BG108254A - ПРОИЗВОДНИ НА ДИХИДРО-БЕНЗО[b][1,4]ДИАЗЕПИН-2-ОН КАТО MGLUR2 АНТАГОНИСТИ II - Google Patents

ПРОИЗВОДНИ НА ДИХИДРО-БЕНЗО[b][1,4]ДИАЗЕПИН-2-ОН КАТО MGLUR2 АНТАГОНИСТИ II Download PDF

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Publication number: BG108254A
Authority: BG; Bulgaria
Prior art keywords: phenyl; methyl; amino; butyl ester; acid tert
Prior art date: 2001-04-12

Application number

BG108254A

Other languages

Bulgarian (bg)

English (en)

Inventor

Geo Adam

Erwin Goetschi

Vincent Mutel

Juergen Wichmann

Johannes T. 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

2004-09-30

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

2004-09-30 Publication of BG108254A publication Critical patent/BG108254A/bg

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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 83
102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 title description 4
101150016175 Grm2 gene Proteins 0.000 title 1
239000005557 antagonist Substances 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 682
150000001875 compounds Chemical class 0.000 claims abstract description 594
238000011282 treatment Methods 0.000 claims abstract description 262
238000002360 preparation method Methods 0.000 claims abstract description 31
239000003814 drug Substances 0.000 claims abstract description 11
230000001154 acute effect Effects 0.000 claims abstract description 7
230000001684 chronic effect Effects 0.000 claims abstract description 7
208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
208000025966 Neurological disease Diseases 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 4
230000002265 prevention Effects 0.000 claims abstract 3
-1 pyrrole -1-yl Chemical group 0.000 claims description 727
125000000217 alkyl group Chemical group 0.000 claims description 52
125000003545 alkoxy group Chemical group 0.000 claims description 43
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
125000004093 cyano group Chemical group *C#N 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 22
229910052736 halogen Inorganic materials 0.000 claims description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
125000001153 fluoro group Chemical group F* 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 6
208000028017 Psychotic disease Diseases 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
238000007363 ring formation reaction Methods 0.000 claims description 5
PFXSUPYIBPKVQN-UHFFFAOYSA-N 8-chloro-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-(2-methylpropylamino)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(NCC(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 PFXSUPYIBPKVQN-UHFFFAOYSA-N 0.000 claims description 4
208000024827 Alzheimer disease Diseases 0.000 claims description 4
208000000044 Amnesia Diseases 0.000 claims description 4
208000026139 Memory disease Diseases 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
238000010511 deprotection reaction Methods 0.000 claims description 4
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
230000006984 memory degeneration Effects 0.000 claims description 4
208000023060 memory loss Diseases 0.000 claims description 4
201000000980 schizophrenia Diseases 0.000 claims description 4
DJMZLSQXQSZBAN-UHFFFAOYSA-N 4-[2-oxo-7-(2,2,2-trifluoroethoxy)-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(F)(F)F)=CC=2N=C1C1=CC=NC(C#N)=C1 DJMZLSQXQSZBAN-UHFFFAOYSA-N 0.000 claims description 3
KGBAJRRLCNCMNT-UHFFFAOYSA-N 4-[3-[5-(hydroxymethyl)-1,3,4-thiadiazol-2-yl]phenyl]-7-[methyl(propyl)amino]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)CCC)=CC=2N=C1C(C=1)=CC=CC=1C1=NN=C(CO)S1 KGBAJRRLCNCMNT-UHFFFAOYSA-N 0.000 claims description 3
CZLWEHDNIPKFTN-UHFFFAOYSA-N 4-[7-[cyclopropylmethyl(methyl)amino]-2-oxo-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound C=1C=2N=C(C=3C=C(N=CC=3)C#N)CC(=O)NC=2C=C(C(F)(F)F)C=1N(C)CC1CC1 CZLWEHDNIPKFTN-UHFFFAOYSA-N 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
ASXHDONHHPHYRD-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-2-oxo-7-piperidin-1-yl-1,3-dihydro-1,5-benzodiazepine-8-carbonitrile Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCCCC4)C=C3N=2)C#N)=C1 ASXHDONHHPHYRD-UHFFFAOYSA-N 0.000 claims description 2
