BG108253A - ДИХИДРО-БЕНЗО[b][1,4] ДИАЗЕПИН-2-ОН ПРОИЗВОДНИ КАТО mGluR2 АНТАГОНИСТИ I - Google Patents

ДИХИДРО-БЕНЗО[b][1,4] ДИАЗЕПИН-2-ОН ПРОИЗВОДНИ КАТО mGluR2 АНТАГОНИСТИ I Download PDF

Info

Publication number: BG108253A
Authority: BG; Bulgaria
Prior art keywords: phenyl; diazepin; trifluoromethyl; oxo; dihydro
Prior art date: 2001-04-12

Application number

BG108253A

Other languages

Bulgarian (bg)

English (en)

Inventor

Geo Adam

Erwin Goetschi

Vincent Mutel

Juergen Wichmann

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

2003-10-10

Publication date

2005-03-31

2003-10-10 Application filed by F.Hoffmann - La Roche Ag filed Critical F.Hoffmann - La Roche Ag

2005-03-31 Publication of BG108253A publication Critical patent/BG108253A/bg

Links

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102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 title description 7
239000005557 antagonist Substances 0.000 title description 2
101150016175 Grm2 gene Proteins 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 373
150000001875 compounds Chemical class 0.000 claims abstract description 368
238000002360 preparation method Methods 0.000 claims abstract description 34
239000003814 drug Substances 0.000 claims abstract description 13
230000001154 acute 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
230000001684 chronic effect Effects 0.000 claims abstract description 6
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230000008569 process Effects 0.000 claims abstract description 4
-1 pyrrole-yl Chemical group 0.000 claims description 233
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150000003839 salts Chemical class 0.000 claims description 23
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 22
230000009467 reduction Effects 0.000 claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims description 18
125000001153 fluoro group Chemical group F* 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
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150000002431 hydrogen Chemical class 0.000 claims description 11
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208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
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BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
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KJFSUONZDZKWIS-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-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=1N1C=CN=C1 KJFSUONZDZKWIS-UHFFFAOYSA-N 0.000 claims description 2
SUAXBFLWHZKRPH-UHFFFAOYSA-N 4-[3-(2-methylpyrazol-3-yl)phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CN1N=CC=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 SUAXBFLWHZKRPH-UHFFFAOYSA-N 0.000 claims description 2
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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
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 2
NYXFGEQQLGOZMF-UHFFFAOYSA-N 4-[3-[5-[(cyclopropylamino)methyl]triazol-1-yl]phenyl]-7-ethoxy-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=C1CNC1CC1 NYXFGEQQLGOZMF-UHFFFAOYSA-N 0.000 claims description 2
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QNDQOKDXZJHKLB-UHFFFAOYSA-N 7-ethoxy-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(OCC)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 QNDQOKDXZJHKLB-UHFFFAOYSA-N 0.000 claims description 2
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ODQYJHWUPRAXER-UHFFFAOYSA-N 7-methoxy-4-[3-[5-(pyrrolidin-1-ylmethyl)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=1N1N=NC=C1CN1CCCC1 ODQYJHWUPRAXER-UHFFFAOYSA-N 0.000 claims description 2
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IFSVVGUGJSGMGT-UHFFFAOYSA-N ethyl 5-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazole-4-carboxylate Chemical compound N1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1C(=O)OCC IFSVVGUGJSGMGT-UHFFFAOYSA-N 0.000 claims description 2
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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 2
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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 1
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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
