CA2902135A1 - Azetidine amide derivatives as orexin receptor antagonists - Google Patents
Azetidine amide derivatives as orexin receptor antagonists Download PDFInfo
- Publication number
- CA2902135A1 CA2902135A1 CA2902135A CA2902135A CA2902135A1 CA 2902135 A1 CA2902135 A1 CA 2902135A1 CA 2902135 A CA2902135 A CA 2902135A CA 2902135 A CA2902135 A CA 2902135A CA 2902135 A1 CA2902135 A1 CA 2902135A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- triazol
- azetidin
- methyl
- oxadiazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- -1 Azetidine amide Chemical class 0.000 title claims abstract description 92
- 229940123730 Orexin receptor antagonist Drugs 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 125000001424 substituent group Chemical group 0.000 claims description 80
- 238000000034 method Methods 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- 229910052736 halogen Inorganic materials 0.000 claims description 53
- 150000002367 halogens Chemical class 0.000 claims description 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 51
- 208000035475 disorder Diseases 0.000 claims description 37
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 35
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 34
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- 208000019901 Anxiety disease Diseases 0.000 claims description 24
- 206010012335 Dependence Diseases 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 208000019116 sleep disease Diseases 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 14
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 13
- 208000010877 cognitive disease Diseases 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 208000019022 Mood disease Diseases 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 208000027559 Appetite disease Diseases 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000005549 heteroarylene group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- PXTRDUIXBONJAT-INIZCTEOSA-N (2-methyl-5-phenyl-1,3-thiazol-4-yl)-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2N=C(SC=2C=2C=CC=CC=2)C)=NC=1C1=CC=CC=C1OC(F)(F)F PXTRDUIXBONJAT-INIZCTEOSA-N 0.000 claims 1
- WJAVKAMJLUFNGC-FQEVSTJZSA-N (2-phenylphenyl)-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound FC(F)(F)OC1=CC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 WJAVKAMJLUFNGC-FQEVSTJZSA-N 0.000 claims 1
- YOMMAMLAEKBFAP-NRFANRHFSA-N (5-methyl-2-phenylphenyl)-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N1([C@@H](CC1)C=1ON=C(N=1)C=1C(=CC=CC=1)OC(F)(F)F)C(=O)C1=CC(C)=CC=C1C1=CC=CC=C1 YOMMAMLAEKBFAP-NRFANRHFSA-N 0.000 claims 1
- CPFLJHAIJBNXIU-NRFANRHFSA-N (5-methyl-2-phenylphenyl)-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound N1([C@@H](CC1)C=1NN=C(N=1)C=1C(=CC=CC=1)OC(F)(F)F)C(=O)C1=CC(C)=CC=C1C1=CC=CC=C1 CPFLJHAIJBNXIU-NRFANRHFSA-N 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- JTLJRVQNBMKZDI-FQEVSTJZSA-N [(2s)-2-[3-(2,5-dimethylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NC=1C1=CC(C)=CC=C1C JTLJRVQNBMKZDI-FQEVSTJZSA-N 0.000 claims 1
- GLQGXTZSKHQCMH-SFHVURJKSA-N [(2s)-2-[3-(2-chlorophenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NC=1C1=CC=CC=C1Cl GLQGXTZSKHQCMH-SFHVURJKSA-N 0.000 claims 1
- LYYKWNVLVHCKFB-IBGZPJMESA-N [(2s)-2-[3-(2-ethoxy-3-fluorophenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound CCOC1=C(F)C=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=C(C)C=2)N2N=CC=N2)=N1 LYYKWNVLVHCKFB-IBGZPJMESA-N 0.000 claims 1
- WNPVWEYECZTFJN-INIZCTEOSA-N [(2s)-2-[3-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4-fluoro-5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound CCOC1=NC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC(F)=C(OC)C=2)N2N=CC=N2)=N1 WNPVWEYECZTFJN-INIZCTEOSA-N 0.000 claims 1
- QEVORAQYJWWNCK-KRWDZBQOSA-N [(2s)-2-[3-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound CCOC1=NC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(OC)C=2)N2N=CC=N2)=N1 QEVORAQYJWWNCK-KRWDZBQOSA-N 0.000 claims 1
- LQMOSTNDDQUZPY-SFHVURJKSA-N [(2s)-2-[3-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound CCOC1=NC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=C(C)C=2)N2N=CC=N2)=N1 LQMOSTNDDQUZPY-SFHVURJKSA-N 0.000 claims 1
- SARRGDZBWKLYAF-SFHVURJKSA-N [(2s)-2-[3-(2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=CC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=C(C)C=2)N2N=CC=N2)=N1 SARRGDZBWKLYAF-SFHVURJKSA-N 0.000 claims 1
- RTSMIOKUBXCXSN-IBGZPJMESA-N [(2s)-2-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NC=1C1=CC=CC=C1C RTSMIOKUBXCXSN-IBGZPJMESA-N 0.000 claims 1
- UURIGNWNCNVBPD-QFIPXVFZSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-(2-phenylphenyl)methanone Chemical compound CC1=C(Cl)C=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 UURIGNWNCNVBPD-QFIPXVFZSA-N 0.000 claims 1
- DCQOXBJPZPFZLC-QHCPKHFHSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-(5-methyl-2-phenylphenyl)methanone Chemical compound N1([C@@H](CC1)C=1ON=C(N=1)C=1C(=C(Cl)C=CC=1)C)C(=O)C1=CC(C)=CC=C1C1=CC=CC=C1 DCQOXBJPZPFZLC-QHCPKHFHSA-N 0.000 claims 1
- JYFGNZSAXLBHMX-SFHVURJKSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[2-(dimethylamino)-5-phenyl-1,3-thiazol-4-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2N=C(SC=2C=2C=CC=CC=2)N(C)C)=NC=1C1=CC=CC(Cl)=C1C JYFGNZSAXLBHMX-SFHVURJKSA-N 0.000 claims 1
- LBFZDWZNFZCFTN-IBGZPJMESA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4,5-dimethyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)C)=NC=1C1=CC=CC(Cl)=C1C LBFZDWZNFZCFTN-IBGZPJMESA-N 0.000 claims 1
- OIGNSHLFYCBDJY-KRWDZBQOSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4-chloro-2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=C(Cl)C=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC(Cl)=CC=2)N2N=CC=N2)=N1 OIGNSHLFYCBDJY-KRWDZBQOSA-N 0.000 claims 1
- PULMNWLUTSSJBJ-KRWDZBQOSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4-fluoro-5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)F)OC)=NC=1C1=CC=CC(Cl)=C1C PULMNWLUTSSJBJ-KRWDZBQOSA-N 0.000 claims 1
- MZXQGKTUYBYETL-SFHVURJKSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C2=CC=C(C=C2N2N=CC=N2)C)=NC=1C1=CC=CC(Cl)=C1C MZXQGKTUYBYETL-SFHVURJKSA-N 0.000 claims 1
- HAOGPYPOEIIKFU-SFHVURJKSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-chloro-2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=C(Cl)C=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=C(Cl)C=2)N2N=CC=N2)=N1 HAOGPYPOEIIKFU-SFHVURJKSA-N 0.000 claims 1
- OOKVSHJMCQIHFA-SFHVURJKSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-chloro-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C2=C(C=C(C(=C2)Cl)C)N2N=CC=N2)=NC=1C1=CC=CC(Cl)=C1C OOKVSHJMCQIHFA-SFHVURJKSA-N 0.000 claims 1
- XABSGZKQRPNJSC-SFHVURJKSA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NC=1C1=CC=CC(Cl)=C1C XABSGZKQRPNJSC-SFHVURJKSA-N 0.000 claims 1
- RLHMXBUVBZHSSE-IBGZPJMESA-N [(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NC=1C1=CC=CC(Cl)=C1C RLHMXBUVBZHSSE-IBGZPJMESA-N 0.000 claims 1
