HRP20030792A2 - DIHYDRO-BENZO[b][1,4]DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS II - Google Patents
DIHYDRO-BENZO[b][1,4]DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS IIInfo
- Publication number
- HRP20030792A2 HRP20030792A2 HR20030792A HRP20030792A HRP20030792A2 HR P20030792 A2 HRP20030792 A2 HR P20030792A2 HR 20030792 A HR20030792 A HR 20030792A HR P20030792 A HRP20030792 A HR P20030792A HR P20030792 A2 HRP20030792 A2 HR P20030792A2
- Authority
- HR
- Croatia
- Prior art keywords
- phenyl
- methyl
- tert
- amino
- butyl ester
- Prior art date
Links
- AZIZBYRGIGKTLW-UHFFFAOYSA-N 1,4-diazepin-2-one Chemical class O=C1C=NC=CC=N1 AZIZBYRGIGKTLW-UHFFFAOYSA-N 0.000 title claims description 39
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 title description 5
- 101150016175 Grm2 gene Proteins 0.000 title 1
- 239000005557 antagonist Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims description 650
- 150000001875 compounds Chemical class 0.000 claims description 588
- -1 3-oxo-piperazin-1-yl Chemical group 0.000 claims description 296
- 239000002253 acid Substances 0.000 claims description 131
- 238000006243 chemical reaction Methods 0.000 claims description 79
- 125000000217 alkyl group Chemical group 0.000 claims description 53
- 125000003545 alkoxy group Chemical group 0.000 claims description 46
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 150000002367 halogens Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 208000012902 Nervous system disease Diseases 0.000 claims description 5
- 208000025966 Neurological disease Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 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
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 4
- 230000002265 prevention Effects 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
- GBRPDPUYJNPHFW-UHFFFAOYSA-N 4-[2-oxo-7-pyrrolidin-1-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=C1N1CCCC1 GBRPDPUYJNPHFW-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 3
- MMFHASXGTDQSPH-UHFFFAOYSA-N 4-[7-[methyl(propan-2-yl)amino]-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(N(C)C(C)C)=CC=2N=C1C1=CC=NC(C#N)=C1 MMFHASXGTDQSPH-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- VAQIGIYSLWNPSM-UHFFFAOYSA-N 7-(dimethylamino)-4-[3-[4-(hydroxymethyl)-1,3-oxazol-2-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=NC(CO)=CO1 VAQIGIYSLWNPSM-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- PKAGRYFXAAQOOC-UHFFFAOYSA-N 8-chloro-4-(3-imidazol-1-ylphenyl)-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=1N1C=CN=C1 PKAGRYFXAAQOOC-UHFFFAOYSA-N 0.000 claims description 3
- GZPCGGQMFQCOJG-UHFFFAOYSA-N 8-chloro-4-[3-[5-[[methyl(2-methylpropyl)amino]methyl]triazol-1-yl]phenyl]-7-[methyl(propan-2-yl)amino]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC(C)CN(C)CC1=CN=NN1C1=CC=CC(C=2CC(=O)NC3=CC(Cl)=C(N(C)C(C)C)C=C3N=2)=C1 GZPCGGQMFQCOJG-UHFFFAOYSA-N 0.000 claims description 3
- DHDNESILTRMMAB-UHFFFAOYSA-N 8-chloro-7-[methyl(2-methylpropyl)amino]-4-[3-[5-(pyrrolidin-1-ylmethyl)triazol-1-yl]phenyl]-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=1N1N=NC=C1CN1CCCC1 DHDNESILTRMMAB-UHFFFAOYSA-N 0.000 claims description 3
- PUMGQYZLUWHXDO-UHFFFAOYSA-N 8-methyl-7-[methyl(2-methylpropyl)amino]-4-[3-[5-(pyrrolidin-1-ylmethyl)triazol-1-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=1N1N=NC=C1CN1CCCC1 PUMGQYZLUWHXDO-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 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
- SLZWQLBLGIMSRX-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-7-(2-methylpropylamino)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(NCC(C)C)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=C1 SLZWQLBLGIMSRX-UHFFFAOYSA-N 0.000 claims description 2
- MOZPRFSXXYUWQA-UHFFFAOYSA-N 4-[3-[5-(azetidin-1-ylmethyl)triazol-1-yl]phenyl]-8-chloro-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=1N1N=NC=C1CN1CCC1 MOZPRFSXXYUWQA-UHFFFAOYSA-N 0.000 claims description 2
- 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 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
- 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
