JP2004520299A - スピロ［イソベンゾフラン−１，４’−ピペリジン］−３−オン類及び３ｈ−スピロイソベンゾフラン−１，４’−ピペリジン類 - Google Patents
スピロ［イソベンゾフラン−１，４’−ピペリジン］−３−オン類及び３ｈ−スピロイソベンゾフラン−１，４’−ピペリジン類 Download PDFInfo
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- JP2004520299A JP2004520299A JP2002549683A JP2002549683A JP2004520299A JP 2004520299 A JP2004520299 A JP 2004520299A JP 2002549683 A JP2002549683 A JP 2002549683A JP 2002549683 A JP2002549683 A JP 2002549683A JP 2004520299 A JP2004520299 A JP 2004520299A
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- alkyl
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- halogen
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- alkoxy
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- RNMPNVBLQHYANU-UHFFFAOYSA-N spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical class C12=CC=CC=C2C(=O)OC21CCNCC2 RNMPNVBLQHYANU-UHFFFAOYSA-N 0.000 title abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 240
- 102000028582 Neuropeptide Y5 receptor Human genes 0.000 claims abstract description 132
- 108010046593 Neuropeptide Y5 receptor Proteins 0.000 claims abstract description 132
- 238000000034 method Methods 0.000 claims abstract description 56
- 230000027455 binding Effects 0.000 claims abstract description 48
- 238000009739 binding Methods 0.000 claims abstract description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 239000003446 ligand Substances 0.000 claims abstract description 19
- 238000000338 in vitro Methods 0.000 claims abstract description 17
- 208000030814 Eating disease Diseases 0.000 claims abstract description 13
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 13
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 13
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 11
- 238000001514 detection method Methods 0.000 claims abstract description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 9
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 181
- 229910052736 halogen Inorganic materials 0.000 claims description 122
- 150000002367 halogens Chemical class 0.000 claims description 119
- -1 hydroxy, amino Chemical group 0.000 claims description 111
- 229910052739 hydrogen Inorganic materials 0.000 claims description 93
- 239000001257 hydrogen Substances 0.000 claims description 93
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 87
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 78
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 75
- 125000001424 substituent group Chemical group 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 65
- 101710151321 Melanostatin Proteins 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 62
- 125000000623 heterocyclic group Chemical group 0.000 claims description 58
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 52
- 150000002431 hydrogen Chemical class 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 48
- 125000002837 carbocyclic group Chemical group 0.000 claims description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 43
- 102000005962 receptors Human genes 0.000 claims description 43
- 108020003175 receptors Proteins 0.000 claims description 43
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000003342 alkenyl group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 101100460788 Arabidopsis thaliana NPY5 gene Proteins 0.000 claims description 22
- 101150111774 NPY5R gene Proteins 0.000 claims description 22
- 229910052720 vanadium Inorganic materials 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 208000035475 disorder Diseases 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 19
- 229910052721 tungsten Inorganic materials 0.000 claims description 18
- 239000000651 prodrug Substances 0.000 claims description 16