- QUGFWCRVJYFFFS-INIZCTEOSA-N [(2s)-2-[3-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4-fluoro-5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)F)OC)=NC=1C1=CC=CC(F)=C1OC QUGFWCRVJYFFFS-INIZCTEOSA-N 0.000 claims 1
- HJDKRWJGSBWZFK-KRWDZBQOSA-N [(2s)-2-[3-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=C(F)C=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=CC=2)N2N=CC=N2)=N1 HJDKRWJGSBWZFK-KRWDZBQOSA-N 0.000 claims 1
- HQHRHVVXQYRDCR-KRWDZBQOSA-N [(2s)-2-[3-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NC=1C1=CC=CC(F)=C1OC HQHRHVVXQYRDCR-KRWDZBQOSA-N 0.000 claims 1
- LBWZEGBRYDWCLD-SFHVURJKSA-N [(2s)-2-[3-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=C(F)C=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=C(C)C=2)N2N=CC=N2)=N1 LBWZEGBRYDWCLD-SFHVURJKSA-N 0.000 claims 1
- FXCHFTLQCHKYDZ-SFHVURJKSA-N [(2s)-2-[3-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C2=CC=C(C=C2N2N=CC=N2)C)=NC=1C1=CC=CC(F)=C1C FXCHFTLQCHKYDZ-SFHVURJKSA-N 0.000 claims 1
- GVFDXVKQDXCIBM-SFHVURJKSA-N [(2s)-2-[3-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NC=1C1=CC=CC(F)=C1C GVFDXVKQDXCIBM-SFHVURJKSA-N 0.000 claims 1
- YIGGVJZHZCFJLK-IBGZPJMESA-N [(2s)-2-[3-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NC=1C1=CC=CC(F)=C1C YIGGVJZHZCFJLK-IBGZPJMESA-N 0.000 claims 1
- DREBVPAPAKBWSB-IBGZPJMESA-N [(2s)-2-[3-(3-methoxyphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=CC=CC(C=2N=C(ON=2)[C@H]2N(CC2)C(=O)C=2C(=CC=C(C)C=2)N2N=CC=N2)=C1 DREBVPAPAKBWSB-IBGZPJMESA-N 0.000 claims 1
- INUGQCZFOVWYOH-KRWDZBQOSA-N [(2s)-2-[5-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound CCOC1=NC=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=CC=2)N2N=CC=N2)=NO1 INUGQCZFOVWYOH-KRWDZBQOSA-N 0.000 claims 1
- ACZVEIWPNAHIKZ-KRWDZBQOSA-N [(2s)-2-[5-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound CCOC1=NC=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(OC)C=2)N2N=CC=N2)=NO1 ACZVEIWPNAHIKZ-KRWDZBQOSA-N 0.000 claims 1
- VWAPJTCYQBYLJV-SFHVURJKSA-N [(2s)-2-[5-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound CCOC1=NC=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC=C(C)C=2)N2N=CC=N2)=NO1 VWAPJTCYQBYLJV-SFHVURJKSA-N 0.000 claims 1
- KRHUCICAAYFNCG-SFHVURJKSA-N [(2s)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4,5-dimethyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(C)C=2)N2N=CC=N2)=NO1 KRHUCICAAYFNCG-SFHVURJKSA-N 0.000 claims 1
- NWUOMBGAQQVYBN-INIZCTEOSA-N [(2s)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4-chloro-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(Cl)=CC=2)N2N=CC=N2)=NO1 NWUOMBGAQQVYBN-INIZCTEOSA-N 0.000 claims 1
- FVVNULVSBLTYIJ-INIZCTEOSA-N [(2s)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)Cl)OC)=NOC=1C1=CC=CC(Cl)=C1OC FVVNULVSBLTYIJ-INIZCTEOSA-N 0.000 claims 1
- OEGZSCPWVIHGEV-KRWDZBQOSA-N [(2s)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=CC=2)N2N=CC=N2)=NO1 OEGZSCPWVIHGEV-KRWDZBQOSA-N 0.000 claims 1
- BDRONGXINZAOHD-KRWDZBQOSA-N [(2s)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-chloro-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(Cl)C=2)N2N=CC=N2)=NO1 BDRONGXINZAOHD-KRWDZBQOSA-N 0.000 claims 1
- JTRBZPNNQMWVFP-KRWDZBQOSA-N [(2s)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NOC=1C1=CC=CC(Cl)=C1OC JTRBZPNNQMWVFP-KRWDZBQOSA-N 0.000 claims 1
- DFTNMZQQCIARPX-SFHVURJKSA-N [(2s)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound COC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC=C(C)C=2)N2N=CC=N2)=NO1 DFTNMZQQCIARPX-SFHVURJKSA-N 0.000 claims 1
- PMPLHHCEDONMDL-FQEVSTJZSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-(5-methoxy-4-methyl-2-pyrimidin-2-ylphenyl)methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2C=2N=CC=CN=2)C)OC)=NOC=1C1=CC=CC(Cl)=C1C PMPLHHCEDONMDL-FQEVSTJZSA-N 0.000 claims 1
- ZYAAECIWBVGBRR-QHCPKHFHSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-(5-methyl-2-phenylphenyl)methanone Chemical compound N1([C@@H](CC1)C=1N=C(ON=1)C=1C(=C(Cl)C=CC=1)C)C(=O)C1=CC(C)=CC=C1C1=CC=CC=C1 ZYAAECIWBVGBRR-QHCPKHFHSA-N 0.000 claims 1
- YUWCCHXLRVUFMI-FQEVSTJZSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-(5-methyl-2-pyrimidin-2-ylphenyl)methanone Chemical compound N1([C@@H](CC1)C=1N=C(ON=1)C=1C(=C(Cl)C=CC=1)C)C(=O)C1=CC(C)=CC=C1C1=NC=CC=N1 YUWCCHXLRVUFMI-FQEVSTJZSA-N 0.000 claims 1
- VGTPHDXDMLGZBB-KRWDZBQOSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[2-(triazol-2-yl)-4-(trifluoromethyl)phenyl]methanone Chemical compound CC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(=CC=2)C(F)(F)F)N2N=CC=N2)=NO1 VGTPHDXDMLGZBB-KRWDZBQOSA-N 0.000 claims 1
- QXNDPXJOGZQXCO-SFHVURJKSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC=CC=2)N2N=CC=N2)=NO1 QXNDPXJOGZQXCO-SFHVURJKSA-N 0.000 claims 1
- BAWRVITXGCLSQL-IBGZPJMESA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4,5-dimethyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)C)=NOC=1C1=CC=CC(Cl)=C1C BAWRVITXGCLSQL-IBGZPJMESA-N 0.000 claims 1
- IQCZVXGNNIRPOI-KRWDZBQOSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4-chloro-2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=C(Cl)C=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(Cl)=CC=2)N2N=CC=N2)=NO1 IQCZVXGNNIRPOI-KRWDZBQOSA-N 0.000 claims 1
- QOBNXSVQORJTRZ-SFHVURJKSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C2=CC=C(C=C2N2N=CC=N2)C)=NOC=1C1=CC=CC(Cl)=C1C QOBNXSVQORJTRZ-SFHVURJKSA-N 0.000 claims 1
- ZNWYWQNASHEVMR-SFHVURJKSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-chloro-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C2=C(C=C(C(=C2)Cl)C)N2N=CC=N2)=NOC=1C1=CC=CC(Cl)=C1C ZNWYWQNASHEVMR-SFHVURJKSA-N 0.000 claims 1
- ZBWQCFJDDIQKRB-SFHVURJKSA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NOC=1C1=CC=CC(Cl)=C1C ZBWQCFJDDIQKRB-SFHVURJKSA-N 0.000 claims 1
- FLQDYYVTSHSWMA-IBGZPJMESA-N [(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NOC=1C1=CC=CC(Cl)=C1C FLQDYYVTSHSWMA-IBGZPJMESA-N 0.000 claims 1
- ZLLNKWYYCZAOMM-KRWDZBQOSA-N [(2s)-2-[5-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NOC=1C1=CC=CC(F)=C1OC ZLLNKWYYCZAOMM-KRWDZBQOSA-N 0.000 claims 1
- XODWTMJEFQLUSV-IBGZPJMESA-N [(2s)-2-[5-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NOC=1C1=CC=CC(F)=C1C XODWTMJEFQLUSV-IBGZPJMESA-N 0.000 claims 1
- DXOIVXMYAPKKGN-HNNXBMFYSA-N [2-(triazol-2-yl)-4-(trifluoromethyl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound FC(F)(F)OC1=CC=CC=C1C1=NNC([C@H]2N(CC2)C(=O)C=2C(=CC(=CC=2)C(F)(F)F)N2N=CC=N2)=N1 DXOIVXMYAPKKGN-HNNXBMFYSA-N 0.000 claims 1
- AZUOKLYRZOAHGG-SFHVURJKSA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound CCOC1=NC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(C)C=2)N2N=CC=N2)=N1 AZUOKLYRZOAHGG-SFHVURJKSA-N 0.000 claims 1
- WJWLJCVPRGJCKV-SFHVURJKSA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound COC1=C(F)C=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(C)C=2)N2N=CC=N2)=N1 WJWLJCVPRGJCKV-SFHVURJKSA-N 0.000 claims 1
- YJLVUGVRJGAYCT-IBGZPJMESA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)C)=NC=1C1=CC=CC(F)=C1C YJLVUGVRJGAYCT-IBGZPJMESA-N 0.000 claims 1