LGGCNWMQSRYKEK-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-[methyl(propan-2-yl)amino]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)C(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 LGGCNWMQSRYKEK-UHFFFAOYSA-N 0.000 claims description 2
RMBIAVCOZGNTCG-UHFFFAOYSA-N 4-[3-[5-[(cyclopropylmethylamino)methyl]triazol-1-yl]phenyl]-8-methyl-7-[methyl(2-methylpropyl)amino]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C)C(N(C)CC(C)C)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CNCC1CC1 RMBIAVCOZGNTCG-UHFFFAOYSA-N 0.000 claims description 2
QPHLWEQWHSMTNX-UHFFFAOYSA-N 4-[7-[cyclopropyl(methyl)amino]-2-oxo-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound C=1C=2N=C(C=3C=C(N=CC=3)C#N)CC(=O)NC=2C=C(C(F)(F)F)C=1N(C)C1CC1 QPHLWEQWHSMTNX-UHFFFAOYSA-N 0.000 claims description 2
VYNUPTPNOCSSBJ-UHFFFAOYSA-N 7-(diethylamino)-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-2-oxo-1,3-dihydro-1,5-benzodiazepine-8-carbonitrile Chemical compound C1C(=O)NC=2C=C(C#N)C(N(CC)CC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 VYNUPTPNOCSSBJ-UHFFFAOYSA-N 0.000 claims description 2
DDDRVKGHRFVCSK-UHFFFAOYSA-N 7-(dimethylamino)-4-(3-imidazol-1-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)C)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=C1 DDDRVKGHRFVCSK-UHFFFAOYSA-N 0.000 claims description 2
ZZVIUNYEAUAGMT-UHFFFAOYSA-N 7-(dimethylamino)-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 ZZVIUNYEAUAGMT-UHFFFAOYSA-N 0.000 claims description 2
OHWFEQKMVFNWLV-UHFFFAOYSA-N 7-(dimethylamino)-8-methyl-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C)C(N(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 OHWFEQKMVFNWLV-UHFFFAOYSA-N 0.000 claims description 2
HWPJVWXJTPQBEF-UHFFFAOYSA-N 7-[methyl(2-methylpropyl)amino]-4-[3-[5-[[methyl(propan-2-yl)amino]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(N(C)CC(C)C)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CN(C)C(C)C HWPJVWXJTPQBEF-UHFFFAOYSA-N 0.000 claims description 2
BMMSJPYGKWFQKH-UHFFFAOYSA-N 8-chloro-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-(propan-2-ylamino)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(NC(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 BMMSJPYGKWFQKH-UHFFFAOYSA-N 0.000 claims description 2
FNVVDXIMWWBIRY-UHFFFAOYSA-N 8-chloro-4-[3-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenyl]-7-[methyl(propyl)amino]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(N(C)CCC)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CO1 FNVVDXIMWWBIRY-UHFFFAOYSA-N 0.000 claims description 2
ADOSEGKIEQRXKL-UHFFFAOYSA-N 8-chloro-4-[3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]phenyl]-7-[methyl(propyl)amino]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(N(C)CCC)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CS1 ADOSEGKIEQRXKL-UHFFFAOYSA-N 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
230000006806 disease prevention Effects 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
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
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims 5
OWPXWLMWINGIJA-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-[methyl(propyl)amino]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)CCC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 OWPXWLMWINGIJA-UHFFFAOYSA-N 0.000 claims 1
UYLWLBKJGHXHEJ-UHFFFAOYSA-N 7-(dimethylamino)-4-[3-(2-methylpyrazol-3-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NN1C UYLWLBKJGHXHEJ-UHFFFAOYSA-N 0.000 claims 1
AKHVLIYLESRYKL-UHFFFAOYSA-N 7-(dimethylamino)-8-(2-phenylethynyl)-4-[3-(triazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CN(C)C1=CC=2N=C(C=3C=C(C=CC=3)N3N=NC=C3)CC(=O)NC=2C=C1C#CC1=CC=CC=C1 AKHVLIYLESRYKL-UHFFFAOYSA-N 0.000 claims 1
HAAZRBAMJKYOAA-UHFFFAOYSA-N 7-[ethyl(methyl)amino]-8-methyl-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C)C(N(C)CC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 HAAZRBAMJKYOAA-UHFFFAOYSA-N 0.000 claims 1
OGFPVPFGOGJHSX-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-[3-(triazol-1-yl)phenyl]-7-(2,2,2-trifluoroethoxy)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC1=CC=CC=C1C(C(=C1)OCC(F)(F)F)=CC2=C1N=C(C=1C=C(C=CC=1)N1N=NC=C1)CC(=O)N2 OGFPVPFGOGJHSX-UHFFFAOYSA-N 0.000 claims 1
