AU2003205695B8 - Dihydro-benzo[B][1,4]diazepin-2-one derivatives - Google Patents

Info

Publication number

AU2003205695B8

AU2003205695B8 AU2003205695A AU2003205695A AU2003205695B8 AU 2003205695 B8 AU2003205695 B8 AU 2003205695B8 AU 2003205695 A AU2003205695 A AU 2003205695A AU 2003205695 A AU2003205695 A AU 2003205695A AU 2003205695 B8 AU2003205695 B8 AU 2003205695B8

Authority

AU

Australia

Prior art keywords

phenyl

fluoro

mmol

pyridin

acid tert

Prior art date

2002-02-06

Legal status (The legal status 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 status listed.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• AZIZBYRGIGKTLW-UHFFFAOYSA-N 1,4-diazepin-2-one Chemical class O=C1C=NC=CC=N1 AZIZBYRGIGKTLW-UHFFFAOYSA-N 0.000 title claims description 16
• 238000000034 method Methods 0.000 claims description 866
• 150000001875 compounds Chemical class 0.000 claims description 755
• -1 -NR'R" Chemical group 0.000 claims description 328
• 125000000217 alkyl group Chemical group 0.000 claims description 135
• 125000003545 alkoxy group Chemical group 0.000 claims description 93
• 239000001257 hydrogen Substances 0.000 claims description 55
• 229910052739 hydrogen Inorganic materials 0.000 claims description 55
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
• 229910052736 halogen Inorganic materials 0.000 claims description 52
• 125000003282 alkyl amino group Chemical group 0.000 claims description 50
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
• 125000005605 benzo group Chemical group 0.000 claims description 39
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 36
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
• 125000001424 substituent group Chemical group 0.000 claims description 32
• 150000002367 halogens Chemical group 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000001153 fluoro group Chemical group F* 0.000 claims description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 22
• 239000002253 acid Substances 0.000 claims description 22
• 125000004414 alkyl thio group Chemical group 0.000 claims description 19
• ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 14
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 11
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
• 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 10
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• 125000003277 amino group Chemical group 0.000 claims description 6
• 230000008569 process Effects 0.000 claims description 6
• 238000007363 ring formation reaction Methods 0.000 claims description 6
• 208000028017 Psychotic disease Diseases 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• QDKZHQGXPVFLHU-UHFFFAOYSA-N 1,5-benzodiazepin-2-one Chemical compound O=C1C=CN=C2C=CC=CC2=N1 QDKZHQGXPVFLHU-UHFFFAOYSA-N 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• 201000000980 schizophrenia Diseases 0.000 claims description 4
• 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 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 238000010511 deprotection reaction Methods 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims 21
• DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 claims 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 2
• LDCMTXMRTVOLKA-UHFFFAOYSA-N 1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N1C(=O)CC=NC2=CC=CC=C21 LDCMTXMRTVOLKA-UHFFFAOYSA-N 0.000 claims 1
• GMNRSMAPXMAKAW-UHFFFAOYSA-N 1-(fluoromethyl)-3h-1,5-benzodiazepin-2-one Chemical compound N1=CCC(=O)N(CF)C2=CC=CC=C21 GMNRSMAPXMAKAW-UHFFFAOYSA-N 0.000 claims 1
• ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical compound N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 claims 1
• PXNOUTUNFINTTA-UHFFFAOYSA-N 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-(2,2,2-trifluoroethoxy)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(OCC(F)(F)F)C=C3N=2)C(F)(F)F)=C1 PXNOUTUNFINTTA-UHFFFAOYSA-N 0.000 claims 1
• YQKASQGOPRPMLH-UHFFFAOYSA-N 7-(dimethylamino)-4-(3-pyridin-4-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=1C1=CC=NC=C1 YQKASQGOPRPMLH-UHFFFAOYSA-N 0.000 claims 1
• JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 claims 1
• 239000007787 solid Substances 0.000 description 421
