JP4043953B2 - ｍＧｌｕＲ２アンタゴニストＩとしてのジヒドロ−ベンゾ〔ｂ〕〔１，４〕ジアゼピン−２−オン誘導体 - Google Patents

Info

Publication number

JP4043953B2

JP4043953B2 JP2002581420A JP2002581420A JP4043953B2 JP 4043953 B2 JP4043953 B2 JP 4043953B2 JP 2002581420 A JP2002581420 A JP 2002581420A JP 2002581420 A JP2002581420 A JP 2002581420A JP 4043953 B2 JP4043953 B2 JP 4043953B2

Authority

JP

Japan

Prior art keywords

phenyl

dihydro

benzo

diazepin

trifluoromethyl

Prior art date

2001-04-12

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

• AZIZBYRGIGKTLW-UHFFFAOYSA-N 1,4-diazepin-2-one Chemical class O=C1C=NC=CC=N1 AZIZBYRGIGKTLW-UHFFFAOYSA-N 0.000 title claims description 5
• 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 title description 5
• 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 title description 2
• 239000005557 antagonist Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 363
• 238000000034 method Methods 0.000 claims description 336
• 125000000217 alkyl group Chemical group 0.000 claims description 57
• -1 chloro, cyano, phenyl Chemical group 0.000 claims description 51
• 125000003545 alkoxy group Chemical group 0.000 claims description 43
• 238000002360 preparation method Methods 0.000 claims description 25
• 150000003839 salts Chemical class 0.000 claims description 22
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 125000001153 fluoro group Chemical group F* 0.000 claims description 17
• 239000001257 hydrogen Substances 0.000 claims description 17
• 230000009467 reduction Effects 0.000 claims description 17
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 13
• 150000002367 halogens Chemical group 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 239000002253 acid Substances 0.000 claims description 8
• 238000007363 ring formation reaction Methods 0.000 claims description 7
• XSGXUFLAJGGFLE-UHFFFAOYSA-N 4-(3-iodophenyl)-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound IC1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 XSGXUFLAJGGFLE-UHFFFAOYSA-N 0.000 claims description 6
• RJNFOFBZNNRQNC-UHFFFAOYSA-N 4-[3-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 RJNFOFBZNNRQNC-UHFFFAOYSA-N 0.000 claims description 6
• 230000001154 acute effect Effects 0.000 claims description 6
• 125000003277 amino group Chemical group 0.000 claims description 6
• 230000001684 chronic effect Effects 0.000 claims description 6
• IFSVVGUGJSGMGT-UHFFFAOYSA-N ethyl 5-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazole-4-carboxylate Chemical compound N1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1C(=O)OCC IFSVVGUGJSGMGT-UHFFFAOYSA-N 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 230000008569 process Effects 0.000 claims description 6
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• 208000012902 Nervous system disease Diseases 0.000 claims description 5
• 208000025966 Neurological disease Diseases 0.000 claims description 5
• 208000028017 Psychotic disease Diseases 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• 208000026139 Memory disease Diseases 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 208000010877 cognitive disease Diseases 0.000 claims description 4
• 201000000980 schizophrenia Diseases 0.000 claims description 4
• 125000001424 substituent group Chemical group 0.000 claims description 4
• KOZJGDMRNUDJER-UHFFFAOYSA-N 3-[2-oxo-8-(3-phenylpyrrol-1-yl)-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=C1N(C=1)C=CC=1C1=CC=CC=C1 KOZJGDMRNUDJER-UHFFFAOYSA-N 0.000 claims description 3
• GKNOKZUSPOGUGF-UHFFFAOYSA-N 3-[8-(2-tert-butylpyrrol-1-yl)-7-methoxy-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1N1C=CC=C1C(C)(C)C GKNOKZUSPOGUGF-UHFFFAOYSA-N 0.000 claims description 3
• DJNCHHLJNKAOEQ-UHFFFAOYSA-N 4-(2-chlorophenyl)-1-[4-(3-cyanophenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-8-yl]pyrrole-3-carbonitrile Chemical compound ClC1=CC=CC=C1C1=CN(C=2C=C3NC(=O)CC(=NC3=CC=2)C=2C=C(C=CC=2)C#N)C=C1C#N DJNCHHLJNKAOEQ-UHFFFAOYSA-N 0.000 claims description 3
• ZMKXDWYSWILRNU-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)N3C=NC=C3)=NC2=CC=C1N1C=CC=C1 ZMKXDWYSWILRNU-UHFFFAOYSA-N 0.000 claims description 3
• SIBGDQMTMOWUFB-UHFFFAOYSA-N 4-[2-oxo-7-thiomorpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound FC(F)(F)C1=CC=2NC(=O)CC(C=3C=C(N=CC=3)C#N)=NC=2C=C1N1CCSCC1 SIBGDQMTMOWUFB-UHFFFAOYSA-N 0.000 claims description 3
• SRKGMKKYVLEGFO-UHFFFAOYSA-N 4-[3-(1,3-oxazol-2-yl)phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C=3OC=CN=3)=NC2=CC=C1N1C=CC=C1 SRKGMKKYVLEGFO-UHFFFAOYSA-N 0.000 claims description 3