NGCNTLZHOWWZPG-UHFFFAOYSA-N 8-chloro-4-[3-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenyl]-7-[methyl(2-methylpropyl)amino]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(N(C)CC(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CO1 NGCNTLZHOWWZPG-UHFFFAOYSA-N 0.000 claims 1
CWRWLBCLNIXFEP-UHFFFAOYSA-N 8-chloro-4-[3-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenyl]-7-[methyl(propan-2-yl)amino]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(N(C)C(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CO1 CWRWLBCLNIXFEP-UHFFFAOYSA-N 0.000 claims 1
WHTNPSQCYHTFRC-UHFFFAOYSA-N 8-chloro-4-[3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]phenyl]-7-[methyl(propan-2-yl)amino]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(N(C)C(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CS1 WHTNPSQCYHTFRC-UHFFFAOYSA-N 0.000 claims 1
MDZRWNNRILAEHU-UHFFFAOYSA-N 8-chloro-7-[ethyl(methyl)amino]-4-[3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(N(C)CC)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CS1 MDZRWNNRILAEHU-UHFFFAOYSA-N 0.000 claims 1
QBSNFNKYIAYAHP-UHFFFAOYSA-N 8-methyl-7-[methyl(2-methylpropyl)amino]-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C)C(N(C)CC(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 QBSNFNKYIAYAHP-UHFFFAOYSA-N 0.000 claims 1
208000028698 Cognitive impairment Diseases 0.000 claims 1
208000020764 Sensation disease Diseases 0.000 claims 1
208000010877 cognitive disease Diseases 0.000 claims 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 1
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 356
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 345
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 334
239000007787 solid Substances 0.000 description 261
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 150
239000000203 mixture Substances 0.000 description 147
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 137
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
235000019439 ethyl acetate Nutrition 0.000 description 111
239000000126 substance Substances 0.000 description 110
239000000460 chlorine Substances 0.000 description 108
239000000243 solution Substances 0.000 description 107
239000003921 oil Substances 0.000 description 101
235000019198 oils Nutrition 0.000 description 101
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 83
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 82
238000006243 chemical reaction Methods 0.000 description 78
MEGIEGFVRNXYSU-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(dimethylamino)-4-(trifluoromethyl)phenyl]carbamate Chemical compound CN(C)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C(F)(F)F MEGIEGFVRNXYSU-UHFFFAOYSA-N 0.000 description 71
239000006260 foam Substances 0.000 description 65
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 64
239000012267 brine Substances 0.000 description 63
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 63
PCIUUFCHBGXPMZ-UHFFFAOYSA-N tert-butyl n-[4-chloro-2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(dimethylamino)phenyl]carbamate Chemical compound C1=C(Cl)C(N(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 PCIUUFCHBGXPMZ-UHFFFAOYSA-N 0.000 description 61
239000000047 product Substances 0.000 description 46
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 42
ZTCGGBIFOFASKI-UHFFFAOYSA-N tert-butyl acetate;lithium Chemical compound [Li].CC(=O)OC(C)(C)C ZTCGGBIFOFASKI-UHFFFAOYSA-N 0.000 description 41
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
239000012044 organic layer Substances 0.000 description 33
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
239000000741 silica gel Substances 0.000 description 32
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239000003480 eluent Substances 0.000 description 31
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230000009467 reduction Effects 0.000 description 31
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 31
FLCGMVBKTAMPQY-UHFFFAOYSA-N 3-[8-chloro-7-(dimethylamino)-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C1C(=O)NC=2C=C(Cl)C(N(C)C)=CC=2N=C1C1=CC=CC(C#N)=C1 FLCGMVBKTAMPQY-UHFFFAOYSA-N 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
239000002904 solvent Substances 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 26