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 290
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 246
• 150000002148 esters Chemical class 0.000 description 163
• 239000000203 mixture Substances 0.000 description 127
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 116
• 239000006260 foam Substances 0.000 description 114
• 235000019439 ethyl acetate Nutrition 0.000 description 101
• 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 98
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 96
• 239000003921 oil Substances 0.000 description 94
• 235000019198 oils Nutrition 0.000 description 94
• 239000000243 solution Substances 0.000 description 94
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 93
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
• AEHYHZHQKIYWHR-UHFFFAOYSA-N tert-butyl 3-oxo-3-(3-pyridin-3-ylphenyl)propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2C=NC=CC=2)=C1 AEHYHZHQKIYWHR-UHFFFAOYSA-N 0.000 description 74
• 239000000460 chlorine Substances 0.000 description 67
• WSUXSDFUECNYSX-UHFFFAOYSA-N tert-butyl n-[2-amino-5-methyl-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C(F)(F)F WSUXSDFUECNYSX-UHFFFAOYSA-N 0.000 description 64
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 61
• SAHCRZHMDWJEMU-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C(F)(F)F)C=C1N SAHCRZHMDWJEMU-UHFFFAOYSA-N 0.000 description 59
• 239000002904 solvent Substances 0.000 description 58
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 55
• 239000000126 substance Substances 0.000 description 54
• VTSJYKYERZLMEK-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(OCC(F)(F)F)=C(C(F)(F)F)C=C1N VTSJYKYERZLMEK-UHFFFAOYSA-N 0.000 description 54
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 53
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
• 239000012267 brine Substances 0.000 description 52
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 52
• 239000011734 sodium Substances 0.000 description 51
• RENOIBALUBTYLS-UHFFFAOYSA-N tert-butyl 3-[3-(2-methylpyridin-4-yl)phenyl]-3-oxopropanoate Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C(=O)CC(=O)OC(C)(C)C)=C1 RENOIBALUBTYLS-UHFFFAOYSA-N 0.000 description 49
• XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 48
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• LGAJSDWFYQMSMX-UHFFFAOYSA-N tert-butyl 3-oxo-3-(3-pyridin-4-ylphenyl)propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2C=CN=CC=2)=C1 LGAJSDWFYQMSMX-UHFFFAOYSA-N 0.000 description 46
• 238000010898 silica gel chromatography Methods 0.000 description 42
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 37
• 238000006243 chemical reaction Methods 0.000 description 37
• JNOTVBKCTMWNCH-UHFFFAOYSA-N tert-butyl n-(2-amino-4-chloro-5-methylphenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1Cl JNOTVBKCTMWNCH-UHFFFAOYSA-N 0.000 description 35
• UXKVDHBWXZINNK-UHFFFAOYSA-N tert-butyl n-[2-amino-5-ethoxy-4-(trifluoromethyl)phenyl]carbamate Chemical compound CCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C(F)(F)F UXKVDHBWXZINNK-UHFFFAOYSA-N 0.000 description 35
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 34
• 238000005984 hydrogenation reaction Methods 0.000 description 31
• AEYBBZRWQPBSDJ-UHFFFAOYSA-N tert-butyl 3-oxo-3-(3-pyridin-2-ylphenyl)propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2N=CC=CC=2)=C1 AEYBBZRWQPBSDJ-UHFFFAOYSA-N 0.000 description 31
• ZTCGGBIFOFASKI-UHFFFAOYSA-N tert-butyl acetate;lithium Chemical compound [Li].CC(=O)OC(C)(C)C ZTCGGBIFOFASKI-UHFFFAOYSA-N 0.000 description 31
• 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 29
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
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• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 27
• 239000000741 silica gel Substances 0.000 description 27
• 229910002027 silica gel Inorganic materials 0.000 description 27
• 239000012043 crude product Substances 0.000 description 26
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• FVZIFCWZBOPYIS-UHFFFAOYSA-N tert-butyl 3-oxo-3-(3-pyrazin-2-ylphenyl)propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2N=CC=NC=2)=C1 FVZIFCWZBOPYIS-UHFFFAOYSA-N 0.000 description 23
• 230000007062 hydrolysis Effects 0.000 description 22
