SK13692003A3 - Deriváty dihydrobenzo[b][4,1]diazepín-2-ónu ako antagonisty mGluR2 - Google Patents

Deriváty dihydrobenzo[b][4,1]diazepín-2-ónu ako antagonisty mGluR2 Download PDF

Info

Publication number: SK13692003A3
Authority: SK; Slovakia
Prior art keywords: phenyl; diazepin; trifluoromethyl; mmol; oxo
Prior art date: 2001-04-12

Application number

SK1369-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Geo Adam

Erwin Goetschi

Vincent Mutel

Juergen Wichmann

Thomas Johannes Woltering

Original Assignee

F. Hoffmann-La Roche Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-04-12

Filing date

2002-04-02

Publication date

2004-05-04

2002-04-02 Application filed by F. Hoffmann-La Roche Ag filed Critical F. Hoffmann-La Roche Ag

2004-05-04 Publication of SK13692003A3 publication Critical patent/SK13692003A3/sk

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AZIZBYRGIGKTLW-UHFFFAOYSA-N 1,4-diazepin-2-one Chemical class O=C1C=NC=CC=N1 AZIZBYRGIGKTLW-UHFFFAOYSA-N 0.000 title claims abstract description 38
102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 title description 7
239000005557 antagonist Substances 0.000 title description 4
108010038421 metabotropic glutamate receptor 2 Proteins 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 374
238000000034 method Methods 0.000 claims abstract description 367
239000003814 drug Substances 0.000 claims abstract description 12
230000001684 chronic effect Effects 0.000 claims abstract description 8
208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
208000025966 Neurological disease Diseases 0.000 claims abstract description 6
230000001154 acute effect Effects 0.000 claims abstract description 6
230000002265 prevention Effects 0.000 claims abstract description 4
-1 chloro, cyano, phenyl Chemical group 0.000 claims description 241
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 60
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 53
125000000217 alkyl group Chemical group 0.000 claims description 51
125000003545 alkoxy group Chemical group 0.000 claims description 43
150000003839 salts Chemical class 0.000 claims description 21
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims description 19
230000009467 reduction Effects 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 13
150000002367 halogens Chemical class 0.000 claims description 13
125000004093 cyano group Chemical group *C#N 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 12
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
150000002431 hydrogen Chemical class 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
238000007363 ring formation reaction Methods 0.000 claims description 8
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
JBCFJMYPJJWIRG-UHFFFAOYSA-N 1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC=N1 JBCFJMYPJJWIRG-UHFFFAOYSA-N 0.000 claims description 5
XSGXUFLAJGGFLE-UHFFFAOYSA-N 4-(3-iodophenyl)-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound IC1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 XSGXUFLAJGGFLE-UHFFFAOYSA-N 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
208000024827 Alzheimer disease Diseases 0.000 claims description 4
208000026139 Memory disease Diseases 0.000 claims description 4
208000028017 Psychotic disease Diseases 0.000 claims description 4
208000010877 cognitive disease Diseases 0.000 claims description 4
238000010511 deprotection reaction Methods 0.000 claims description 4
