JP4931823B2 - チアジアゾール化合物及び使用方法 - Google Patents

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Publication number

JP4931823B2

JP4931823B2 JP2007537015A JP2007537015A JP4931823B2 JP 4931823 B2 JP4931823 B2 JP 4931823B2 JP 2007537015 A JP2007537015 A JP 2007537015A JP 2007537015 A JP2007537015 A JP 2007537015A JP 4931823 B2 JP4931823 B2 JP 4931823B2

Authority

JP

Japan

Prior art keywords

thiadiazol

indazol

amine

methyl

amino

Prior art date

2004-10-18

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

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• 238000000034 method Methods 0.000 title description 51
• 150000004867 thiadiazoles Chemical class 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims description 102
• -1 C 1 -C 6 alkyl Chemical group 0.000 claims description 71
• 125000003118 aryl group Chemical group 0.000 claims description 25
• 125000001072 heteroaryl group Chemical group 0.000 claims description 22
• 125000000217 alkyl group Chemical group 0.000 claims description 17
• 150000003839 salts Chemical class 0.000 claims description 17
• 125000000623 heterocyclic group Chemical group 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 150000001412 amines Chemical class 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• ZNEYXIQCZSZWHZ-UHFFFAOYSA-N 5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-amine Chemical class C1=C2C(C)=NNC2=CC=C1C1=NN=C(N)S1 ZNEYXIQCZSZWHZ-UHFFFAOYSA-N 0.000 claims description 6
• GGQSOEXSCZITMC-HNNXBMFYSA-N (2s)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-[3-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC(C(F)(F)F)=C1 GGQSOEXSCZITMC-HNNXBMFYSA-N 0.000 claims description 4
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims description 4
• CIYWRUPCUDLZQJ-SFHVURJKSA-N (2s)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)-3-(3-methoxyphenyl)propane-1,2-diamine Chemical compound COC1=CC=CC(C[C@H](N)CNC=2SC(=NN=2)C=2C=C3C=CN=CC3=CC=2)=C1 CIYWRUPCUDLZQJ-SFHVURJKSA-N 0.000 claims description 3
• MPVYGYCIQMIWIP-IBGZPJMESA-N (2s)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)-3-(3-methylphenyl)propane-1,2-diamine Chemical compound CC1=CC=CC(C[C@H](N)CNC=2SC(=NN=2)C=2C=C3C=CN=CC3=CC=2)=C1 MPVYGYCIQMIWIP-IBGZPJMESA-N 0.000 claims description 3
• SKWJYWSNFQTPIW-SFHVURJKSA-N (2s)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)-3-(4-methoxyphenyl)propane-1,2-diamine Chemical compound C1=CC(OC)=CC=C1C[C@H](N)CNC1=NN=C(C=2C=C3C=CN=CC3=CC=2)S1 SKWJYWSNFQTPIW-SFHVURJKSA-N 0.000 claims description 3
• UFFYOAWCSOACPD-SFHVURJKSA-N (2s)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)-3-[3-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=CN=CC2=CC=1)N)C1=CC=CC(C(F)(F)F)=C1 UFFYOAWCSOACPD-SFHVURJKSA-N 0.000 claims description 3
• WZOVTPHXONVIIJ-SFHVURJKSA-N (2s)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)-3-[4-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=CN=CC2=CC=1)N)C1=CC=C(C(F)(F)F)C=C1 WZOVTPHXONVIIJ-SFHVURJKSA-N 0.000 claims description 3
• MHOYBFWKTMXWPK-INIZCTEOSA-N (2s)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-(2-methylphenyl)propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC=C1C MHOYBFWKTMXWPK-INIZCTEOSA-N 0.000 claims description 3
• QOVXYSJPVFXJRF-INIZCTEOSA-N (2s)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-(3-methylphenyl)propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC(C)=C1 QOVXYSJPVFXJRF-INIZCTEOSA-N 0.000 claims description 3
• SUQRKPOSKOIDNI-AWEZNQCLSA-N (2s)-1-n-[5-(3-methyl-2h-pyrazolo[3,4-b]pyridin-5-yl)-1,3,4-thiadiazol-2-yl]-3-[3-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CN=C2NN=C(C2=C1)C)C1=CC=CC(C(F)(F)F)=C1 SUQRKPOSKOIDNI-AWEZNQCLSA-N 0.000 claims description 3