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 25
238000000354 decomposition reaction Methods 0.000 description 24
FCIBAVBCBAXBFX-UHFFFAOYSA-N tert-butyl n-(4,5-dichloro-2-nitrophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(Cl)C=C1[N+]([O-])=O FCIBAVBCBAXBFX-UHFFFAOYSA-N 0.000 description 24
PVCLQUXXFKCAPM-UHFFFAOYSA-N tert-butyl n-[2-amino-4-chloro-5-(dimethylamino)phenyl]carbamate Chemical compound CN(C)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1Cl PVCLQUXXFKCAPM-UHFFFAOYSA-N 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
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NSUKZHPOWCPFRY-UHFFFAOYSA-N methyl 3-[2-methyl-5-(oxan-2-yloxymethyl)-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(SC(C)=N2)COC2OCCCC2)=C1 NSUKZHPOWCPFRY-UHFFFAOYSA-N 0.000 description 3
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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 3
GRJKSWGQVPXVKL-UHFFFAOYSA-N methyl 3-[5-(bromomethyl)-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(SC=N2)CBr)=C1 GRJKSWGQVPXVKL-UHFFFAOYSA-N 0.000 description 3
UHVAXAIDJRUUTK-UHFFFAOYSA-N methyl 3-[5-(hydroxymethyl)-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(SC=N2)CO)=C1 UHVAXAIDJRUUTK-UHFFFAOYSA-N 0.000 description 3
AUGFTAYXXLVEEC-UHFFFAOYSA-N methyl 3-[5-(oxan-2-yloxymethyl)-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(SC=N2)COC2OCCCC2)=C1 AUGFTAYXXLVEEC-UHFFFAOYSA-N 0.000 description 3
RDEKSPBPFHLJBK-UHFFFAOYSA-N methyl 3-[5-methyl-4-(oxan-2-yloxymethyl)-5h-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2(COC3OCCCC3)C(SC=N2)C)=C1 RDEKSPBPFHLJBK-UHFFFAOYSA-N 0.000 description 3
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
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CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
HWSZZLVAJGOAAY-UHFFFAOYSA-L lead(II) chloride Chemical compound Cl[Pb]Cl HWSZZLVAJGOAAY-UHFFFAOYSA-L 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
229940040692 lithium hydroxide monohydrate Drugs 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
229910001629 magnesium chloride Inorganic materials 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
230000000873 masking effect Effects 0.000 description 1
108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
108010038445 metabotropic glutamate receptor 3 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
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229940098779 methanesulfonic acid Drugs 0.000 description 1
VYXBNKUFCQQDDQ-UHFFFAOYSA-N methyl 2-(3-bromobenzoyl)-3-(propan-2-ylamino)prop-2-enoate Chemical compound CC(C)NC=C(C(=O)OC)C(=O)C1=CC=CC(Br)=C1 VYXBNKUFCQQDDQ-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
XXOKMYMXDALOEN-UHFFFAOYSA-N methyl 2-iodopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(I)=C1 XXOKMYMXDALOEN-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
PSSQBUQWZUHXSD-UHFFFAOYSA-N methyl 3-(propan-2-ylamino)prop-2-enoate Chemical compound COC(=O)C=CNC(C)C PSSQBUQWZUHXSD-UHFFFAOYSA-N 0.000 description 1
KUGUVCXSMYNPIW-UHFFFAOYSA-N methyl 3-[2-methyl-5-(oxan-2-yloxymethyl)pyrazol-3-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2N(N=C(COC3OCCCC3)C=2)C)=C1 KUGUVCXSMYNPIW-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
RJMQKNVGFXRGTN-UHFFFAOYSA-N methyl 3-[4-(chloromethyl)-1,3-oxazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC=C(CCl)N=2)=C1 RJMQKNVGFXRGTN-UHFFFAOYSA-N 0.000 description 1
LCXIEMPOGIQGOT-UHFFFAOYSA-N methyl 3-[4-(hydroxymethyl)-3-methyl-1,2-oxazol-5-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(C(C)=NO2)CO)=C1 LCXIEMPOGIQGOT-UHFFFAOYSA-N 0.000 description 1
DTEDTUIKLPLDAD-UHFFFAOYSA-N methyl 3-[4-(hydroxymethyl)pyrazol-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2N=CC(CO)=C2)=C1 DTEDTUIKLPLDAD-UHFFFAOYSA-N 0.000 description 1
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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
OBALLCFRLYMDPH-UHFFFAOYSA-N methyl 3-hydrazinylbenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=CC(NN)=C1 OBALLCFRLYMDPH-UHFFFAOYSA-N 0.000 description 1
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IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
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QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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229910052760 oxygen Inorganic materials 0.000 description 1