• SUAXBFLWHZKRPH-UHFFFAOYSA-N 4-[3-(2-methylpyrazol-3-yl)phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CN1N=CC=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 SUAXBFLWHZKRPH-UHFFFAOYSA-N 0.000 claims description 3
• CNSZNKCNRBFDTH-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 CNSZNKCNRBFDTH-UHFFFAOYSA-N 0.000 claims description 3
• JVRGZDKVGJVXFP-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-thiomorpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCSCC4)C=C3N=2)C(F)(F)F)=C1 JVRGZDKVGJVXFP-UHFFFAOYSA-N 0.000 claims description 3
• VLPCKCKTCMYPOC-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 VLPCKCKTCMYPOC-UHFFFAOYSA-N 0.000 claims description 3
• ZDQNHJAROPROLE-UHFFFAOYSA-N 4-[3-[2-(hydroxymethyl)-5-methyl-1,3-thiazol-4-yl]phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound S1C(CO)=NC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1C ZDQNHJAROPROLE-UHFFFAOYSA-N 0.000 claims description 3
• LTODSASAOXHZES-UHFFFAOYSA-N 4-[3-[3-(hydroxymethyl)-1,2-oxazol-5-yl]phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(CO)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 LTODSASAOXHZES-UHFFFAOYSA-N 0.000 claims description 3
• WUDWBYFHFWLKLM-UHFFFAOYSA-N 4-[3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=NC(CO)=CS1 WUDWBYFHFWLKLM-UHFFFAOYSA-N 0.000 claims description 3
• YTWOESKGYZDURL-UHFFFAOYSA-N 4-[3-[5-(hydroxymethyl)-1,2-oxazol-3-yl]phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1C(CO)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=N1 YTWOESKGYZDURL-UHFFFAOYSA-N 0.000 claims description 3
• NYXFGEQQLGOZMF-UHFFFAOYSA-N 4-[3-[5-[(cyclopropylamino)methyl]triazol-1-yl]phenyl]-7-ethoxy-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CNC1CC1 NYXFGEQQLGOZMF-UHFFFAOYSA-N 0.000 claims description 3
• WMLMNBINHLZFDW-UHFFFAOYSA-N 4-[3-[5-[(cyclopropylamino)methyl]triazol-1-yl]phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CNC1CC1 WMLMNBINHLZFDW-UHFFFAOYSA-N 0.000 claims description 3
• NHGJLWKIZLSRKG-UHFFFAOYSA-N 4-[7-ethoxy-2-oxo-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C1=CC=NC(C#N)=C1 NHGJLWKIZLSRKG-UHFFFAOYSA-N 0.000 claims description 3
• CPFQVRMETORQSM-UHFFFAOYSA-N 4-[7-methyl-2-oxo-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C1=CC=NC(C#N)=C1 CPFQVRMETORQSM-UHFFFAOYSA-N 0.000 claims description 3
• MSXOSLFRXQXVGU-UHFFFAOYSA-N 4-[7-morpholin-4-yl-2-oxo-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound FC(F)(F)C1=CC=2NC(=O)CC(C=3C=C(N=CC=3)C#N)=NC=2C=C1N1CCOCC1 MSXOSLFRXQXVGU-UHFFFAOYSA-N 0.000 claims description 3
• KUMADDIKXWCDPV-UHFFFAOYSA-N 7-chloro-4-(3-imidazol-1-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1N1C=CN=C1 KUMADDIKXWCDPV-UHFFFAOYSA-N 0.000 claims description 3
• BAEZFZTUGYMZBO-UHFFFAOYSA-N 7-chloro-4-[3-(1,2,4-triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1N1C=NC=N1 BAEZFZTUGYMZBO-UHFFFAOYSA-N 0.000 claims description 3
• OKALWKDYRBEXTK-UHFFFAOYSA-N 7-chloro-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(Cl)C=C3N=2)C(F)(F)F)=C1 OKALWKDYRBEXTK-UHFFFAOYSA-N 0.000 claims description 3
• PXTUROXJUIVEOU-UHFFFAOYSA-N 7-chloro-4-[3-(triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1N1C=CN=N1 PXTUROXJUIVEOU-UHFFFAOYSA-N 0.000 claims description 3
• QNDQOKDXZJHKLB-UHFFFAOYSA-N 7-ethoxy-4-[3-(triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 QNDQOKDXZJHKLB-UHFFFAOYSA-N 0.000 claims description 3
• JGHOKBYVKJKPER-UHFFFAOYSA-N 7-ethoxy-4-[3-[5-[(2,2,2-trifluoroethylamino)methyl]triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CNCC(F)(F)F JGHOKBYVKJKPER-UHFFFAOYSA-N 0.000 claims description 3
• WTFSUCJKQXRBRH-UHFFFAOYSA-N 7-methoxy-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NO1 WTFSUCJKQXRBRH-UHFFFAOYSA-N 0.000 claims description 3
• CTYSQPFUDGNBKL-UHFFFAOYSA-N 7-methoxy-4-[3-(triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OC)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 CTYSQPFUDGNBKL-UHFFFAOYSA-N 0.000 claims description 3
• ODQYJHWUPRAXER-UHFFFAOYSA-N 7-methoxy-4-[3-[5-(pyrrolidin-1-ylmethyl)triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OC)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CN1CCCC1 ODQYJHWUPRAXER-UHFFFAOYSA-N 0.000 claims description 3
• ILOJIYYHDKPLLX-UHFFFAOYSA-N 7-methyl-4-[3-(1,2,4-triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1N1C=NC=N1 ILOJIYYHDKPLLX-UHFFFAOYSA-N 0.000 claims description 3
• KSFDHAWWRWUGAG-UHFFFAOYSA-N 7-methyl-4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1 KSFDHAWWRWUGAG-UHFFFAOYSA-N 0.000 claims description 3