239000000463 material Substances 0.000 description 1
108010038445 metabotropic glutamate receptor 3 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
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 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
JZSAEGOONAZWSA-UHFFFAOYSA-N methyl 1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC=N1 JZSAEGOONAZWSA-UHFFFAOYSA-N 0.000 description 1
YUDUYCUJCQMCCJ-UHFFFAOYSA-N methyl 2,5-dimethoxyoxolane-2-carboxylate Chemical compound COC1CCC(OC)(C(=O)OC)O1 YUDUYCUJCQMCCJ-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
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
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
KZGRSYGDDBGHOO-POHAHGRESA-N methyl 3-[(z)-hydroxyiminomethyl]benzoate Chemical compound COC(=O)C1=CC=CC(\C=N/O)=C1 KZGRSYGDDBGHOO-POHAHGRESA-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
GGRYEDQOBPIMKX-UHFFFAOYSA-N methyl 3-[4-(oxan-2-yloxymethyl)-1,3-thiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2SC=C(COC3OCCCC3)N=2)=C1 GGRYEDQOBPIMKX-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
IEQAKGLBTYFPEP-UHFFFAOYSA-N methyl 3-[5-methyl-2-(oxan-2-yloxymethyl)-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(SC(COC3OCCCC3)=N2)C)=C1 IEQAKGLBTYFPEP-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
GAKCQFDXNPITFA-UHFFFAOYSA-N methyl 3-propanoylbenzoate Chemical compound CCC(=O)C1=CC=CC(C(=O)OC)=C1 GAKCQFDXNPITFA-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
JUHDUIDUEUEQND-UHFFFAOYSA-N methylium Chemical compound [CH3+] JUHDUIDUEUEQND-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
MVCQUSKTBSVSRY-UHFFFAOYSA-N n-(2-methoxyethylidene)hydroxylamine Chemical compound COCC=NO MVCQUSKTBSVSRY-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
229960004927 neomycin Drugs 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
GSUBXIVOZXWGKF-UHFFFAOYSA-N oxolane-3-carbaldehyde Chemical compound O=CC1CCOC1 GSUBXIVOZXWGKF-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
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239000002798 polar solvent Substances 0.000 description 1
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
OCAAZRFBJBEVPS-UHFFFAOYSA-N prop-2-enyl carbamate Chemical compound NC(=O)OCC=C OCAAZRFBJBEVPS-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
239000012264 purified product Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
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229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
229930000044 secondary metabolite Natural products 0.000 description 1
210000002265 sensory receptor cell Anatomy 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
PSUBOCPMHUULFZ-UHFFFAOYSA-N tert-butyl 1,3-oxazole-4-carboxylate Chemical compound CC(C)(C)OC(=O)C1=COC=N1 PSUBOCPMHUULFZ-UHFFFAOYSA-N 0.000 description 1
QKUXMIVMLPOOQJ-UHFFFAOYSA-N tert-butyl 3-[2-(3-methyl-1,2-oxazol-5-yl)pyridin-4-yl]-3-oxopropanoate Chemical compound O1N=C(C)C=C1C1=CC(C(=O)CC(=O)OC(C)(C)C)=CC=N1 QKUXMIVMLPOOQJ-UHFFFAOYSA-N 0.000 description 1
JODVYMGVCMRARO-UHFFFAOYSA-N tert-butyl 3-[2-(5-methyl-1,3-oxazol-4-yl)phenyl]-3-oxopropanoate Chemical compound O1C=NC(C=2C(=CC=CC=2)C(=O)CC(=O)OC(C)(C)C)=C1C JODVYMGVCMRARO-UHFFFAOYSA-N 0.000 description 1
IEIAOGRUQMUPSY-UHFFFAOYSA-N tert-butyl 3-[3-[3-(methoxymethyl)-1,2-oxazol-5-yl]phenyl]-3-oxopropanoate Chemical compound O1N=C(COC)C=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 IEIAOGRUQMUPSY-UHFFFAOYSA-N 0.000 description 1
BUDAECSKCNVXAI-UHFFFAOYSA-N tert-butyl 3-[3-[4-(oxan-2-yloxymethyl)-1,3-thiazol-2-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2SC=C(COC3OCCCC3)N=2)=C1 BUDAECSKCNVXAI-UHFFFAOYSA-N 0.000 description 1
WXSHWXSHDJJFMX-UHFFFAOYSA-N tert-butyl 3-[3-[5-(oxan-2-yloxymethyl)-1,2-oxazol-3-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C2=NOC(COC3OCCCC3)=C2)=C1 WXSHWXSHDJJFMX-UHFFFAOYSA-N 0.000 description 1
AXHICXOCVDBIIU-UHFFFAOYSA-N tert-butyl 3-[3-[5-methyl-2-(oxan-2-yloxymethyl)-1,3-thiazol-4-yl]phenyl]-3-oxopropanoate Chemical compound N=1C(C=2C=C(C=CC=2)C(=O)CC(=O)OC(C)(C)C)=C(C)SC=1COC1CCCCO1 AXHICXOCVDBIIU-UHFFFAOYSA-N 0.000 description 1
WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 0.000 description 1
