JP4942045B2 - ２−アシルアミノチアゾール誘導体 - Google Patents

Info

Publication number

JP4942045B2

JP4942045B2 JP2007531600A JP2007531600A JP4942045B2 JP 4942045 B2 JP4942045 B2 JP 4942045B2 JP 2007531600 A JP2007531600 A JP 2007531600A JP 2007531600 A JP2007531600 A JP 2007531600A JP 4942045 B2 JP4942045 B2 JP 4942045B2

Authority

JP

Japan

Prior art keywords

phenyl

thiazol

oxadiazol

methyl

tetrazol

Prior art date

2004-09-22

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.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• -1 [1,2,4] -oxadiazol-3-yl Chemical group 0.000 claims description 135
• 150000001875 compounds Chemical class 0.000 claims description 89
• 239000003814 drug Substances 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 125000001072 heteroaryl group Chemical group 0.000 claims description 11
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 7
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 claims description 5
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
• MBOQNIDBHUJTDE-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(C=2C=CC=CC=2)=C1C1=NOC(C)=N1 MBOQNIDBHUJTDE-UHFFFAOYSA-N 0.000 claims description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• YJMUPDQBCZLIPM-UHFFFAOYSA-N 2,2-dimethyl-n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]propanamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(=O)C(C)(C)C)S2)C=2C=CC=CC=2)=N1 YJMUPDQBCZLIPM-UHFFFAOYSA-N 0.000 claims description 3
• HZEHNKMAXIJJDB-UHFFFAOYSA-N 2,2-dimethyl-n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)C(C)(C)C)S2)C=2C=CC=CC=2)=N1 HZEHNKMAXIJJDB-UHFFFAOYSA-N 0.000 claims description 3
• RRWUSGXPQRIAEQ-UHFFFAOYSA-N 2,2-dimethyl-n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)C(C)(C)C)S2)C=2C=CC=CC=2)=N1 RRWUSGXPQRIAEQ-UHFFFAOYSA-N 0.000 claims description 3
• RAVBJNZNMCAMRX-UHFFFAOYSA-N 2,2-dimethyl-n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)C(C)(C)C)S2)C=2C=CC=CC=2)=N1 RAVBJNZNMCAMRX-UHFFFAOYSA-N 0.000 claims description 3
• SZZOCASQZRDVMZ-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)CC=3C=C(OC)C(OC)=CC=3)S2)C=2C=CC=CC=2)=N1 SZZOCASQZRDVMZ-UHFFFAOYSA-N 0.000 claims description 3
• YIMSOEBELHIPSS-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-[5-(2-methyltetrazol-5-yl)-4-thiophen-2-yl-1,3-thiazol-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC(=O)NC1=NC(C=2SC=CC=2)=C(C2=NN(C)N=N2)S1 YIMSOEBELHIPSS-UHFFFAOYSA-N 0.000 claims description 3
• FBLXTZCXECQRNZ-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-[5-(furan-2-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC(=O)NC1=NC(C=2C=CC=CC=2)=C(C=2OC=CC=2)S1 FBLXTZCXECQRNZ-UHFFFAOYSA-N 0.000 claims description 3
• DVSMWCMMCOIFLM-UHFFFAOYSA-N 2-(3-methoxyphenyl)-n-[4-phenyl-5-[2-(2-phenylethyl)tetrazol-5-yl]-1,3-thiazol-2-yl]acetamide Chemical compound COC1=CC=CC(CC(=O)NC=2SC(=C(N=2)C=2C=CC=CC=2)C2=NN(CCC=3C=CC=CC=3)N=N2)=C1 DVSMWCMMCOIFLM-UHFFFAOYSA-N 0.000 claims description 3
• VXTHKNTYOBFSGE-UHFFFAOYSA-N 2-cyclopentyl-n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)CC3CCCC3)S2)C=2C=CC=CC=2)=N1 VXTHKNTYOBFSGE-UHFFFAOYSA-N 0.000 claims description 3
• LJSYJCKQYVWCLM-UHFFFAOYSA-N 2-cyclopentyl-n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)CC3CCCC3)S2)C=2C=CC=CC=2)=N1 LJSYJCKQYVWCLM-UHFFFAOYSA-N 0.000 claims description 3
• IFWHOCPGRCHRGC-UHFFFAOYSA-N 2-cyclopentyl-n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)CC3CCCC3)S2)C=2C=CC=CC=2)=N1 IFWHOCPGRCHRGC-UHFFFAOYSA-N 0.000 claims description 3
• UFJPYHWBOUADFF-UHFFFAOYSA-N 2-cyclopentyl-n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)CC3CCCC3)S2)C=2C=CC=CC=2)=N1 UFJPYHWBOUADFF-UHFFFAOYSA-N 0.000 claims description 3
• BHADIZAVLCNBQV-UHFFFAOYSA-N 2-cyclopentyl-n-[5-(5-ethyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound O1C(CC)=NC(C2=C(N=C(NC(=O)CC3CCCC3)S2)C=2C=CC=CC=2)=N1 BHADIZAVLCNBQV-UHFFFAOYSA-N 0.000 claims description 3
• GMLWMWAYRUOBJE-UHFFFAOYSA-N 2-cyclopentyl-n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)CC3CCCC3)S2)C=2C=CC=CC=2)=N1 GMLWMWAYRUOBJE-UHFFFAOYSA-N 0.000 claims description 3
• QNJIDHZBZLFVLS-UHFFFAOYSA-N 2-cyclopentyl-n-[5-[2-(2-methylpropyl)tetrazol-5-yl]-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound CC(C)CN1N=NC(C2=C(N=C(NC(=O)CC3CCCC3)S2)C=2C=CC=CC=2)=N1 QNJIDHZBZLFVLS-UHFFFAOYSA-N 0.000 claims description 3
• ISEDGFCSFDUQQA-UHFFFAOYSA-N 2-methyl-n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]propanamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(=O)C(C)C)S2)C=2C=CC=CC=2)=N1 ISEDGFCSFDUQQA-UHFFFAOYSA-N 0.000 claims description 3
• BMTLTGDTKJZHRI-UHFFFAOYSA-N 2-methyl-n-[4-phenyl-5-[2-(2-phenylethyl)tetrazol-5-yl]-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)C(C)C)=NC(C=2C=CC=CC=2)=C1C(=N1)N=NN1CCC1=CC=CC=C1 BMTLTGDTKJZHRI-UHFFFAOYSA-N 0.000 claims description 3
• AKZUTNGSOOVYBV-UHFFFAOYSA-N 2-methyl-n-[5-(1-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)C(C)C)=NC(C=2C=CC=CC=2)=C1C1=NN=NN1C AKZUTNGSOOVYBV-UHFFFAOYSA-N 0.000 claims description 3
• GMDQIGGANHXKEX-UHFFFAOYSA-N 2-methyl-n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)C(C)C)=NC(C=2C=CC=CC=2)=C1C=1N=NN(C)N=1 GMDQIGGANHXKEX-UHFFFAOYSA-N 0.000 claims description 3
• NAWVILKLJXWGAY-UHFFFAOYSA-N 3,3-dimethyl-n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]butanamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)CC(C)(C)C)S2)C=2C=CC=CC=2)=N1 NAWVILKLJXWGAY-UHFFFAOYSA-N 0.000 claims description 3
• JZUAORJWLKBCFR-UHFFFAOYSA-N 3,3-dimethyl-n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]butanamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)CC(C)(C)C)S2)C=2C=CC=CC=2)=N1 JZUAORJWLKBCFR-UHFFFAOYSA-N 0.000 claims description 3
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
• YASZJAHOLUHLEF-UHFFFAOYSA-N 3-methyl-n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]butanamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(=O)CC(C)C)S2)C=2C=CC=CC=2)=N1 YASZJAHOLUHLEF-UHFFFAOYSA-N 0.000 claims description 3
