WO2016137260A1 - Imidazopyrimidine and imidazotriazine derivative, and pharmaceutical composition comprising the same - Google Patents
Imidazopyrimidine and imidazotriazine derivative, and pharmaceutical composition comprising the same Download PDFInfo
- Publication number
- WO2016137260A1 WO2016137260A1 PCT/KR2016/001887 KR2016001887W WO2016137260A1 WO 2016137260 A1 WO2016137260 A1 WO 2016137260A1 KR 2016001887 W KR2016001887 W KR 2016001887W WO 2016137260 A1 WO2016137260 A1 WO 2016137260A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- imidazo
- pyrimidine
- fluoro
- methyl
- pyridyl
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 19
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title description 10
- XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical class N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 284
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract description 49
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 239000000126 substance Substances 0.000 claims abstract description 27
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 26
- 229930195712 glutamate Natural products 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 208000035475 disorder Diseases 0.000 claims abstract description 16
- 230000004064 dysfunction Effects 0.000 claims abstract description 15
- 230000001404 mediated effect Effects 0.000 claims abstract description 13
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 125000005843 halogen group Chemical group 0.000 claims description 63
- -1 cyano, formyl Chemical group 0.000 claims description 57
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 50
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 12
- 229910052805 deuterium Inorganic materials 0.000 claims description 12
- QSOBFLOJUBOUCJ-UHFFFAOYSA-N 2-(4-fluoro-2-methylphenyl)-6-(pyridin-2-yloxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(N=1)C=C(N=2)COC1=NC=CC=C1)C QSOBFLOJUBOUCJ-UHFFFAOYSA-N 0.000 claims description 11
- FMZKBYVCUHZMQM-UHFFFAOYSA-N [5-fluoro-2-[2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol Chemical compound FC=1C=CC(=C(C=1)CO)C=1C=NC=2N(C=1)C=C(N=2)COC1=NC=CC=C1 FMZKBYVCUHZMQM-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 201000000980 schizophrenia Diseases 0.000 claims description 9
- ZOZBTAFZWGYWOJ-UHFFFAOYSA-N [5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol Chemical compound FC=1C=CC(=C(C=1)CO)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=C(C=C1)F ZOZBTAFZWGYWOJ-UHFFFAOYSA-N 0.000 claims description 8
- UQZIDUTYHFQTND-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=C(C=CC(=C1)F)C=1C=NC=2N(N=1)C=C(N=2)COC1=CC=CC=C1 UQZIDUTYHFQTND-UHFFFAOYSA-N 0.000 claims description 7
- VPSHEACHQHTIHA-UHFFFAOYSA-N 6-(4-fluoro-2-methylphenyl)-2-[(5-fluoropyridin-2-yl)oxymethyl]imidazo[1,2-a]pyrimidine Chemical compound CC1=CC(F)=CC=C1C1=CN2C=C(COC3=CC=C(F)C=N3)N=C2N=C1 VPSHEACHQHTIHA-UHFFFAOYSA-N 0.000 claims description 7
- NZZFGGDYXPYFTG-UHFFFAOYSA-N 6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(C=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=NC=CC=C1 NZZFGGDYXPYFTG-UHFFFAOYSA-N 0.000 claims description 7
- XWNNOWCUMSBYEM-UHFFFAOYSA-N 6-(4-fluorophenyl)-2-[(5-fluoropyridin-2-yl)oxymethyl]imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(C=C1)C1=CN2C=C(COC3=CC=C(F)C=N3)N=C2N=C1 XWNNOWCUMSBYEM-UHFFFAOYSA-N 0.000 claims description 7
- YIYRPDPLWOTFED-UHFFFAOYSA-N 6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=NC=CC=C1)CF YIYRPDPLWOTFED-UHFFFAOYSA-N 0.000 claims description 7
- KIFRLEAVMPIBNS-UHFFFAOYSA-N 6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=NC=CC=C1)C(F)(F)F KIFRLEAVMPIBNS-UHFFFAOYSA-N 0.000 claims description 7
- CJYLXPVFFUJBQZ-UHFFFAOYSA-N [5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=CC=C1)CO CJYLXPVFFUJBQZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- SGNPNDMFWIUWGO-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-6-(pyridin-2-yloxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=C(C=CC(=C1)F)C=1C=NC=2N(N=1)C=C(N=2)COC1=NC=CC=C1 SGNPNDMFWIUWGO-UHFFFAOYSA-N 0.000 claims description 6
- TZXWXADSLKMVOY-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-6-(pyridin-4-yloxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=C(C=CC(=C1)F)C=1C=NC=2N(N=1)C=C(N=2)COC1=CC=NC=C1 TZXWXADSLKMVOY-UHFFFAOYSA-N 0.000 claims description 6
- RJRGEGSFOXAORI-UHFFFAOYSA-N 2-[(2-fluoropyridin-4-yl)oxymethyl]-6-(2-methylphenyl)imidazo[1,2-a]pyrimidine Chemical compound CC1=C(C=CC=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC(=NC=C1)F RJRGEGSFOXAORI-UHFFFAOYSA-N 0.000 claims description 6
- VREYAGREWZJHPE-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)pyridin-3-yl]imidazo[1,2-a]pyrimidine Chemical compound FC1=CC(OCC2=CN3C=C(C=NC3=N2)C2=CC=C(N=C2)C(F)(F)F)=CC=C1 VREYAGREWZJHPE-UHFFFAOYSA-N 0.000 claims description 6
- FCTRHAQWHVDNDD-UHFFFAOYSA-N 2-[(5-chloropyridin-3-yl)oxymethyl]-6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(C=1)C=C(N=2)COC=1C=NC=C(C=1)Cl)C FCTRHAQWHVDNDD-UHFFFAOYSA-N 0.000 claims description 6