• IXYCOMDIYWCTHT-KRWDZBQOSA-N (2s)-3-(2,4-dichlorophenyl)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=CN=CC2=CC=1)N)C1=CC=C(Cl)C=C1Cl IXYCOMDIYWCTHT-KRWDZBQOSA-N 0.000 claims description 3
• BKIUGHHFPOHSFU-ZDUSSCGKSA-N (2s)-3-(3,4-dichlorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(Cl)C(Cl)=C1 BKIUGHHFPOHSFU-ZDUSSCGKSA-N 0.000 claims description 3
• NQKAFIFFMXPFFK-ZDUSSCGKSA-N (2s)-3-(3,4-difluorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(F)C(F)=C1 NQKAFIFFMXPFFK-ZDUSSCGKSA-N 0.000 claims description 3
• WLUVOFFSQYABAV-SFHVURJKSA-N (2s)-3-(3,5-difluorophenyl)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=CN=CC2=CC=1)N)C1=CC(F)=CC(F)=C1 WLUVOFFSQYABAV-SFHVURJKSA-N 0.000 claims description 3
• BDYKWAPSVQOKEM-HNNXBMFYSA-N (2s)-3-(3-bromophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC(Br)=C1 BDYKWAPSVQOKEM-HNNXBMFYSA-N 0.000 claims description 3
• ONUGNDNQFFQLIQ-HNNXBMFYSA-N (2s)-3-(4-bromophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(Br)C=C1 ONUGNDNQFFQLIQ-HNNXBMFYSA-N 0.000 claims description 3
• OKMSQBGAVTWSMQ-ORAYPTAESA-N (2s,3s)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)-3-[4-(trifluoromethyl)phenyl]butane-1,2-diamine Chemical compound C1([C@@H]([C@H](N)CNC=2SC(=NN=2)C=2C=C3C=CN=CC3=CC=2)C)=CC=C(C(F)(F)F)C=C1 OKMSQBGAVTWSMQ-ORAYPTAESA-N 0.000 claims description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• AKPXLNAJRWSZJY-HNNXBMFYSA-N (2s)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-(4-methoxyphenyl)propane-1,2-diamine Chemical compound C1=CC(OC)=CC=C1C[C@H](N)CNC1=NN=C(C=2C=C3C=NNC3=CC=2)S1 AKPXLNAJRWSZJY-HNNXBMFYSA-N 0.000 claims description 2
• JCNFACQBFPFBPG-SFHVURJKSA-N (2s)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-(4-propan-2-ylphenyl)propane-1,2-diamine Chemical compound C1=CC(C(C)C)=CC=C1C[C@H](N)CNC1=NN=C(C=2C=C3C=NNC3=CC=2)S1 JCNFACQBFPFBPG-SFHVURJKSA-N 0.000 claims description 2
• OSHTXJHXSUZMOX-HNNXBMFYSA-N (2s)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-[3-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=NNC2=CC=1)N)C1=CC=CC(C(F)(F)F)=C1 OSHTXJHXSUZMOX-HNNXBMFYSA-N 0.000 claims description 2
• BRTIFMBVAUCZIX-HNNXBMFYSA-N (2s)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-[4-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=NNC2=CC=1)N)C1=CC=C(C(F)(F)F)C=C1 BRTIFMBVAUCZIX-HNNXBMFYSA-N 0.000 claims description 2
• VTWBUGFMCLNISB-IBGZPJMESA-N (2s)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-naphthalen-2-ylpropane-1,2-diamine Chemical compound C1=CC=CC2=CC(C[C@@H](CNC=3SC(=NN=3)C=3C=C4C=NNC4=CC=3)N)=CC=C21 VTWBUGFMCLNISB-IBGZPJMESA-N 0.000 claims description 2
• RJESZRNJZYVXEA-INIZCTEOSA-N (2s)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-(4-methylphenyl)propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(C)C=C1 RJESZRNJZYVXEA-INIZCTEOSA-N 0.000 claims description 2
• GATDANXASIBFTP-SFHVURJKSA-N (2s)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-(4-propan-2-ylphenyl)propane-1,2-diamine Chemical compound C1=CC(C(C)C)=CC=C1C[C@H](N)CNC1=NN=C(C=2C=C3C(C)=NNC3=CC=2)S1 GATDANXASIBFTP-SFHVURJKSA-N 0.000 claims description 2
• JBXAHSUTPSPXBN-IBGZPJMESA-N (2s)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-naphthalen-2-ylpropane-1,2-diamine Chemical compound C1=CC=CC2=CC(C[C@H](N)CNC3=NN=C(S3)C3=CC=C4NN=C(C4=C3)C)=CC=C21 JBXAHSUTPSPXBN-IBGZPJMESA-N 0.000 claims description 2
• QGBOALFDSLDKNK-AWEZNQCLSA-N (2s)-3-(2,4-dichlorophenyl)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=NNC2=CC=1)N)C1=CC=C(Cl)C=C1Cl QGBOALFDSLDKNK-AWEZNQCLSA-N 0.000 claims description 2
• ZJVCNOOQHUYJRJ-AWEZNQCLSA-N (2s)-3-(2,4-dichlorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(Cl)C=C1Cl ZJVCNOOQHUYJRJ-AWEZNQCLSA-N 0.000 claims description 2