- MAGHQKODSAVJCO-KRWDZBQOSA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)C)=NC=1C1=CC=CC=C1OC(F)(F)F MAGHQKODSAVJCO-KRWDZBQOSA-N 0.000 claims 1
- BAWCOWUDXWBFRL-KRWDZBQOSA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1NC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)C)=NC=1C1=CC=CC=C1OC(F)(F)F BAWCOWUDXWBFRL-KRWDZBQOSA-N 0.000 claims 1
- XLYJJZDMAYDCNN-SFHVURJKSA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound CCOC1=NC=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(C)C=2)N2N=CC=N2)=NO1 XLYJJZDMAYDCNN-SFHVURJKSA-N 0.000 claims 1
- RCEJXBQPZVAORI-IBGZPJMESA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)C)=NOC=1C1=CC=CC(F)=C1C RCEJXBQPZVAORI-IBGZPJMESA-N 0.000 claims 1
- NVMMJCQLJCPAQZ-KRWDZBQOSA-N [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)C)=NOC=1C1=CC=CC=C1OC(F)(F)F NVMMJCQLJCPAQZ-KRWDZBQOSA-N 0.000 claims 1
- UTROGYBGAXJJHW-HNNXBMFYSA-N [4-chloro-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound FC(F)(F)OC1=CC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC(Cl)=CC=2)N2N=CC=N2)=N1 UTROGYBGAXJJHW-HNNXBMFYSA-N 0.000 claims 1
- WAFPJAJOSTZPHL-HNNXBMFYSA-N [4-chloro-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound FC(F)(F)OC1=CC=CC=C1C1=NNC([C@H]2N(CC2)C(=O)C=2C(=CC(Cl)=CC=2)N2N=CC=N2)=N1 WAFPJAJOSTZPHL-HNNXBMFYSA-N 0.000 claims 1
- TWOGTHWXONLTPL-KRWDZBQOSA-N [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)Cl)OC)=NC=1C1=CC=CC(Cl)=C1C TWOGTHWXONLTPL-KRWDZBQOSA-N 0.000 claims 1
- NFWMNFOBAJJBIB-HNNXBMFYSA-N [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)Cl)OC)=NC=1C1=CC=CC=C1OC(F)(F)F NFWMNFOBAJJBIB-HNNXBMFYSA-N 0.000 claims 1
- VMOMVQOYYDQOCJ-HNNXBMFYSA-N [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1NC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)Cl)OC)=NC=1C1=CC=CC=C1OC(F)(F)F VMOMVQOYYDQOCJ-HNNXBMFYSA-N 0.000 claims 1
- MWJLXCJLYMSCEX-INIZCTEOSA-N [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound CCOC1=NC=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(Cl)=C(OC)C=2)N2N=CC=N2)=NO1 MWJLXCJLYMSCEX-INIZCTEOSA-N 0.000 claims 1
- PYSYNIPKARHMJB-KRWDZBQOSA-N [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-(3-chloro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)Cl)OC)=NOC=1C1=CC=CC(Cl)=C1C PYSYNIPKARHMJB-KRWDZBQOSA-N 0.000 claims 1
- DCCVKITYDJJUIE-KRWDZBQOSA-N [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)Cl)OC)=NOC=1C1=CC=CC(F)=C1C DCCVKITYDJJUIE-KRWDZBQOSA-N 0.000 claims 1
- CXSOMSKKVALFEI-HNNXBMFYSA-N [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)Cl)OC)=NOC=1C1=CC=CC=C1OC(F)(F)F CXSOMSKKVALFEI-HNNXBMFYSA-N 0.000 claims 1
- MJIDNGCQJQMYMY-KRWDZBQOSA-N [4-fluoro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-(3-fluoro-2-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)F)OC)=NC=1C1=CC=CC(F)=C1C MJIDNGCQJQMYMY-KRWDZBQOSA-N 0.000 claims 1
- FLEPWMSNJHLEST-HNNXBMFYSA-N [4-fluoro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)F)OC)=NC=1C1=CC=CC=C1OC(F)(F)F FLEPWMSNJHLEST-HNNXBMFYSA-N 0.000 claims 1
- RQIZDINFFVTDAT-INIZCTEOSA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C2=CC=C(C=C2N2N=CC=N2)C)=NC=1C1=CC=CC=C1OC(F)(F)F RQIZDINFFVTDAT-INIZCTEOSA-N 0.000 claims 1
- BTIVAWUUKLYCEZ-INIZCTEOSA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1NC([C@@H]2CCN2C(=O)C2=CC=C(C=C2N2N=CC=N2)C)=NC=1C1=CC=CC=C1OC(F)(F)F BTIVAWUUKLYCEZ-INIZCTEOSA-N 0.000 claims 1
- XMZZFGIXZKGXJC-INIZCTEOSA-N [5-chloro-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound FC(F)(F)OC1=CC=CC=C1C1=NOC([C@H]2N(CC2)C(=O)C=2C(=CC=C(Cl)C=2)N2N=CC=N2)=N1 XMZZFGIXZKGXJC-INIZCTEOSA-N 0.000 claims 1
- FYXHSPBAUOZDFS-INIZCTEOSA-N [5-chloro-4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C2=C(C=C(C(=C2)Cl)C)N2N=CC=N2)=NC=1C1=CC=CC=C1OC(F)(F)F FYXHSPBAUOZDFS-INIZCTEOSA-N 0.000 claims 1
- QTOBFNXXJGXRBN-INIZCTEOSA-N [5-chloro-4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1NC([C@@H]2CCN2C(=O)C2=C(C=C(C(=C2)Cl)C)N2N=CC=N2)=NC=1C1=CC=CC=C1OC(F)(F)F QTOBFNXXJGXRBN-INIZCTEOSA-N 0.000 claims 1
- KYNVYTOEXFMNLS-KRWDZBQOSA-N [5-chloro-4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-(2-ethoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound CCOC1=NC=CC=C1C1=NC([C@H]2N(CC2)C(=O)C=2C(=CC(C)=C(Cl)C=2)N2N=CC=N2)=NO1 KYNVYTOEXFMNLS-KRWDZBQOSA-N 0.000 claims 1
- OGUYVKJUECVEBN-INIZCTEOSA-N [5-chloro-4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C2=C(C=C(C(=C2)Cl)C)N2N=CC=N2)=NOC=1C1=CC=CC=C1OC(F)(F)F OGUYVKJUECVEBN-INIZCTEOSA-N 0.000 claims 1
- CTKBFWJKMMLDTD-INIZCTEOSA-N [5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1OC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NC=1C1=CC=CC=C1OC(F)(F)F CTKBFWJKMMLDTD-INIZCTEOSA-N 0.000 claims 1
- BTUQEMRGQGEBRH-INIZCTEOSA-N [5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[3-[2-(trifluoromethoxy)phenyl]-1h-1,2,4-triazol-5-yl]azetidin-1-yl]methanone Chemical compound N=1NC([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NC=1C1=CC=CC=C1OC(F)(F)F BTUQEMRGQGEBRH-INIZCTEOSA-N 0.000 claims 1
- LUOTWXJCSHQCCF-INIZCTEOSA-N [5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C=C(C(=CC=2N2N=CC=N2)C)OC)=NOC=1C1=CC=CC=C1OC(F)(F)F LUOTWXJCSHQCCF-INIZCTEOSA-N 0.000 claims 1
- WBZDMZRGDRRDCR-KRWDZBQOSA-N [5-methyl-2-(triazol-2-yl)phenyl]-[(2s)-2-[5-[2-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone Chemical compound N=1C([C@@H]2CCN2C(=O)C=2C(=CC=C(C=2)C)N2N=CC=N2)=NOC=1C1=CC=CC=C1OC(F)(F)F WBZDMZRGDRRDCR-KRWDZBQOSA-N 0.000 claims 1
- 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 166
- 102000002512 Orexin Human genes 0.000 description 45
- 108060005714 orexin Proteins 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 239000000203 mixture Substances 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 36
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 125000000217 alkyl group Chemical group 0.000 description 29
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 25
- 239000002904 solvent Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 238000003786 synthesis reaction Methods 0.000 description 20
- 230000015654 memory Effects 0.000 description 19
- 238000000746 purification Methods 0.000 description 17
- 230000035882 stress Effects 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 14
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 14
- 210000004556 brain Anatomy 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 238000007429 general method Methods 0.000 description 13
- 239000012317 TBTU Substances 0.000 description 12
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 208000002193 Pain Diseases 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 230000004064 dysfunction Effects 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 239000002585 base Substances 0.000 description 10
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- 125000001153 fluoro group Chemical group F* 0.000 description 10
- 206010022437 insomnia Diseases 0.000 description 10
- 230000036407 pain Effects 0.000 description 10