• XXNKTJDJVHNUMX-UHFFFAOYSA-N 3-methyl-n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]butanamide Chemical compound S1C(NC(=O)CC(C)C)=NC(C=2C=CC=CC=2)=C1C=1N=NN(C)N=1 XXNKTJDJVHNUMX-UHFFFAOYSA-N 0.000 claims description 3
• MLURKVCBYPYHPF-UHFFFAOYSA-N 3-methyl-n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]butanamide Chemical compound S1C(NC(=O)CC(C)C)=NC(C=2C=CC=CC=2)=C1C1=NC(C)=NO1 MLURKVCBYPYHPF-UHFFFAOYSA-N 0.000 claims description 3
• HUQKHKNVVBHZSD-UHFFFAOYSA-N 3-methyl-n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]butanamide Chemical compound S1C(NC(=O)CC(C)C)=NC(C=2C=CC=CC=2)=C1C1=NOC(C)=N1 HUQKHKNVVBHZSD-UHFFFAOYSA-N 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• BYDGJSJCEZIIFQ-UHFFFAOYSA-N n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]-2-thiophen-2-ylacetamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(=O)CC=3SC=CC=3)S2)C=2C=CC=CC=2)=N1 BYDGJSJCEZIIFQ-UHFFFAOYSA-N 0.000 claims description 3
• LNXCYMFSMQCWCD-UHFFFAOYSA-N n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]propanamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(=O)CC)S2)C=2C=CC=CC=2)=N1 LNXCYMFSMQCWCD-UHFFFAOYSA-N 0.000 claims description 3
• HNHQMXDBRQATEU-UHFFFAOYSA-N n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]thiophene-3-carboxamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(=O)C3=CSC=C3)S2)C=2C=CC=CC=2)=N1 HNHQMXDBRQATEU-UHFFFAOYSA-N 0.000 claims description 3
• SWQXEJXCRFKPBZ-UHFFFAOYSA-N n-[4-phenyl-5-[2-(2-phenylethyl)tetrazol-5-yl]-1,3-thiazol-2-yl]furan-3-carboxamide Chemical compound C1=COC=C1C(=O)NC(S1)=NC(C=2C=CC=CC=2)=C1C(=N1)N=NN1CCC1=CC=CC=C1 SWQXEJXCRFKPBZ-UHFFFAOYSA-N 0.000 claims description 3
• WBCDSCLOXKDRCV-UHFFFAOYSA-N n-[5-(1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound C1CC1C(=O)NC(S1)=NC(C=2C=CC=CC=2)=C1C=1N=CON=1 WBCDSCLOXKDRCV-UHFFFAOYSA-N 0.000 claims description 3
• PDFPSWBCSYEQOV-UHFFFAOYSA-N n-[5-(2-butyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound CCCCN1N=NC(C2=C(N=C(NC(=O)C(C)C)S2)C=2C=CC=CC=2)=N1 PDFPSWBCSYEQOV-UHFFFAOYSA-N 0.000 claims description 3
• MQASJKWMDAPLLD-UHFFFAOYSA-N n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)C(C)C)S2)C=2C=CC=CC=2)=N1 MQASJKWMDAPLLD-UHFFFAOYSA-N 0.000 claims description 3
• CUMFNEBBXXPQLQ-UHFFFAOYSA-N n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]cyclohexanecarboxamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)C3CCCCC3)S2)C=2C=CC=CC=2)=N1 CUMFNEBBXXPQLQ-UHFFFAOYSA-N 0.000 claims description 3
• DIDLQFLXXMMQHA-UHFFFAOYSA-N n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)C3CC3)S2)C=2C=CC=CC=2)=N1 DIDLQFLXXMMQHA-UHFFFAOYSA-N 0.000 claims description 3
• SKRPIZKCJOMGQH-UHFFFAOYSA-N n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]furan-2-carboxamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)C=3OC=CC=3)S2)C=2C=CC=CC=2)=N1 SKRPIZKCJOMGQH-UHFFFAOYSA-N 0.000 claims description 3
• GNTQJACNFWKUAI-UHFFFAOYSA-N n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]furan-3-carboxamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)C3=COC=C3)S2)C=2C=CC=CC=2)=N1 GNTQJACNFWKUAI-UHFFFAOYSA-N 0.000 claims description 3
• MUGNCFXCRBJEML-UHFFFAOYSA-N n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C=1N=NN(CC)N=1 MUGNCFXCRBJEML-UHFFFAOYSA-N 0.000 claims description 3
• ZBMAIJSMSFZGHJ-UHFFFAOYSA-N n-[5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]thiophene-3-carboxamide Chemical compound CCN1N=NC(C2=C(N=C(NC(=O)C3=CSC=C3)S2)C=2C=CC=CC=2)=N1 ZBMAIJSMSFZGHJ-UHFFFAOYSA-N 0.000 claims description 3
• NRHXTKWLGXUCSV-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-phenylacetamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)CC=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 NRHXTKWLGXUCSV-UHFFFAOYSA-N 0.000 claims description 3
• OYGVDJNQRWNRHM-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-thiophen-2-ylacetamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)CC=3SC=CC=3)S2)C=2C=CC=CC=2)=N1 OYGVDJNQRWNRHM-UHFFFAOYSA-N 0.000 claims description 3
• CAIIZBBBJGPUAE-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(C=2C=CC=CC=2)=C1C=1N=NN(C)N=1 CAIIZBBBJGPUAE-UHFFFAOYSA-N 0.000 claims description 3
• MAIYLOSWCGHOEL-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)C3CC3)S2)C=2C=CC=CC=2)=N1 MAIYLOSWCGHOEL-UHFFFAOYSA-N 0.000 claims description 3
• XVAAJDOWOCSRLN-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]furan-2-carboxamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)C=3OC=CC=3)S2)C=2C=CC=CC=2)=N1 XVAAJDOWOCSRLN-UHFFFAOYSA-N 0.000 claims description 3
• VRPLZIIKPBOSOH-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]hexanamide Chemical compound S1C(NC(=O)CCCCC)=NC(C=2C=CC=CC=2)=C1C=1N=NN(C)N=1 VRPLZIIKPBOSOH-UHFFFAOYSA-N 0.000 claims description 3
• FMXVGFMDRGCGCX-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C=1N=NN(C)N=1 FMXVGFMDRGCGCX-UHFFFAOYSA-N 0.000 claims description 3
• GFOKXGHIKOBQCN-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]thiophene-3-carboxamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)C3=CSC=C3)S2)C=2C=CC=CC=2)=N1 GFOKXGHIKOBQCN-UHFFFAOYSA-N 0.000 claims description 3
• JKGJTCPROQXWMY-UHFFFAOYSA-N n-[5-(2-oxo-3h-1,3,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-phenylacetamide Chemical compound N=1C(C=2C=CC=CC=2)=C(C=2OC(=O)NN=2)SC=1NC(=O)CC1=CC=CC=C1 JKGJTCPROQXWMY-UHFFFAOYSA-N 0.000 claims description 3
• LTJBSVXRMRTZFQ-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2,2-dimethylpropanamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)C(C)(C)C)S2)C=2C=CC=CC=2)=N1 LTJBSVXRMRTZFQ-UHFFFAOYSA-N 0.000 claims description 3
• JABWEAZJMIIXFQ-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)C(C)C)S2)C=2C=CC=CC=2)=N1 JABWEAZJMIIXFQ-UHFFFAOYSA-N 0.000 claims description 3