- VKWTYBJRKFHDNU-UHFFFAOYSA-N 6-(2,4-difluorophenyl)-2-(phenoxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=C(C=CC(=C1)F)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=CC=C1 VKWTYBJRKFHDNU-UHFFFAOYSA-N 0.000 claims description 6
- ZDVKRNCCNJMNJN-UHFFFAOYSA-N 6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=C(C=CC(=C1)F)C=1C=NC=2N(C=1)C=C(N=2)COC1=NC=CC=C1 ZDVKRNCCNJMNJN-UHFFFAOYSA-N 0.000 claims description 6
- ONKTXFKIMBAOOH-UHFFFAOYSA-N 6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=C(C=CC(=C1)F)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=NC=C1 ONKTXFKIMBAOOH-UHFFFAOYSA-N 0.000 claims description 6
- YECFHEXXZFLCCV-UHFFFAOYSA-N 6-(2-chloro-4-fluorophenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine Chemical compound ClC1=C(C=CC(=C1)F)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=C(C=C1)F YECFHEXXZFLCCV-UHFFFAOYSA-N 0.000 claims description 6
- VBHFTSMLOUWHSA-UHFFFAOYSA-N 6-(2-fluorophenyl)-2-(phenoxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=C(C=CC=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=CC=C1 VBHFTSMLOUWHSA-UHFFFAOYSA-N 0.000 claims description 6
- CUDUJCNBJDTSPQ-UHFFFAOYSA-N 6-(2-fluoropyridin-4-yl)-2-(phenoxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=NC=CC(=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=CC=C1 CUDUJCNBJDTSPQ-UHFFFAOYSA-N 0.000 claims description 6
- GTJVPLQOLWXHQD-UHFFFAOYSA-N 6-(2-methylphenyl)-2-(phenoxymethyl)imidazo[1,2-a]pyrimidine Chemical compound CC1=C(C=CC=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=CC=C1 GTJVPLQOLWXHQD-UHFFFAOYSA-N 0.000 claims description 6
- QBCUGJPAKITWHA-UHFFFAOYSA-N 6-(3-chloropyridin-4-yl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine Chemical compound ClC=1C=NC=CC=1C=1C=NC=2N(C=1)C=C(N=2)COC1=CC(=CC=C1)F QBCUGJPAKITWHA-UHFFFAOYSA-N 0.000 claims description 6
- DHWRCIZWVQBZFX-UHFFFAOYSA-N 6-(4-fluoro-2-methylphenyl)-2-(phenoxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=CC=C1)C DHWRCIZWVQBZFX-UHFFFAOYSA-N 0.000 claims description 6
- JDZKFIVNOLGGND-UHFFFAOYSA-N 6-(4-fluoro-2-methylphenyl)-2-[(2-fluoropyridin-4-yl)oxymethyl]imidazo[1,2-a]pyrimidine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC(=NC=C1)F)C JDZKFIVNOLGGND-UHFFFAOYSA-N 0.000 claims description 6
- OTSWJPKLSPJLGQ-UHFFFAOYSA-N 6-(4-fluoro-2-methylphenyl)-2-[(4-fluoropyridin-2-yl)oxymethyl]imidazo[1,2-a]pyrimidine Chemical compound CC1=CC(F)=CC=C1C1=CN2C=C(COC3=CC(F)=CC=N3)N=C2N=C1 OTSWJPKLSPJLGQ-UHFFFAOYSA-N 0.000 claims description 6
- HVWDAXPIWUHEQF-UHFFFAOYSA-N 6-(5-fluoropyridin-2-yl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine Chemical compound FC=1C=CC(=NC=1)C=1C=NC=2N(C=1)C=C(N=2)COC1=NC=CC=C1 HVWDAXPIWUHEQF-UHFFFAOYSA-N 0.000 claims description 6
- OFIPUHXNYUITNL-UHFFFAOYSA-N 6-(6-fluoro-5-methylpyridin-3-yl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine Chemical compound FC1=C(C=C(C=N1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC=C(C=C1)F)C OFIPUHXNYUITNL-UHFFFAOYSA-N 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- VRDYQASBTHFWTR-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-6-[(2-fluoropyridin-4-yl)oxymethyl]imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=C(C=CC(=C1)F)C=1C=NC=2N(N=1)C=C(N=2)COC1=CC(=NC=C1)F VRDYQASBTHFWTR-UHFFFAOYSA-N 0.000 claims description 5
- JKXALYQGTGKKNB-UHFFFAOYSA-N 2-(2-methylphenyl)-6-(pyridin-4-yloxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CC1=C(C=CC=C1)C=1C=NC=2N(N=1)C=C(N=2)COC1=CC=NC=C1 JKXALYQGTGKKNB-UHFFFAOYSA-N 0.000 claims description 5
- DTBBLVAFOSZOOM-UHFFFAOYSA-N 2-(3-fluoro-2-methylphenyl)-6-(pyridin-2-yloxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC=1C(=C(C=CC=1)C=1C=NC=2N(N=1)C=C(N=2)COC1=NC=CC=C1)C DTBBLVAFOSZOOM-UHFFFAOYSA-N 0.000 claims description 5
- QPNGDPJSXNYZFC-UHFFFAOYSA-N 2-(4-chloro-2-methylphenyl)-6-(pyridin-2-yloxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound ClC1=CC(=C(C=C1)C=1C=NC=2N(N=1)C=C(N=2)COC1=NC=CC=C1)C QPNGDPJSXNYZFC-UHFFFAOYSA-N 0.000 claims description 5
- FSRJECZYHCVMMV-UHFFFAOYSA-N 2-(4-fluoro-2-methylphenyl)-6-[(2-fluoropyridin-4-yl)oxymethyl]imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(N=1)C=C(N=2)COC1=CC(=NC=C1)F)C FSRJECZYHCVMMV-UHFFFAOYSA-N 0.000 claims description 5
- HFGQRUCPXDYQNQ-UHFFFAOYSA-N 2-(4-fluoro-2-methylphenyl)-6-[(5-fluoropyridin-2-yl)oxymethyl]imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC(=C(C=C1)C=1C=NC=2N(N=1)C=C(N=2)COC1=NC=C(C=C1)F)C HFGQRUCPXDYQNQ-UHFFFAOYSA-N 0.000 claims description 5
- BPOVCZWPIOWZMU-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-(pyridin-4-yloxymethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=C1)C=1C=NC=2N(N=1)C=C(N=2)COC1=CC=NC=C1 BPOVCZWPIOWZMU-UHFFFAOYSA-N 0.000 claims description 5
- WBAPRXGEMPHIGL-UHFFFAOYSA-N 2-(phenoxymethyl)-6-phenylimidazo[1,2-a]pyrimidine Chemical compound O(C1=CC=CC=C1)CC=1N=C2N(C=C(C=N2)C2=CC=CC=C2)C=1 WBAPRXGEMPHIGL-UHFFFAOYSA-N 0.000 claims description 5