RSMRRBWYKHRNAQ-UHFFFAOYSA-N tert-butyl n-(2-amino-4-cyano-5-thiomorpholin-4-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CCSCC2)=C1C#N RSMRRBWYKHRNAQ-UHFFFAOYSA-N 0.000 description 1
QEWLQARQZLEWQL-UHFFFAOYSA-N tert-butyl n-(4-cyano-5-morpholin-4-yl-2-nitrophenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCOCC2)=C1C#N QEWLQARQZLEWQL-UHFFFAOYSA-N 0.000 description 1
XGQHBSIICHBIAH-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-ethoxy-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OCC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=NC(C#N)=C1 XGQHBSIICHBIAH-UHFFFAOYSA-N 0.000 description 1
UUHKKKQFVBICOL-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-methoxy-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=NC(C#N)=C1 UUHKKKQFVBICOL-UHFFFAOYSA-N 0.000 description 1
JSFSELOLAWYUBJ-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-thiomorpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(N=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N1CCSCC1 JSFSELOLAWYUBJ-UHFFFAOYSA-N 0.000 description 1
NJEDSZJNYRSQSF-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-methoxy-4-pyrrol-1-ylphenyl]carbamate Chemical compound C1=C(N2C=CC=C2)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 NJEDSZJNYRSQSF-UHFFFAOYSA-N 0.000 description 1
JSVCVCLCZJIDJW-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-4-pyrrol-1-ylphenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 JSVCVCLCZJIDJW-UHFFFAOYSA-N 0.000 description 1
VFDVOVMYBYYDGF-UHFFFAOYSA-N tert-butyl n-[2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-5-thiomorpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C=2)C(F)(F)F)N2CCSCC2)NC(=O)OC(C)(C)C)=C1 VFDVOVMYBYYDGF-UHFFFAOYSA-N 0.000 description 1
WMNNXUOGEOFGLX-UHFFFAOYSA-N tert-butyl n-[2-[[3-[3-[5-[(dimethylamino)methyl]triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-5-morpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound CN(C)CC1=CN=NN1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C=2)C(F)(F)F)N2CCOCC2)NC(=O)OC(C)(C)C)=C1 WMNNXUOGEOFGLX-UHFFFAOYSA-N 0.000 description 1
NHFRKTUQCATLRK-UHFFFAOYSA-N tert-butyl n-[2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-pyrrol-1-ylphenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=N1 NHFRKTUQCATLRK-UHFFFAOYSA-N 0.000 description 1
JOTUHPUAZYWWGE-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2-tert-butylpyrrol-1-yl)-5-methoxyphenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1N1C(C(C)(C)C)=CC=C1 JOTUHPUAZYWWGE-UHFFFAOYSA-N 0.000 description 1
IHBAJMOUDHLFLJ-UHFFFAOYSA-N tert-butyl n-[4-(2-tert-butylpyrrol-1-yl)-2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-methoxyphenyl]carbamate Chemical compound C1=C(N2C(=CC=C2)C(C)(C)C)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 IHBAJMOUDHLFLJ-UHFFFAOYSA-N 0.000 description 1
DPXYWAQPWQVGSO-UHFFFAOYSA-N tert-butyl n-[5-(2-methoxyethoxy)-2-nitro-4-pyrrol-1-ylphenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1N1C=CC=C1 DPXYWAQPWQVGSO-UHFFFAOYSA-N 0.000 description 1
YYGVXQHLJAEIBI-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]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(N2C(=CN=N2)COC2OCCCC2)=C1 YYGVXQHLJAEIBI-UHFFFAOYSA-N 0.000 description 1
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
IWYNYIRMZJXRJQ-UHFFFAOYSA-N tert-butyl n-[5-ethoxy-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C(F)(F)F IWYNYIRMZJXRJQ-UHFFFAOYSA-N 0.000 description 1
MSWSXATZCFSMHP-UHFFFAOYSA-N tert-butyl n-[5-methoxy-2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C=2ON=C(C)C=2)=C1 MSWSXATZCFSMHP-UHFFFAOYSA-N 0.000 description 1
XRFWKHHRUYJYEE-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(C)=C(C=2)C(F)(F)F)NC(=O)OC(C)(C)C)=C1 XRFWKHHRUYJYEE-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
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
230000001225 therapeutic effect Effects 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [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
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000006250 trifluoro ethyl amino group Chemical group [H]N(*)C([H])([H])C(F)(F)F 0.000 description 1
239000013598 vector Substances 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