• UNSQIBLQWIGVJC-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-phenylacetamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)CC=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 UNSQIBLQWIGVJC-UHFFFAOYSA-N 0.000 claims description 3
• DMKPSNVCMWIMHJ-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-thiophen-2-ylacetamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)CC=3SC=CC=3)S2)C=2C=CC=CC=2)=N1 DMKPSNVCMWIMHJ-UHFFFAOYSA-N 0.000 claims description 3
• FLDDVCHAFURDFN-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-3-methylbutanamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)CC(C)C)S2)C=2C=CC=CC=2)=N1 FLDDVCHAFURDFN-UHFFFAOYSA-N 0.000 claims description 3
• IXJFYQZCLPOTSY-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound CCC1=NOC(C2=C(N=C(NC(C)=O)S2)C=2C=CC=CC=2)=N1 IXJFYQZCLPOTSY-UHFFFAOYSA-N 0.000 claims description 3
• LUPODRKELBWUHI-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]benzamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 LUPODRKELBWUHI-UHFFFAOYSA-N 0.000 claims description 3
• RUPQLVVGEIUZCK-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]cyclohexanecarboxamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)C3CCCCC3)S2)C=2C=CC=CC=2)=N1 RUPQLVVGEIUZCK-UHFFFAOYSA-N 0.000 claims description 3
• IYFMBIFUJNAOJE-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)C3CC3)S2)C=2C=CC=CC=2)=N1 IYFMBIFUJNAOJE-UHFFFAOYSA-N 0.000 claims description 3
• GXXBTFNHXPXHMC-UHFFFAOYSA-N n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C1=NC(CC)=NO1 GXXBTFNHXPXHMC-UHFFFAOYSA-N 0.000 claims description 3
• DNZVZJABDLWHPR-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-phenylacetamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)CC=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 DNZVZJABDLWHPR-UHFFFAOYSA-N 0.000 claims description 3
• ROROLJFELRMFDT-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]-2-thiophen-2-ylacetamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)CC=3SC=CC=3)S2)C=2C=CC=CC=2)=N1 ROROLJFELRMFDT-UHFFFAOYSA-N 0.000 claims description 3
• YTYHMGOWKQWFEY-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(C=2C=CC=CC=2)=C1C1=NC(C)=NO1 YTYHMGOWKQWFEY-UHFFFAOYSA-N 0.000 claims description 3
• VXICBIKGZNYPSZ-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]benzamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 VXICBIKGZNYPSZ-UHFFFAOYSA-N 0.000 claims description 3
• LFDZEIXGTUUMNR-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]cyclohexanecarboxamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)C3CCCCC3)S2)C=2C=CC=CC=2)=N1 LFDZEIXGTUUMNR-UHFFFAOYSA-N 0.000 claims description 3
• LEMHEWSZQBDQCZ-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)C3CC3)S2)C=2C=CC=CC=2)=N1 LEMHEWSZQBDQCZ-UHFFFAOYSA-N 0.000 claims description 3
• DLZCZGZCBOABLZ-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]furan-2-carboxamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)C=3OC=CC=3)S2)C=2C=CC=CC=2)=N1 DLZCZGZCBOABLZ-UHFFFAOYSA-N 0.000 claims description 3
• APDWNDSMLCZTCW-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C1=NC(C)=NO1 APDWNDSMLCZTCW-UHFFFAOYSA-N 0.000 claims description 3
• ADKHYZXIQZGENX-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]thiophene-3-carboxamide Chemical compound CC1=NOC(C2=C(N=C(NC(=O)C3=CSC=C3)S2)C=2C=CC=CC=2)=N1 ADKHYZXIQZGENX-UHFFFAOYSA-N 0.000 claims description 3
• HDOXKWIAZKMBSV-UHFFFAOYSA-N n-[5-(5-ethyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]-3-phenylprop-2-enamide Chemical compound O1C(CC)=NC(C2=C(N=C(NC(=O)C=CC=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 HDOXKWIAZKMBSV-UHFFFAOYSA-N 0.000 claims description 3
• SRSPDZOFHBVECE-UHFFFAOYSA-N n-[5-(5-ethyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound O1C(CC)=NC(C2=C(N=C(NC(=O)C3CC3)S2)C=2C=CC=CC=2)=N1 SRSPDZOFHBVECE-UHFFFAOYSA-N 0.000 claims description 3
• BRLKYKRCBSWGPU-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]-2-phenylacetamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)CC=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 BRLKYKRCBSWGPU-UHFFFAOYSA-N 0.000 claims description 3
• AQENRZPNRPHALA-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]-2-thiophen-2-ylacetamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)CC=3SC=CC=3)S2)C=2C=CC=CC=2)=N1 AQENRZPNRPHALA-UHFFFAOYSA-N 0.000 claims description 3
• GQSYOZRSKJHINW-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]benzamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 GQSYOZRSKJHINW-UHFFFAOYSA-N 0.000 claims description 3
• UVMAIZSRDYYXLF-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]cyclohexanecarboxamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)C3CCCCC3)S2)C=2C=CC=CC=2)=N1 UVMAIZSRDYYXLF-UHFFFAOYSA-N 0.000 claims description 3
• GINNJZRPRVSARM-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)C3CC3)S2)C=2C=CC=CC=2)=N1 GINNJZRPRVSARM-UHFFFAOYSA-N 0.000 claims description 3
• IHHAGGFDQFYYIF-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C1=NOC(C)=N1 IHHAGGFDQFYYIF-UHFFFAOYSA-N 0.000 claims description 3
• GFPUBCLVHDDSOL-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]thiophene-3-carboxamide Chemical compound O1C(C)=NC(C2=C(N=C(NC(=O)C3=CSC=C3)S2)C=2C=CC=CC=2)=N1 GFPUBCLVHDDSOL-UHFFFAOYSA-N 0.000 claims description 3
• SICGAFJPGXFKPC-UHFFFAOYSA-N n-[5-(furan-2-yl)-4-phenyl-1,3-thiazol-2-yl]-2,2-dimethylpropanamide Chemical compound S1C(NC(=O)C(C)(C)C)=NC(C=2C=CC=CC=2)=C1C1=CC=CO1 SICGAFJPGXFKPC-UHFFFAOYSA-N 0.000 claims description 3
• HPSDXCKBOUGYPZ-UHFFFAOYSA-N n-[5-(furan-2-yl)-4-phenyl-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound S1C(NC(=O)C(C)C)=NC(C=2C=CC=CC=2)=C1C1=CC=CO1 HPSDXCKBOUGYPZ-UHFFFAOYSA-N 0.000 claims description 3
• RVZZWRCDYZDUTC-UHFFFAOYSA-N n-[5-(furan-2-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C1=CC=CO1 RVZZWRCDYZDUTC-UHFFFAOYSA-N 0.000 claims description 3
• QFZIBXNIBOPOBC-UHFFFAOYSA-N n-[5-(furan-3-yl)-4-phenyl-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound S1C(NC(=O)C(C)C)=NC(C=2C=CC=CC=2)=C1C=1C=COC=1 QFZIBXNIBOPOBC-UHFFFAOYSA-N 0.000 claims description 3