- SVFNUZJMYHDDPO-UHFFFAOYSA-N 2-(pyridin-2-yloxymethyl)-6-[6-(trifluoromethyl)pyridin-3-yl]imidazo[1,2-a]pyrimidine Chemical compound N1=C(C=CC=C1)OCC=1N=C2N(C=C(C=N2)C=2C=NC(=CC=2)C(F)(F)F)C=1 SVFNUZJMYHDDPO-UHFFFAOYSA-N 0.000 claims description 5
- RGKVUQCYTIIDCX-UHFFFAOYSA-N 2-[(2-chloropyridin-4-yl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine Chemical compound ClC1=NC=CC(=C1)OCC=1N=C2N(C=C(C=N2)C2=CC=C(C=C2)F)C=1 RGKVUQCYTIIDCX-UHFFFAOYSA-N 0.000 claims description 5
- RVBLZELTOBFVKX-UHFFFAOYSA-N 2-[(2-fluoropyridin-4-yl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine Chemical compound FC1=NC=CC(=C1)OCC=1N=C2N(C=C(C=N2)C2=C(C=C(C=C2)F)C(F)(F)F)C=1 RVBLZELTOBFVKX-UHFFFAOYSA-N 0.000 claims description 5
- ULKVFSJXASZNKY-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyrimidine Chemical compound FC=1C=C(OCC=2N=C3N(C=C(C=N3)C=3C(=NC=CC=3)F)C=2)C=CC=1 ULKVFSJXASZNKY-UHFFFAOYSA-N 0.000 claims description 5
- JIDPSRYNEAIRMZ-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-(2-fluoropyridin-4-yl)imidazo[1,2-a]pyrimidine Chemical compound FC=1C=C(OCC=2N=C3N(C=C(C=N3)C3=CC(=NC=C3)F)C=2)C=CC=1 JIDPSRYNEAIRMZ-UHFFFAOYSA-N 0.000 claims description 5
- HXLXLDXDIOIWID-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine Chemical compound FC=1C=C(OCC=2N=C3N(C=C(C=N3)C3=CC=C(C=C3)F)C=2)C=CC=1 HXLXLDXDIOIWID-UHFFFAOYSA-N 0.000 claims description 5
- HAMXXFQXQMTJLN-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyrimidine Chemical compound CC1=C(C=NC=C1)C=1C=NC=2N(C=1)C=C(N=2)COC1=CC(=CC=C1)F HAMXXFQXQMTJLN-UHFFFAOYSA-N 0.000 claims description 5
- YEEYOZONQNWWAP-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-(5-fluoropyridin-2-yl)imidazo[1,2-a]pyrimidine Chemical compound FC=1C=C(OCC=2N=C3N(C=C(C=N3)C3=NC=C(C=C3)F)C=2)C=CC=1 YEEYOZONQNWWAP-UHFFFAOYSA-N 0.000 claims description 5
- BNUCGTYEEGGTPT-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-(6-fluoropyridin-3-yl)imidazo[1,2-a]pyrimidine Chemical compound FC=1C=C(OCC=2N=C3N(C=C(C=N3)C=3C=NC(=CC=3)F)C=2)C=CC=1 BNUCGTYEEGGTPT-UHFFFAOYSA-N 0.000 claims description 5
- BJAYNHBTGGEEOW-UHFFFAOYSA-N 2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine Chemical compound FC=1C=C(OCC=2N=C3N(C=C(C=N3)C3=C(C=C(C=C3)F)C(F)(F)F)C=2)C=CC=1 BJAYNHBTGGEEOW-UHFFFAOYSA-N 0.000 claims description 5
- HZJCWKZKMNBKEQ-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]-6-(2-fluoropyridin-4-yl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(OCC=2N=C3N(C=C(C=N3)C3=CC(=NC=C3)F)C=2)C=C1 HZJCWKZKMNBKEQ-UHFFFAOYSA-N 0.000 claims description 5
- GRAXOLFOOYKYSM-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]-6-(2-methoxypyridin-4-yl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(OCC=2N=C3N(C=C(C=N3)C3=CC(=NC=C3)OC)C=2)C=C1 GRAXOLFOOYKYSM-UHFFFAOYSA-N 0.000 claims description 5
- SWHJNEULPKGBJP-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]-6-(2-methylphenyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(OCC=2N=C3N(C=C(C=N3)C3=C(C=CC=C3)C)C=2)C=C1 SWHJNEULPKGBJP-UHFFFAOYSA-N 0.000 claims description 5
- RTRMXLCDQBCROX-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(OCC=2N=C3N(C=C(C=N3)C3=CC=C(C=C3)F)C=2)C=C1 RTRMXLCDQBCROX-UHFFFAOYSA-N 0.000 claims description 5
- MKTDONUFXBNNJE-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(OCC=2N=C3N(C=C(C=N3)C=3C=NC=CC=3C)C=2)C=C1 MKTDONUFXBNNJE-UHFFFAOYSA-N 0.000 claims description 5
- MRHUUQKPQUBUHR-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]-6-(5-fluoropyridin-2-yl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(OCC=2N=C3N(C=C(C=N3)C3=NC=C(C=C3)F)C=2)C=C1 MRHUUQKPQUBUHR-UHFFFAOYSA-N 0.000 claims description 5
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- NBMWKTYJUGGPTH-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]-6-(5-methoxypyridin-3-yl)imidazo[1,2-a]pyrimidine Chemical compound FC1=CC=C(OCC=2N=C3N(C=C(C=N3)C=3C=NC=C(C=3)OC)C=2)C=C1 NBMWKTYJUGGPTH-UHFFFAOYSA-N 0.000 claims description 5
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Definitions
- the present disclosure generally relates to a compound modulating receptor activity, pharmaceutical compositions comprising the compound, and methods useful for treating diseases.
- the present disclosure relates to a compound useful as a positive allosteric modulator (PAM) of metabotropic glutamate receptor subtype 5 (mGluR5) or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for the prevention and/or treatment of disorders mediated by glutamate dysfunction and mGluR5 comprising a therapeutically effective amount of the same.
- PAM positive allosteric modulator
- Glutamate is the most prevalent excitatory neurotransmitter in the central nervous system (CNS) of mammals. Glutamate plays an important role in numerous physiological functions such as cardiovascular regulation, perception and recognition, and synaptogenesis as well as learning and memory. As such, in the occurrence of imbalance in glutamate neurotransmission, various nervous and mental diseases such as schizophrenia may be caused, and thus glutamate plays an important role in physiology.