- 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 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
- UXWOBRYNOZWNRK-UHFFFAOYSA-N 7-(dimethylamino)-4-[3-[4-(hydroxymethyl)-1,3-thiazol-2-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=NC(CO)=CS1 UXWOBRYNOZWNRK-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
- GKGGRNXTYYJBPH-UHFFFAOYSA-N 7-[methyl(2-methylpropyl)amino]-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(N(C)CC(C)C)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 GKGGRNXTYYJBPH-UHFFFAOYSA-N 0.000 claims description 2
- JHMOJYCUDSVXIH-UHFFFAOYSA-N 7-[methyl(propyl)amino]-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(N(C)CCC)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 JHMOJYCUDSVXIH-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 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
- VGCFBGKWKFNEIC-UHFFFAOYSA-N 8-chloro-4-[3-[5-[(dimethylamino)methyl]triazol-1-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=1N1N=NC=C1CN(C)C VGCFBGKWKFNEIC-UHFFFAOYSA-N 0.000 claims description 2
- KMRCILAGDOXKQR-UHFFFAOYSA-N 8-chloro-7-[methyl(2-methylpropyl)amino]-4-[3-(triazol-1-yl)phenyl]-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=1N1C=CN=N1 KMRCILAGDOXKQR-UHFFFAOYSA-N 0.000 claims description 2
- SOYNHYRIQYZWGC-UHFFFAOYSA-N 8-chloro-7-[methyl(2-methylpropyl)amino]-4-[3-[5-(piperidin-1-ylmethyl)triazol-1-yl]phenyl]-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=1N1N=NC=C1CN1CCCCC1 SOYNHYRIQYZWGC-UHFFFAOYSA-N 0.000 claims description 2
- SAVDHCKDKXITDB-UHFFFAOYSA-N 8-chloro-7-[methyl(propan-2-yl)amino]-4-[3-[5-(pyrrolidin-1-ylmethyl)triazol-1-yl]phenyl]-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=1N1N=NC=C1CN1CCCC1 SAVDHCKDKXITDB-UHFFFAOYSA-N 0.000 claims description 2
- VHBNDJVFQOPHQL-UHFFFAOYSA-N 8-chloro-7-[methyl(propan-2-yl)amino]-4-[3-[5-[[methyl(propan-2-yl)amino]methyl]triazol-1-yl]phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC(C)N(C)CC1=CN=NN1C1=CC=CC(C=2CC(=O)NC3=CC(Cl)=C(N(C)C(C)C)C=C3N=2)=C1 VHBNDJVFQOPHQL-UHFFFAOYSA-N 0.000 claims description 2
- YTKAPOCJJREWCQ-UHFFFAOYSA-N 8-chloro-7-[methyl(propyl)amino]-4-[3-[5-(pyrrolidin-1-ylmethyl)triazol-1-yl]phenyl]-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=1N1N=NC=C1CN1CCCC1 YTKAPOCJJREWCQ-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
- 238000010511 deprotection reaction Methods 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
- 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 4
- 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 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 561
- 239000007787 solid Substances 0.000 description 375
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 358
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 205
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 200
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 153
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 134
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 129
- 239000000203 mixture Substances 0.000 description 126
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
- 239000003921 oil Substances 0.000 description 107
- 235000019198 oils Nutrition 0.000 description 107
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 95
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 80
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 66
- 239000006260 foam Substances 0.000 description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 57
- 150000004702 methyl esters Chemical class 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- 235000011121 sodium hydroxide Nutrition 0.000 description 50
- 235000019439 ethyl acetate Nutrition 0.000 description 46
- 239000000463 material Substances 0.000 description 46
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- WHDYGVAGQYOHSV-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-[cyclopropylmethyl(methyl)amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C=1C(NC(=O)OC(C)(C)C)=C(NC(=O)CC(=O)C=2C=C(N=CC=2)C#N)C=C(C(F)(F)F)C=1N(C)CC1CC1 WHDYGVAGQYOHSV-UHFFFAOYSA-N 0.000 description 1