• GBXAMFNGEMDBKL-UHFFFAOYSA-N 8-pyrrol-1-yl-4-[3-(triazol-1-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)N3N=NC=C3)=NC2=CC=C1N1C=CC=C1 GBXAMFNGEMDBKL-UHFFFAOYSA-N 0.000 claims description 3
• 125000004414 alkyl thio group Chemical group 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• NPEZFSNOQFPSSH-UHFFFAOYSA-N 4-[3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=CSC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 NPEZFSNOQFPSSH-UHFFFAOYSA-N 0.000 claims description 2
• 208000028698 Cognitive impairment Diseases 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
• 238000010511 deprotection reaction Methods 0.000 claims description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 claims description 2
• 201000010099 disease Diseases 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
• 239000007787 solid Substances 0.000 description 208
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 183
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 165
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 140
• 239000000203 mixture Substances 0.000 description 104
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 100
• 239000000243 solution Substances 0.000 description 99
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
• 235000019439 ethyl acetate Nutrition 0.000 description 72
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 68
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 59
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• 238000002844 melting Methods 0.000 description 41
• 230000008018 melting Effects 0.000 description 41
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
• 238000006243 chemical reaction Methods 0.000 description 37
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 36
• 239000012267 brine Substances 0.000 description 36
• 239000003921 oil Substances 0.000 description 36
• 235000019198 oils Nutrition 0.000 description 36
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• 239000000463 material Substances 0.000 description 34
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
• RAVMZWQUVKTGBS-UHFFFAOYSA-N 3-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)benzonitrile Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(C#N)=C1 RAVMZWQUVKTGBS-UHFFFAOYSA-N 0.000 description 28
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 28
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 27
• 239000002904 solvent Substances 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• 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 25
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
• 238000010898 silica gel chromatography Methods 0.000 description 24
• 229910004373 HOAc Inorganic materials 0.000 description 23
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
• WSUXSDFUECNYSX-UHFFFAOYSA-N tert-butyl n-[2-amino-5-methyl-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C(F)(F)F WSUXSDFUECNYSX-UHFFFAOYSA-N 0.000 description 21
• 238000000354 decomposition reaction Methods 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 20
• XNDOVDWSIUOOET-UHFFFAOYSA-N tert-butyl n-(2-amino-4-pyrrol-1-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC=C1N1C=CC=C1 XNDOVDWSIUOOET-UHFFFAOYSA-N 0.000 description 20
• IDIHNUHJKRFJHR-UHFFFAOYSA-N tert-butyl n-[2-amino-5-morpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CCOCC2)=C1C(F)(F)F IDIHNUHJKRFJHR-UHFFFAOYSA-N 0.000 description 20
• BSPODPDIDGXFDC-UHFFFAOYSA-N tert-butyl 3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 BSPODPDIDGXFDC-UHFFFAOYSA-N 0.000 description 18
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
• 239000002244 precipitate Substances 0.000 description 17
• 239000000047 product Substances 0.000 description 17
• JTBNUOXTNBABIE-UHFFFAOYSA-N tert-butyl 3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 JTBNUOXTNBABIE-UHFFFAOYSA-N 0.000 description 17
• ZTCGGBIFOFASKI-UHFFFAOYSA-N tert-butyl acetate;lithium Chemical compound [Li].CC(=O)OC(C)(C)C ZTCGGBIFOFASKI-UHFFFAOYSA-N 0.000 description 17
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 16
• 238000006722 reduction reaction Methods 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 239000000460 chlorine Substances 0.000 description 15
• 239000000741 silica gel Substances 0.000 description 15
• 229910002027 silica gel Inorganic materials 0.000 description 15
• QQJNABOVYNTCRV-UHFFFAOYSA-N tert-butyl 3-(2-cyanopyridin-4-yl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=NC(C#N)=C1 QQJNABOVYNTCRV-UHFFFAOYSA-N 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 14