201000000980 schizophrenia Diseases 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
ZMKXDWYSWILRNU-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)N3C=NC=C3)=NC2=CC=C1N1C=CC=C1 ZMKXDWYSWILRNU-UHFFFAOYSA-N 0.000 claims description 3
SIBGDQMTMOWUFB-UHFFFAOYSA-N 4-[2-oxo-7-thiomorpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound FC(F)(F)C1=CC=2NC(=O)CC(C=3C=C(N=CC=3)C#N)=NC=2C=C1N1CCSCC1 SIBGDQMTMOWUFB-UHFFFAOYSA-N 0.000 claims description 3
CNSZNKCNRBFDTH-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 CNSZNKCNRBFDTH-UHFFFAOYSA-N 0.000 claims description 3
ZDQNHJAROPROLE-UHFFFAOYSA-N 4-[3-[2-(hydroxymethyl)-5-methyl-1,3-thiazol-4-yl]phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound S1C(CO)=NC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1C ZDQNHJAROPROLE-UHFFFAOYSA-N 0.000 claims description 3
RJNFOFBZNNRQNC-UHFFFAOYSA-N 4-[3-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 RJNFOFBZNNRQNC-UHFFFAOYSA-N 0.000 claims description 3
YTWOESKGYZDURL-UHFFFAOYSA-N 4-[3-[5-(hydroxymethyl)-1,2-oxazol-3-yl]phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1C(CO)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=N1 YTWOESKGYZDURL-UHFFFAOYSA-N 0.000 claims description 3
JGHOKBYVKJKPER-UHFFFAOYSA-N 7-ethoxy-4-[3-[5-[(2,2,2-trifluoroethylamino)methyl]triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CNCC(F)(F)F JGHOKBYVKJKPER-UHFFFAOYSA-N 0.000 claims description 3
CTYSQPFUDGNBKL-UHFFFAOYSA-N 7-methoxy-4-[3-(triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OC)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 CTYSQPFUDGNBKL-UHFFFAOYSA-N 0.000 claims description 3
JOYIPFAAAYEHOM-UHFFFAOYSA-N 7-methyl-4-[3-(triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 JOYIPFAAAYEHOM-UHFFFAOYSA-N 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 claims description 2
DJNCHHLJNKAOEQ-UHFFFAOYSA-N 4-(2-chlorophenyl)-1-[4-(3-cyanophenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-8-yl]pyrrole-3-carbonitrile Chemical compound ClC1=CC=CC=C1C1=CN(C=2C=C3NC(=O)CC(=NC3=CC=2)C=2C=C(C=CC=2)C#N)C=C1C#N DJNCHHLJNKAOEQ-UHFFFAOYSA-N 0.000 claims description 2
SRKGMKKYVLEGFO-UHFFFAOYSA-N 4-[3-(1,3-oxazol-2-yl)phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C=3OC=CN=3)=NC2=CC=C1N1C=CC=C1 SRKGMKKYVLEGFO-UHFFFAOYSA-N 0.000 claims description 2
JVRGZDKVGJVXFP-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-thiomorpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCSCC4)C=C3N=2)C(F)(F)F)=C1 JVRGZDKVGJVXFP-UHFFFAOYSA-N 0.000 claims description 2
VLPCKCKTCMYPOC-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 VLPCKCKTCMYPOC-UHFFFAOYSA-N 0.000 claims description 2
LTODSASAOXHZES-UHFFFAOYSA-N 4-[3-[3-(hydroxymethyl)-1,2-oxazol-5-yl]phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(CO)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 LTODSASAOXHZES-UHFFFAOYSA-N 0.000 claims description 2
WUDWBYFHFWLKLM-UHFFFAOYSA-N 4-[3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CS1 WUDWBYFHFWLKLM-UHFFFAOYSA-N 0.000 claims description 2
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NHGJLWKIZLSRKG-UHFFFAOYSA-N 4-[7-ethoxy-2-oxo-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C1=CC=NC(C#N)=C1 NHGJLWKIZLSRKG-UHFFFAOYSA-N 0.000 claims description 2
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238000006192 iodination reaction Methods 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 1
LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
150000002690 malonic acid derivatives Chemical class 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 1