• XSOKAWLHACXEQV-UHFFFAOYSA-N n-[5-(furan-3-yl)-4-phenyl-1,3-thiazol-2-yl]cyclopropanecarboxamide Chemical compound C1CC1C(=O)NC(S1)=NC(C=2C=CC=CC=2)=C1C=1C=COC=1 XSOKAWLHACXEQV-UHFFFAOYSA-N 0.000 claims description 3
• UVKCPTWDXYCNOC-UHFFFAOYSA-N n-[5-(furan-3-yl)-4-phenyl-1,3-thiazol-2-yl]furan-2-carboxamide Chemical compound C=1C=COC=1C(=O)NC(S1)=NC(C=2C=CC=CC=2)=C1C=1C=COC=1 UVKCPTWDXYCNOC-UHFFFAOYSA-N 0.000 claims description 3
• PEBNGPCUMCMWJQ-UHFFFAOYSA-N n-[5-(furan-3-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C=1C=COC=1 PEBNGPCUMCMWJQ-UHFFFAOYSA-N 0.000 claims description 3
• MZJZDPGZBZPCOX-UHFFFAOYSA-N n-[5-[2-(2-methylpropyl)tetrazol-5-yl]-4-phenyl-1,3-thiazol-2-yl]-2-thiophen-2-ylacetamide Chemical compound CC(C)CN1N=NC(C2=C(N=C(NC(=O)CC=3SC=CC=3)S2)C=2C=CC=CC=2)=N1 MZJZDPGZBZPCOX-UHFFFAOYSA-N 0.000 claims description 3
• WBKZUZBZQHFPMX-UHFFFAOYSA-N n-[5-[2-(cyclopropylmethyl)tetrazol-5-yl]-4-phenyl-1,3-thiazol-2-yl]-3-methylbutanamide Chemical compound S1C(NC(=O)CC(C)C)=NC(C=2C=CC=CC=2)=C1C(=N1)N=NN1CC1CC1 WBKZUZBZQHFPMX-UHFFFAOYSA-N 0.000 claims description 3
• TXBSBIRNMYIRPG-UHFFFAOYSA-N 2-phenyl-n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]acetamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(=O)CC=3C=CC=CC=3)S2)C=2C=CC=CC=2)=N1 TXBSBIRNMYIRPG-UHFFFAOYSA-N 0.000 claims description 2
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 2
• PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical group C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 2
• 125000003545 alkoxy group Chemical group 0.000 claims description 2
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 229910052799 carbon Inorganic materials 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• KMRGUAWTLWDJGF-UHFFFAOYSA-N n-[5-(2-methyltetrazol-5-yl)-4-thiophen-2-yl-1,3-thiazol-2-yl]furan-3-carboxamide Chemical compound CN1N=NC(C2=C(N=C(NC(=O)C3=COC=C3)S2)C=2SC=CC=2)=N1 KMRGUAWTLWDJGF-UHFFFAOYSA-N 0.000 claims description 2
• QXVWNYFESBAWOA-UHFFFAOYSA-N n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]hexanamide Chemical compound S1C(NC(=O)CCCCC)=NC(C=2C=CC=CC=2)=C1C1=NC(C)=NO1 QXVWNYFESBAWOA-UHFFFAOYSA-N 0.000 claims description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 74
• 238000000105 evaporative light scattering detection Methods 0.000 description 50
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
• 239000011541 reaction mixture Substances 0.000 description 40
• 108020003175 receptors Proteins 0.000 description 36
• 102000005962 receptors Human genes 0.000 description 36
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
• 239000002904 solvent Substances 0.000 description 28
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
• 235000019439 ethyl acetate Nutrition 0.000 description 25
• 239000000203 mixture Substances 0.000 description 23
• 238000000034 method Methods 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 239000000243 solution Substances 0.000 description 18
• 239000012043 crude product Substances 0.000 description 17
• 230000002829 reductive effect Effects 0.000 description 16
• ZYFZWAOJVXDIPE-UHFFFAOYSA-N 5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound CC1=NOC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 ZYFZWAOJVXDIPE-UHFFFAOYSA-N 0.000 description 14
• HLDNAWOFSJCBTQ-UHFFFAOYSA-N 5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound O1C(C)=NC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 HLDNAWOFSJCBTQ-UHFFFAOYSA-N 0.000 description 14
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• 239000000556 agonist Substances 0.000 description 13
• 238000010992 reflux Methods 0.000 description 13
• 229910052938 sodium sulfate Inorganic materials 0.000 description 13
• 235000011152 sodium sulphate Nutrition 0.000 description 13
• UHFNPCMCZDINAT-UHFFFAOYSA-N 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound CCC1=NOC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 UHFNPCMCZDINAT-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• 239000005557 antagonist Substances 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 11
• 238000003818 flash chromatography Methods 0.000 description 11
• 239000002464 receptor antagonist Substances 0.000 description 11
• 229940044551 receptor antagonist Drugs 0.000 description 11
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 239000003480 eluent Substances 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 208000018737 Parkinson disease Diseases 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 239000003446 ligand Substances 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 125000006239 protecting group Chemical group 0.000 description 8
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
• 229910052740 iodine Inorganic materials 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 238000011282 treatment Methods 0.000 description 7
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
• NZBXRSDWYKBGIV-UHFFFAOYSA-N 5-(furan-3-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C=1C=COC=1 NZBXRSDWYKBGIV-UHFFFAOYSA-N 0.000 description 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• 210000004556 brain Anatomy 0.000 description 6
• 239000012267 brine Substances 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• BZZONORRUOGFRL-UHFFFAOYSA-N 5-(1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C=1N=CON=1 BZZONORRUOGFRL-UHFFFAOYSA-N 0.000 description 5
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 5
• UTLPKQYUXOEJIL-UHFFFAOYSA-N LSM-3822 Chemical compound N1=CC=2C3=NC(C=4OC=CC=4)=NN3C(N)=NC=2N1CCC1=CC=CC=C1 UTLPKQYUXOEJIL-UHFFFAOYSA-N 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 241000700159 Rattus Species 0.000 description 5
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 229960005305 adenosine Drugs 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 5