• 239000013078 crystal Substances 0.000 description 14
• 239000006260 foam Substances 0.000 description 14
• 238000003786 synthesis reaction Methods 0.000 description 14
• KXLAIFIPGIZAJM-UHFFFAOYSA-N tert-butyl n-[2-amino-5-chloro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1N KXLAIFIPGIZAJM-UHFFFAOYSA-N 0.000 description 14
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
• 238000001914 filtration Methods 0.000 description 13
• SNQDIHJPOWWBNA-UHFFFAOYSA-N 2-nitro-4-pyrrol-1-ylaniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1N1C=CC=C1 SNQDIHJPOWWBNA-UHFFFAOYSA-N 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 125000001309 chloro group Chemical group Cl* 0.000 description 12
• 239000003480 eluent Substances 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 11
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 11
• 230000003197 catalytic effect Effects 0.000 description 11
• 239000011541 reaction mixture Substances 0.000 description 11
• 238000006476 reductive cyclization reaction Methods 0.000 description 11
• 238000010992 reflux Methods 0.000 description 11
• HIZCQCCCJZHWDD-UHFFFAOYSA-N tert-butyl n-[2-amino-5-methoxy-4-(trifluoromethyl)phenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C(F)(F)F HIZCQCCCJZHWDD-UHFFFAOYSA-N 0.000 description 11
• GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical class COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• 239000007832 Na2SO4 Substances 0.000 description 10
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• OGSLJJIKZWJNQH-UHFFFAOYSA-N methyl 2-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 OGSLJJIKZWJNQH-UHFFFAOYSA-N 0.000 description 10
• 229910052938 sodium sulfate Inorganic materials 0.000 description 10
• 235000011152 sodium sulphate Nutrition 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
• ORGWIRYVLUFIPM-UHFFFAOYSA-N 4-[3-[4-(chloromethyl)-1,3-oxazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound ClCC1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 ORGWIRYVLUFIPM-UHFFFAOYSA-N 0.000 description 9
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
• 230000006196 deacetylation Effects 0.000 description 9
• 238000003381 deacetylation reaction Methods 0.000 description 9
• 238000005984 hydrogenation reaction Methods 0.000 description 9
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical class NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 8
• SYPKBCYLBCOWKW-UHFFFAOYSA-N 3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzonitrile Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=C1N1C=CC=C1 SYPKBCYLBCOWKW-UHFFFAOYSA-N 0.000 description 8
• ZCWXYZBQDNFULS-UHFFFAOYSA-N 5-chloro-2-nitroaniline Chemical compound NC1=CC(Cl)=CC=C1[N+]([O-])=O ZCWXYZBQDNFULS-UHFFFAOYSA-N 0.000 description 8
• OABSXOMYUDYCAN-UHFFFAOYSA-N 6-(3-imidazol-1-ylphenyl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(N2C=NC=C2)=C1 OABSXOMYUDYCAN-UHFFFAOYSA-N 0.000 description 8
• HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 8
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 239000013058 crude material Substances 0.000 description 8
• KUHMJDSOPHMSDX-UHFFFAOYSA-N ethyl 3-oxo-3-[3-(triazol-1-yl)phenyl]propanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 KUHMJDSOPHMSDX-UHFFFAOYSA-N 0.000 description 8
• WVWNSCFNPFJERV-UHFFFAOYSA-N ethyl 4-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-thiazole-2-carboxylate Chemical compound S1C(C(=O)OCC)=NC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 WVWNSCFNPFJERV-UHFFFAOYSA-N 0.000 description 8
• 150000002431 hydrogen Chemical group 0.000 description 8
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• ZGYINRLWLIWJBM-UHFFFAOYSA-N n-(5-amino-2-nitrophenyl)acetamide Chemical class CC(=O)NC1=CC(N)=CC=C1[N+]([O-])=O ZGYINRLWLIWJBM-UHFFFAOYSA-N 0.000 description 8
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• SMBJPOFTNVETJI-UHFFFAOYSA-N tert-butyl n-(2-amino-4-cyano-5-morpholin-4-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CCOCC2)=C1C#N SMBJPOFTNVETJI-UHFFFAOYSA-N 0.000 description 8
• UXKVDHBWXZINNK-UHFFFAOYSA-N tert-butyl n-[2-amino-5-ethoxy-4-(trifluoromethyl)phenyl]carbamate Chemical compound CCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1C(F)(F)F UXKVDHBWXZINNK-UHFFFAOYSA-N 0.000 description 8
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• ATCKJLDGNXGLAO-UHFFFAOYSA-N bis(trimethylsilyl) propanedioate Chemical compound C[Si](C)(C)OC(=O)CC(=O)O[Si](C)(C)C ATCKJLDGNXGLAO-UHFFFAOYSA-N 0.000 description 7