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GMAMRGUSLZPGRI-UHFFFAOYSA-N tert-butyl 3-[3-[4-(oxan-2-yloxymethyl)-1,3-oxazol-2-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2OC=C(COC3OCCCC3)N=2)=C1 GMAMRGUSLZPGRI-UHFFFAOYSA-N 0.000 description 1
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QRUDPZAAJNYWAD-UHFFFAOYSA-N tert-butyl n-[4-methyl-5-[methyl(propyl)amino]-2-nitrophenyl]carbamate Chemical compound CCCN(C)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C QRUDPZAAJNYWAD-UHFFFAOYSA-N 0.000 description 1
AETHUAXRRRBRHZ-UHFFFAOYSA-N tert-butyl n-[5-(2-methylpropylamino)-2-[[3-oxo-3-[3-(1,2,4-triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(NCC(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=CN=C2)=C1 AETHUAXRRRBRHZ-UHFFFAOYSA-N 0.000 description 1
LCKRVRMZHMPLEV-UHFFFAOYSA-N tert-butyl n-[5-(2-methylpropylamino)-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(NCC(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 LCKRVRMZHMPLEV-UHFFFAOYSA-N 0.000 description 1
XBYNEZWMJVZREW-UHFFFAOYSA-N tert-butyl n-[5-(2-methylpropylamino)-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)CNC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C(F)(F)F XBYNEZWMJVZREW-UHFFFAOYSA-N 0.000 description 1
DAJXIWKXTKDKEW-UHFFFAOYSA-N tert-butyl n-[5-(azetidin-1-yl)-2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-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=1N1CCC1 DAJXIWKXTKDKEW-UHFFFAOYSA-N 0.000 description 1
ZSAHBWVCBUULTF-UHFFFAOYSA-N tert-butyl n-[5-(azetidin-1-yl)-4-chloro-2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound ClC=1C=C(NC(=O)CC(=O)C=2C=C(N=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N1CCC1 ZSAHBWVCBUULTF-UHFFFAOYSA-N 0.000 description 1
VIMUEBPPVHTZRI-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-2-[[3-[3-(2-methylsulfanylimidazol-1-yl)phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CSC1=NC=CN1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C=2)C(F)(F)F)N(C)C)NC(=O)OC(C)(C)C)=C1 VIMUEBPPVHTZRI-UHFFFAOYSA-N 0.000 description 1
VSSKZVZRHASLJE-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-2-[[3-oxo-3-(3-pyrazol-1-ylphenyl)propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(N(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=CC=C2)=C1 VSSKZVZRHASLJE-UHFFFAOYSA-N 0.000 description 1
NDYUIOKHGZXUOJ-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-4-fluoro-2-nitrophenyl]carbamate Chemical compound CN(C)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1F NDYUIOKHGZXUOJ-UHFFFAOYSA-N 0.000 description 1
JTCQABVWBNJJBB-UHFFFAOYSA-N tert-butyl n-[5-(hydroxymethyl)-2-nitro-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(CO)=C1C#CC1=CC=CC=C1 JTCQABVWBNJJBB-UHFFFAOYSA-N 0.000 description 1
AMUSXOZSIRDJQN-UHFFFAOYSA-N tert-butyl n-[5-[methyl(2-methylpropyl)amino]-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(N(C)CC(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 AMUSXOZSIRDJQN-UHFFFAOYSA-N 0.000 description 1
ORLXKBASFWRZMF-UHFFFAOYSA-N tert-butyl n-[5-[methyl(propyl)amino]-2-[[3-oxo-3-[3-(1,2,4-triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(N(C)CCC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=CN=C2)=C1 ORLXKBASFWRZMF-UHFFFAOYSA-N 0.000 description 1
KVLYBUAHJPTZFY-UHFFFAOYSA-N tert-butyl n-[5-[methyl(propyl)amino]-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CCCN(C)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C(F)(F)F KVLYBUAHJPTZFY-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 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
229930192474 thiophene Natural products 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000001890 transfection Methods 0.000 description 1
238000000844 transformation 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
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
239000013598 vector Substances 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- 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
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—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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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