- CNS central nervous system
- Glutamate mediates synaptic neurotransmission via ionotropic glutamate receptors (iGluR) ⁇ i.e., the activation of NMDA receptors, AMPA receptors and kainate receptors involved in rapid excitatory transmission (Nakanishi S. et al., Brain Res. Rev., (1998) 26: 230-235).
- glutamate plays a role in subtly regulating excitatory synaptic neurotransmission via the activation of metabotropic glutamate receptor (mGluR).
- Metabotropic glutamate receptors consist of eight (8) subtypes and are sub-divided into three groups (Groups I, II and III) according to arrangement, homology and pharmacological property.
- mGluR5 belongs to Group I, and it is known that mGluR5 interacts with NMDA receptors via various proteins and neurotransmission pathways. Therefore, because the balance of deficiency or hyperactivity of physiological function by NMDA receptors can be regulated via the modulation of mGluR5, to modulate mGluR5 is very important.
- mGluR5 receptor modulators could be therapeutically beneficial in the treatment of various CNS diseases.
- mGluR5 receptor modulators which act through allosteric binding site have some advantages such as subtype selectivity, brain penetration and safety potential, many studies have reported that the mGluR5 positive allosteric modulators were useful for the treatment of schizophrenia and CNS diseases.
- International Publication Nos. WO 2008/151184 and WO 2011/035324 disclose benzamide and O-benzyl nicotinamide derivatives as an mGluR5 positive allosteric modulator, respectively.
- International Publication No. WO 2010/124055 discloses 2-alkyl piperidine derivatives as an mGluR5 positive allosteric modulator, and International Publication No. WO 2011/082010 discloses tetrahydrotriazolopyridine derivative compounds.
- International Publication Nos. WO 2012/078817 and WO 2012/083224 disclose bicyclic pyrazole and bicyclic triazole compounds as an mGluR5 positive allosteric modulator, respectively.
- imidazopyrimidine and imidazotriazine derivative compound as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) or a pharmaceutically acceptable salt thereof.
- composition comprising the above imidazopyrimidine and imidazotriazine derivative compound or a pharmaceutically acceptable salt thereof as an active ingredient.
- the present inventors have synthesized imidazopyrimidine and imidazotriazine derivative compounds of Chemical Formula (1) and confirmed that said compounds show effective and selective effects as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5), thereby being useful in the treatment of disorders mediated by glutamate dysfunction and mGluR5 such as schizophrenia.
- mGluR5 metabotropic glutamate receptor subtype 5
- the present disclosure provides a compound of Chemical Formula (1) and a pharmaceutically acceptable salt thereof:
- X represents CH or N
- Z represents O or S
- R 1 represents aryl which is unsubstituted or substituted with one or more substituents selected from halo, hydroxy, alkyl, alkoxy, alkylthio, amino, dialkylamino, cyano, formyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carbamoyloxy alkyl, alkyl-C(O)O-alkyl, dialkylaminoalkyl and 5- or 6-membered heterocycloalkylalkyl in which the heterocycloalkyl has 1-3 heteroatoms selected from N, O and S; or 5- to 12-membered, unsaturated heterocyclyl having 1-5 heteroatoms selected from N, O and S, which is unsubstituted or substituted with one or more substituents selected from halo, hydroxy, alkyl, alkoxy and haloalkyl; and
- R 2 represents aryl which is unsubstituted or substituted with one or more substituents selected from halo, deuterium, hydroxy and alkyl; or 5- to 12-membered, unsaturated heterocyclyl having 1-3 heteroatoms selected from N, O and S, which is unsubstituted or substituted with one or more substituents selected from halo and alkyl.
- R 1 represents aryl which is unsubstituted or substituted with one or more substituents selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 alkyl, hydroxy-C 1 -C 5 alkyl, C 1 -C 5 alkoxy-C 1 -C 5 alkyl, carbamoyloxy-C 1 -C 5 alkyl, C 1 -C 5 alkyl-C(O)O-C 1 -C 5 alkyl, di(C 1 -C 5 alkyl)amino-C 1 -C 5 alkyl and 5- or 6-membered heterocycloalkyl-C 1 -C 5 alkyl wherein the heterocycloalkyl has 1-3 heteroatoms selected from N, O
- alkyl means a radical of saturated aliphatic hydrocarbyl group having 1 to 5 carbon atoms, which may be linear or branched.
- alkyl group include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl and 1,2-dimethylpropyl.
- halo either alone or in combination with further terms (for example, haloalkyl), means a radical of F, Cl, Br or I.
- heterocycloalkyl means a 5- or 6-membered, saturated monocyclic ring having 1 to 3 heteroatoms selected from N, O and S, and preferably a 5- or 6-membered, saturated monocyclic ring having 1 or 2 heteroatoms selected from N and O.
- heterocycloalkyl include, but are not limited to, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl and morpholinyl.
- aryl means an aromatic radical having 6 to 12 carbon atoms. Concrete examples of aryl include, but are not limited to, phenyl and naphthyl.
- unsaturated heterocyclyl means a 5- or 12-membered, unsaturated monocyclic or bicyclic ring having 1 to 5 heteroatoms selected from N, O and S.
- unsaturated heterocyclyl include, but are not limited to, 1,3-benzodioxolyl, or heteroaryl such as pyridyl, pyrimidinyl, thienyl, pyrazinyl, quinolinyl and isoquinolinyl.
- R 1 is selected from the group consisting of:
- each R 3 is selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 alkyl, hydroxy-C 1 -C 5 alkyl, C 1 -C 5 alkoxy-C 1 -C 5 alkyl, carbamoyloxy-C 1 -C 5 alkyl, C 1 -C 5 alkyl-C(O)O-C 1 -C 5 alkyl, di(C 1 -C 5 alkyl)amino-C 1 -C 5 alkyl and 5- or 6-membered heterocycloalkyl-C 1 -C 5 alkyl; and each R 4 is selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy
- R 2 is selected from the group consisting of:
- R 5 is selected from halo, deuterium, hydroxy and C 1 -C 5 alkyl; and R 5 is selected from halo and C 1 -C 5 alkyl.