• BSQWYELDCUXPSJ-UHFFFAOYSA-N methyl 3-azidobenzoate Chemical compound COC(=O)C1=CC=CC(N=[N+]=[N-])=C1 BSQWYELDCUXPSJ-UHFFFAOYSA-N 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• KYJUQFYMKDBYQY-UHFFFAOYSA-N tert-butyl n-[2-amino-5-thiomorpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CCSCC2)=C1C(F)(F)F KYJUQFYMKDBYQY-UHFFFAOYSA-N 0.000 description 7
• JTINFGZXLGQQRI-UHFFFAOYSA-N tert-butyl n-[4-cyano-2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-5-morpholin-4-ylphenyl]carbamate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C#N)C=2)N2CCOCC2)NC(=O)OC(C)(C)C)=C1 JTINFGZXLGQQRI-UHFFFAOYSA-N 0.000 description 7
• HIHLPWFEZHZXPD-UHFFFAOYSA-N tert-butyl n-[5-fluoro-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(F)=C(C(F)(F)F)C=C1[N+]([O-])=O HIHLPWFEZHZXPD-UHFFFAOYSA-N 0.000 description 7
• BZVZBKJBMILRFM-UHFFFAOYSA-N 2,2-dimethyl-6-[3-(triazol-1-yl)phenyl]-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(N2N=NC=C2)=C1 BZVZBKJBMILRFM-UHFFFAOYSA-N 0.000 description 6
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
• RDLCUQONHJOGLP-UHFFFAOYSA-N 2-nitro-5-(3-phenylpyrrol-1-yl)aniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC(N2C=C(C=C2)C=2C=CC=CC=2)=C1 RDLCUQONHJOGLP-UHFFFAOYSA-N 0.000 description 6
• HVHNMNGARPCGGD-UHFFFAOYSA-N 2-nitro-p-phenylenediamine Chemical compound NC1=CC=C(N)C([N+]([O-])=O)=C1 HVHNMNGARPCGGD-UHFFFAOYSA-N 0.000 description 6
• AAMCWLIPRMIPBN-UHFFFAOYSA-N 5-chloro-2-nitro-4-(trifluoromethyl)aniline Chemical compound NC1=CC(Cl)=C(C(F)(F)F)C=C1[N+]([O-])=O AAMCWLIPRMIPBN-UHFFFAOYSA-N 0.000 description 6
• OQZSZUKPUHEUBM-UHFFFAOYSA-N 5-chloro-2-nitro-4-pyrrol-1-ylaniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC(Cl)=C1N1C=CC=C1 OQZSZUKPUHEUBM-UHFFFAOYSA-N 0.000 description 6
• YHHJYFODFOUATG-UHFFFAOYSA-N 7-ethoxy-4-[3-[5-(hydroxymethyl)triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CO YHHJYFODFOUATG-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 6
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 6
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 6
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 239000000969 carrier Substances 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 235000011149 sulphuric acid Nutrition 0.000 description 6
• FEPASYFSULWDNV-UHFFFAOYSA-N tert-butyl 3-(3-imidazol-1-ylphenyl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 FEPASYFSULWDNV-UHFFFAOYSA-N 0.000 description 6
• JODVYMGVCMRARO-UHFFFAOYSA-N tert-butyl 3-[2-(5-methyl-1,3-oxazol-4-yl)phenyl]-3-oxopropanoate Chemical compound O1C=NC(C=2C(=CC=CC=2)C(=O)CC(=O)OC(C)(C)C)=C1C JODVYMGVCMRARO-UHFFFAOYSA-N 0.000 description 6
• AUDSAJIZWLBHRN-UHFFFAOYSA-N tert-butyl 3-[3-[3-(oxan-2-yloxymethyl)-1,2-oxazol-5-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2ON=C(COC3OCCCC3)C=2)=C1 AUDSAJIZWLBHRN-UHFFFAOYSA-N 0.000 description 6
• BUDAECSKCNVXAI-UHFFFAOYSA-N tert-butyl 3-[3-[4-(oxan-2-yloxymethyl)-1,3-thiazol-2-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C=2SC=C(COC3OCCCC3)N=2)=C1 BUDAECSKCNVXAI-UHFFFAOYSA-N 0.000 description 6
• UJFGZNBJAVEEGG-UHFFFAOYSA-N tert-butyl 3-oxo-3-(3-pyrazol-1-ylphenyl)propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2N=CC=C2)=C1 UJFGZNBJAVEEGG-UHFFFAOYSA-N 0.000 description 6
• QJRUGCDPBLUQTE-UHFFFAOYSA-N tert-butyl 3-oxo-3-[3-(1,2,4-triazol-1-yl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2N=CN=C2)=C1 QJRUGCDPBLUQTE-UHFFFAOYSA-N 0.000 description 6
• JTJFEWDXNKYBOE-UHFFFAOYSA-N tert-butyl n-(2-nitrophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=C1[N+]([O-])=O JTJFEWDXNKYBOE-UHFFFAOYSA-N 0.000 description 6
• UZERPUAWQOHXES-UHFFFAOYSA-N tert-butyl n-(4-cyano-5-fluoro-2-nitrophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(F)=C(C#N)C=C1[N+]([O-])=O UZERPUAWQOHXES-UHFFFAOYSA-N 0.000 description 6
• HXZFITILXOESLM-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1[N+]([O-])=O HXZFITILXOESLM-UHFFFAOYSA-N 0.000 description 6
• CCJHZEYABFTNGW-UHFFFAOYSA-N tert-butyl n-[5-morpholin-4-yl-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCOCC2)=C1C(F)(F)F CCJHZEYABFTNGW-UHFFFAOYSA-N 0.000 description 6
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
• KRACGKZHKWZOCG-UHFFFAOYSA-N 7-chloro-4-[3-[5-(hydroxymethyl)-1,2,4-triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=NC=NN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(Cl)C=C3N=2)C(F)(F)F)=C1 KRACGKZHKWZOCG-UHFFFAOYSA-N 0.000 description 5
• 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 5