• LNUQTGZAAJAREX-AWEZNQCLSA-N (2s)-3-(2-bromophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC=C1Br LNUQTGZAAJAREX-AWEZNQCLSA-N 0.000 claims description 2
• MEXRTWCANVVSBH-AWEZNQCLSA-N (2s)-3-(2-chlorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC=C1Cl MEXRTWCANVVSBH-AWEZNQCLSA-N 0.000 claims description 2
• HWNFHXRWNZRYDL-HNNXBMFYSA-N (2s)-3-(2-methoxyphenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound COC1=CC=CC=C1C[C@H](N)CNC1=NN=C(C=2C=C3C(C)=NNC3=CC=2)S1 HWNFHXRWNZRYDL-HNNXBMFYSA-N 0.000 claims description 2
• UDIXICAWQICGPN-ZDUSSCGKSA-N (2s)-3-(3,4-dichlorophenyl)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=NNC2=CC=1)N)C1=CC=C(Cl)C(Cl)=C1 UDIXICAWQICGPN-ZDUSSCGKSA-N 0.000 claims description 2
• WGKWUIDLGLLSSD-HNNXBMFYSA-N (2s)-3-(3,5-difluorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical class C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC(F)=CC(F)=C1 WGKWUIDLGLLSSD-HNNXBMFYSA-N 0.000 claims description 2
• HHNFRVFYHNQUPY-HNNXBMFYSA-N (2s)-3-(3-chlorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC(Cl)=C1 HHNFRVFYHNQUPY-HNNXBMFYSA-N 0.000 claims description 2
• GJYYNOOZSHSFLL-HNNXBMFYSA-N (2s)-3-(3-fluorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC(F)=C1 GJYYNOOZSHSFLL-HNNXBMFYSA-N 0.000 claims description 2
• WUJAVWRRJCESGL-HNNXBMFYSA-N (2s)-3-(4-bromophenyl)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=NNC2=CC=1)N)C1=CC=C(Br)C=C1 WUJAVWRRJCESGL-HNNXBMFYSA-N 0.000 claims description 2
• NHCKWRFRGQYSQI-HNNXBMFYSA-N (2s)-3-(4-chlorophenyl)-1-n-[5-(1h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=NNC2=CC=1)N)C1=CC=C(Cl)C=C1 NHCKWRFRGQYSQI-HNNXBMFYSA-N 0.000 claims description 2
• VFMSDTSKEUYQCV-HNNXBMFYSA-N (2s)-3-(4-chlorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(Cl)C=C1 VFMSDTSKEUYQCV-HNNXBMFYSA-N 0.000 claims description 2
• KGPGGEAIINZPGB-KRWDZBQOSA-N (2s)-3-(4-ethylphenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C1=CC(CC)=CC=C1C[C@H](N)CNC1=NN=C(C=2C=C3C(C)=NNC3=CC=2)S1 KGPGGEAIINZPGB-KRWDZBQOSA-N 0.000 claims description 2
• DAVGDRIAVUPUIO-HNNXBMFYSA-N (2s)-3-(4-fluorophenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC1=NN=C(S1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(F)C=C1 DAVGDRIAVUPUIO-HNNXBMFYSA-N 0.000 claims description 2
• LTZPKHBMMKQKEQ-HNNXBMFYSA-N (2s)-3-(4-methoxyphenyl)-1-n-[5-(3-methyl-2h-indazol-5-yl)-1,3,4-thiadiazol-2-yl]propane-1,2-diamine Chemical compound C1=CC(OC)=CC=C1C[C@H](N)CNC1=NN=C(C=2C=C3C(C)=NNC3=CC=2)S1 LTZPKHBMMKQKEQ-HNNXBMFYSA-N 0.000 claims description 2
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
• HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 claims description 2
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 239000003795 chemical substances by application Substances 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• RFPGTVPPSYVZOU-SFHVURJKSA-N (2s)-3-(4-chlorophenyl)-1-n-(5-isoquinolin-6-yl-1,3,4-thiadiazol-2-yl)propane-1,2-diamine Chemical compound C([C@@H](CNC=1SC(=NN=1)C=1C=C2C=CN=CC2=CC=1)N)C1=CC=C(Cl)C=C1 RFPGTVPPSYVZOU-SFHVURJKSA-N 0.000 claims 1
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims 1
• 238000001819 mass spectrum Methods 0.000 description 89
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
• 108091008611 Protein Kinase B Proteins 0.000 description 57
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 57
• 238000004252 FT/ICR mass spectrometry Methods 0.000 description 41
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• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
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• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
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