108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
NDBQJIBNNUJNHA-DFWYDOINSA-N methyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CO NDBQJIBNNUJNHA-DFWYDOINSA-N 0.000 description 1
SRLROYBBFDQUJL-UHFFFAOYSA-N methyl 2-(3-carbonochloridoylphenyl)-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(C=2C=C(C=CC=2)C(Cl)=O)=N1 SRLROYBBFDQUJL-UHFFFAOYSA-N 0.000 description 1
OIQHKKSYHZIDLX-UHFFFAOYSA-N methyl 2-(3-methyl-1,2-oxazol-5-yl)pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C=2ON=C(C)C=2)=C1 OIQHKKSYHZIDLX-UHFFFAOYSA-N 0.000 description 1
ABDJBBRMKCVSHX-UHFFFAOYSA-N methyl 2-[3-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)phenyl]-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(C=2C=C(C=CC=2)C=2OC(C)(C)OC(=O)C=2)=N1 ABDJBBRMKCVSHX-UHFFFAOYSA-N 0.000 description 1
KYIORMVOQPQUEK-UHFFFAOYSA-N methyl 2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenyl]acetate Chemical class COC(=O)CC1=CC=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=C1 KYIORMVOQPQUEK-UHFFFAOYSA-N 0.000 description 1
XXOKMYMXDALOEN-UHFFFAOYSA-N methyl 2-iodopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(I)=C1 XXOKMYMXDALOEN-UHFFFAOYSA-N 0.000 description 1
PKFNYIJQJRDTKG-UHFFFAOYSA-N methyl 3-(1,3-oxazol-2-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC=CN=2)=C1 PKFNYIJQJRDTKG-UHFFFAOYSA-N 0.000 description 1
JKNYFEXHKRIDTA-UHFFFAOYSA-N methyl 3-(2,2-dimethoxyethylcarbamoyl)benzoate Chemical compound COC(OC)CNC(=O)C1=CC=CC(C(=O)OC)=C1 JKNYFEXHKRIDTA-UHFFFAOYSA-N 0.000 description 1
LEIJXXQQGMEHKW-UHFFFAOYSA-N methyl 3-(2-methylpyrazol-3-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2N(N=CC=2)C)=C1 LEIJXXQQGMEHKW-UHFFFAOYSA-N 0.000 description 1
IYFCPKFXJHLORW-UHFFFAOYSA-N methyl 3-(2-oxoethylcarbamoyl)benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)NCC=O)=C1 IYFCPKFXJHLORW-UHFFFAOYSA-N 0.000 description 1
FXIPLAQQNNBNPC-UHFFFAOYSA-N methyl 3-[3-(methoxymethyl)-1,2-oxazol-5-yl]benzoate Chemical compound O1N=C(COC)C=C1C1=CC=CC(C(=O)OC)=C1 FXIPLAQQNNBNPC-UHFFFAOYSA-N 0.000 description 1
OUEQQZHRRCUGRX-UHFFFAOYSA-N methyl 3-[3-(oxan-2-yloxymethyl)-1,2-oxazol-5-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2ON=C(COC3OCCCC3)C=2)=C1 OUEQQZHRRCUGRX-UHFFFAOYSA-N 0.000 description 1
GCRVOUCLHCAJSR-UHFFFAOYSA-N methyl 3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2SC=C(CO)N=2)=C1 GCRVOUCLHCAJSR-UHFFFAOYSA-N 0.000 description 1
YKRNIIORQBLEDF-UHFFFAOYSA-N methyl 3-[5-(oxan-2-yloxymethyl)-1,2-oxazol-3-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=NOC(COC3OCCCC3)=C2)=C1 YKRNIIORQBLEDF-UHFFFAOYSA-N 0.000 description 1
MLCIBDZPKBPFBY-UHFFFAOYSA-N methyl 3-[5-(oxan-2-yloxymethyl)triazol-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 MLCIBDZPKBPFBY-UHFFFAOYSA-N 0.000 description 1
DGMIWLZFGRRVIS-UHFFFAOYSA-N methyl 3-[5-[(dimethylamino)methyl]triazol-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(=CN=N2)CN(C)C)=C1 DGMIWLZFGRRVIS-UHFFFAOYSA-N 0.000 description 1
MBBRSLODSVCTGY-UHFFFAOYSA-N methyl 3-carbamothioylbenzoate Chemical compound COC(=O)C1=CC=CC(C(N)=S)=C1 MBBRSLODSVCTGY-UHFFFAOYSA-N 0.000 description 1
XPBHWSMZTSSEJE-UHFFFAOYSA-N methyl 3-cyanobenzoate Chemical compound COC(=O)C1=CC=CC(C#N)=C1 XPBHWSMZTSSEJE-UHFFFAOYSA-N 0.000 description 1
CWINGXPWIXWOBS-UHFFFAOYSA-N methyl 3-imidazol-1-ylbenzoate Chemical compound COC(=O)C1=CC=CC(N2C=NC=C2)=C1 CWINGXPWIXWOBS-UHFFFAOYSA-N 0.000 description 1