- ZAAPBVPUTMYLCV-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-pyrrolidin-1-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=1N1CCCC1 ZAAPBVPUTMYLCV-UHFFFAOYSA-N 0.000 description 1
- ZBJKSZQKXWZHQR-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-(2,3-difluorophenyl)-5-(dimethylamino)phenyl]carbamate Chemical compound C1=C(C=2C(=C(F)C=CC=2)F)C(N(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 ZBJKSZQKXWZHQR-UHFFFAOYSA-N 0.000 description 1
- JYTVKBWKBHSTMD-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(dimethylamino)-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(C#N)=C1 JYTVKBWKBHSTMD-UHFFFAOYSA-N 0.000 description 1
- CHCLFKQUCNAXTK-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2,3-difluorophenyl)-5-(dimethylamino)phenyl]carbamate Chemical compound CN(C)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C1=CC=CC(F)=C1F CHCLFKQUCNAXTK-UHFFFAOYSA-N 0.000 description 1
- AVXDDDSVQMREIQ-UHFFFAOYSA-N tert-butyl n-[2-amino-4-chloro-5-[2-methoxyethyl(methyl)amino]phenyl]carbamate Chemical compound COCCN(C)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1Cl AVXDDDSVQMREIQ-UHFFFAOYSA-N 0.000 description 1
- ISKUUZNVPWUNTC-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(dimethylamino)-4-fluorophenyl]carbamate Chemical compound CN(C)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1F ISKUUZNVPWUNTC-UHFFFAOYSA-N 0.000 description 1
- FBTJEKMDVKZHDX-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(dimethylamino)-4-methylphenyl]carbamate Chemical compound CN(C)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C FBTJEKMDVKZHDX-UHFFFAOYSA-N 0.000 description 1
- HBMYBFUHFGSHSZ-UHFFFAOYSA-N tert-butyl n-[2-amino-5-[methyl(propyl)amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CCCN(C)C1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C(F)(F)F HBMYBFUHFGSHSZ-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- PUEZFVQDVZKFKJ-UHFFFAOYSA-N tert-butyl n-[4-chloro-5-(dimethylamino)-2-[[3-oxo-3-[3-(1,2,4-triazol-1-yl)phenyl]propanoyl]amino]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(N2N=CN=C2)=C1 PUEZFVQDVZKFKJ-UHFFFAOYSA-N 0.000 description 1
- VQHDTNKXJNFGJP-UHFFFAOYSA-N tert-butyl n-[4-chloro-5-(dimethylamino)-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]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(N2N=NC=C2)=C1 VQHDTNKXJNFGJP-UHFFFAOYSA-N 0.000 description 1
- UWIPDKGOVLNYQV-UHFFFAOYSA-N tert-butyl n-[4-chloro-5-[2-methoxyethyl(methyl)amino]-2-nitrophenyl]carbamate Chemical compound COCCN(C)C1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1Cl UWIPDKGOVLNYQV-UHFFFAOYSA-N 0.000 description 1
- GNSCRQCDBOWMBM-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]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(N2C=NC=C2)=C1 GNSCRQCDBOWMBM-UHFFFAOYSA-N 0.000 description 1
- TUWYUPFKTNBXFX-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-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)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=CN=C2)=C1 TUWYUPFKTNBXFX-UHFFFAOYSA-N 0.000 description 1
- FBLVKWULSZQOPE-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-2-[[3-oxo-3-[3-(1,2,4-triazol-4-yl)phenyl]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(N2C=NN=C2)=C1 FBLVKWULSZQOPE-UHFFFAOYSA-N 0.000 description 1
- HPFHUXWRNWPFDC-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(2-phenylethynyl)phenyl]carbamate Chemical compound C1=C(C#CC=2C=CC=CC=2)C(N(C)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=N1 HPFHUXWRNWPFDC-UHFFFAOYSA-N 0.000 description 1
- ZAUJSZSKPPUOAZ-UHFFFAOYSA-N tert-butyl n-[5-(dimethylamino)-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)C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 ZAUJSZSKPPUOAZ-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
- 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
- 238000004809 thin layer chromatography Methods 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 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
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 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 class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 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