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
- A—HUMAN NECESSITIES
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BG108253A 2001-04-12 2003-10-10 ДИХИДРО-БЕНЗО[b][1,4] ДИАЗЕПИН-2-ОН ПРОИЗВОДНИ КАТО mGluR2 АНТАГОНИСТИ I BG108253A (bg)

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EP01109126		2001-04-12

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BG108253A BG108253A (bg)	2001-04-12	2003-10-10	ДИХИДРО-БЕНЗО[b][1,4] ДИАЗЕПИН-2-ОН ПРОИЗВОДНИ КАТО mGluR2 АНТАГОНИСТИ I

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

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MXPA02003740A (es) *	1999-10-15	2002-09-30	Hoffmann La Roche	Derivados de benzodiazepina.
KR100764330B1 (ko) *	2003-07-25	2007-10-05	에프. 호프만-라 로슈 아게	급성 및/또는 만성 신경학적 장애의 치료를 위한ｍＧｌｕＲ2 길항제 및 ＡＣｈＥ 억제제의 조합물
CA2586931C (en)	2004-11-05	2013-08-06	Paul Spurr	Process for preparation of isonicotinic acid derivatives
TWI417095B (zh)	2006-03-15	2013-12-01	Janssen Pharmaceuticals Inc	１，４-二取代之３-氰基-吡啶酮衍生物及其作為ｍＧｌｕＲ２-受體之正向異位性調節劑之用途
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
JP2010524879A (ja) *	2007-04-19	2010-07-22	エフ．ホフマン−ラロシュアーゲー	ジヒドロ−ベンゾ［ｂ］［１，４］ジアゼピン−２−オンスルホンアミド誘導体
CA2696948C (en)	2007-09-14	2013-04-30	Jose Maria Cid-Nunez	1',3'-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2h,1'h-[1,4']bipyridinyl-2'-ones
KR20100080597A (ko) *	2007-09-14	2010-07-09	오르토-맥닐-얀센 파마슈티칼스 인코포레이티드	１,３-이치환된-４-페닐-1ｈ-피리딘-2-온
KR20100065191A (ko)	2007-09-14	2010-06-15	오르토-맥닐-얀센 파마슈티칼스 인코포레이티드	１,３-이치환된 ４-(아릴-ｘ-페닐)-１ｈ-피리딘-２-온
EP2220083B1 (de)	2007-11-14	2017-07-19	Janssen Pharmaceuticals, Inc.	Imidazo[1,2-a]-pyridin-derivate und ihre verwendung als positive allosterische modulatoren von mglur2-rezeptoren
CA2735764C (en)	2008-09-02	2016-06-14	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors
AU2009304293B2 (en)	2008-10-16	2012-04-26	Addex Pharma S.A.	Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors
BRPI0921333A2 (pt)	2008-11-28	2015-12-29	Addex Pharmaceuticals Sa	derivados de indol e benzoxazina como moduladores de receptores de glutamato metabotrópicos
NZ596078A (en)	2009-05-12	2013-06-28	Janssen Pharmaceuticals Inc	1,2,4-TRIAZOLO [4,3-a] PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
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
EA020671B1 (ru)	2009-05-12	2014-12-30	Янссен Фармасьютикалз, Инк.	ПРОИЗВОДНЫЕ 1,2,4-ТРИАЗОЛО[4,3-a]ПИРИДИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ПОЛОЖИТЕЛЬНЫХ АЛЛОСТЕРИЧЕСКИХ МОДУЛЯТОРОВ РЕЦЕПТОРОВ mGluR2
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
EP2643320B1 (de)	2010-11-08	2015-03-04	Janssen Pharmaceuticals, Inc.	1,2,4-triazolo[4,3-a]pyridinderivate und ihre verwendung als positiv allosterische modulatoren des mglur2 receptors
CN103298810B (zh)	2010-11-08	2016-03-16	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 (de)	2011-12-05	2013-06-12	University Of Leicester	Neue Pyrrol Verbindungen
KR20150070187A (ko)	2012-10-23	2015-06-24	에프. 호프만-라 로슈 아게	자폐 장애의 치료를 위한 ｍｇｌｕ２／３ 길항제
PL2963043T3 (pl) *	2013-02-28	2018-10-31	Eisai R&D Management Co., Ltd.	Pochodna tetrahydroimidazo[1,5-d][1,4]oksazepiny
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
LT3431106T (lt)	2014-01-21	2021-02-10	Janssen Pharmaceutica Nv	Deriniai, apimantys 2 potipio metabotropinio glutamaterginio receptoriaus teigiamus alosterinius moduliatorius arba ortosterinius agonistus, ir jų panaudojimas
KR102414246B1 (ko)	2014-01-21	2022-06-27	얀센 파마슈티카 엔.브이.	대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도
EP3134089A2 (de)	2014-04-23	2017-03-01	F. Hoffmann-La Roche AG	Mglu2/3-antagonisten zur behandlung von geistigen behinderungen
JP6552061B2 (ja) *	2014-06-10	2019-07-31	サンフォード−バーンハムメディカルリサーチインスティテュート	代謝型グルタミン酸受容体の負のアロステリックモジュレーター（ｎａｍｓ）とその使用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SU953819A1 (ru) *	1980-08-25	1991-09-23	Физико-химический институт АН УССР	1-(Гидразинокарбонил)алкил-1,2-дигидро-3Н-1,4-бенздиазепин-2-оны, обладающие транквилизирующими и противосудорожными свойствами
EP1210338A2 (de) *	1999-08-05	2002-06-05	IGT Pharma Inc.	1,4-diazepin-derivate zur behandlung von krankheiten des zentralen nervensystems
TR200201023T2 (tr) *	1999-10-15	2002-09-23	F. Hoffmann-La Roche Ag	Benzodiazepin türevleri.
MXPA02003740A (es) *	1999-10-15	2002-09-30	Hoffmann La Roche	Derivados de benzodiazepina.