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
• 239000007868 Raney catalyst Substances 0.000 description 5
• 229910000564 Raney nickel Inorganic materials 0.000 description 5
• 229910006124 SOCl2 Inorganic materials 0.000 description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
• 239000000010 aprotic solvent Substances 0.000 description 5
• 239000012300 argon atmosphere Substances 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 239000007903 gelatin capsule Substances 0.000 description 5
• 239000008101 lactose Substances 0.000 description 5
• 239000003880 polar aprotic solvent Substances 0.000 description 5
• AXHICXOCVDBIIU-UHFFFAOYSA-N tert-butyl 3-[3-[5-methyl-2-(oxan-2-yloxymethyl)-1,3-thiazol-4-yl]phenyl]-3-oxopropanoate Chemical compound N=1C(C=2C=C(C=CC=2)C(=O)CC(=O)OC(C)(C)C)=C(C)SC=1COC1CCCCO1 AXHICXOCVDBIIU-UHFFFAOYSA-N 0.000 description 5
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 5
• 238000010626 work up procedure Methods 0.000 description 5
• DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 4
• SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 4
• ODRZAZBEQWAOGU-UHFFFAOYSA-N 1,4-dioxin-2-one Chemical compound O=C1COC=CO1 ODRZAZBEQWAOGU-UHFFFAOYSA-N 0.000 description 4
• XLKLPYFSHXWWHX-UHFFFAOYSA-N 1-(3-amino-4-nitrophenyl)-4-(2-chlorophenyl)pyrrole-3-carbonitrile Chemical compound C1=C([N+]([O-])=O)C(N)=CC(N2C=C(C(C#N)=C2)C=2C(=CC=CC=2)Cl)=C1 XLKLPYFSHXWWHX-UHFFFAOYSA-N 0.000 description 4
• FNHOOIZXAKMYRF-UHFFFAOYSA-N 1-(3-amino-4-nitrophenyl)-4-phenylpyrrole-3-carbonitrile Chemical compound C1=C([N+]([O-])=O)C(N)=CC(N2C=C(C(C#N)=C2)C=2C=CC=CC=2)=C1 FNHOOIZXAKMYRF-UHFFFAOYSA-N 0.000 description 4
• OQLFFWYYYBROLG-UHFFFAOYSA-N 1-(3-amino-4-nitrophenyl)pyrrole-3-carbaldehyde Chemical compound C1=C([N+]([O-])=O)C(N)=CC(N2C=C(C=O)C=C2)=C1 OQLFFWYYYBROLG-UHFFFAOYSA-N 0.000 description 4
• IBKVYPCLNGARQY-UHFFFAOYSA-N 2,2-dimethyl-6-[3-(1,3-oxazol-2-yl)phenyl]-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(C=2OC=CN=2)=C1 IBKVYPCLNGARQY-UHFFFAOYSA-N 0.000 description 4
• VUNAQOGRLGNALG-UHFFFAOYSA-N 2-chloro-5-nitrobenzene-1,4-diamine Chemical compound NC1=CC([N+]([O-])=O)=C(N)C=C1Cl VUNAQOGRLGNALG-UHFFFAOYSA-N 0.000 description 4
• JFPJVTNYCURRAB-UHFFFAOYSA-N 2-nitro-n-phenylacetamide Chemical class [O-][N+](=O)CC(=O)NC1=CC=CC=C1 JFPJVTNYCURRAB-UHFFFAOYSA-N 0.000 description 4
• WSHLBYVEIWICMK-UHFFFAOYSA-N 3-(3-cyanophenyl)-n-(2-nitro-5-pyrrol-1-ylphenyl)-3-oxopropanamide Chemical compound [O-][N+](=O)C1=CC=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 WSHLBYVEIWICMK-UHFFFAOYSA-N 0.000 description 4
• GSXFEQFNYXVNTP-UHFFFAOYSA-N 3-(3-cyanophenyl)-n-(4-iodo-2-nitro-5-pyrrol-1-ylphenyl)-3-oxopropanamide Chemical compound [O-][N+](=O)C1=CC(I)=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 GSXFEQFNYXVNTP-UHFFFAOYSA-N 0.000 description 4
• IRSQIJRVXURGAC-UHFFFAOYSA-N 3-(3-cyanophenyl)-n-[2-nitro-5-(3-phenylpyrrol-1-yl)phenyl]-3-oxopropanamide Chemical compound [O-][N+](=O)C1=CC=C(N2C=C(C=C2)C=2C=CC=CC=2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 IRSQIJRVXURGAC-UHFFFAOYSA-N 0.000 description 4
• VIHIVZJJUABUSD-UHFFFAOYSA-N 3-(3-cyanophenyl)-n-[5-(3-cyano-4-phenylpyrrol-1-yl)-2-nitrophenyl]-3-oxopropanamide Chemical compound [O-][N+](=O)C1=CC=C(N2C=C(C(C#N)=C2)C=2C=CC=CC=2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 VIHIVZJJUABUSD-UHFFFAOYSA-N 0.000 description 4
• XEECUWCKQFECNQ-UHFFFAOYSA-N 3-(3-cyanophenyl)-n-[5-[3-(hydroxymethyl)pyrrol-1-yl]-2-nitrophenyl]-3-oxopropanamide Chemical compound C1=C(CO)C=CN1C1=CC=C([N+]([O-])=O)C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)=C1 XEECUWCKQFECNQ-UHFFFAOYSA-N 0.000 description 4
• UUNBHESHKBJFNR-UHFFFAOYSA-N 3-(3-cyanophenyl)-n-[5-[3-(methoxymethyl)pyrrol-1-yl]-2-nitrophenyl]-3-oxopropanamide Chemical compound C1=C(COC)C=CN1C1=CC=C([N+]([O-])=O)C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)=C1 UUNBHESHKBJFNR-UHFFFAOYSA-N 0.000 description 4
• AYDBUKCOTGOOQC-UHFFFAOYSA-N 3-(3-imidazol-1-ylphenyl)-n-(2-nitro-5-pyrrol-1-ylphenyl)-3-oxopropanamide Chemical compound [O-][N+](=O)C1=CC=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 AYDBUKCOTGOOQC-UHFFFAOYSA-N 0.000 description 4
• WZMLNBCKVXILPW-UHFFFAOYSA-N 3-(3-iodophenyl)-n-(2-nitro-4-pyrrol-1-ylphenyl)-3-oxopropanamide Chemical compound [O-][N+](=O)C1=CC(N2C=CC=C2)=CC=C1NC(=O)CC(=O)C1=CC=CC(I)=C1 WZMLNBCKVXILPW-UHFFFAOYSA-N 0.000 description 4
• WXHAKCASYYCJED-UHFFFAOYSA-N 3-imidazol-1-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC(N2C=NC=C2)=C1 WXHAKCASYYCJED-UHFFFAOYSA-N 0.000 description 4