BG108254A 2001-04-12 2003-10-10 ПРОИЗВОДНИ НА ДИХИДРО-БЕНЗО[b][1,4]ДИАЗЕПИН-2-ОН КАТО MGLUR2 АНТАГОНИСТИ II BG108254A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP01109125		2001-04-12
PCT/EP2002/003644 WO2002083652A1 (fr)	2001-04-12	2002-04-02	Derives dihydro-benzo[b][1,4]diazepin-2-one utilises comme antagonistes de mglur2(ii)

Publications (1)

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BG108254A true BG108254A (bg)	2004-09-30

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BG108254A BG108254A (bg)	2001-04-12	2003-10-10	ПРОИЗВОДНИ НА ДИХИДРО-БЕНЗО[b][1,4]ДИАЗЕПИН-2-ОН КАТО MGLUR2 АНТАГОНИСТИ II

Country Status (37)

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US (1)	US6544985B2 (fr)
EP (1)	EP1379511B1 (fr)
JP (1)	JP4071115B2 (fr)
KR (1)	KR100566171B1 (fr)
CN (1)	CN1264825C (fr)
AR (1)	AR035816A1 (fr)
AT (1)	ATE299868T1 (fr)
AU (1)	AU2002312788B2 (fr)
BG (1)	BG108254A (fr)
BR (1)	BR0208891A (fr)
CA (1)	CA2442557C (fr)
CZ (1)	CZ20033003A3 (fr)
DE (1)	DE60205100T2 (fr)
DK (1)	DK1379511T3 (fr)
EC (1)	ECSP034797A (fr)
ES (1)	ES2246012T3 (fr)
GT (1)	GT200200073A (fr)
HR (1)	HRP20030792A2 (fr)
HU (1)	HUP0400851A3 (fr)
IL (2)	IL157873A0 (fr)
JO (1)	JO2285B1 (fr)
MA (1)	MA27012A1 (fr)
MX (1)	MXPA03009311A (fr)
MY (1)	MY140271A (fr)
NO (1)	NO20034576L (fr)
NZ (1)	NZ528315A (fr)
PA (1)	PA8543301A1 (fr)
PE (1)	PE20021041A1 (fr)
PL (1)	PL367064A1 (fr)
PT (1)	PT1379511E (fr)
RU (1)	RU2263112C2 (fr)
SI (1)	SI1379511T1 (fr)
SK (1)	SK13682003A3 (fr)
UY (1)	UY27258A1 (fr)
WO (1)	WO2002083652A1 (fr)
YU (1)	YU79003A (fr)
ZA (1)	ZA200307243B (fr)