2002
- 2002-04-02 SK SK1369-2003A patent/SK13692003A3/sk unknown
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Publication number	Publication date
US6548495B2 (en)	2003-04-15
YU79103A (sh)	2006-05-25
KR100566178B1 (ko)	2006-03-29
HUP0400991A3 (en)	2009-06-29
EP1379522B1 (de)	2005-01-26
CN1268626C (zh)	2006-08-09
CA2441771A1 (en)	2002-10-24
GT200200072A (es)	2003-06-19
NO20034496L (no)	2003-10-08
HK1068339A1 (en)	2005-04-29
IL158021A (en)	2010-04-15
ES2235044T3 (es)	2005-07-01
JO2273B1 (en)	2005-04-07
MA27011A1 (fr)	2004-12-20
BR0208887A (pt)	2004-06-29
SK13692003A3 (sk)	2004-05-04
HUP0400991A2 (hu)	2004-08-30
CN1522252A (zh)	2004-08-18
ATE287883T1 (de)	2005-02-15
PT1379522E (pt)	2005-05-31
SI1379522T1 (en)	2005-04-30
US20020198197A1 (en)	2002-12-26
HRP20030791B1 (en)	2006-06-30
PE20021072A1 (es)	2002-12-07
ZA200307242B (en)	2004-12-16
EP1379522A1 (de)	2004-01-14
ECSP034796A (es)	2003-12-01
DE60202761D1 (de)	2005-03-03
AU2002310912B2 (en)	2005-06-16
PA8543201A1 (es)	2002-10-31
JP4043953B2 (ja)	2008-02-06
DE60202761T2 (de)	2006-01-12
JP2004525965A (ja)	2004-08-26
DK1379522T3 (da)	2005-05-30
NO325300B1 (no)	2008-03-25
CA2441771C (en)	2008-12-30
PL367086A1 (en)	2005-02-21
MXPA03009317A (es)	2004-02-12
AR035456A1 (es)	2004-05-26
NZ528345A (en)	2005-04-29
RU2270197C2 (ru)	2006-02-20
UY27259A1 (es)	2002-10-31
NO20034496D0 (no)	2003-10-08
WO2002083665A1 (en)	2002-10-24
KR20030088502A (ko)	2003-11-19
IL158021A0 (en)	2004-03-28
MY130369A (en)	2007-06-29
RU2003130648A (ru)	2005-04-10
HRP20030791A2 (en)	2005-06-30
CZ20033002A3 (cs)	2004-03-17

Publication	Publication Date	Title
EP1379522B1 (de)	2005-01-26	Dihydro-benzo(b)(1,4)diazepin-2-on-derivate als mglur2 antagonisten
EP1379511B1 (de)	2005-07-20	DIHYDRO-BENZO (b) (1,4) DIAZEPIN-2-ON-DERIVATE ALS MGLUR2 ANTAGONISTEN
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