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc 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
Landscapes
- 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)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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EP01109125 | 2001-04-12 | ||
PCT/EP2002/003644 WO2002083652A1 (en) | 2001-04-12 | 2002-04-02 | DIHYDRO-BENZO [b] [1, 4] DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS II |
Publications (1)
Publication Number | Publication Date |
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HRP20030792A2 true HRP20030792A2 (en) | 2005-10-31 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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HR20030792A HRP20030792A2 (en) | 2001-04-12 | 2003-10-01 | DIHYDRO-BENZO[b][1,4]DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS II |
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US (1) | US6544985B2 (sh) |
EP (1) | EP1379511B1 (sh) |
JP (1) | JP4071115B2 (sh) |
KR (1) | KR100566171B1 (sh) |
CN (1) | CN1264825C (sh) |
AR (1) | AR035816A1 (sh) |
AT (1) | ATE299868T1 (sh) |
AU (1) | AU2002312788B2 (sh) |
BG (1) | BG108254A (sh) |
BR (1) | BR0208891A (sh) |
CA (1) | CA2442557C (sh) |
CZ (1) | CZ20033003A3 (sh) |
DE (1) | DE60205100T2 (sh) |
DK (1) | DK1379511T3 (sh) |
EC (1) | ECSP034797A (sh) |
ES (1) | ES2246012T3 (sh) |
GT (1) | GT200200073A (sh) |
HK (1) | HK1068888A1 (sh) |
HR (1) | HRP20030792A2 (sh) |
HU (1) | HUP0400851A3 (sh) |
IL (2) | IL157873A0 (sh) |
JO (1) | JO2285B1 (sh) |
MA (1) | MA27012A1 (sh) |
MX (1) | MXPA03009311A (sh) |
MY (1) | MY140271A (sh) |
NO (1) | NO20034576L (sh) |
NZ (1) | NZ528315A (sh) |
PA (1) | PA8543301A1 (sh) |
PE (1) | PE20021041A1 (sh) |
PL (1) | PL367064A1 (sh) |
PT (1) | PT1379511E (sh) |
RU (1) | RU2263112C2 (sh) |
SI (1) | SI1379511T1 (sh) |
SK (1) | SK13682003A3 (sh) |
UY (1) | UY27258A1 (sh) |
WO (1) | WO2002083652A1 (sh) |
YU (1) | YU79003A (sh) |
ZA (1) | ZA200307243B (sh) |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
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JP3886805B2 (ja) * | 1999-10-15 | 2007-02-28 | エフ.ホフマン−ラ ロシュ アーゲー | ベンゾジアゼピン誘導体 |
PL208123B1 (pl) * | 2001-12-27 | 2011-03-31 | Taisho Pharmaceutical Co Ltd | Pochodna kwasu 2-amino-3-alkoksy-6-fluorobicyklo [3.1.0] heksano-2, 6-dikarboksylowego, zawierająca ją kompozycja farmaceutyczna i lek, oraz jej zastosowanie |
EP1925614A1 (en) * | 2002-03-28 | 2008-05-28 | Wisys Technology Foundation, Inc. | Anxiolytic agents with reduced sedative and ataxic effects |
MXPA04009332A (es) | 2002-03-28 | 2005-12-12 | Wisys Technology Found Inc | Agentes ansioliticos con efectos sedantes y ataxicos. |
PT1651234E (pt) * | 2003-07-25 | 2007-12-28 | Hoffmann La Roche | Combinação de um antagonista de mglur2 e de um inibidor de ache para tratamento de perturbações neurólgicas agudas e/ou crónicas |
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 |
CA2597608C (en) | 2005-02-11 | 2013-12-24 | F. Hoffmann-La Roche Ag | Pyrazolo-pyrimidine derivatives as mglur2 antagonists |
ES2339477T3 (es) | 2005-03-23 | 2010-05-20 | F.Hoffmann-La Roche Ag | Derivados de acetilenil-pirazolo-pirimidina como antagonistas de mglur2. |
MX351820B (es) | 2005-06-23 | 2017-10-30 | Astrazeneca Ab | Proceso para preparar compuestos de bencimidazol. |
CA2623721C (en) | 2005-09-27 | 2014-05-13 | F. Hoffmann-La Roche Ag | Oxadiazolyl pyrazolo-pyrimidines as mglur2 antagonists |
GB0600228D0 (en) * | 2006-01-06 | 2006-02-15 | Fermentas Uab | Inactivation method |
AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
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 |
TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
KR101151993B1 (ko) | 2007-04-19 | 2012-06-01 | 에프. 호프만-라 로슈 아게 | 다이하이드로-벤조[b][1,4]다이아제핀-2-온 설폰아미드 유도체 |
CA2697399C (en) | 2007-09-14 | 2016-01-19 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | 1,3-disubstituted 4-(aryl-x-phenyl)-1h-pyridin-2-ones |
CA2698929C (en) * | 2007-09-14 | 2016-01-19 | Addex Pharma S.A. | 1,3-disubstituted-4-phenyl-1h-pyridin-2-ones |