- R 1 represents phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 alkyl, hydroxy-C 1 -C 5 alkyl, C 1 -C 5 alkoxy-C 1 -C 5 alkyl, carbamoyloxy-C 1 -C 5 alkyl and C 1 -C 5 alkyl-C(O)O-C 1 -C 5 alkyl; or 5- to 10-membered, unsaturated heterocyclyl having 1-3 heteroatoms selected from N, O and S, which is unsubstituted or substituted with 1 to 3 substituents selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5
- R 2 represents phenyl unsubstituted or substituted with 1 to 5 substituents selected from halo, deuterium, hydroxy and C 1 -C 5 alkyl; or 5- or 6-membered heteroaryl having 1 to 3 heteroatoms selected from N, O and S, which is unsubstituted or substituted with 1 to 3 substituents selected from halo and C 1 -C 5 alkyl.
- X represents CH or N
- Z represents O
- R 1 represents phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 alkyl, hydroxy-C 1 -C 5 alkyl, C 1 -C 5 alkoxy-C 1 -C 5 alkyl, carbamoyloxy-C 1 -C 5 alkyl and C 1 -C 5 alkyl-C(O)O-C 1 -C 5 alkyl; or 5- to 9-membered, unsaturated heterocyclyl having 1 or 2 heteroatoms selected from N, O and S, which is unsubstituted or substituted with 1 or 2 substituents selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -
- R 2 represents phenyl which is unsubstituted or substituted with 1 to 5 substituents selected from halo, deuterium, hydroxy and C 1 -C 5 alkyl; or 6-membered heteroaryl having 1 or 2 nitrogen atoms, which is unsubstituted or substituted with 1 or 2 substituents selected from halo and C 1 -C 5 alkyl.
- R 1 represents phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 alkyl, hydroxy-C 1 -C 5 alkyl, C 1 -C 5 alkoxy-C 1 -C 5 alkyl, carbamoyloxy-C 1 -C 5 alkyl and C 1 -C 5 alkyl-C(O)O-C 1 -C 5 alkyl; 1,3-benzodioxolyl which is unsubstituted or substituted with 1 or 2 halo; or pyridyl or pyrimidinyl which is unsubstituted or substituted with 1 or 2 substituents selected from halo, hydroxy,
- R 2 represents phenyl which is unsubstituted or substituted with 1 to 5 substituents selected from halo, deuterium, hydroxy and C 1 -C 5 alkyl; or pyridyl which is unsubstituted or substituted with 1 or 2 substituents selected from halo and C 1 -C 5 alkyl.
- X represents CH
- Z represents O
- R 1 represents phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 alkylthio, amino, halo-C 1 -C 5 alkyl, hydroxy-C 1 -C 5 alkyl and C 1 -C 5 alkoxy-C 1 -C 5 alkyl; and
- R 2 represents pyridyl which is unsubstituted or substituted with 1 or 2 substituents selected from halo and C 1 -C 5 alkyl.
- n 0, 1, 2 or 3;
- each R 3 is independently selected from halo, hydroxy, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 alkyl, hydroxy-C 1 -C 5 alkyl, C 1 -C 5 alkoxy-C 1 -C 5 alkyl, carbamoyloxy-C 1 -C 5 alkyl, C 1 -C 5 alkyl-C(O)O-C 1 -C 5 alkyl, di(C 1 -C 5 alkyl)amino-C 1 -C 5 alkyl and 5- or 6-membered heterocycloalkyl-C 1 -C 5 alkyl wherein the heterocycloalkyl has 1-3 heteroatoms selected from N, O and S;
- n 0, 1, 2 or 3;
- each R 6 is independently selected from halo and C 1 -C 5 alkyl.
- n is 0, 1 or 2; each R 3 is selected from halo, halo-C 1 -C 5 alkyl, C 1 -C 5 alkyl, and hydroxy-C 1 -C 5 alkyl; m is 0 or 1; and R 6 is halo.
- n is 1 or 2; each R 3 is selected from fluoro, fluoromethyl, trifluoromethyl, methyl, and hydroxymethyl; m is 0 or 1; and R 6 is fluoro.
- the compounds of Chemical Formula (1) according to the present disclosure include, but are not limited to, the following compounds:
- R 1 and R 2 are optionally substituted phenyl and such compounds include, but are not limited to, the following compounds:
- R 1 is optionally substituted pyridinyl and R 2 is optionally substituted phenyl, and such compounds include, but are not limited to, the following compounds:
- R 1 is optionally substituted phenyl and R 2 is optionally substituted pyridinyl, and such compounds include, but are not limited to, the following compounds:
- both R 1 and R 2 are optionally substituted pyridinyl, and such compounds include, but are not limited to, the following compounds:
- the compounds of Chemical Formula (1) are effective as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5 PAM). Also, they have selective activity as a positive allosteric modulator of mGluR5 PAM. Such medicinal effects of the compounds of Chemical Formula (1) can be maintained in the form of pharmaceutically acceptable salts.
- a pharmaceutical composition for the prevention or treatment of disorder mediated by glutamate dysfunction and metabotropic glutamate receptor subtype 5 comprising a therapeutically effective amount of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient, together with a pharmaceutically acceptable carrier or excipient.
- the pharmaceutical composition may further comprise one or more additives selected from the group consisting of a pharmaceutically acceptable carrier, diluent and adjuvant.
- the pharmaceutical composition may be a composition for a positive allosteric modulator of mGluR5.
- the pharmaceutical composition may be a composition for the prevention and/or treatment of disorders mediated by glutamate dysfunction and mGluR5.
- the disorders mediated by glutamate dysfunction and mGluR5 may be, for example, schizophrenia, and include any disorders known as being related to glutamate dysfunction and mGluR5.
- the article (N. Matosin et al., Schizophrenia Research , 2013, Vol. 146, pp. 170-176) reported the relation between a positive allosteric modulator of mGluR5 and the treatment of schizophrenia.
- the pharmaceutically acceptable salt includes any acid or base addition salts, and any stereochemical isomer thereof. These salts are not specifically limited and may be any salt that is able to retain activity of a parent compound thereof in a target subject and does not cause any undesirable effect. Examples of these salts are both inorganic and organic salts, such as acetic acid, nitric acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid, glutamic acid, formic acid, succinic acid, phosphoric acid, phthalic acid, tannic acid, tartaric acid, hydrobromic acid, propionic acid, benzenesulfonic acid, benzoic acid, stearic acid, cresylic acid, lactic acid, bicarbonic acid, bisulfuric acid, bitartaric acid, oxalic acid, butylic acid, calcium edatate, camsylic acid, carbonic acid, chlorobenzoic acid, citric acid, edetic acid, toluenes
- a basic salt examples include an ammonium salt, a salt of an alkali or alkali earth metal such as lithium, sodium, potassium, magnesium, or calcium, a salt containing an organic base such as benzathine, N-methyl-D-glucamine, or hydrabamine, and a salt containing an amino acid such as arginine or lysine. These salts may be converted into a free form by treatment with appropriate acid or base.
