RU2270197C2 - ПРОИЗВОДНЫЕ ДИГИДРОБЕНЗО[b][1,4]ДИАЗЕПИН-2-ОНА В КАЧЕСТВЕ АНТАГОНИСТОВ I mGluR2 - Google Patents

Info

Publication number

RU2270197C2

RU2270197C2 RU2003130648/04A RU2003130648A RU2270197C2 RU 2270197 C2 RU2270197 C2 RU 2270197C2 RU 2003130648/04 A RU2003130648/04 A RU 2003130648/04A RU 2003130648 A RU2003130648 A RU 2003130648A RU 2270197 C2 RU2270197 C2 RU 2270197C2

Authority

RU

Russia

Prior art keywords

diazepin

phenyl

dihydrobenzo

trifluoromethyl

mmol

Prior art date

2001-04-12

Links

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• Global Dossier
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• 239000005557 antagonist Substances 0.000 title claims abstract description 6
• 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 title abstract description 6
• 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 title abstract description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 452
• 238000000034 method Methods 0.000 claims abstract description 322
• -1 pyrrole-1-yl Chemical group 0.000 claims abstract description 130
• 238000011282 treatment Methods 0.000 claims abstract description 70
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 54
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 42
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 40
• 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 30
• 150000003839 salts Chemical class 0.000 claims abstract description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
• 239000003814 drug Substances 0.000 claims abstract description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
• 229940079593 drug Drugs 0.000 claims abstract description 8
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 7
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
• 125000005843 halogen group Chemical group 0.000 claims abstract description 6
• 125000004849 alkoxymethyl group Chemical group 0.000 claims abstract description 3
• 239000000654 additive Substances 0.000 claims abstract 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 34
• 230000015572 biosynthetic process Effects 0.000 claims description 28
• 239000002253 acid Substances 0.000 claims description 24
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 19
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
• 125000006239 protecting group Chemical group 0.000 claims description 13
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 150000002431 hydrogen Chemical class 0.000 claims description 8
• 230000003993 interaction Effects 0.000 claims description 8
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 claims description 7
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 claims description 7
• 230000002829 reductive effect Effects 0.000 claims description 7
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
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• RJNFOFBZNNRQNC-UHFFFAOYSA-N 4-[3-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 RJNFOFBZNNRQNC-UHFFFAOYSA-N 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 125000001424 substituent group Chemical group 0.000 claims description 4
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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 description 3
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• LTODSASAOXHZES-UHFFFAOYSA-N 4-[3-[3-(hydroxymethyl)-1,2-oxazol-5-yl]phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(CO)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 LTODSASAOXHZES-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
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• PXTUROXJUIVEOU-UHFFFAOYSA-N 7-chloro-4-[3-(triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1N1C=CN=N1 PXTUROXJUIVEOU-UHFFFAOYSA-N 0.000 claims description 3
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