- 229940002612 prodrug Drugs 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000001544 thienyl group Chemical group 0.000 claims description 16
- 229910052727 yttrium Inorganic materials 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 14
- 125000002971 oxazolyl group Chemical group 0.000 claims description 14
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 14
- 125000000335 thiazolyl group Chemical group 0.000 claims description 14
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 230000004913 activation Effects 0.000 claims description 12
- 229940075993 receptor modulator Drugs 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000004193 piperazinyl group Chemical group 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 238000000159 protein binding assay Methods 0.000 claims description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 7
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- FAGMFPJUDWIQNI-UHFFFAOYSA-N 4-[[(3-oxospiro[2-benzofuran-1,4'-piperidine]-1'-carbonyl)amino]methyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1CNC(=O)N1CCC2(C3=CC=CC=C3C(=O)O2)CC1 FAGMFPJUDWIQNI-UHFFFAOYSA-N 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- ZETIZXFYVDSTGO-UHFFFAOYSA-N 1'-(5-phenyl-3h-imidazo[4,5-b]pyrazin-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound C12=CC=CC=C2C(=O)OC1(CC1)CCN1C(NC1=NC=2)=NC1=NC=2C1=CC=CC=C1 ZETIZXFYVDSTGO-UHFFFAOYSA-N 0.000 claims description 5
- IRDOMFKPNLFWGW-UHFFFAOYSA-N 1'-(6-methyl-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(C)=CC=C2N1 IRDOMFKPNLFWGW-UHFFFAOYSA-N 0.000 claims description 5
- JIVDRBRZFUEQBM-UHFFFAOYSA-N 1'-(6-pyridin-3-yl-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound C12=CC=CC=C2C(=O)OC1(CC1)CCN1C(NC1=CC=2)=NC1=CC=2C1=CC=CN=C1 JIVDRBRZFUEQBM-UHFFFAOYSA-N 0.000 claims description 5
- RQMKJTJDJCTLMI-UHFFFAOYSA-N 1'-[6-(1,3-oxazol-2-yl)-1h-benzimidazol-2-yl]spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound C12=CC=CC=C2C(=O)OC1(CC1)CCN1C(NC1=CC=2)=NC1=CC=2C1=NC=CO1 RQMKJTJDJCTLMI-UHFFFAOYSA-N 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims 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 claims description 5
- QCYXSEHOIKPNEU-UHFFFAOYSA-N 1'-(1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound C12=CC=CC=C2C(=O)OC11CCN(C=2NC3=CC=CC=C3N=2)CC1 QCYXSEHOIKPNEU-UHFFFAOYSA-N 0.000 claims description 4
- CLDMDFGJPGYXPI-UHFFFAOYSA-N 1'-(6-acetyl-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(C(=O)C)=CC=C2N1 CLDMDFGJPGYXPI-UHFFFAOYSA-N 0.000 claims description 4
- LPOLBQTZZHSRGO-UHFFFAOYSA-N 1'-(6-propylsulfonyl-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(S(=O)(=O)CCC)=CC=C2N1 LPOLBQTZZHSRGO-UHFFFAOYSA-N 0.000 claims description 4
- FGCDLQZYHPYSSV-UHFFFAOYSA-N 1'-[6-(trifluoromethylsulfonyl)-1h-benzimidazol-2-yl]spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(S(=O)(=O)C(F)(F)F)=CC=C2N1 FGCDLQZYHPYSSV-UHFFFAOYSA-N 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 4
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- QGOAHRMVFCYWPZ-UHFFFAOYSA-N 1'-(5,6-difluoro-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC(C=C(C(=C2)F)F)=C2N1 QGOAHRMVFCYWPZ-UHFFFAOYSA-N 0.000 claims description 3
- MYGKOPZLGWXONJ-UHFFFAOYSA-N 1'-(6-benzoyl-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound C=1C=C2NC(N3CCC4(CC3)C3=CC=CC=C3C(=O)O4)=NC2=CC=1C(=O)C1=CC=CC=C1 MYGKOPZLGWXONJ-UHFFFAOYSA-N 0.000 claims description 3
- ZMIPLTFCRFYPCJ-UHFFFAOYSA-N 1'-(6-chloro-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(Cl)=CC=C2N1 ZMIPLTFCRFYPCJ-UHFFFAOYSA-N 0.000 claims description 3
- QNXVMYVJXUTGAH-UHFFFAOYSA-N 1'-(6-fluoro-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(F)=CC=C2N1 QNXVMYVJXUTGAH-UHFFFAOYSA-N 0.000 claims description 3