- the term "addition salt” may be taken to include solvates obtainable from any of the compounds of Chemical Formula (1) and salts thereof. Examples of these solvates are hydrates and alcoholates.
- the pharmaceutical composition may be formulated into various types for oral or parenteral administration.
- it may be formulated into any dosage form for oral administration such as tablets, pills, soft/hard capsules, solutions, suspensions, emulsions, syrups, granules and elixirs.
- a dosage form for oral administration may further include any pharmaceutically acceptable carriers depending on a typical construction of each formulation ⁇ for example, diluents such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine, or lubricants such as silica, talc, steric acid and its magnesium or calcium salt, and/or polyethylene glycol.
- the formulation for oral administration may also comprise binding agents such magnesium aluminum silicate, starch paste, gelatin, gum tragacanth, methyl cellulose, sodium carboxymethyl cellulose, and/or polyvinyl pyrrolidone, and if desired, it may also include disintegrating agents such as starch, agar, or alginic acid or its sodium salt, or a boiling mixture, and/or an absorbing agent, a colorant, a flavoring agent, or a sweetening agent.
- binding agents such magnesium aluminum silicate, starch paste, gelatin, gum tragacanth, methyl cellulose, sodium carboxymethyl cellulose, and/or polyvinyl pyrrolidone
- disintegrating agents such as starch, agar, or alginic acid or its sodium salt, or a boiling mixture, and/or an absorbing agent, a colorant, a flavoring agent, or a sweetening agent.
- the pharmaceutical composition may be formulated into a form of parenteral administration.
- it may be administered by means of parenteral administration methods such as a hypodermic injection, an intravenous injection, an intramuscular injection or an intrathoracic injection.
- parenteral administration methods such as a hypodermic injection, an intravenous injection, an intramuscular injection or an intrathoracic injection.
- the effective ingredient i.e., the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof
- the effective ingredient i.e., the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof
- a stabilizer or a buffering agent in water to prepare as a solution or a suspension, and this solution or suspension may then be produced as a unit dosage form such as an ampoule or a vial.
- the pharmaceutical composition may be sterilized or may further comprise an adjuvant such as a preservative, a stabilizing agent, a hydrating agent, an emulsifying agent, or a salt for controlling osmotic pressure and/or a buffering agent, and it may further include other therapeutically beneficial substances and may be formulated in accordance with conventional methods of mixing, granulation or coating.
- an adjuvant such as a preservative, a stabilizing agent, a hydrating agent, an emulsifying agent, or a salt for controlling osmotic pressure and/or a buffering agent
- the pharmaceutical composition may comprise the effective ingredient ⁇ i.e., the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof in an effective amount of 0.1 to 500 mg/kg (body weight), preferably 0.5 to 100 mg/kg (body weight) per day in case of mammals including a human, and such a pharmaceutical composition may be divided into one, or two or more doses per day and administered via an oral or parenteral route.
- the effective ingredient i.e., the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof in an effective amount of 0.1 to 500 mg/kg (body weight), preferably 0.5 to 100 mg/kg (body weight) per day in case of mammals including a human, and such a pharmaceutical composition may be divided into one, or two or more doses per day and administered via an oral or parenteral route.
- the present disclosure also provides a role as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5), comprising the step of administering a therapeutically effective amount of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof to a patient in need thereof.
- the modulation method may further comprise a step of identifying the patient who is in need of positive allosteric modulation of mGluR5 prior to the step of administration.
- the present disclosure provides a method for the prevention and/or treatment of disorders mediated by glutamate dysfunction and mGluR5, comprising the step of administering a therapeutically effective amount of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof to a patient in need thereof.
- the method for the prevention and/or treatment may further comprise a step of identifying the patient who is in need of the prevention and/or treatment of disorders mediated by glutamate dysfunction and mGluR5 prior to the step of administration.
- the disorders mediated by glutamate dysfunction and mGluR5 may be ⁇ for example, schizophrenia, and include any disorders known as being related to glutamate dysfunction and the modulation of mGluR5.
- the patient may be a mammal, preferably a human.
- a person skilled in the art may easily select a specific administration method and a therapeutically effective amount of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof with no particular limitations, taking the type of the mammals to be administered and the disorder, and the specific type of the compound of Chemical Formula (1) and its activity on positive allosteric modulation of mGluR5.
- the present disclosure provides a method of preparing the compound of Chemical Formula (1).
- the preparation of the compound of Chemical Formula (1) may be conducted by using a known compound or a compound easily prepared therefrom in the perspective of a person skilled in the art regarding a chemical synthesis. Therefore, the following explanations about the method of preparing the compound of Chemical Formula (1) merely present exemplary methods and if necessary, the order of the unit operation may be selectively altered and does not limit the scope of the disclosure.
- a heterocycle synthesis reaction is carried out with compound (5) obtained in Reaction Scheme 2 and 1-acetoxy-3-chloroacetone to obtain compound (7), and the obtained compound is then hydrolyzed to obtain compound (8).
- An aromatic nucleophilic reaction of compound (8) is carried out to obtain the final compound (9).
- a novel imidazopyrimidine and imidazotriazine derivative, and a pharmaceutically acceptable salt thereof showing excellent effect on positive allosteric modulation of metabotropic glutamate receptor subtype 5 (mGluR5) are provided. Therefore, such imidazopyrimidine and imidazotriazine derivative, and a pharmaceutically acceptable salt thereof can be effectively used in the prevention or treatment of disorders mediated by glutamate dysfunction and mGluR5 such as schizophrenia.
- a method of preparing the novel imidazopyrimidine and imidazotriazine derivative, a pharmaceutical composition comprising the same and a method of positive allosteric modulation of mGluR5 by using the same, and a method for the treatment of disorders mediated by glutamate dysfunction and mGluR5 are provided.
- 6-Bromo-2-chloromethylimidazo[1,2-a]pyrimidine (2 g, 8.11 mmol) and phenol (1.5 g, 16.23 mmol) were dissolved in DMF (40 ml), and potassium carbonate (3.4 g, 24.34 mmol) was added thereto at room temperature. Then, the reaction solution was agitated at 60°C for 15 hours. After confirmation of the reaction termination by liquid chromatography, the reaction solution was diluted with ethyl acetate and washed three times with water. Then, the solution was dried with magnesium sulfate and filtrated. This was under reduced pressure, and the resulting solids were washed with ethyl acetate to obtain the title compound (amount: 0.9 g, yield: 38%).