• 238000006460 hydrolysis reaction Methods 0.000 description 22
• 238000003756 stirring Methods 0.000 description 22
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 22
• KXLAIFIPGIZAJM-UHFFFAOYSA-N tert-butyl n-[2-amino-5-chloro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1N KXLAIFIPGIZAJM-UHFFFAOYSA-N 0.000 description 22
• 230000009467 reduction Effects 0.000 description 20
• 150000003751 zinc Chemical class 0.000 description 20
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
• 238000004440 column chromatography Methods 0.000 description 19
• 238000010992 reflux Methods 0.000 description 19
• VXDQRQWDMCRSRI-UHFFFAOYSA-N tert-butyl 3-oxo-3-(3-pyrimidin-5-ylphenyl)propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2C=NC=NC=2)=C1 VXDQRQWDMCRSRI-UHFFFAOYSA-N 0.000 description 19
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• 239000010502 orange oil Substances 0.000 description 18
• 239000008096 xylene Substances 0.000 description 18
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 17
• 150000004702 methyl esters Chemical class 0.000 description 17
• 238000002360 preparation method Methods 0.000 description 17
• HYTGYTLUYPRXTL-UHFFFAOYSA-N tert-butyl 3-[3-(2,6-dimethylpyridin-4-yl)phenyl]-3-oxopropanoate Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C(=O)CC(=O)OC(C)(C)C)=C1 HYTGYTLUYPRXTL-UHFFFAOYSA-N 0.000 description 17
• 238000010626 work up procedure Methods 0.000 description 17
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• 239000000463 material Substances 0.000 description 16
• 150000002431 hydrogen Chemical group 0.000 description 15
• RAAXZOKVGWKKCP-UHFFFAOYSA-N tert-butyl n-(2-amino-4-chlorophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(Cl)C=C1N RAAXZOKVGWKKCP-UHFFFAOYSA-N 0.000 description 15
• 238000004587 chromatography analysis Methods 0.000 description 14
• 229940093499 ethyl acetate Drugs 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 14
• DBVFWZMQJQMJCB-UHFFFAOYSA-N 3-boronobenzoic acid Chemical compound OB(O)C1=CC=CC(C(O)=O)=C1 DBVFWZMQJQMJCB-UHFFFAOYSA-N 0.000 description 13
• VNHPYPILBWQVTL-UHFFFAOYSA-N tert-butyl 3-[3-(6-methylpyridin-3-yl)phenyl]-3-oxopropanoate Chemical compound C1=NC(C)=CC=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 VNHPYPILBWQVTL-UHFFFAOYSA-N 0.000 description 13
• MHOIZXNWGRDLBM-UHFFFAOYSA-N tert-butyl 3-[3-[2-(oxan-2-yloxymethyl)pyridin-4-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2C=C(COC3OCCCC3)N=CC=2)=C1 MHOIZXNWGRDLBM-UHFFFAOYSA-N 0.000 description 13
• KYHFBBURZMZTII-UHFFFAOYSA-N tert-butyl n-[2-amino-4-methyl-5-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(N)=C(NC(=O)OC(C)(C)C)C=C1C(F)(F)F KYHFBBURZMZTII-UHFFFAOYSA-N 0.000 description 13
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• 239000002244 precipitate Substances 0.000 description 12
• MGYGCOIPDVEYEN-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(trifluoromethoxy)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(OC(F)(F)F)C=C1N MGYGCOIPDVEYEN-UHFFFAOYSA-N 0.000 description 12
• 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 12
• 239000012300 argon atmosphere Substances 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
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• WHHWCCNXCHLQEH-UHFFFAOYSA-N tert-butyl 3-[3-(2-methylpyridin-3-yl)phenyl]-3-oxopropanoate Chemical compound CC1=NC=CC=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 WHHWCCNXCHLQEH-UHFFFAOYSA-N 0.000 description 10
• RXHRIUDEGZJSQX-UHFFFAOYSA-N tert-butyl 3-[3-(6-cyclopropylpyridin-3-yl)phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2C=NC(=CC=2)C2CC2)=C1 RXHRIUDEGZJSQX-UHFFFAOYSA-N 0.000 description 10
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• 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 9
• CDQRKSLMPFFDHX-UHFFFAOYSA-N tert-butyl 3-[3-(2-ethylpyridin-4-yl)phenyl]-3-oxopropanoate Chemical compound C1=NC(CC)=CC(C=2C=C(C=CC=2)C(=O)CC(=O)OC(C)(C)C)=C1 CDQRKSLMPFFDHX-UHFFFAOYSA-N 0.000 description 9
• XRLMKPLJDSCXIZ-UHFFFAOYSA-N tert-butyl 3-[3-(6-methylpyrazin-2-yl)phenyl]-3-oxopropanoate Chemical compound CC1=CN=CC(C=2C=C(C=CC=2)C(=O)CC(=O)OC(C)(C)C)=N1 XRLMKPLJDSCXIZ-UHFFFAOYSA-N 0.000 description 9
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