GAKCQFDXNPITFA-UHFFFAOYSA-N methyl 3-propanoylbenzoate Chemical compound CCC(=O)C1=CC=CC(C(=O)OC)=C1 GAKCQFDXNPITFA-UHFFFAOYSA-N 0.000 description 1
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125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
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HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
MVCQUSKTBSVSRY-UHFFFAOYSA-N n-(2-methoxyethylidene)hydroxylamine Chemical compound COCC=NO MVCQUSKTBSVSRY-UHFFFAOYSA-N 0.000 description 1
AMOIXNOVGONYIG-UHFFFAOYSA-N n-(2-nitro-5-pyrrol-1-ylphenyl)acetamide Chemical class C1=C([N+]([O-])=O)C(NC(=O)C)=CC(N2C=CC=C2)=C1 AMOIXNOVGONYIG-UHFFFAOYSA-N 0.000 description 1
PMVSHAGCQJRAKP-UHFFFAOYSA-N n-(5-amino-4-iodo-2-nitrophenyl)acetamide Chemical compound CC(=O)NC1=CC(N)=C(I)C=C1[N+]([O-])=O PMVSHAGCQJRAKP-UHFFFAOYSA-N 0.000 description 1
NPOLCELBYKFCMB-UHFFFAOYSA-N n-fluoro-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NF NPOLCELBYKFCMB-UHFFFAOYSA-N 0.000 description 1
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235000005985 organic acids Nutrition 0.000 description 1
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WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
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150000002940 palladium Chemical class 0.000 description 1
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WDIAMDMEFPLYPI-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 WDIAMDMEFPLYPI-UHFFFAOYSA-N 0.000 description 1
HMBLOASJUYQYAH-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 HMBLOASJUYQYAH-UHFFFAOYSA-N 0.000 description 1
JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
DOACLJQAMVULSD-UHFFFAOYSA-N tert-butyl-(2-nitrophenyl)carbamic acid Chemical compound CC(C)(C)N(C(O)=O)C1=CC=CC=C1[N+]([O-])=O DOACLJQAMVULSD-UHFFFAOYSA-N 0.000 description 1
CRAJFVNFDNRPAS-UHFFFAOYSA-N tert-butyl-dimethyl-[3-(oxan-2-yloxy)prop-1-ynyl]silane Chemical compound CC(C)(C)[Si](C)(C)C#CCOC1CCCCO1 CRAJFVNFDNRPAS-UHFFFAOYSA-N 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
238000010257 thawing Methods 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
238000001890 transfection Methods 0.000 description 1
238000000844 transformation Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
239000013598 vector Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000011995 wilkinson's catalyst Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
- C07D403/10—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 aromatic rings
- 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
- C07D403/14—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 three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
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Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
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Animal Behavior & Ethology (AREA)
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Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
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Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Addiction (AREA)
Pain & Pain Management (AREA)
Psychology (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK1369-2003A 2001-04-12 2002-04-02 Deriváty dihydrobenzo[b][4,1]diazepín-2-ónu ako antagonisty mGluR2 SK13692003A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP01109126		2001-04-12
PCT/EP2002/003643 WO2002083665A1 (en)	2001-04-12	2002-04-02	DIHYDRO-BENZO[b][1,4]DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS I