• 229960003638 dopamine Drugs 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• IQVRBWUUXZMOPW-PKNBQFBNSA-N istradefylline Chemical compound CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=C(OC)C(OC)=C1 IQVRBWUUXZMOPW-PKNBQFBNSA-N 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 239000004031 partial agonist Substances 0.000 description 5
• 230000002441 reversible effect Effects 0.000 description 5
• KITPGOBUTFZBFW-UHFFFAOYSA-N 2-(1-methyltetrazol-5-yl)-1-phenylethanone Chemical compound CN1N=NN=C1CC(=O)C1=CC=CC=C1 KITPGOBUTFZBFW-UHFFFAOYSA-N 0.000 description 4
• NILLIUYSJFTTRH-UHFFFAOYSA-N 2-cyclopentylacetyl chloride Chemical compound ClC(=O)CC1CCCC1 NILLIUYSJFTTRH-UHFFFAOYSA-N 0.000 description 4
• VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 4
• FVUGXPRQUILBPM-UHFFFAOYSA-N 3-[(2-phenyl-1,3-dithian-2-yl)methyl]furan Chemical compound S1CCCSC1(C=1C=CC=CC=1)CC=1C=COC=1 FVUGXPRQUILBPM-UHFFFAOYSA-N 0.000 description 4
• 229910018072 Al 2 O 3 Inorganic materials 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
• 208000023105 Huntington disease Diseases 0.000 description 4
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 239000000654 additive Substances 0.000 description 4
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 4
• 150000008064 anhydrides Chemical class 0.000 description 4
• 239000011324 bead Substances 0.000 description 4
• ZJRCIQAMTAINCB-UHFFFAOYSA-N benzoylacetonitrile Chemical compound N#CCC(=O)C1=CC=CC=C1 ZJRCIQAMTAINCB-UHFFFAOYSA-N 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 4
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
• 208000028867 ischemia Diseases 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 210000001577 neostriatum Anatomy 0.000 description 4
• 210000002569 neuron Anatomy 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 230000006977 prepulse inhibition Effects 0.000 description 4
• RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 150000003839 salts Chemical class 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 239000011550 stock solution Substances 0.000 description 4
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 3
• PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 3
• UZBGMRJCHOMLNR-UHFFFAOYSA-N 1-phenyl-2-(2h-tetrazol-5-yl)ethanone Chemical compound C=1C=CC=CC=1C(=O)CC=1N=NNN=1 UZBGMRJCHOMLNR-UHFFFAOYSA-N 0.000 description 3
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
• GZXPAZDRDZAMAT-UHFFFAOYSA-N 2-(furan-2-yl)-1-phenylethanone Chemical compound C=1C=CC=CC=1C(=O)CC1=CC=CO1 GZXPAZDRDZAMAT-UHFFFAOYSA-N 0.000 description 3
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
• JHEXUURKXQZMDP-UHFFFAOYSA-N 2-amino-4-phenyl-1,3-thiazole-5-carbonitrile Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C#N JHEXUURKXQZMDP-UHFFFAOYSA-N 0.000 description 3
• KSUKZNGCBYOMHZ-UHFFFAOYSA-N 2-amino-n'-hydroxy-4-phenyl-1,3-thiazole-5-carboximidamide Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C(=N)NO KSUKZNGCBYOMHZ-UHFFFAOYSA-N 0.000 description 3
• GXKPARDRBFURON-UHFFFAOYSA-N 2-phenyl-1,3-dithiane Chemical compound S1CCCSC1C1=CC=CC=C1 GXKPARDRBFURON-UHFFFAOYSA-N 0.000 description 3
• AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 description 3
• ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 3
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
• OVNATMPFIRAWQD-UHFFFAOYSA-N 5-(2-ethyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound CCN1N=NC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 OVNATMPFIRAWQD-UHFFFAOYSA-N 0.000 description 3
• QATWFPOLIWXMLE-UHFFFAOYSA-N 5-(2-methyltetrazol-5-yl)-4-thiophen-2-yl-1,3-thiazol-2-amine Chemical compound CN1N=NC(C2=C(N=C(N)S2)C=2SC=CC=2)=N1 QATWFPOLIWXMLE-UHFFFAOYSA-N 0.000 description 3
• IODMEJAMAOTLNA-UHFFFAOYSA-N 5-(furan-2-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C1=CC=CO1 IODMEJAMAOTLNA-UHFFFAOYSA-N 0.000 description 3
• VLJCCDZUWHLWKY-UHFFFAOYSA-N 5-ethyl-3-(4-phenyl-1,3-thiazol-5-yl)-1,2,4-oxadiazole Chemical compound O1C(CC)=NC(C2=C(N=CS2)C=2C=CC=CC=2)=N1 VLJCCDZUWHLWKY-UHFFFAOYSA-N 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 206010021143 Hypoxia Diseases 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• 241001590997 Moolgarda engeli Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• 235000011054 acetic acid Nutrition 0.000 description 3
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
• 239000012346 acetyl chloride Substances 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 239000002467 adenosine A2a receptor antagonist Substances 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 229940025084 amphetamine Drugs 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 229910052786 argon Inorganic materials 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 229940125904 compound 1 Drugs 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 3
• 230000003247 decreasing effect Effects 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
• 230000003291 dopaminomimetic effect Effects 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 229930195712 glutamate Natural products 0.000 description 3
• 229940049906 glutamate Drugs 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000011630 iodine Substances 0.000 description 3
• 238000011813 knockout mouse model Methods 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• LEVUCQNNOLWCSS-UHFFFAOYSA-N n-[5-(furan-3-yl)-4-phenyl-1,3-thiazol-2-yl]formamide Chemical compound S1C(NC=O)=NC(C=2C=CC=CC=2)=C1C=1C=COC=1 LEVUCQNNOLWCSS-UHFFFAOYSA-N 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 239000000018 receptor agonist Substances 0.000 description 3
• 229940044601 receptor agonist Drugs 0.000 description 3
• 230000024188 startle response Effects 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 150000003536 tetrazoles Chemical class 0.000 description 3
• ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 3
• FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