- 230000007958 sleep Effects 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000011121 sodium hydroxide Nutrition 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 230000003542 behavioural effect Effects 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 230000037007 arousal Effects 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 230000000446 orexinergic effect Effects 0.000 description 8
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 8
- 208000028173 post-traumatic stress disease Diseases 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 208000024827 Alzheimer disease Diseases 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 235000014632 disordered eating Nutrition 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 230000013016 learning Effects 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 208000030814 Eating disease Diseases 0.000 description 6
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 6
- 206010026749 Mania Diseases 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 208000008589 Obesity Diseases 0.000 description 6
- 102000008834 Orexin receptor Human genes 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000001309 chloro group Chemical group Cl* 0.000 description 6
- 230000001276 controlling effect Effects 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 235000020824 obesity Nutrition 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 239000005711 Benzoic acid Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 238000010640 amide synthesis reaction Methods 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 230000036528 appetite Effects 0.000 description 5
- 235000019789 appetite Nutrition 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 5
- 235000010233 benzoic acid Nutrition 0.000 description 5
- 229960003920 cocaine Drugs 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 230000007787 long-term memory Effects 0.000 description 5
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 5
- 208000024714 major depressive disease Diseases 0.000 description 5
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 5
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 208000020016 psychiatric disease Diseases 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 208000011117 substance-related disease Diseases 0.000 description 5
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 5
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 4
- BFPGCWOVXJFKPY-UHFFFAOYSA-N 2-bromo-5-methoxy-4-methylbenzoic acid Chemical compound COC1=CC(C(O)=O)=C(Br)C=C1C BFPGCWOVXJFKPY-UHFFFAOYSA-N 0.000 description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 4
- 208000032841 Bulimia Diseases 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 206010013980 Dyssomnias Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108050000742 Orexin Receptor Proteins 0.000 description 4
- 208000006199 Parasomnias Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 229940025084 amphetamine Drugs 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 208000014679 binge eating disease Diseases 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 230000001143 conditioned effect Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000006735 deficit Effects 0.000 description 4
- 230000002996 emotional effect Effects 0.000 description 4
- 235000012631 food intake Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 230000004630 mental health Effects 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- OFNHNCAUVYOTPM-IIIOAANCSA-N orexin-a Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@H](C(N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N2)[C@@H](C)O)=O)CSSC1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CNC=N1 OFNHNCAUVYOTPM-IIIOAANCSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- NDEIKFCAPOYPHU-LURJTMIESA-N tert-butyl (2s)-2-carbamoylazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1C(N)=O NDEIKFCAPOYPHU-LURJTMIESA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 3
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 208000020925 Bipolar disease Diseases 0.000 description 3
- 206010006550 Bulimia nervosa Diseases 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- 208000012661 Dyskinesia Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000011688 Generalised anxiety disease Diseases 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000005793 Restless legs syndrome Diseases 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 150000003950 cyclic amides Chemical class 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000003001 depressive effect Effects 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 230000003467 diminishing effect Effects 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 150000002148 esters Chemical group 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 208000029364 generalized anxiety disease Diseases 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 230000005056 memory consolidation Effects 0.000 description 3
- CHNOQXRIMCFHKZ-BYPYZUCNSA-N methyl (2s)-azetidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCN1 CHNOQXRIMCFHKZ-BYPYZUCNSA-N 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 229960002715 nicotine Drugs 0.000 description 3
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 description 3
- 208000023515 periodic limb movement disease Diseases 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000008313 sensitization Effects 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- JWJVSDZKYYXDDN-LURJTMIESA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]azetidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1C(O)=O JWJVSDZKYYXDDN-LURJTMIESA-N 0.000 description 2
- SJLVEBUBGAEOLJ-UHFFFAOYSA-N 2-cyclobutyloxypyridine-3-carbonitrile Chemical compound N#CC1=CC=CN=C1OC1CCC1 SJLVEBUBGAEOLJ-UHFFFAOYSA-N 0.000 description 2
- WERLSUXUIBERMU-UHFFFAOYSA-N 2-ethoxy-3-fluorobenzonitrile Chemical compound CCOC1=C(F)C=CC=C1C#N WERLSUXUIBERMU-UHFFFAOYSA-N 0.000 description 2
- LISKAOIANGDBTB-UHFFFAOYSA-N 2-ethoxypyridine Chemical compound CCOC1=CC=CC=N1 LISKAOIANGDBTB-UHFFFAOYSA-N 0.000 description 2
- GLPDBPGNFRRABU-UHFFFAOYSA-N 2-methylbenzenecarboximidamide Chemical compound CC1=CC=CC=C1C(N)=N GLPDBPGNFRRABU-UHFFFAOYSA-N 0.000 description 2
- HXGHMCLCSPQMOR-UHFFFAOYSA-N 3-chloro-2-methylbenzoic acid Chemical compound CC1=C(Cl)C=CC=C1C(O)=O HXGHMCLCSPQMOR-UHFFFAOYSA-N 0.000 description 2
- CEAVPXDEPGAVDA-UHFFFAOYSA-N 3-methoxy-4-methylbenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1C CEAVPXDEPGAVDA-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 2
- 206010004716 Binge eating Diseases 0.000 description 2
- 208000021500 Breathing-related sleep disease Diseases 0.000 description 2
- 206010006895 Cachexia Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 description 2
- 101000598921 Homo sapiens Orexin Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 208000004454 Hyperalgesia Diseases 0.000 description 2
- 201000001916 Hypochondriasis Diseases 0.000 description 2
- 208000001456 Jet Lag Syndrome Diseases 0.000 description 2