Publications (1)

Publication Number	Publication Date
SK13692003A3 true SK13692003A3 (sk)	2004-05-04

Family

ID=8177127

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1369-2003A SK13692003A3 (sk)	2001-04-12	2002-04-02	Deriváty dihydrobenzo[b][4,1]diazepín-2-ónu ako antagonisty mGluR2

Country Status (37)

Country	Link
US (1)	US6548495B2 (es)
EP (1)	EP1379522B1 (es)
JP (1)	JP4043953B2 (es)
KR (1)	KR100566178B1 (es)
CN (1)	CN1268626C (es)
AR (1)	AR035456A1 (es)
AT (1)	ATE287883T1 (es)
AU (1)	AU2002310912B2 (es)
BG (1)	BG108253A (es)
BR (1)	BR0208887A (es)
CA (1)	CA2441771C (es)
CZ (1)	CZ20033002A3 (es)
DE (1)	DE60202761T2 (es)
DK (1)	DK1379522T3 (es)
EC (1)	ECSP034796A (es)
ES (1)	ES2235044T3 (es)
GT (1)	GT200200072A (es)
HR (1)	HRP20030791B1 (es)
HU (1)	HUP0400991A3 (es)
IL (2)	IL158021A0 (es)
JO (1)	JO2273B1 (es)
MA (1)	MA27011A1 (es)
MX (1)	MXPA03009317A (es)
MY (1)	MY130369A (es)
NO (1)	NO325300B1 (es)
NZ (1)	NZ528345A (es)
PA (1)	PA8543201A1 (es)
PE (1)	PE20021072A1 (es)
PL (1)	PL367086A1 (es)
PT (1)	PT1379522E (es)
RU (1)	RU2270197C2 (es)
SI (1)	SI1379522T1 (es)
SK (1)	SK13692003A3 (es)
UY (1)	UY27259A1 (es)
WO (1)	WO2002083665A1 (es)
YU (1)	YU79103A (es)
ZA (1)	ZA200307242B (es)

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TW200845978A (en)	2007-03-07	2008-12-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
TW200900065A (en)	2007-03-07	2009-01-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives
ATE519751T1 (de) *	2007-04-19	2011-08-15	Hoffmann La Roche	Dihydro-benzoäbüä1,4üdiazepin-2-on- sulfonamidderivate
HRP20110278T1 (hr)	2007-09-14	2011-05-31	Ortho-Mcneil-Janssen Pharmaceuticals	1',3'-disupstituirani-4-fenil,3,4,5,6-tetrahidro-2h,1'h[1,4']bipiridinil-2'-oni
TW200927731A (en) *	2007-09-14	2009-07-01	Ortho Mcneil Janssen Pharm	1,3-disubstituted-4-phenyl-1H-pyridin-2-ones
NZ584152A (en)	2007-09-14	2011-11-25	Ortho Mcneil Janssen Pharm	1,3-disubstituted 4-(aryl-x-phenyl)-1h-pyridin-2-ones
ES2637794T3 (es)	2007-11-14	2017-10-17	Janssen Pharmaceuticals, Inc.	Derivados de imidazo[1,2-A]piridina y su uso como moduladores alostéricos positivos de receptores MGLUR2
JP5547194B2 (ja)	2008-09-02	2014-07-09	ジャンセンファーマシューティカルズ，インコーポレイテッド．	代謝型グルタミン酸受容体の調節因子としての３−アザビシクロ［３．１．０］ヘキシル誘導体
MX2011003691A (es)	2008-10-16	2011-09-06	Ortho Mcneil Janssen Pharm	Derivados de indol y benzomorfolina como moduladores de los receptores de glutamato metabotropico.
CN102232074B (zh)	2008-11-28	2014-12-03	奥梅-杨森制药有限公司	作为代谢性谷氨酸盐受体调节剂的吲哚和苯并噁嗪衍生物
CA2760259C (en)	2009-05-12	2018-05-01	Janssen Pharmaceuticals, Inc.	1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
CN102439008B (zh)	2009-05-12	2015-04-29	杨森制药有限公司	1,2,4-三唑并[4,3-a]吡啶衍生物及其用于治疗或预防神经和精神病症的用途
MY153913A (en)	2009-05-12	2015-04-15	Janssen Pharmaceuticals Inc	7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
CA2814996C (en)	2010-11-08	2019-10-01	Janssen Pharmaceuticals, Inc.	1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
CA2815002C (en)	2010-11-08	2019-10-22	Janssen Pharmaceuticals, Inc.	1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
CN103261195B (zh)	2010-11-08	2015-09-02	杨森制药公司	1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途
EP2602248A1 (en)	2011-12-05	2013-06-12	University Of Leicester	Novel pyrrole compounds
AR093077A1 (es)	2012-10-23	2015-05-20	Hoffmann La Roche	ANTAGONISTAS DE mGlu2/3 PARA EL TRATAMIENTO DE LOS TRASTORNOS AUTISTAS
JP5654715B1 (ja) *	2013-02-28	2015-01-14	エーザイ・アール・アンド・ディー・マネジメント株式会社	テトラヒドロイミダゾ［１，５−ｄ］［１，４］オキサゼピン誘導体（ＴＥＴＲＡＨＹＤＲＯＩＭＩＤＡＺＯ［１，５−ｄ］［１，４］ＯＸＡＺＥＰＩＮＥＤＥＲＩＶＡＴＩＶＥ）
JO3368B1 (ar)	2013-06-04	2019-03-13	Janssen Pharmaceutica Nv	مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JO3367B1 (ar)	2013-09-06	2019-03-13	Janssen Pharmaceutica Nv	مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2
KR20200036063A (ko)	2014-01-21	2020-04-06	얀센 파마슈티카 엔.브이.	대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도
EP3096790B1 (en)	2014-01-21	2019-07-10	Janssen Pharmaceutica, N.V.	Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use
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2002
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- 2002-04-02 PT PT02735209T patent/PT1379522E/pt unknown
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Also Published As