• RTSNKZUMQFFAFK-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)-1-thiophen-2-ylethanone Chemical compound C=1C=CSC=1C(=O)CC1=NN=NN1 RTSNKZUMQFFAFK-UHFFFAOYSA-N 0.000 description 2
• QBJIMTPENIGDOG-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1OC QBJIMTPENIGDOG-UHFFFAOYSA-N 0.000 description 2
• SCZKAQIZHIMAFK-UHFFFAOYSA-N 2-(furan-3-yl)-1-phenylethanone Chemical compound C=1C=CC=CC=1C(=O)CC=1C=COC=1 SCZKAQIZHIMAFK-UHFFFAOYSA-N 0.000 description 2
• UQRXCMSKYISJJV-UHFFFAOYSA-N 2-amino-4-phenyl-1,3-thiazole-5-carbohydrazide Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C(=O)NN UQRXCMSKYISJJV-UHFFFAOYSA-N 0.000 description 2
• KMQDAYBDKOKVNY-UHFFFAOYSA-N 2-bromo-3-oxo-3-phenylpropanenitrile Chemical compound N#CC(Br)C(=O)C1=CC=CC=C1 KMQDAYBDKOKVNY-UHFFFAOYSA-N 0.000 description 2
• DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 2
• HOEQXFUBJFGJKA-UHFFFAOYSA-N 3-(bromomethyl)furan Chemical compound BrCC=1C=COC=1 HOEQXFUBJFGJKA-UHFFFAOYSA-N 0.000 description 2
• IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 description 2
• WBLZUCOIBUDNBV-UHFFFAOYSA-N 3-nitropropanoic acid Chemical compound OC(=O)CC[N+]([O-])=O WBLZUCOIBUDNBV-UHFFFAOYSA-N 0.000 description 2
• ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
• CLZSJUKZBNYTKS-UHFFFAOYSA-N 5-(1-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound CN1N=NN=C1C1=C(C=2C=CC=CC=2)N=C(N)S1 CLZSJUKZBNYTKS-UHFFFAOYSA-N 0.000 description 2
• VIZLJELYEMIQLV-UHFFFAOYSA-N 5-(2-amino-4-phenyl-1,3-thiazol-5-yl)-3h-1,3,4-oxadiazol-2-one Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C1=NNC(=O)O1 VIZLJELYEMIQLV-UHFFFAOYSA-N 0.000 description 2
• 102000009346 Adenosine receptors Human genes 0.000 description 2
• 108050000203 Adenosine receptors Proteins 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• 201000006474 Brain Ischemia Diseases 0.000 description 2
• 208000009132 Catalepsy Diseases 0.000 description 2
• 206010008120 Cerebral ischaemia Diseases 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 206010018341 Gliosis Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 208000010496 Heart Arrest Diseases 0.000 description 2
• 208000016988 Hemorrhagic Stroke Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
• 239000002841 Lewis acid Substances 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
• 208000028017 Psychotic disease Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 208000030886 Traumatic Brain injury Diseases 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 206010047853 Waxy flexibility Diseases 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 238000003016 alphascreen Methods 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 230000001430 anti-depressive effect Effects 0.000 description 2
• 230000000561 anti-psychotic effect Effects 0.000 description 2
• 239000000935 antidepressant agent Substances 0.000 description 2
• 229940005513 antidepressants Drugs 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 210000004227 basal ganglia Anatomy 0.000 description 2
• 230000006736 behavioral deficit Effects 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 229910052796 boron Inorganic materials 0.000 description 2
• WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical group CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 206010008118 cerebral infarction Diseases 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical compound [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 description 2
• 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 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 229960003368 croscarmellose sodium type a Drugs 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000018044 dehydration Effects 0.000 description 2
• 238000006297 dehydration reaction Methods 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 2
• ZOXQRNFZFFTCSQ-UHFFFAOYSA-N ethyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenyl-1,3-thiazole-5-carboxylate Chemical compound S1C(NC(=O)OC(C)(C)C)=NC(C=2C=CC=CC=2)=C1C(=O)OCC ZOXQRNFZFFTCSQ-UHFFFAOYSA-N 0.000 description 2
• MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 2
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
• 230000007954 hypoxia Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 230000010354 integration Effects 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 150000007517 lewis acids Chemical class 0.000 description 2
• 238000012417 linear regression Methods 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 238000006263 metalation reaction Methods 0.000 description 2
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 2
• ZIXGFBCKNCRYJK-UHFFFAOYSA-N n-[4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-yl]acetamide Chemical compound CCCN1N=NC(C2=C(N=C(NC(C)=O)S2)C=2C=CC=CC=2)=N1 ZIXGFBCKNCRYJK-UHFFFAOYSA-N 0.000 description 2
• GVAYMNZQWBYKFD-UHFFFAOYSA-N n-[5-(5-ethyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]propanamide Chemical compound S1C(NC(=O)CC)=NC(C=2C=CC=CC=2)=C1C1=NOC(CC)=N1 GVAYMNZQWBYKFD-UHFFFAOYSA-N 0.000 description 2
• NKJXUXSCMCTFHM-UHFFFAOYSA-N n-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-yl]hexanamide Chemical compound S1C(NC(=O)CCCCC)=NC(C=2C=CC=CC=2)=C1C1=NOC(C)=N1 NKJXUXSCMCTFHM-UHFFFAOYSA-N 0.000 description 2
• MGWDMVBTTVLADQ-UHFFFAOYSA-N n-[5-(furan-2-yl)-4-phenyl-1,3-thiazol-2-yl]formamide Chemical compound S1C(NC=O)=NC(C=2C=CC=CC=2)=C1C1=CC=CO1 MGWDMVBTTVLADQ-UHFFFAOYSA-N 0.000 description 2
• 210000004498 neuroglial cell Anatomy 0.000 description 2
• 230000016273 neuron death Effects 0.000 description 2
• 231100000189 neurotoxic Toxicity 0.000 description 2
• 230000002887 neurotoxic effect Effects 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 239000008194 pharmaceutical composition Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 238000003752 polymerase chain reaction Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 230000004224 protection Effects 0.000 description 2
