials 0.000 claims description 2
• 208000020016 psychiatric disease Diseases 0.000 claims description 2
• 210000000278 spinal cord Anatomy 0.000 claims description 2
• 208000024891 symptom Diseases 0.000 claims description 2
• GKEUODMJRFDLJY-UHFFFAOYSA-N 1-Methylfluorene Chemical compound C12=CC=CC=C2CC2=C1C=CC=C2C GKEUODMJRFDLJY-UHFFFAOYSA-N 0.000 claims 1
• 125000006508 2,6-difluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C(F)=C1[H])C([H])([H])* 0.000 claims 1
• 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims 1
• UAEMLKAEMJIUKO-UHFFFAOYSA-N 6-(2-phenylethenyl)cyclohexa-2,4-dien-1-one Chemical compound C1(C(C=CC=C1)=O)C=CC1=CC=CC=C1 UAEMLKAEMJIUKO-UHFFFAOYSA-N 0.000 claims 1
• 229920000877 Melamine resin Polymers 0.000 claims 1
• 125000004103 aminoalkyl group Chemical group 0.000 claims 1
• 125000006267 biphenyl group Chemical group 0.000 claims 1
• 208000015114 central nervous system disease Diseases 0.000 claims 1
• 230000000739 chaotic effect Effects 0.000 claims 1
• 230000006735 deficit Effects 0.000 claims 1
• 230000037406 food intake Effects 0.000 claims 1
• 235000012631 food intake Nutrition 0.000 claims 1
• 150000002366 halogen compounds Chemical class 0.000 claims 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
• JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 claims 1
• 125000006178 methyl benzyl group Chemical group 0.000 claims 1
• 230000001114 myogenic effect Effects 0.000 claims 1
• UFZNZKGKBWOSJG-UHFFFAOYSA-N purin-2-one Chemical compound O=C1N=CC2=NC=NC2=N1 UFZNZKGKBWOSJG-UHFFFAOYSA-N 0.000 claims 1
• RONWGALEIBILOG-VMJVVOMYSA-N quinine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 RONWGALEIBILOG-VMJVVOMYSA-N 0.000 claims 1
• 125000003118 aryl group Chemical group 0.000 abstract description 21
• 229910052799 carbon Inorganic materials 0.000 abstract description 17
• 125000001424 substituent group Chemical group 0.000 abstract description 9
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• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 abstract description 5
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• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
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• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 abstract 1
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