- 6-Bromo-2-phenoxymethylimidazo[1,2-a]pyrimidine (0.3 g, 0.99 mmol) obtained in Example 1-2 and 2-fluorophenylboronic acid (0.2 g, 1.43 mmol) were dissolved in 1,2-dimethoxyethane (8 ml), and [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium(II) complex dichloromethane (0.2 g, 0.24 mmol) and 2N sodium carbonate aqueous solution (1.8 ml, 3.6 mmol) were then added thereto at room temperature. Then, the reaction solution was agitated under reflux at 90°C for 6 hours.
- reaction solution was diluted with methylene chloride and filtrated by the use of Cellite TM .
- Phenylboronic acid as a starting material was used in the same manner as in Example 1-3 to obtain the title compound.
- 6-Methoxypyridin-3-ylboronic acid as a starting material was used in the same manner as in Example 1-3 to obtain the title compound.
- 6-Fluoropyridin-3-ylboronic acid as a starting material was used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine and 2,4-difluorophenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 4-fluoro-2-methoxyphenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 4-fluoro-3-hydroxyphenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 2-aminophenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethylimidazo[1,2-a]pyrimidine and 3-chloropyridin-4-ylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 4-methylpyridin-3-ylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethylimidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethylimidazo[1,2-a]pyrimidine and 2,4-difluorophenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 4-fluoro-2-methylphenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 3-chloropyridin-4-ylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 2,6-dimethylphenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (6-fluoro-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Benzene-1,4-diol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-hydroxyphenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-hydroxyphenoxymethyl)imidazo[1,2-a]pyrimidine and 4-fluorophenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 4-fluorophenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and 4-fluorophenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (4-fluoro-3-hydroxy-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and phenylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (4-fluoro-2-hydroxy-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (4-fluoro-2-hydroxy-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 2,3,4,5,6-Pentadeuteriophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(2,3,4,5,6-pentadeuteriophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(2,3,4,5,6-pentadeuteriophenoxymethyl)imidazo[1,2-a]pyrimidine and (4-fluorophenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and o-tolylboronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (5-fluoro-2-methyl-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-fluoro-4-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-hydroxyphenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-fluoro-4-methyl-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and [6-(trifluoromethyl)-3-pyridyl]boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-aminophenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-chloro-4-fluoro-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (4-cyano-2-methoxy-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (4-chloro-2-methoxy-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (3-amino-4-fluoro-phenyl)boronic acid as a starting material were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2,6-difluoro-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (3-amino-4-methyl-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-amino-4,5-difluoro-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-amino-4-methyl-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-amino-4-chloro-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-amino-5-methyl-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-amino-4-fluoro-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-fluoro-4-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 80 Synthesis of 2-[(3- fluorophenoxy ) methyl ]-6- [6-(trifluoromethyl) -3-pyridyl)imidazo[1,2-a]pyrimidine
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and [6-(trifluoromethyl)-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (6-fluoro-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- 3-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (2-fluoro-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (5,6-difluoro-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (3-amino-4-methoxy-phenyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (5-fluoro-2-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (5-methoxy-2-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (4-chloro-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (5-chloro-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
- Example 1-2 4-Fluorophenol as a starting material was used in the same manner as in Example 1-2 to obtain 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine.
- the obtained 6-bromo-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine and (5-methoxy-3-pyridyl)boronic acid were used in the same manner as in Example 1-3 to obtain the title compound.
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Abstract
Description
Claims (20)
- A compound of the following Chemical Formula (1) or a pharmaceutically acceptable salt thereof:whereinX is CH or N;Z is O or S;R1 is aryl optionally substituted with one or more substituents selected from halo, hydroxy, alkyl, alkoxy, alkylthio, amino, dialkylamino, cyano, formyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carbamoyloxy alkyl, alkyl-C(O)O-alkyl, dialkylaminoalkyl and 5- or 6-membered heterocycloalkylalkyl; or 5- to 12-membered, unsaturated heterocyclyl optionally substituted with one or more substituents selected from halo, hydroxy, alkyl, alkoxy and haloalkyl; andR2 is aryl optionally substituted with one or more substituents selected from halo, deuterium, hydroxy and alkyl; or 5- to 12-membered, unsaturated heterocyclyl optionally substituted with one or more substituents selected from halo and alkyl.