• 208000020016 psychiatric disease Diseases 0.000 description 2
• 239000003368 psychostimulant agent Substances 0.000 description 2
• 125000005493 quinolyl group Chemical group 0.000 description 2
• 125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
• 238000011552 rat model Methods 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 229940085605 saccharin sodium Drugs 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• 239000012265 solid product Substances 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 238000003860 storage Methods 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
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
• ZVOTZMQDCPITGV-UHFFFAOYSA-N tert-butyl n-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]carbamate Chemical compound CCC1=NOC(C2=C(N=C(NC(=O)OC(C)(C)C)S2)C=2C=CC=CC=2)=N1 ZVOTZMQDCPITGV-UHFFFAOYSA-N 0.000 description 2
• HEKQYNIUMGIJEM-UHFFFAOYSA-N tert-butyl n-[5-(3-methyl-1,2,4-oxadiazol-5-yl)-4-phenyl-1,3-thiazol-2-yl]carbamate Chemical compound CC1=NOC(C2=C(N=C(NC(=O)OC(C)(C)C)S2)C=2C=CC=CC=2)=N1 HEKQYNIUMGIJEM-UHFFFAOYSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• QTWBEVAYYDZLQL-UHFFFAOYSA-N thiophene-3-carbonyl chloride Chemical compound ClC(=O)C=1C=CSC=1 QTWBEVAYYDZLQL-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000009529 traumatic brain injury Effects 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
• VJLYHTOSFSGXGH-CQSZACIVSA-N (2R)-1-[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxybenzoyl]pyrrolidine-2-carboxylic acid Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)N2[C@H](CCC2)C(=O)O)C=CC=1 VJLYHTOSFSGXGH-CQSZACIVSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• BIXYYZIIJIXVFW-UUOKFMHZSA-N (2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BIXYYZIIJIXVFW-UUOKFMHZSA-N 0.000 description 1
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
• 125000006636 (C3-C8) cycloalkylcarbonyl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WOGITNXCNOTRLK-VOTSOKGWSA-N (e)-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CC=C1 WOGITNXCNOTRLK-VOTSOKGWSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
• HCYFGRCYSCXKNQ-UHFFFAOYSA-N 2-(1,3-dimethyl-2,6-dioxo-7-purinyl)acetic acid Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)=O)C=N2 HCYFGRCYSCXKNQ-UHFFFAOYSA-N 0.000 description 1
• YLLZTGMRRUAAHT-UHFFFAOYSA-N 2-(2-methyltetrazol-5-yl)-1-phenylethanone Chemical compound CN1N=NC(CC(=O)C=2C=CC=CC=2)=N1 YLLZTGMRRUAAHT-UHFFFAOYSA-N 0.000 description 1
• DWUJDNHHQKEOPR-UHFFFAOYSA-N 2-(2-piperidin-4-ylethyl)pyridine Chemical compound C1CNCCC1CCC1=CC=CC=N1 DWUJDNHHQKEOPR-UHFFFAOYSA-N 0.000 description 1
• JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
• 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 1
• OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 1
• BKFSUZNMFPCJNJ-UHFFFAOYSA-N 2-hydroxy-3,4-dimethylidenecyclohexa-1,5-diene-1-carboxylic acid Chemical compound OC(=O)C=1C=CC(=C)C(=C)C=1O BKFSUZNMFPCJNJ-UHFFFAOYSA-N 0.000 description 1
• 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• XWWUQBHVRILEPB-UHFFFAOYSA-N 3-oxo-3-thiophen-2-ylpropanenitrile Chemical compound N#CCC(=O)C1=CC=CS1 XWWUQBHVRILEPB-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• VUKCJBWTKRRPMC-UHFFFAOYSA-N 4-phenyl-5-(2-propyltetrazol-5-yl)-1,3-thiazol-2-amine Chemical compound CCCN1N=NC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 VUKCJBWTKRRPMC-UHFFFAOYSA-N 0.000 description 1
• NIYLQJJJCAIYQB-UHFFFAOYSA-N 4-phenyl-5-[2-(2-phenylethyl)tetrazol-5-yl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C(=N1)N=NN1CCC1=CC=CC=C1 NIYLQJJJCAIYQB-UHFFFAOYSA-N 0.000 description 1
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
• DHHIWHABXKDRMI-UHFFFAOYSA-N 5-(2-butyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound CCCCN1N=NC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 DHHIWHABXKDRMI-UHFFFAOYSA-N 0.000 description 1
• XFGVJUGZSPZPSZ-UHFFFAOYSA-N 5-(2-methyltetrazol-5-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound CN1N=NC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 XFGVJUGZSPZPSZ-UHFFFAOYSA-N 0.000 description 1
• CWTWCDHJXSZOEY-UHFFFAOYSA-N 5-(5-ethyl-1,2,4-oxadiazol-3-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound O1C(CC)=NC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 CWTWCDHJXSZOEY-UHFFFAOYSA-N 0.000 description 1
• OUWRVWOEYYWORM-UHFFFAOYSA-N 5-[2-(2-methylpropyl)tetrazol-5-yl]-4-phenyl-1,3-thiazol-2-amine Chemical compound CC(C)CN1N=NC(C2=C(N=C(N)S2)C=2C=CC=CC=2)=N1 OUWRVWOEYYWORM-UHFFFAOYSA-N 0.000 description 1
• SRCCWNZRPHECOU-UHFFFAOYSA-N 5-[2-(cyclopropylmethyl)tetrazol-5-yl]-4-phenyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C(=N1)N=NN1CC1CC1 SRCCWNZRPHECOU-UHFFFAOYSA-N 0.000 description 1
• FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 1
• SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
• RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
• 102000055025 Adenosine deaminases Human genes 0.000 description 1
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
• 229910015900 BF3 Inorganic materials 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• XHSDWBLSWMFXOM-UHFFFAOYSA-N CCC(NO)=N.NO.Cl Chemical compound CCC(NO)=N.NO.Cl XHSDWBLSWMFXOM-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 101150049660 DRD2 gene Proteins 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 241000699694 Gerbillinae Species 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
• 241001562081 Ikeda Species 0.000 description 1
• 241000581650 Ivesia Species 0.000 description 1
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 JADDQZYHOWSFJD-FLNNQWSLSA-N 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 101150101537 Olah gene Proteins 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• 206010034010 Parkinsonism 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