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ20021663A3 (cs)	1999-10-15	2002-09-11	F. Hoffmann-La Roche Ag	Nové deriváty benzodiazepinu
PT1459765E (pt) *	2001-12-27	2008-10-03	Taisho Pharmaceutical Co Ltd	Derivados de 6-fluorobiciclo [3.1.0] hexano
KR100865410B1 (ko) *	2002-03-28	2008-10-24	위시스 테크놀로지 파운데이션, 인크.	진정 및 운동실조 효과가 감소된 항불안제
EP1925614A1 (fr) *	2002-03-28	2008-05-28	Wisys Technology Foundation, Inc.	Agents anxiolytiques avec effets ataxiques et sédatifs réduits
HRP20070552T3 (en) *	2003-07-25	2008-05-31	F. Hoffmann - La Roche Ag	Combination of mglur2 antagonist and ache inhibitor for treatment of acute and/or chronic neurological disorders
US7329662B2 (en)	2003-10-03	2008-02-12	Hoffmann-La Roche Inc.	Pyrazolo-pyridine
US20060160823A1 (en) *	2004-05-28	2006-07-20	Leonore Witchey-Lakshmanan	Particulate-stabilized injectable pharmaceutical compositions of Posaconazole
ATE383361T1 (de) *	2004-06-21	2008-01-15	Hoffmann La Roche	Pyrrazolopyrimidinderivate
CN101115755B (zh) *	2005-02-11	2013-01-16	弗·哈夫曼-拉罗切有限公司	作为mglur2拮抗剂的吡唑并-嘧啶衍生物
WO2006099972A1 (fr)	2005-03-23	2006-09-28	F. Hoffmann-La Roche Ag	Derives d'acetylenyl-pyrazolo-pyrimidine comme antagonistes mglur2
KR101351190B1 (ko) *	2005-06-23	2014-01-14	아스트라제네카 아베	벤즈이미다졸 화합물의 제조 방법
BRPI0616571A2 (pt)	2005-09-27	2011-06-21	Hoffmann La Roche	oxadiazolil pirazol-piridiminas como antagonistas de mglur2, processo para sua preparação, composição farmacêutica que os contém e uso dos mesmo
GB0600228D0 (en) *	2006-01-06	2006-02-15	Fermentas Uab	Inactivation method
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
TW200808751A (en) *	2006-04-13	2008-02-16	Astrazeneca Ab	New compounds
AU2007299129A1 (en) *	2006-09-20	2008-03-27	F. Hoffmann-La Roche Ag	4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine derivatives
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
PL2203439T3 (pl)	2007-09-14	2011-06-30	Addex Pharmaceuticals Sa	1',3'-dipodstawione-4-fenylo-3,4,5,6-tetrahydro-2H, 1'H-[1, 4']bipirydynylo-2'-ketony
WO2009033702A1 (fr)	2007-09-14	2009-03-19	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	4-(aryl-x-phényl)-1h-pyridine-2-ones 1,3-disubstituées
CA2698929C (fr) *	2007-09-14	2016-01-19	Addex Pharma S.A.	4-phenyle-1h-pyridine-2-ones 1,3-disubstituees
US8785486B2 (en)	2007-11-14	2014-07-22	Janssen Pharmaceuticals, Inc.	Imidazo[1,2-A]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors
ES2439291T3 (es)	2008-09-02	2014-01-22	Janssen Pharmaceuticals, Inc.	Derivados de 3-azabiciclo[3.1.0]hexilo como moduladores de receptores de glutamato metabotrópicos
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.
ES2401691T3 (es)	2008-11-28	2013-04-23	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	Derivados de indol y de benzoxacina como moduladores de los receptores metabotrópicos de glutamato
AU2010246607B2 (en)	2009-05-12	2012-09-27	Addex Pharma S.A.	1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors
JP5634506B2 (ja)	2009-05-12	2014-12-03	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	１，２，３−トリアゾロ［４，３−ａ］ピリジン誘導体ならびに神経障害および精神障害の治療または予防のためのその使用
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
BR112013000925A2 (pt)	2010-07-15	2020-12-01	Bayer Intellectual Property Gmbh	compostos heterocíclicos como pesticidas
WO2012059431A1 (fr)	2010-11-01	2012-05-10	Abbott Gmbh & Co. Kg	Composés de type benzènesulfonyle ou sulfonamide appropriés pour le traitement de troubles qui répondent à la modulation du récepteur 5-ht6 de la sérotonine
WO2012059432A1 (fr)	2010-11-01	2012-05-10	Abbott Gmbh & Co. Kg	Composés de type n-phényl-(homo)pipérazinyl-benzènesulfonyle ou benzènesulfonamide appropriés pour le traitement de troubles qui répondent à la modulation du récepteur 5-ht6
ES2552455T3 (es)	2010-11-08	2015-11-30	Janssen Pharmaceuticals, Inc.	Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2
JP5852666B2 (ja)	2010-11-08	2016-02-03	ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド	１，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用
JP5852665B2 (ja)	2010-11-08	2016-02-03	ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド	１，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用
EP2701699B1 (fr)	2011-04-28	2019-10-16	The Broad Institute, Inc.	Inhibiteurs de l'histone désacétylase
JP5790195B2 (ja) *	2011-06-22	2015-10-07	セントラル硝子株式会社	ピラゾール化合物の製造方法
CA2847247C (fr)	2011-08-29	2019-10-15	Sanford-Burnham Medical Research Institute	Benzodiazepinones en tant que modulateurs de fonctions d'un recepteur metabotropique du glutamate, et utilisations neurologiques de ceux-ci
WO2014018979A1 (fr)	2012-07-27	2014-01-30	The Broad Institute, Inc.	Inhibiteurs d'histone-désacétylases
SG11201503192XA (en)	2012-10-23	2015-06-29	Hoffmann La Roche	Mglu2/3 antagonists for the treatment of autistic disorders
US9914717B2 (en)	2012-12-20	2018-03-13	The Broad Institute, Inc.	Cycloalkenyl hydroxamic acid derivatives and their use as histone deacetylase inhibitors
AU2013371146C1 (en) *	2012-12-28	2019-01-17	Crystalgenomics, Inc.	2,3-dihydro-isoindole-1-on derivative as BTK kinase suppressant, and pharmaceutical composition including same
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
KR20220038826A (ko)	2014-01-21	2022-03-29	얀센 파마슈티카 엔.브이.	대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도
SMT202300002T1 (it)	2014-03-07	2023-03-17	Biocryst Pharm Inc	Pirazoli sostituiti come inibitori della callicreina plasmatica umana
KR20160143853A (ko) *	2014-04-23	2016-12-14	에프. 호프만-라 로슈 아게	지적 장애의 치료를 위한 mglu2/3 길항제
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
CN108727345B (zh) *	2017-04-25	2023-06-27	广东东阳光药业有限公司	一种咪唑环中间体的制备方法
JP2021510733A (ja)	2018-01-12	2021-04-30	ケーディーエーシーセラピューティクス，インコーポレーテッドＫｄａｃＴｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ．	がんの処置のための選択的ヒストンデアセチラーゼ３（ｈｄａｃ３）インヒビターと免疫治療剤との組み合わせ
CN108586447B (zh) *	2018-01-19	2021-01-29	中国人民解放军第四军医大学	一种苯二氮杂卓化合物及其制备方法和应用
PT3980013T (pt) *	2019-06-06	2024-10-23	Arcus Biosciences Inc	Processos de preparação de compostos de aminopirimidina