Publication number	Publication date
NZ528345A (en)	2005-04-29
CA2441771A1 (en)	2002-10-24
HUP0400991A3 (en)	2009-06-29
CN1522252A (zh)	2004-08-18
UY27259A1 (es)	2002-10-31
DE60202761T2 (de)	2006-01-12
AU2002310912B2 (en)	2005-06-16
WO2002083665A1 (en)	2002-10-24
GT200200072A (es)	2003-06-19
IL158021A0 (en)	2004-03-28
JO2273B1 (en)	2005-04-07
RU2003130648A (ru)	2005-04-10
ES2235044T3 (es)	2005-07-01
CA2441771C (en)	2008-12-30
HRP20030791A2 (en)	2005-06-30
HRP20030791B1 (en)	2006-06-30
KR20030088502A (ko)	2003-11-19
HUP0400991A2 (hu)	2004-08-30
EP1379522B1 (en)	2005-01-26
MA27011A1 (fr)	2004-12-20
NO20034496D0 (no)	2003-10-08
PT1379522E (pt)	2005-05-31
RU2270197C2 (ru)	2006-02-20
BG108253A (bg)	2005-03-31
US6548495B2 (en)	2003-04-15
CN1268626C (zh)	2006-08-09
SI1379522T1 (en)	2005-04-30
NO20034496L (no)	2003-10-08
PL367086A1 (en)	2005-02-21
PE20021072A1 (es)	2002-12-07
JP2004525965A (ja)	2004-08-26
ECSP034796A (es)	2003-12-01
DK1379522T3 (da)	2005-05-30
US20020198197A1 (en)	2002-12-26
JP4043953B2 (ja)	2008-02-06
EP1379522A1 (en)	2004-01-14
HK1068339A1 (en)	2005-04-29
YU79103A (sh)	2006-05-25
ATE287883T1 (de)	2005-02-15
BR0208887A (pt)	2004-06-29
DE60202761D1 (de)	2005-03-03
ZA200307242B (en)	2004-12-16
AR035456A1 (es)	2004-05-26
PA8543201A1 (es)	2002-10-31
MY130369A (en)	2007-06-29
IL158021A (en)	2010-04-15
MXPA03009317A (es)	2004-02-12
KR100566178B1 (ko)	2006-03-29
NO325300B1 (no)	2008-03-25
CZ20033002A3 (cs)	2004-03-17

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AU2002310912A1 (en)	2003-04-10	Dihydro-benzo[b][1,4]diazepin-2-one derivatives as mGluR2 antagonists I
AU2002312788A1 (en)	2003-04-10	Dihydro-benzo [b] [1, 4] diazepin-2-one derivatives as mGluR2 antagonists II
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PH12014502775B1 (en)	2015-02-02	TRIAZOLONE COMPOUNDS AS mPGES-1 INHIBITORS
JP2008540554A (ja)	2008-11-20	選択的なアンドロゲン受容体調節物質としての置換型ｎ−アリールピロリジン
ES2543750T3 (es)	2015-08-21	N-fenetiltriazolonacetamidas sustituidas y su uso
RU45093U1 (ru)	2005-04-27	Пылеуловитель

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