• GJVDDKCZVBMVNP-UHFFFAOYSA-N 4-[3-[5-(hydroxymethyl)triazol-1-yl]phenyl]-7-methoxy-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OC)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CO GJVDDKCZVBMVNP-UHFFFAOYSA-N 0.000 description 4
• SPYAFLKKPXAWLZ-UHFFFAOYSA-N 4-[3-[5-(hydroxymethyl)triazol-1-yl]phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1N1N=NC=C1CO SPYAFLKKPXAWLZ-UHFFFAOYSA-N 0.000 description 4
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 4
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• DTFJFRYDWYTMOW-UHFFFAOYSA-N 5-(2-methoxyethoxy)-2-nitro-4-pyrrol-1-ylaniline Chemical compound COCCOC1=CC(N)=C([N+]([O-])=O)C=C1N1C=CC=C1 DTFJFRYDWYTMOW-UHFFFAOYSA-N 0.000 description 4
• VOYNKTMLCXAVTK-UHFFFAOYSA-N 5-[2-(methoxymethyl)pyrrol-1-yl]-2-nitroaniline Chemical compound COCC1=CC=CN1C1=CC=C([N+]([O-])=O)C(N)=C1 VOYNKTMLCXAVTK-UHFFFAOYSA-N 0.000 description 4
• RQGNJZDNWJOWCC-UHFFFAOYSA-N 5-[3-(methoxymethyl)pyrrol-1-yl]-2-nitroaniline Chemical compound C1=C(COC)C=CN1C1=CC=C([N+]([O-])=O)C(N)=C1 RQGNJZDNWJOWCC-UHFFFAOYSA-N 0.000 description 4
• NSUBCFDZJGKSLM-UHFFFAOYSA-N 5-ethoxy-2-nitro-4-(trifluoromethyl)aniline Chemical compound CCOC1=CC(N)=C([N+]([O-])=O)C=C1C(F)(F)F NSUBCFDZJGKSLM-UHFFFAOYSA-N 0.000 description 4
• HJFCWKRMUCQYHF-UHFFFAOYSA-N 5-methoxy-2-nitro-4-(trifluoromethyl)aniline Chemical compound COC1=CC(N)=C([N+]([O-])=O)C=C1C(F)(F)F HJFCWKRMUCQYHF-UHFFFAOYSA-N 0.000 description 4
• IRNNTXDWOQPKGN-UHFFFAOYSA-N 5-methoxy-2-nitro-4-pyrrol-1-ylaniline Chemical compound COC1=CC(N)=C([N+]([O-])=O)C=C1N1C=CC=C1 IRNNTXDWOQPKGN-UHFFFAOYSA-N 0.000 description 4
• IXGGSHYJYYQPGR-UHFFFAOYSA-N 6-(3-iodophenyl)-2,2-dimethyl-1,3-dioxin-4-one Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=CC(I)=C1 IXGGSHYJYYQPGR-UHFFFAOYSA-N 0.000 description 4
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 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
• 208000002193 Pain Diseases 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical group [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• QRMIONGNTCSBDS-UHFFFAOYSA-N [1-(3-amino-4-nitrophenyl)pyrrol-3-yl]methanol Chemical compound C1=C([N+]([O-])=O)C(N)=CC(N2C=C(CO)C=C2)=C1 QRMIONGNTCSBDS-UHFFFAOYSA-N 0.000 description 4
• 230000021736 acetylation Effects 0.000 description 4
• 238000006640 acetylation reaction Methods 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• 238000007275 deallylation reaction Methods 0.000 description 4
• 238000006114 decarboxylation reaction Methods 0.000 description 4
• 230000008034 disappearance Effects 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• DIZFWJVCPSJKGW-UHFFFAOYSA-N ethyl 3-ethynylbenzoate Chemical compound CCOC(=O)C1=CC=CC(C#C)=C1 DIZFWJVCPSJKGW-UHFFFAOYSA-N 0.000 description 4
• YRVQQBPZXNSNKM-UHFFFAOYSA-N ethyl 5-[3-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)phenyl]-1,3-oxazole-4-carboxylate Chemical compound N1=COC(C=2C=C(C=CC=2)C=2OC(C)(C)OC(=O)C=2)=C1C(=O)OCC YRVQQBPZXNSNKM-UHFFFAOYSA-N 0.000 description 4
• 229910052740 iodine Inorganic materials 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• 229910001629 magnesium chloride Inorganic materials 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• QSKPXSPIUIDQRQ-UHFFFAOYSA-N methyl 1-(3-amino-4-nitrophenyl)pyrrole-2-carboxylate Chemical compound COC(=O)C1=CC=CN1C1=CC=C([N+]([O-])=O)C(N)=C1 QSKPXSPIUIDQRQ-UHFFFAOYSA-N 0.000 description 4
• TZUFUYCDQAZLRB-UHFFFAOYSA-N methyl 1-[3-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-nitrophenyl]pyrrole-2-carboxylate Chemical compound COC(=O)C1=CC=CN1C1=CC=C([N+]([O-])=O)C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)=C1 TZUFUYCDQAZLRB-UHFFFAOYSA-N 0.000 description 4
• ABDJBBRMKCVSHX-UHFFFAOYSA-N methyl 2-[3-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)phenyl]-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(C=2C=C(C=CC=2)C=2OC(C)(C)OC(=O)C=2)=N1 ABDJBBRMKCVSHX-UHFFFAOYSA-N 0.000 description 4
• NKGYSGGAEUCELQ-UHFFFAOYSA-N methyl 3-(1,2,4-triazol-1-yl)benzoate Chemical compound COC(=O)C1=CC=CC(N2N=CN=C2)=C1 NKGYSGGAEUCELQ-UHFFFAOYSA-N 0.000 description 4
• 238000006396 nitration reaction Methods 0.000 description 4
• 150000002828 nitro derivatives Chemical class 0.000 description 4
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 4
• 239000000825 pharmaceutical preparation Substances 0.000 description 4
• 229920005862 polyol Polymers 0.000 description 4