- 201000002832 Lewy body dementia Diseases 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 206010027944 Mood disorder due to a general medical condition Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 108090000189 Neuropeptides Proteins 0.000 description 2
- 208000008705 Nocturnal Myoclonus Syndrome Diseases 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 206010033664 Panic attack Diseases 0.000 description 2
- 206010062519 Poor quality sleep Diseases 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 206010041250 Social phobia Diseases 0.000 description 2
- 208000027520 Somatoform disease Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 208000011962 Substance-induced mood disease Diseases 0.000 description 2
- 231100000395 Substance-induced mood disorder Toxicity 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000006389 acute stress response Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000002060 circadian Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 2
- 238000007596 consolidation process Methods 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000000994 depressogenic effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000008451 emotion Effects 0.000 description 2
- 230000019439 energy homeostasis Effects 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 230000001073 episodic memory Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 230000004634 feeding behavior Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000002267 hypothalamic effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003137 locomotive effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- RHCSKNNOAZULRK-UHFFFAOYSA-N mescaline Chemical compound COC1=CC(CCN)=CC(OC)=C1OC RHCSKNNOAZULRK-UHFFFAOYSA-N 0.000 description 2
- PVSLEQAPQWFIEI-UHFFFAOYSA-N methyl 2-bromo-5-methoxy-4-methylbenzoate Chemical compound COC(=O)C1=CC(OC)=C(C)C=C1Br PVSLEQAPQWFIEI-UHFFFAOYSA-N 0.000 description 2
- DHYMLHOXGMUIDZ-UHFFFAOYSA-N methyl 2-iodo-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC=C1I DHYMLHOXGMUIDZ-UHFFFAOYSA-N 0.000 description 2
- CHNOQXRIMCFHKZ-UHFFFAOYSA-N methyl azetidine-2-carboxylate Chemical compound COC(=O)C1CCN1 CHNOQXRIMCFHKZ-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- OHOWSYIKESXDMN-WMQZXSDYSA-N orexin-b Chemical compound C([C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCSC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(N)=O)C1=CNC=N1 OHOWSYIKESXDMN-WMQZXSDYSA-N 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000000063 preceeding effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- FVGUUJNEJJPLCS-UHFFFAOYSA-N pyridine-3-carboximidamide Chemical compound NC(=N)C1=CC=CN=C1 FVGUUJNEJJPLCS-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical group 0.000 description 2
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000003938 response to stress Effects 0.000 description 2
- 201000002859 sleep apnea Diseases 0.000 description 2
- 230000008454 sleep-wake cycle Effects 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 201000009032 substance abuse Diseases 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- WUFVFANOTQZHBP-ZETCQYMHSA-N tert-butyl (2s)-2-cyanoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1C#N WUFVFANOTQZHBP-ZETCQYMHSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- GKPHNZYMLJPYJJ-UHFFFAOYSA-N 2,3-difluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1F GKPHNZYMLJPYJJ-UHFFFAOYSA-N 0.000 description 1
- QXKPABNWQSEPEM-UHFFFAOYSA-N 2,3-dimethylbenzenecarboximidamide Chemical compound CC1=CC=CC(C(N)=N)=C1C QXKPABNWQSEPEM-UHFFFAOYSA-N 0.000 description 1
- PCKNMQJLLATEAO-UHFFFAOYSA-N 2-(dimethylamino)-5-phenyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(N(C)C)=NC(C(O)=O)=C1C1=CC=CC=C1 PCKNMQJLLATEAO-UHFFFAOYSA-N 0.000 description 1
- UTENUPFWBIFKPW-UHFFFAOYSA-N 2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1N=CC=N1 UTENUPFWBIFKPW-UHFFFAOYSA-N 0.000 description 1
- CVSKRXMBFVFYJW-UHFFFAOYSA-N 2-(trifluoromethoxy)benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1OC(F)(F)F CVSKRXMBFVFYJW-UHFFFAOYSA-N 0.000 description 1
- GIGWBSOKTZOBDV-LBPRGKRZSA-N 2-O-[[amino(phenyl)methylidene]amino] 1-O-tert-butyl (2S)-azetidine-1,2-dicarboxylate Chemical compound C(C1=CC=CC=C1)(NOC(=O)[C@H]1N(CC1)C(=O)OC(C)(C)C)=N GIGWBSOKTZOBDV-LBPRGKRZSA-N 0.000 description 1
- ATBGJJWZVUNYOV-UHFFFAOYSA-N 2-bromo-4-chloro-5-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=C(Br)C=C1Cl ATBGJJWZVUNYOV-UHFFFAOYSA-N 0.000 description 1
- HECJSMILDFGZPA-UHFFFAOYSA-N 2-bromo-4-fluoro-5-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=C(Br)C=C1F HECJSMILDFGZPA-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- QPWXJJCMGSSOSD-UHFFFAOYSA-N 2-ethoxypyridine-3-carbohydrazide Chemical compound CCOC1=NC=CC=C1C(=O)NN QPWXJJCMGSSOSD-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- USIDQCCXMGJOJM-UHFFFAOYSA-N 2-fluoropyridine-3-carbonitrile Chemical compound FC1=NC=CC=C1C#N USIDQCCXMGJOJM-UHFFFAOYSA-N 0.000 description 1
- IYELGEUXPAPULN-UHFFFAOYSA-N 2-hydroxybenzenecarboximidamide Chemical compound NC(=N)C1=CC=CC=C1O IYELGEUXPAPULN-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- INGWGCDYAJKXKP-UHFFFAOYSA-N 2-iodo-5-methylbenzoic acid Chemical compound CC1=CC=C(I)C(C(O)=O)=C1 INGWGCDYAJKXKP-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- LXUJKONOFALWTA-UHFFFAOYSA-N 2-methyl-5-(2-methylphenyl)-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC=C1C LXUJKONOFALWTA-UHFFFAOYSA-N 0.000 description 1
- OMCWOZYMSYZUTD-UHFFFAOYSA-N 2-methyl-5-(3-methylphenyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(C)=C1 OMCWOZYMSYZUTD-UHFFFAOYSA-N 0.000 description 1
- DHUFXBJQFCCELL-UHFFFAOYSA-N 2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC(C)=C1 DHUFXBJQFCCELL-UHFFFAOYSA-N 0.000 description 1
- YFOICSSNYXWWBW-UHFFFAOYSA-N 2-methyl-5-(4-methylphenyl)-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(C)C=C1 YFOICSSNYXWWBW-UHFFFAOYSA-N 0.000 description 1
- IUPHMHDVSPSLME-UHFFFAOYSA-N 2-methyl-5-phenyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC=C1 IUPHMHDVSPSLME-UHFFFAOYSA-N 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- IANCHLRZCJQZBU-UHFFFAOYSA-N 3-chloro-2-methylbenzohydrazide Chemical compound CC1=C(Cl)C=CC=C1C(=O)NN IANCHLRZCJQZBU-UHFFFAOYSA-N 0.000 description 1
- JLLJPPBGJVCFGG-UHFFFAOYSA-N 3-chloropyridine-4-carbonitrile Chemical compound ClC1=CN=CC=C1C#N JLLJPPBGJVCFGG-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- LRRDANNSUCQNDU-UHFFFAOYSA-N 4-chloro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1I LRRDANNSUCQNDU-UHFFFAOYSA-N 0.000 description 1
- OXUUNDMDOOXPKY-UHFFFAOYSA-N 4-chloro-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1Cl OXUUNDMDOOXPKY-UHFFFAOYSA-N 0.000 description 1
- VFNMQNKUEDYROQ-UHFFFAOYSA-N 4-chloro-5-methoxy-2-(triazol-2-yl)benzoic acid Chemical compound COc1cc(C(O)=O)c(cc1Cl)-n1nccn1 VFNMQNKUEDYROQ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- LWGCZCMLPRMKIZ-UHFFFAOYSA-N 4-fluoro-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1F LWGCZCMLPRMKIZ-UHFFFAOYSA-N 0.000 description 1