- The compound or pharmaceutically acceptable salt thereof of Claim 1, whereinR1 is C6-C12 aryl optionally substituted with one or more substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl, C1-C5 alkyl-C(O)O-C1-C5 alkyl, di(C1-C5 alkyl)amino-C1-C5 alkyl and 5- or 6-membered heterocycloalkyl-C1-C5 alkyl in which the heterocycloalkyl has 1-3 heteroatoms selected from N, O and S; or 5- to 12-membered, unsaturated heterocyclyl having 1-5 heteroatoms selected from N, O and S, which is optionally substituted with one or more substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl; andR2 is C6-C12 aryl optionally substituted with one or more substituents selected from halo, deuterium, hydroxy and C1-C5 alkyl; or 5- to 12-membered, unsaturated heterocyclyl having 1-3 heteroatoms selected from N, O and S, which is optionally substituted with one or more substituents selected from halo and C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof of Claim 1, whereinR1 is selected from the group consisting of:wherein n is 0, 1, 2, 3 or 4; each R3 is selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl, C1-C5 alkyl-C(O)O-C1-C5 alkyl, di(C1-C5 alkyl)amino-C1-C5 alkyl and 5- or 6-membered heterocycloalkyl-C1-C5 alkyl; and each R4 is selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl; andR2 is selected from the group consisting of:wherein m is 0, 1, 2, 3 or 4; R5 is selected from halo, deuterium, hydroxy and C1-C5 alkyl; and R5 is selected from halo and C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein R1 is phenyl optionally substituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl and C1-C5 alkyl-C(O)O-C1-C5 alkyl; or 5- to 10-membered, unsaturated heterocyclyl having 1-3 heteroatoms selected from N, O and S, which is optionally substituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein R2 is phenyl optionally substituted with 1 to 5 substituents selected from halo, deuterium, hydroxy and C1-C5 alkyl; or 5- or 6-membered heteroaryl having 1 to 3 heteroatoms selected from N, O and S, which is optionally substituted with 1 to 3 substituents selected from halo and C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, whereinX is CH or N;Z is O;R1 is phenyl optionally substituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl and C1-C5 alkyl-C(O)O-C1-C5 alkyl; or 5- to 9-membered, unsaturated heterocyclyl having 1 or 2 heteroatoms selected from N, O and S, which is optionally substituted with 1 or 2 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl; andR2 is phenyl optionally substituted with 1 to 5 substituents selected from halo, deuterium, hydroxy and C1-C5 alkyl; or 6-membered heteroaryl having 1 or 2 nitrogen atoms, which is optionally substituted with 1 or 2 substituents selected from halo and C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, whereinR1 is phenyl optionally substituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl and C1-C5 alkyl-C(O)O-C1-C5 alkyl; 1,3-benzodioxolyl which is unsubstituted or substituted with 1 or 2 halo; or pyridyl or pyrimidinyl which is optionally substituted with 1 or 2 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl; andR2 is phenyl optionally substituted with 1 to 5 substituents selected from halo, deuterium, hydroxy and C1-C5 alkyl; or pyridyl optionally substituted with 1 or 2 substituents selected from halo and C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1,whereinX is CH;Z is O;R1 is phenyl optionally substituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl and C1-C5 alkoxy-C1-C5 alkyl; andR2 is pyridyl optionally substituted with 1 or 2 substituents selected from halo and C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein the compound is selected from the group consisting of:6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;2-phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-methoxypyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-3-hydroxyphenyl)-2-(3-fluorophenoxymethyl)-imidazo[1,2-a]pyrimidine;6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-methylpyridin-3-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;4-[[6-(4-fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]phenol;2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine;5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine;6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile;6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methyl-aniline;4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-aniline;5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-aniline;5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methoxy-aniline;2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a]pyrimidine;6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyrimidine;5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyridin-2-ol;6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile;[5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidine;2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-aniline;5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine;6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]aniline;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;3-methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile;6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;[5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;[2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethyl)phenyl]methanol;6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluoromethyl)benzaldehyde;6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(5-fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;[5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2,4-difluorophenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-b][1,2,4]triazine;[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl carbamate;[5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl carbamate;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl carbamate;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl acetate;6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1,2-a]pyrimidine;6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; and6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein the compound is selected from the group consisting of:6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2-a]pyrimidine;6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine; and6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein the compound is selected from the group consisting of:6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-3-hydroxyphenyl)-2-(3-fluorophenoxymethyl)-imidazo[1,2-a]pyrimidine;6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;4-[[6-(4-fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]phenol;2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine;5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine;6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol;6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile;6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methyl-aniline;4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-aniline;5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-aniline;5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methoxy-aniline;2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile;[5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-aniline;5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triazine;[5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl carbamate;[5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl carbamate;6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1,2-a]pyrimidine; and6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein the compound is selected from the group consisting of:6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-methoxypyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;6-(4-methylpyridin-3-yl)-2-(3-fluorophenoxymethyl)imidazo [1,2-a]pyrimidine;6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a]pyrimidine;6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyrimidine;5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyridin-2-ol;6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine;2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine; and2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidine.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein the compound is selected from the group consisting of:6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine;6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;2-fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]aniline;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;3-methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile;6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;[5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile;6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;[2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethyl)phenyl]methanol;6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluoromethyl)benzaldehyde;6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(5-fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline;[5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol;2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2,4-difluorophenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-(2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-b][1,2,4]triazine;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl carbamate;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methyl acetate; and6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein the compound is selected from the group consisting of:2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine; and6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.
- The compound or pharmaceutically acceptable salt thereof according to Claim 1, wherein the compound is a compound of Formula (2):wherein n is 0, 1, 2 or 3;each R3 is independently selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl, C1-C5 alkyl-C(O)O-C1-C5 alkyl, di(C1-C5 alkyl)amino-C1-C5 alkyl and 5- or 6-membered heterocycloalkyl-C1-C5 alkyl wherein the heterocycloalkyl has 1-3 heteroatoms selected from N, O and S;m is 0, 1, 2 or 3; andeach R6 is independently selected from halo and C1-C5 alkyl.
- The compound or pharmaceutically acceptable salt thereof according to Claim 15, wherein n is 0, 1 or 2; each R3 is selected from halo, halo-C1-C5 alkyl, C1-C5 alkyl, and hydroxy-C1-C5 alkyl; m is 0 or 1; and R6 is halo.
- The compound or pharmaceutically acceptable salt thereof according to Claim 15, wherein n is 1 or 2; each R3 is selected from fluoro, fluoromethyl, trifluoromethyl, methyl, and hydroxymethyl; m is 0 or 1; and R6 is fluoro.
- The compound or pharmaceutically acceptable salt thereof according to Claim 15, wherein the compound is selected from the group consisting of:6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine;6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;[5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; and6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.
- A pharmaceutical composition for the prevention or treatment of disorder mediated by glutamate dysfunction and metabotropic glutamate receptor subtype 5 (mGluR5) comprising a therapeutically effective amount of the compound of Chemical Formula (1) as defined in Claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient, together with a pharmaceutically acceptable carrier or excipient.
- The pharmaceutical composition according to Claim 19, wherein the disorder mediated by glutamate dysfunction and mGluR5 is schizophrenia.
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WO2021080313A1 (en) | 2019-10-21 | 2021-04-29 | 에스케이바이오팜 주식회사 | Use of imidazopyrimidine or imidazotriazine compound for prevention, alleviation, or treatment of developmental disability |
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WO2021080312A1 (en) | 2019-10-21 | 2021-04-29 | 에스케이바이오팜 주식회사 | Use of imidazopyrimidine or imidazotriazine compounds for prevention, alleviation, or treatment of cognitive disorders, or for improving cognitive function |
WO2021080313A1 (en) | 2019-10-21 | 2021-04-29 | 에스케이바이오팜 주식회사 | Use of imidazopyrimidine or imidazotriazine compound for prevention, alleviation, or treatment of developmental disability |
EP4049662A4 (en) * | 2019-10-21 | 2023-11-01 | SK Biopharmaceuticals Co., Ltd. | Use of imidazopyrimidine or imidazotriazine compounds for prevention, alleviation, or treatment of cognitive disorders, or for improving cognitive function |
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