• 108010002747 Pfu DNA polymerase Proteins 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 101001030728 Rattus norvegicus Huntingtin Proteins 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 241001125815 Triglidae Species 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 229950003769 acefylline Drugs 0.000 description 1
• PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
• QMUISQISXDPSPD-UHFFFAOYSA-N acetyl chloride;2-amino-n'-hydroxy-4-phenyl-1,3-thiazole-5-carboximidamide Chemical compound CC(Cl)=O.S1C(N)=NC(C=2C=CC=CC=2)=C1C(=N)NO QMUISQISXDPSPD-UHFFFAOYSA-N 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 108060000200 adenylate cyclase Proteins 0.000 description 1
• 102000030621 adenylate cyclase Human genes 0.000 description 1
• 238000000246 agarose gel electrophoresis Methods 0.000 description 1
• 125000002009 alkene group Chemical group 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 229960004050 aminobenzoic acid Drugs 0.000 description 1
• 229950003476 aminothiazole Drugs 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 230000000648 anti-parkinson Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000000939 antiparkinson agent Substances 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• 208000037875 astrocytosis Diseases 0.000 description 1
• 230000007341 astrogliosis Effects 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 230000006727 cell loss Effects 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 239000002026 chloroform extract Substances 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
• 229940018557 citraconic acid Drugs 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 229960003920 cocaine Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000001054 cortical effect Effects 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 238000012258 culturing Methods 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
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 1
• 229940052760 dopamine agonists Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
• SQTPDBMMILKVAH-UHFFFAOYSA-N ethyl 2-(furan-2-yl)-3-oxo-3-phenylpropanoate Chemical compound C=1C=COC=1C(C(=O)OCC)C(=O)C1=CC=CC=C1 SQTPDBMMILKVAH-UHFFFAOYSA-N 0.000 description 1
• OZMXFXOHCUEEPD-UHFFFAOYSA-N ethyl 2-amino-4-phenyl-1,3-thiazole-5-carboxylate Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1C(=O)OCC OZMXFXOHCUEEPD-UHFFFAOYSA-N 0.000 description 1
• ZKIBKQZMKDNRGZ-UHFFFAOYSA-N ethyl 2-amino-4-phenyl-1,3-thiazole-5-carboxylate ethyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenyl-1,3-thiazole-5-carboxylate Chemical compound C(C)OC(=O)C1=C(N=C(S1)N)C1=CC=CC=C1.C(C)OC(=O)C1=C(N=C(S1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 ZKIBKQZMKDNRGZ-UHFFFAOYSA-N 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 238000012048 forced swim test Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• BTUIFMCWPFMNRG-UHFFFAOYSA-N furan-3-carbonyl chloride Chemical compound ClC(=O)C=1C=COC=1 BTUIFMCWPFMNRG-UHFFFAOYSA-N 0.000 description 1
• 150000002240 furans Chemical class 0.000 description 1
• 210000001222 gaba-ergic neuron Anatomy 0.000 description 1
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 230000007387 gliosis Effects 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 229950006191 gluconic acid Drugs 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 229960002989 glutamic acid Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229960004275 glycolic acid Drugs 0.000 description 1
• 210000004565 granule cell Anatomy 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 230000001146 hypoxic effect Effects 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229910017053 inorganic salt Inorganic materials 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 208000037906 ischaemic injury Diseases 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
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
• 229950006874 kainic acid Drugs 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960000448 lactic acid Drugs 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 229960004502 levodopa Drugs 0.000 description 1
• 230000002197 limbic effect Effects 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 238000011866 long-term treatment Methods 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 229940099690 malic acid Drugs 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
• RLZPCFQNZGINRP-UHFFFAOYSA-N n'-hydroxypropanimidamide Chemical compound CCC(N)=NO RLZPCFQNZGINRP-UHFFFAOYSA-N 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 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
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 210000001640 nerve ending Anatomy 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 239000012454 non-polar solvent Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical group O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000001898 pallidal effect Effects 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• WUHLVXDDBHWHLQ-UHFFFAOYSA-N pentazole Chemical compound N=1N=NNN=1 WUHLVXDDBHWHLQ-UHFFFAOYSA-N 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940069328 povidone Drugs 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 230000003518 presynaptic effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 229940095574 propionic acid Drugs 0.000 description 1
• FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 238000010839 reverse transcription Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 230000009182 swimming Effects 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 210000000225 synapse Anatomy 0.000 description 1
• 230000005062 synaptic transmission Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 229960001367 tartaric acid Drugs 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 230000000542 thalamic effect Effects 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1