- PIBPDWYOCYEMBG-UHFFFAOYSA-N 4-fluoro-5-methoxy-2-(triazol-2-yl)benzoic acid Chemical compound COc1cc(C(O)=O)c(cc1F)-n1nccn1 PIBPDWYOCYEMBG-UHFFFAOYSA-N 0.000 description 1
- DWKJZFQRPXSDEO-UHFFFAOYSA-N 5-(3-chlorophenyl)-1,3-thiazole-4-carboxylic acid Chemical compound N1=CSC(C=2C=C(Cl)C=CC=2)=C1C(=O)O DWKJZFQRPXSDEO-UHFFFAOYSA-N 0.000 description 1
- FBYNJPSNTIETJB-UHFFFAOYSA-N 5-(3-methylphenyl)-1,3-oxazole-4-carboxylic acid Chemical compound CC1=CC=CC(C2=C(N=CO2)C(O)=O)=C1 FBYNJPSNTIETJB-UHFFFAOYSA-N 0.000 description 1
- STZNEZBOFJDJCN-UHFFFAOYSA-N 5-(3-methylphenyl)-1,3-thiazole-4-carboxylic acid Chemical compound CC1=CC=CC(C2=C(N=CS2)C(O)=O)=C1 STZNEZBOFJDJCN-UHFFFAOYSA-N 0.000 description 1
- SSDOPBMPVFZPFN-UHFFFAOYSA-N 5-chloro-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1N1N=CC=N1 SSDOPBMPVFZPFN-UHFFFAOYSA-N 0.000 description 1
- GWFSRJKDYXADOG-UHFFFAOYSA-N 5-fluoro-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1C1=NC=CC=N1 GWFSRJKDYXADOG-UHFFFAOYSA-N 0.000 description 1
- WKBKHXGASBZRMI-UHFFFAOYSA-N 5-methyl-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1C1=NC=CC=N1 WKBKHXGASBZRMI-UHFFFAOYSA-N 0.000 description 1
- BIIMZWZUYMBFEV-UHFFFAOYSA-N 5-phenyl-1,3-thiazole-4-carboxylic acid Chemical compound N1=CSC(C=2C=CC=CC=2)=C1C(=O)O BIIMZWZUYMBFEV-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002653 Anosmia Diseases 0.000 description 1
- 208000025978 Athletic injury Diseases 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 201000009586 Basophil Adenoma Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000002381 Brain Hypoxia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- QFVUSWUNNFKACX-UHFFFAOYSA-N CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC Chemical compound CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC.CCCCCCC QFVUSWUNNFKACX-UHFFFAOYSA-N 0.000 description 1
- NPVQBFQHYCZCCL-UHFFFAOYSA-N COc1c(Cl)cccc1C(=O)NN Chemical compound COc1c(Cl)cccc1C(=O)NN NPVQBFQHYCZCCL-UHFFFAOYSA-N 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000001387 Causalgia Diseases 0.000 description 1
- SYDJQBDMMJGRJL-ZDUSSCGKSA-N ClC=1C(=C(C(=O)ON=C(N)[C@H]2N(CC2)C(=O)OC(C)(C)C)C=CC1)C Chemical compound ClC=1C(=C(C(=O)ON=C(N)[C@H]2N(CC2)C(=O)OC(C)(C)C)C=CC1)C SYDJQBDMMJGRJL-ZDUSSCGKSA-N 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
- 208000019736 Cranial nerve disease Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 206010011971 Decreased interest Diseases 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
- 208000025967 Dissociative Identity disease Diseases 0.000 description 1
- 206010013883 Dwarfism Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- 208000002091 Febrile Seizures Diseases 0.000 description 1
- 208000010235 Food Addiction Diseases 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 208000001613 Gambling Diseases 0.000 description 1
- 206010018265 Gigantism Diseases 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 101150026303 HEX1 gene Proteins 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 101500025902 Homo sapiens Orexin-A Proteins 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 206010060800 Hot flush Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 208000028482 Hypothalamic disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 208000015814 Intrinsic Sleep disease Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
- 102000028517 Neuropeptide receptor Human genes 0.000 description 1
- 108070000018 Neuropeptide receptor Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 208000000224 Night Terrors Diseases 0.000 description 1
- 206010029412 Nightmare Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010034912 Phobia Diseases 0.000 description 1
- 206010034918 Phobic avoidance Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 206010036832 Prolactinoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000000810 Separation Anxiety Diseases 0.000 description 1
- 208000036623 Severe mental retardation Diseases 0.000 description 1
- 208000022249 Sleep-Wake Transition disease Diseases 0.000 description 1
- 206010041347 Somnambulism Diseases 0.000 description 1
- 208000020307 Spinal disease Diseases 0.000 description 1
- 206010041738 Sports injury Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 231100000643 Substance intoxication Toxicity 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000011622 Testicular disease Diseases 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 208000003554 absence epilepsy Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 201000007034 advanced sleep phase syndrome Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 235000019558 anosmia Nutrition 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 235000021407 appetite control Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 230000035045 associative learning Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 150000001539 azetidines Chemical class 0.000 description 1
- MXOQNVMDKHLYCZ-UHFFFAOYSA-N benzamidoxime Chemical compound ON=C(N)C1=CC=CC=C1 MXOQNVMDKHLYCZ-UHFFFAOYSA-N 0.000 description 1
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 208000027757 bipolar ll disease Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- QFWACQSXKWRSLR-UHFFFAOYSA-N carboniodidic acid Chemical compound OC(I)=O QFWACQSXKWRSLR-UHFFFAOYSA-N 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 208000026725 cyclothymic disease Diseases 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000004665 defense response Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 201000001098 delayed sleep phase syndrome Diseases 0.000 description 1
- 208000033921 delayed sleep phase type circadian rhythm sleep disease Diseases 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 206010013461 dissociative amnesia Diseases 0.000 description 1
- 208000018459 dissociative disease Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 208000009985 drug-induced dyskinesia Diseases 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 230000020595 eating behavior Effects 0.000 description 1
- 239000002895 emetic Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000027950 fever generation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000006589 gland dysfunction Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 208000031424 hyperprolactinemia Diseases 0.000 description 1
- 206010020765 hypersomnia Diseases 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000008991 intestinal motility Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 240000004308 marijuana Species 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000003818 metabolic dysfunction Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- AYHCWHCWQSWWRE-UHFFFAOYSA-N methyl 2-bromo-5-chloro-4-methylbenzoate Chemical compound COC(=O)C1=CC(Cl)=C(C)C=C1Br AYHCWHCWQSWWRE-UHFFFAOYSA-N 0.000 description 1
- DVMKOWMMZIWHBY-UHFFFAOYSA-N methyl 2-methyl-5-phenylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC(C=2C=CC=CC=2)=C1 DVMKOWMMZIWHBY-UHFFFAOYSA-N 0.000 description 1