RS51660B (en) | 2007-09-14 | 2011-10-31 | Ortho-Mcneil-Janssen Pharmaceuticals Inc. | 1`, 3`-DISUPSTITUATED-4-PHENYL-3,4,5,6-TETRAHYDRO-2H, 1`H- [1,4`] BIPYRIDINYL-2`-ONE |
JP5433582B2 (ja) | 2007-11-14 | 2014-03-05 | 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. | イミダゾ[1,2−a]ピリジン誘導体およびmGluR2受容体の正のアロステリック調節因子としてのその使用 |
WO2010025890A1 (en) | 2008-09-02 | 2010-03-11 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc | 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors |
EP2346505B1 (en) | 2008-10-16 | 2014-04-23 | Janssen Pharmaceuticals, Inc. | Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors |
US8691813B2 (en) | 2008-11-28 | 2014-04-08 | Janssen Pharmaceuticals, Inc. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
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 |
EP2430031B1 (en) | 2009-05-12 | 2013-04-17 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
EP2430022B1 (en) | 2009-05-12 | 2013-11-20 | 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 |
CN103140483B (zh) | 2010-07-15 | 2015-06-24 | 拜耳知识产权有限责任公司 | 作为杀虫剂的新杂环化合物 |
WO2012059432A1 (en) | 2010-11-01 | 2012-05-10 | Abbott Gmbh & Co. Kg | N-phenyl-(homo)piperazinyl-benzenesulfonyl or benzenesulfonamide compounds suitable for treating disorders that respond to the modulation of the 5-ht6 receptor |
WO2012059431A1 (en) | 2010-11-01 | 2012-05-10 | Abbott Gmbh & Co. Kg | Benzenesulfonyl or sulfonamide compounds suitable for treating disorders that respond to the modulation of the serotonin 5-ht6 receptor |
WO2012062750A1 (en) | 2010-11-08 | 2012-05-18 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
EP2643320B1 (en) | 2010-11-08 | 2015-03-04 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
AU2011328203B2 (en) | 2010-11-08 | 2015-03-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors |
EP2701699B1 (en) * | 2011-04-28 | 2019-10-16 | The Broad Institute, Inc. | Inhibitors of histone deacetylase |
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 |
EP2751095B1 (en) * | 2011-08-29 | 2021-10-27 | Sanford-Burnham Medical Research Institute | Novel benzodiazepinones as modulators of metabotropic glutamate receptor functions and neurological uses thereof |
EP2877444B1 (en) | 2012-07-27 | 2020-09-02 | The Broad Institute, Inc. | Inhibitors of histone deacetylase |
SG11201503192XA (en) | 2012-10-23 | 2015-06-29 | Hoffmann La Roche | Mglu2/3 antagonists for the treatment of autistic disorders |
WO2014100438A1 (en) | 2012-12-20 | 2014-06-26 | The Broad Institute, Inc. | Cycloalkenyl hydroxamic acid derivatives and their use as histone deacetylase inhibitors |
DK2940014T3 (en) * | 2012-12-28 | 2018-12-10 | Crystalgenomics Inc | 2,3-DIHYDRO-ISOINDOL-1-ON DERIVATIVE AS BTK KINase INHIBITORS AND PHARMACEUTICAL COMPOSITION INCLUDING THE 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 |
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 |
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 |
ES2932406T3 (es) | 2014-03-07 | 2023-01-18 | Biocryst Pharm Inc | Pirazoles sustituidos como inhibidores de calicreína del plasma humano |
MX2016013711A (es) * | 2014-04-23 | 2017-01-13 | Hoffmann La Roche | Antagonistas de receptores de glumato metabotropicos 2/3 (mglu2/3) para el tratamiento de varias discapacidades intelectuales. |
WO2015191630A1 (en) | 2014-06-10 | 2015-12-17 | Sanford-Burnham Medical Research Institute | Metabotropic glutamate receptor negative allosteric modulators (nams) and uses thereof |
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 |
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 |
SG11202112684SA (en) * | 2019-06-06 | 2021-12-30 | Arcus Biosciences Inc | Processes for preparing aminopyrimidine compounds |
Family Cites Families (3)
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JP2003506440A (ja) * | 1999-08-05 | 2003-02-18 | プレサイエント ニューロファーマ インコーポレイテッド | 中枢神経系に関連する疾患の処置のための1,4−ジアゼピン誘導体 |
PT1224174E (pt) * | 1999-10-15 | 2004-01-30 | Hoffmann La Roche | Derivados de benzodiazepina como antagonistas do receptor metabotropico do glutamato |
JP3886805B2 (ja) * | 1999-10-15 | 2007-02-28 | エフ.ホフマン−ラ ロシュ アーゲー | ベンゾジアゼピン誘導体 |
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