- APXYPHDCNPEEPO-UHFFFAOYSA-N 1'-(6-iodo-4-oxo-1h-quinazolin-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC(=O)C2=CC(I)=CC=C2N1 APXYPHDCNPEEPO-UHFFFAOYSA-N 0.000 claims description 3
- BFRHFFHUPOVDTN-UHFFFAOYSA-N 1'-(6-methoxy-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(OC)=CC=C2N1 BFRHFFHUPOVDTN-UHFFFAOYSA-N 0.000 claims description 3
- JNDLYOIUCCIUON-UHFFFAOYSA-N 1'-(6-pyrazin-2-yl-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound C12=CC=CC=C2C(=O)OC1(CC1)CCN1C(NC1=CC=2)=NC1=CC=2C1=CN=CC=N1 JNDLYOIUCCIUON-UHFFFAOYSA-N 0.000 claims description 3
- PUGBOUNLKDOYBK-UHFFFAOYSA-N 1'-[6-(3,5-dimethyl-1,2-oxazol-4-yl)-1h-benzimidazol-2-yl]spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound CC1=NOC(C)=C1C1=CC=C(NC(=N2)N3CCC4(CC3)C3=CC=CC=C3C(=O)O4)C2=C1 PUGBOUNLKDOYBK-UHFFFAOYSA-N 0.000 claims description 3
- XWCWKHBTXAFSRD-UHFFFAOYSA-N 2-(3-oxospiro[2-benzofuran-1,4'-piperidine]-1'-yl)-3h-benzimidazole-5-carbonitrile Chemical compound C12=CC=CC=C2C(=O)OC11CCN(C=2NC3=CC=C(C=C3N=2)C#N)CC1 XWCWKHBTXAFSRD-UHFFFAOYSA-N 0.000 claims description 3
- XVMIZJDINZCQRH-UHFFFAOYSA-N C1=CN=C2NC=NC2=C1.C12=CC=CC=C2C(=O)OC21CCNCC2 Chemical compound C1=CN=C2NC=NC2=C1.C12=CC=CC=C2C(=O)OC21CCNCC2 XVMIZJDINZCQRH-UHFFFAOYSA-N 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 230000008485 antagonism Effects 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 3
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 3
- FSMWTPVKAMLPSN-UHFFFAOYSA-N 1'-(4,6-dichloro-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(Cl)=CC(Cl)=C2N1 FSMWTPVKAMLPSN-UHFFFAOYSA-N 0.000 claims description 2
- PMRYRRQZWAWPNO-UHFFFAOYSA-N 1'-(4-chloro-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC(C=CC=C2Cl)=C2N1 PMRYRRQZWAWPNO-UHFFFAOYSA-N 0.000 claims description 2
- PYRWXXAHWYRCJZ-UHFFFAOYSA-N 1'-(5,6-dimethoxy-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC(C=C(C(=C2)OC)OC)=C2N1 PYRWXXAHWYRCJZ-UHFFFAOYSA-N 0.000 claims description 2
- GOSQWFMKXKORBV-UHFFFAOYSA-N 1'-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(C(F)(F)F)=CC=C2N1 GOSQWFMKXKORBV-UHFFFAOYSA-N 0.000 claims description 2
- UFUKIJYVRWRXGP-UHFFFAOYSA-N 2-(3-oxospiro[2-benzofuran-1,4'-piperidine]-1'-yl)-3h-benzimidazole-5-carboxylic acid Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(C(=O)O)=CC=C2N1 UFUKIJYVRWRXGP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 150000001924 cycloalkanes Chemical class 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- LOFHXKUHUMVONQ-UHFFFAOYSA-N n-cyclohexyl-3-oxospiro[2-benzofuran-1,4'-piperidine]-1'-carboxamide Chemical compound C1CC2(C3=CC=CC=C3C(=O)O2)CCN1C(=O)NC1CCCCC1 LOFHXKUHUMVONQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 238000002601 radiography Methods 0.000 claims description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 17
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 15
- 125000001475 halogen functional group Chemical group 0.000 claims 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 4
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 4
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims 3
- 125000006655 (C3-C8) heteroaryl group Chemical group 0.000 claims 3
- 208000020016 psychiatric disease Diseases 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- UJHHJWQXFSURDR-UHFFFAOYSA-N 1'-(6-ethoxy-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(OCC)=CC=C2N1 UJHHJWQXFSURDR-UHFFFAOYSA-N 0.000 claims 1
- OOFZXDNGMLQFMR-UHFFFAOYSA-N 1'-(6-methylsulfonyl-1h-benzimidazol-2-yl)spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(S(=O)(=O)C)=CC=C2N1 OOFZXDNGMLQFMR-UHFFFAOYSA-N 0.000 claims 1
- VDEGUCQDJLBHGP-UHFFFAOYSA-N 1'-[6-(trifluoromethoxy)-1h-benzimidazol-2-yl]spiro[2-benzofuran-3,4'-piperidine]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C1(CC1)CCN1C1=NC2=CC(OC(F)(F)F)=CC=C2N1 VDEGUCQDJLBHGP-UHFFFAOYSA-N 0.000 claims 1