- RDDAZCURHIJFHM-UHFFFAOYSA-N methyl 5-methyl-2-phenylbenzoate Chemical compound COC(=O)C1=CC(C)=CC=C1C1=CC=CC=C1 RDDAZCURHIJFHM-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000897 modulatory effect Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229940000041 nervous system drug Drugs 0.000 description 1
- 230000006855 networking Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000021363 nonassociative learning Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000001009 nucleus accumben Anatomy 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229940125636 orexin 1 receptor antagonist Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 208000030062 persistent idiopathic facial pain Diseases 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 208000030153 prolactin-producing pituitary gland adenoma Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 208000026961 psychosexual disease Diseases 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 208000025874 separation anxiety disease Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 230000004037 social stress Effects 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 201000006152 substance dependence Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- QUERMGFVJPRMJL-UHFFFAOYSA-N tert-butyl azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC1 QUERMGFVJPRMJL-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- WTFFOOAJSDVASL-UHFFFAOYSA-N tributyl(pyrimidin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CC=N1 WTFFOOAJSDVASL-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13158791 | 2013-03-12 | ||
| EP13158791.7 | 2013-03-12 | ||
| PCT/IB2014/059628 WO2014141065A1 (en) | 2013-03-12 | 2014-03-11 | Azetidine amide derivatives as orexin receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2902135A1 true CA2902135A1 (en) | 2014-09-18 |
Family
ID=47843192
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2902135A Abandoned CA2902135A1 (en) | 2013-03-12 | 2014-03-11 | Azetidine amide derivatives as orexin receptor antagonists |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9403813B2 (https=) |
| EP (1) | EP2970241A1 (https=) |
| JP (1) | JP2016510810A (https=) |
| KR (1) | KR20150130413A (https=) |
| CN (1) | CN105051040A (https=) |
| CA (1) | CA2902135A1 (https=) |
| WO (1) | WO2014141065A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101689093B1 (ko) | 2012-06-04 | 2016-12-22 | 액테리온 파마슈티칼 리미티드 | 벤즈이미다졸-프롤린 유도체 |
| BR112015007516A2 (pt) | 2012-10-10 | 2017-07-04 | Actelion Pharmaceuticals Ltd | antagonistas do receptor de orexina que são derivados de [orto bi-(hetero-)aril]-[2-(meta bi-(hetero-)aril)- pirrolidin-1-il]-metanona |
| HK1225731B (en) | 2013-12-03 | 2017-09-15 | Idorsia Pharmaceuticals Ltd | Crystalline form of (s)-(2-(6-chloro-7-methyl-1h-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1 -yl)(5-methoxy-2-(2h-1,2,3-triazol-2-yl)phenyl)methanone and its use as orexin receptor antagonists |
| UA119151C2 (uk) | 2013-12-03 | 2019-05-10 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА СОЛЬОВА ФОРМА (S)-(2-(6-ХЛОР-7-МЕТИЛ-1H-БЕНЗО[d]ІМІДАЗОЛ-2-ІЛ)-2-МЕТИЛПІРОЛІДИН-1-ІЛ)(5-МЕТОКСИ-2-(2H-1,2,3-ТРИАЗОЛ-2-ІЛ)ФЕНІЛ)МЕТАНОНУ ЯК АНТАГОНІСТ ОРЕКСИНОВОГО РЕЦЕПТОРА |
| HRP20181710T1 (hr) | 2013-12-04 | 2018-12-28 | Idorsia Pharmaceuticals Ltd | Uporaba derivata benzimidazol-prolina |
| HRP20211304T1 (hr) | 2017-05-03 | 2021-11-12 | Idorsia Pharmaceuticals Ltd | Pripravljanje derivata 2-([1,2,3]triazol-2-il)-benzojeve kiseline |
| CN109810067B (zh) * | 2017-11-20 | 2022-05-20 | 扬子江药业集团有限公司 | 一种苏沃雷生中间体的制备方法 |
Family Cites Families (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001247569A (ja) * | 1999-08-12 | 2001-09-11 | Japan Tobacco Inc | ピロリジン誘導体又はピペリジン誘導体及びその医薬用途 |
| AUPQ253199A0 (en) | 1999-08-30 | 1999-09-23 | Fujisawa Pharmaceutical Co., Ltd. | Non-prostanoid prostaglandin I2-agonist |
| US6677354B2 (en) | 2000-06-16 | 2004-01-13 | Smithkline Beecham P.L.C. | Piperdines for use as orexin receptor antagonists |
| JP4246490B2 (ja) | 2000-11-28 | 2009-04-02 | スミスクライン ビーチャム ピー エル シー | オレキシン受容体のアンタゴニストとしてのモルホリン誘導体 |
| US20040192673A1 (en) | 2001-05-05 | 2004-09-30 | Pascale Gaillard | N-aroyl cyclic amine derivatives as orexin receptor antagonists |
| IL158463A0 (en) | 2001-05-05 | 2004-05-12 | Smithkline Beecham Plc | N-aroyl cyclic amines |
| GB0115862D0 (en) | 2001-06-28 | 2001-08-22 | Smithkline Beecham Plc | Compounds |
| BR0210609A (pt) | 2001-06-28 | 2004-07-20 | Smithkline Beecham Plc | Derivados de amina cìclica n-aroila como antagonistas do receptor da orexina |
| GB0124463D0 (en) | 2001-10-11 | 2001-12-05 | Smithkline Beecham Plc | Compounds |
| GB0127145D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Compounds |
| GB0130393D0 (en) | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| GB0130335D0 (en) | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| DE10240818A1 (de) * | 2002-08-30 | 2004-05-13 | Grünenthal GmbH | Substituierte 2-Pyrrolidin-2-yl-[1,3,4]-oxadiazol-Derivate |
| US20060040937A1 (en) | 2002-09-18 | 2006-02-23 | Glaxo Group Limited | N-aroyl cyclic amines as orexin receptor antagonists |
| GB0225938D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225884D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225944D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| PE20050226A1 (es) | 2003-06-04 | 2005-05-18 | Aventis Pharma Sa | Productos aril-heteroaromaticos y composiciones que los contienen |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| PT1751111E (pt) | 2004-03-01 | 2015-04-01 | Actelion Pharmaceuticals Ltd | Derivados de 1,2,3,4-tetrahidroisoquinolina substituída |
| WO2005113522A1 (en) | 2004-05-07 | 2005-12-01 | Janssen Pharmaceutica, N.V. | Azole carboxamide inhibitors of bacterial type iii protein secretion systems |
| EP1604989A1 (en) | 2004-06-08 | 2005-12-14 | Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft | DPP-IV inhibitors |
| US7269781B2 (en) | 2004-06-25 | 2007-09-11 | Hewlett-Packard Development Company, L.P. | Discrete universal denoising with reliability information |
| US20060019975A1 (en) | 2004-07-23 | 2006-01-26 | Pfizer Inc | Novel piperidyl derivatives of quinazoline and isoquinoline |
| GB0510142D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds A1 |
| HUP0500920A2 (en) | 2005-10-05 | 2007-07-30 | Richter Gedeon Nyrt | Oxadiazole derivatives, process for their preparation and their use |
| US20090082394A1 (en) | 2006-03-15 | 2009-03-26 | Actelion Pharmaceuticals, Ltd. | Tetrahydroisoquinoline Derivatives to Enhance Memory Function |
| CA2657623A1 (en) | 2006-07-14 | 2008-01-17 | Merck & Co., Inc. | Bridged diazepan orexin receptor antagonists |
| DE602007012910D1 (de) * | 2006-08-15 | 2011-04-14 | Actelion Pharmaceuticals Ltd | Azetidinverbindungen als orexin-rezeptor-antagonisten |
| TW200823227A (en) | 2006-09-29 | 2008-06-01 | Actelion Pharmaceuticals Ltd | 3-aza-bicyclo[3.1.0]hexane derivatives |