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU224435B1 (hu) *	1995-02-09	2005-10-28	EGIS Gyógyszergyár Rt.	Benzodiazepin-származékok, eljárás előállításukra, alkalmazásukra és ezeket tartalmazó gyógyászati készítmények
SK283859B6 (sk) *	1995-02-09	2004-03-02	Egis Gy�Gyszergy�R Rt.	1-[2'-(Substituovaný)vinyl]-5H-2,3-benzodiazepínové deriváty, spôsob ich prípravy a medziprodukty na ich prípravu, liečivá ich obsahujúce a ich použitie
MXPA02001340A (es) *	1999-08-05	2004-07-16	Prescient Neuropharma Inc	Compuestos novedosos 1,4-benzodiazepina y derivados de los mismos.
CA2386974C (fr) *	1999-10-15	2009-10-13	Geo Adam	Derives de benzodiazepine pouvant etre utilises pour traiter des troubles neurologiques aigus ou chroniques
CZ20021663A3 (cs) *	1999-10-15	2002-09-11	F. Hoffmann-La Roche Ag	Nové deriváty benzodiazepinu

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Also Published As

Publication number	Publication date
DE60205100D1 (de)	2005-08-25
NZ528315A (en)	2005-04-29
RU2263112C2 (ru)	2005-10-27
HK1068888A1 (en)	2005-05-06
HRP20030792A2 (en)	2005-10-31
MY140271A (en)	2009-12-31
ECSP034797A (es)	2003-12-01
IL157873A0 (en)	2004-03-28
US20020193367A1 (en)	2002-12-19
MA27012A1 (fr)	2004-12-20
SI1379511T1 (en)	2005-10-31
JP2004529925A (ja)	2004-09-30
AU2002312788B2 (en)	2005-11-10
ATE299868T1 (de)	2005-08-15
RU2003130637A (ru)	2005-04-10
KR20030087076A (ko)	2003-11-12
ES2246012T3 (es)	2006-02-01
CN1535266A (zh)	2004-10-06
EP1379511A1 (fr)	2004-01-14
IL157873A (en)	2008-11-26
DE60205100T2 (de)	2006-06-01
HUP0400851A2 (hu)	2004-07-28
YU79003A (sh)	2006-05-25
CA2442557A1 (fr)	2002-10-24
MXPA03009311A (es)	2004-02-12
PL367064A1 (en)	2005-02-21
KR100566171B1 (ko)	2006-03-29
WO2002083652A1 (fr)	2002-10-24
JO2285B1 (en)	2005-09-12
US6544985B2 (en)	2003-04-08
JP4071115B2 (ja)	2008-04-02
NO20034576D0 (no)	2003-10-10
UY27258A1 (es)	2002-10-31
PE20021041A1 (es)	2002-11-19
HUP0400851A3 (en)	2010-03-29
NO20034576L (no)	2003-11-12
GT200200073A (es)	2002-11-07
PT1379511E (pt)	2005-10-31
CN1264825C (zh)	2006-07-19
SK13682003A3 (sk)	2004-07-07
DK1379511T3 (da)	2005-11-07
EP1379511B1 (fr)	2005-07-20
CZ20033003A3 (cs)	2004-05-12
CA2442557C (fr)	2008-12-23
AR035816A1 (es)	2004-07-14
BR0208891A (pt)	2004-04-20
PA8543301A1 (es)	2003-01-24
ZA200307243B (en)	2004-12-16

Publication	Publication Date	Title
BG108254A (bg)	2004-09-30	ПРОИЗВОДНИ НА ДИХИДРО-БЕНЗО[b][1,4]ДИАЗЕПИН-2-ОН КАТО MGLUR2 АНТАГОНИСТИ II
AU2002312788A1 (en)	2003-04-10	Dihydro-benzo [b] [1, 4] diazepin-2-one derivatives as mGluR2 antagonists II
EP1379522B1 (fr)	2005-01-26	Derives de dihydro-benzo(b)(1,4)diazepine-2-one utilises comme antagonistes i de mglur2
US6960578B2 (en)	2005-11-01	Glutamate receptor antagonists
AU2002310912A1 (en)	2003-04-10	Dihydro-benzo[b][1,4]diazepin-2-one derivatives as mGluR2 antagonists I
RU45093U1 (ru)	2005-04-27	Пылеуловитель