- 230000008484 agonism Effects 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
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- 230000004043 responsiveness Effects 0.000 claims 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- 102400000064 Neuropeptide Y Human genes 0.000 description 58
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- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- BYOIMOJOKVUNTP-UHFFFAOYSA-N spiro[1h-2-benzofuran-3,4'-piperidine] Chemical compound C12=CC=CC=C2COC21CCNCC2 BYOIMOJOKVUNTP-UHFFFAOYSA-N 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D487/04—Ortho-condensed systems
-
- 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
- A61P25/18—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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25499000P | 2000-12-12 | 2000-12-12 | |
| PCT/US2001/047863 WO2002048152A2 (en) | 2000-12-12 | 2001-12-11 | Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004520299A true JP2004520299A (ja) | 2004-07-08 |
| JP2004520299A5 JP2004520299A5 (enExample) | 2005-12-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002549683A Pending JP2004520299A (ja) | 2000-12-12 | 2001-12-11 | スピロ［イソベンゾフラン−１，４’−ピペリジン］−３−オン類及び３ｈ−スピロイソベンゾフラン−１，４’−ピペリジン類 |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US6566367B2 (enExample) |
| EP (1) | EP1347982B1 (enExample) |
| JP (1) | JP2004520299A (enExample) |
| AT (1) | ATE310004T1 (enExample) |
| AU (1) | AU2002220276A1 (enExample) |
| BR (1) | BR0116113A (enExample) |
| DE (1) | DE60115092T2 (enExample) |
| ES (1) | ES2249384T3 (enExample) |
| MX (1) | MXPA03004245A (enExample) |
| WO (1) | WO2002048152A2 (enExample) |
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| JP2005530760A (ja) * | 2002-05-03 | 2005-10-13 | エクセリクシス， インク． | プロテインキナーゼモジュレーターおよびその使用方法 |
| JP2008521825A (ja) * | 2004-11-29 | 2008-06-26 | バーテックス ファーマシューティカルズ インコーポレイテッド | ムスカリン受容体のモジュレーター |
| JP2009506979A (ja) * | 2005-09-02 | 2009-02-19 | アステラス製薬株式会社 | 新規化合物 |
| WO2020004594A1 (ja) * | 2018-06-27 | 2020-01-02 | 株式会社リボルナバイオサイエンス | 脊髄性筋萎縮症の予防または治療剤 |
| JP2020505340A (ja) * | 2017-01-10 | 2020-02-20 | イーティーエイチ・チューリッヒ | 細胞保護化合物及びそれらの使用 |
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- 2001-12-11 DE DE60115092T patent/DE60115092T2/de not_active Expired - Fee Related
- 2001-12-11 US US10/013,846 patent/US6566367B2/en not_active Expired - Fee Related
- 2001-12-11 AT AT01270536T patent/ATE310004T1/de not_active IP Right Cessation
- 2001-12-11 JP JP2002549683A patent/JP2004520299A/ja active Pending
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| US12012410B2 (en) | 2018-06-27 | 2024-06-18 | Reborna Biosciences, Inc. | Substituted pyrazolo[1,5-a]pyrazines for spinal muscular atrophy |
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| IL279786B1 (en) * | 2018-06-27 | 2024-10-01 | Reborna Biosciences Inc | Prophylactic or therapeutic agent for spinal muscular atrophy |
| IL279786B2 (en) * | 2018-06-27 | 2025-02-01 | Reborna Biosciences Inc | Preventive or therapeutic agent for spinal muscular atrophy |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002220276A1 (en) | 2002-06-24 |
| US20050033048A1 (en) | 2005-02-10 |
| US20060040964A1 (en) | 2006-02-23 |
| EP1347982A2 (en) | 2003-10-01 |
| US20030036652A1 (en) | 2003-02-20 |
| DE60115092D1 (de) | 2005-12-22 |
| US6566367B2 (en) | 2003-05-20 |
| BR0116113A (pt) | 2004-08-03 |
| MXPA03004245A (es) | 2003-09-22 |
| ATE310004T1 (de) | 2005-12-15 |
| ES2249384T3 (es) | 2006-04-01 |
| US6943199B2 (en) | 2005-09-13 |
| US20040072847A1 (en) | 2004-04-15 |
| WO2002048152A2 (en) | 2002-06-20 |
| DE60115092T2 (de) | 2006-03-30 |
| WO2002048152A3 (en) | 2003-05-08 |
| EP1347982B1 (en) | 2005-11-16 |
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