| PE20081229A1 (es) | 2006-12-01 | 2008-08-28 | Merck & Co Inc | Antagonistas de receptor de orexina de diazepam sustituido |
| CA2669060A1 (en) | 2006-12-01 | 2008-06-05 | Actelion Pharmaceuticals Ltd | Piperidine compounds |
| CL2007003827A1 (es) | 2006-12-28 | 2008-09-26 | Actelion Pharmaceuticals Ltd | Compuestos derivados de n-(2-aza-biciclo(3.1.0)hex-3-ilmetil)amida; y su uso para prevenir o tratar la depresion, neurosis, esquizofrenia, ansiedad, adicciones, epilepsia, dolor, enfermedades cardiacas, entre otras. |
| WO2008087611A2 (en) | 2007-01-19 | 2008-07-24 | Actelion Pharmaceuticals Ltd | Pyrrolidine- and piperidine- bis-amide derivatives |
| CL2008000836A1 (es) | 2007-03-26 | 2008-11-07 | Actelion Pharmaceuticals Ltd | Compuestos derivados de tiazolidina, antagonistas del receptor de orexina; composicion farmaceutica que los comprende; y su uso en el tratamiento de neurosis emocional, depresion grave, trastornos psicoticos, alzheimer, parkinson, dolor, entre otras. |
| ATE483707T1 (de) | 2007-05-14 | 2010-10-15 | Actelion Pharmaceuticals Ltd | 2-cyclopropylthiazolderivate |
| US7741347B2 (en) | 2007-05-17 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2008150364A1 (en) | 2007-05-23 | 2008-12-11 | Merck & Co., Inc. | Cyclopropyl pyrrolidine orexin receptor antagonists |
| EP2176258A1 (en) | 2007-07-03 | 2010-04-21 | Glaxo Group Limited | Piperidine derivatives useful as orexin receptor antagonists |
| GB0712888D0 (en) | 2007-07-03 | 2007-08-15 | Glaxo Group Ltd | Novel compounds |
| ATE524466T1 (de) | 2007-07-03 | 2011-09-15 | Actelion Pharmaceuticals Ltd | 3-azabicycloä3.3.0üoktanverbindungen |
| KR20100046047A (ko) | 2007-07-27 | 2010-05-04 | 액테리온 파마슈티칼 리미티드 | 2-아자-비시클로[3.3.0]옥탄 유도체 |
| CA2693817A1 (en) | 2007-07-27 | 2009-02-05 | Actelion Pharmaceuticals Ltd | Trans-3-aza-bicyclo[3.1.0]hexane derivatives |
| AR067665A1 (es) | 2007-07-27 | 2009-10-21 | Actelion Pharmaceuticals Ltd | Derivados de trans-3- aza-biciclo ( 3.1.0) hexano |
| WO2009040730A2 (en) | 2007-09-24 | 2009-04-02 | Actelion Pharmaceuticals Ltd | Pyrrolidines and piperidines as orexin receptor antagonists |
| PE20091010A1 (es) | 2007-10-10 | 2009-08-08 | Actelion Pharmaceuticals Ltd | Derivados de tetrahidroquinolina |
| CN101903378B (zh) | 2007-12-18 | 2014-03-12 | 埃科特莱茵药品有限公司 | 氨基三唑衍生物 |
| MX2010008993A (es) | 2008-02-21 | 2010-09-07 | Actelion Pharmaceuticals Ltd | Derivados de 2-aza-biciclo-[2.2.1]heptano. |
| GB0806536D0 (en) | 2008-04-10 | 2008-05-14 | Glaxo Group Ltd | Novel compounds |
| CN102083827A (zh) | 2008-07-07 | 2011-06-01 | 埃科特莱茵药品有限公司 | 作为食欲素受体拮抗剂的噻唑烷化合物 |
| WO2010038200A1 (en) | 2008-10-01 | 2010-04-08 | Actelion Pharmaceuticals Ltd | Oxazolidine compounds as orexin receptor antagonists |
| KR20110071004A (ko) | 2008-10-14 | 2011-06-27 | 액테리온 파마슈티칼 리미티드 | 페네틸아미드 유도체 및 이의 헤테로시클릭 유사체 |
| EP2349269A4 (en) | 2008-10-21 | 2012-04-25 | Merck Sharp & Dohme | 2,5-DISUBSTITUTED PIPERIDINOREXINE RECEPTOR ANTAGONISTS |
| WO2010060472A1 (en) | 2008-11-26 | 2010-06-03 | Glaxo Group Limited | Imidazopyridazine derivatives acting as orexin antagonists |
| JP2012509910A (ja) | 2008-11-26 | 2012-04-26 | グラクソ グループ リミテッド | 新規の化合物 |
| JP2012509911A (ja) | 2008-11-26 | 2012-04-26 | グラクソ グループ リミテッド | 新規の化合物 |
| JP2012510494A (ja) | 2008-12-02 | 2012-05-10 | グラクソ グループ リミテッド | Ｎ−｛［（ｉｒ、４ｓ、６ｒ）−３−（２−ピリジニルカルボニル）−３−アザビシクロ［４．１．０］ヘプタ−４−イル］メチル｝−２−ヘテロアリールアミン誘導体およびその使用 |
| AR074426A1 (es) | 2008-12-02 | 2011-01-19 | Glaxo Group Ltd | Compuesto de n-(((1s,4s,6s)-3-(2-piridinilcarbonil)3-azabiciclo (4,1.0)hept-4-il) metil)-2-heteroarilamina, su uso para la prepracion de un medicamento para el tratamiento de una enfermedad que requiere un antagonista de un receptor de orexina humana y composicion farmaceutica que lo comprende |
| GB0823467D0 (en) | 2008-12-23 | 2009-01-28 | Glaxo Group Ltd | Novel Compounds |
| AU2010232628A1 (en) | 2009-04-03 | 2011-10-06 | Merck Canada Inc. | Renin inhibitors |
| WO2010122151A1 (en) | 2009-04-24 | 2010-10-28 | Glaxo Group Limited | 3 -azabicyclo [4.1.0] heptanes used as orexin antagonists |
| SG175363A1 (en) | 2009-06-09 | 2011-12-29 | Actelion Pharmaceuticals Ltd | Fluorinated aminotriazole derivatives |
| WO2011050202A1 (en) | 2009-10-23 | 2011-04-28 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as orexin receptor modulators |
| ES2585806T3 (es) | 2009-10-23 | 2016-10-10 | Janssen Pharmaceutica N.V. | Octahidropirrolo [3,4-c] pirroles disustituidos como moduladores de receptores de orexina |
| WO2011050200A1 (en) | 2009-10-23 | 2011-04-28 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as orexin receptor modulators |
| AU2011207679B2 (en) | 2010-01-19 | 2013-10-10 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| CN103249730A (zh) | 2010-09-24 | 2013-08-14 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
| TWI565703B (zh) | 2011-11-08 | 2017-01-11 | 艾克泰聯製藥有限公司 | ２-（１，２，３-三唑-２-基）苯甲醯胺及３-（１，２，３-三唑-２-基）吡啶醯胺衍生物 |
| KR101689093B1 (ko) | 2012-06-04 | 2016-12-22 | 액테리온 파마슈티칼 리미티드 | 벤즈이미다졸-프롤린 유도체 |
| BR112015007516A2 (pt) | 2012-10-10 | 2017-07-04 | Actelion Pharmaceuticals Ltd | antagonistas do receptor de orexina que são derivados de [orto bi-(hetero-)aril]-[2-(meta bi-(hetero-)aril)- pirrolidin-1-il]-metanona |
-
2014
- 2014-03-11 CA CA2902135A patent/CA2902135A1/en not_active Abandoned
- 2014-03-11 WO PCT/IB2014/059628 patent/WO2014141065A1/en not_active Ceased
- 2014-03-11 EP EP14714392.9A patent/EP2970241A1/en not_active Withdrawn
- 2014-03-11 KR KR1020157028022A patent/KR20150130413A/ko not_active Withdrawn
- 2014-03-11 US US14/775,474 patent/US9403813B2/en not_active Expired - Fee Related
- 2014-03-11 JP JP2015562482A patent/JP2016510810A/ja active Pending
- 2014-03-11 CN CN201480015297.7A patent/CN105051040A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN105051040A (zh) | 2015-11-11 |
| JP2016510810A (ja) | 2016-04-11 |
| KR20150130413A (ko) | 2015-11-23 |
| EP2970241A1 (en) | 2016-01-20 |
| WO2014141065A1 (en) | 2014-09-18 |
| US20160024064A1 (en) | 2016-01-28 |
| US9403813B2 (en) | 2016-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2885180C (en) | Orexin receptor antagonists which are [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]-methanone derivatives | |
| US11040966B2 (en) | Benzimidazole-proline derivatives | |
| AU2012335194B2 (en) | 2-(1,2,3-triazol-2-yl)benzamide and 3-(1,2,3-triazol-2-yl)picolinamide derivatives as orexin receptor antagonists | |
| US9403813B2 (en) | Azetidine amide derivatives as orexin receptor antagonists | |
| WO2013050938A1 (en) | 3,7-diazabicyclo[3.3.1]nonane and 9-oxa-3,7-diazabicyclo[3.3.1]nonane derivatives | |
| IL285246B2 (en) | Substituted bicyclic compounds as farnesoid x receptor modulators | |
| EA047337B1 (ru) | Замещенные бициклические соединения в качестве модуляторов фарнезоидного х-рецептора | |
| HK1208449B (en) | Benzimidazole-proline derivatives | |
| NZ625896B2 (en) | 2-(1,2,3-triazol-2-yl)benzamide and 3-(1,2,3-triazol-2-yl)picolinamide derivatives as orexin receptor antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20190312 |