• 150000003077 polyols Chemical class 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• NJGOKCQKYUXLSX-UHFFFAOYSA-N tert-butyl 3-(3-cyanophenyl)-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C#N)=C1 NJGOKCQKYUXLSX-UHFFFAOYSA-N 0.000 description 4
• JUZXQJPXPXGYEY-UHFFFAOYSA-N tert-butyl 3-[3-(2-methylpyrazol-3-yl)phenyl]-3-oxopropanoate Chemical compound CN1N=CC=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 JUZXQJPXPXGYEY-UHFFFAOYSA-N 0.000 description 4
• JJGNFUCMTKEOQN-UHFFFAOYSA-N tert-butyl 3-[3-[5-(oxan-2-yloxymethyl)-1,2,4-triazol-1-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2C(=NC=N2)COC2OCCCC2)=C1 JJGNFUCMTKEOQN-UHFFFAOYSA-N 0.000 description 4
• WXSHWXSHDJJFMX-UHFFFAOYSA-N tert-butyl 3-[3-[5-(oxan-2-yloxymethyl)-1,2-oxazol-3-yl]phenyl]-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(C2=NOC(COC3OCCCC3)=C2)=C1 WXSHWXSHDJJFMX-UHFFFAOYSA-N 0.000 description 4
• CXXUSSYNGZCIJB-UHFFFAOYSA-N tert-butyl 3-oxo-3-[3-(triazol-1-yl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 CXXUSSYNGZCIJB-UHFFFAOYSA-N 0.000 description 4
• RSMRRBWYKHRNAQ-UHFFFAOYSA-N tert-butyl n-(2-amino-4-cyano-5-thiomorpholin-4-ylphenyl)carbamate Chemical compound C1=C(N)C(NC(=O)OC(C)(C)C)=CC(N2CCSCC2)=C1C#N RSMRRBWYKHRNAQ-UHFFFAOYSA-N 0.000 description 4
• KNBRVRDVLBCSAM-UHFFFAOYSA-N tert-butyl n-(2-amino-5-methoxy-4-pyrrol-1-ylphenyl)carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1N1C=CC=C1 KNBRVRDVLBCSAM-UHFFFAOYSA-N 0.000 description 4
• IJKLTMRZHAHGDZ-UHFFFAOYSA-N tert-butyl n-(2-nitro-4-pyrrol-1-ylphenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC=C1N1C=CC=C1 IJKLTMRZHAHGDZ-UHFFFAOYSA-N 0.000 description 4
• SKAGHIGZEMUTAW-UHFFFAOYSA-N tert-butyl n-(4-cyano-2-nitro-5-thiomorpholin-4-ylphenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCSCC2)=C1C#N SKAGHIGZEMUTAW-UHFFFAOYSA-N 0.000 description 4
• QEWLQARQZLEWQL-UHFFFAOYSA-N tert-butyl n-(4-cyano-5-morpholin-4-yl-2-nitrophenyl)carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCOCC2)=C1C#N QEWLQARQZLEWQL-UHFFFAOYSA-N 0.000 description 4
• MVHRYZFZNXFYQR-UHFFFAOYSA-N tert-butyl n-(5-methoxy-2-nitro-4-pyrrol-1-ylphenyl)carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1N1C=CC=C1 MVHRYZFZNXFYQR-UHFFFAOYSA-N 0.000 description 4
• XGQHBSIICHBIAH-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-ethoxy-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OCC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=NC(C#N)=C1 XGQHBSIICHBIAH-UHFFFAOYSA-N 0.000 description 4
• UUHKKKQFVBICOL-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-methoxy-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=NC(C#N)=C1 UUHKKKQFVBICOL-UHFFFAOYSA-N 0.000 description 4
• BKKPNZWUEJFVIV-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-pyrrol-1-ylphenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 BKKPNZWUEJFVIV-UHFFFAOYSA-N 0.000 description 4
• FQPIAUACZCXROM-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-(2-methoxyethoxy)-4-pyrrol-1-ylphenyl]carbamate Chemical compound C1=C(N2C=CC=C2)C(OCCOC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 FQPIAUACZCXROM-UHFFFAOYSA-N 0.000 description 4
• JSVCVCLCZJIDJW-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-4-pyrrol-1-ylphenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=C1 JSVCVCLCZJIDJW-UHFFFAOYSA-N 0.000 description 4
• QHXRBJCCBLLITQ-UHFFFAOYSA-N tert-butyl n-[2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-5-morpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C=2)C(F)(F)F)N2CCOCC2)NC(=O)OC(C)(C)C)=C1 QHXRBJCCBLLITQ-UHFFFAOYSA-N 0.000 description 4
• VFDVOVMYBYYDGF-UHFFFAOYSA-N tert-butyl n-[2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-5-thiomorpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C=2)C(F)(F)F)N2CCSCC2)NC(=O)OC(C)(C)C)=C1 VFDVOVMYBYYDGF-UHFFFAOYSA-N 0.000 description 4
• WMNNXUOGEOFGLX-UHFFFAOYSA-N tert-butyl n-[2-[[3-[3-[5-[(dimethylamino)methyl]triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-5-morpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound CN(C)CC1=CN=NN1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C=2)C(F)(F)F)N2CCOCC2)NC(=O)OC(C)(C)C)=C1 WMNNXUOGEOFGLX-UHFFFAOYSA-N 0.000 description 4
• JOTUHPUAZYWWGE-UHFFFAOYSA-N tert-butyl n-[2-amino-4-(2-tert-butylpyrrol-1-yl)-5-methoxyphenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1N1C(C(C)(C)C)=CC=C1 JOTUHPUAZYWWGE-UHFFFAOYSA-N 0.000 description 4
• XUCFTALIKRJAME-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(2-methoxyethoxy)-4-pyrrol-1-ylphenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C(N)C=C1N1C=CC=C1 XUCFTALIKRJAME-UHFFFAOYSA-N 0.000 description 4
• YVLSWRDCRIHEOK-UHFFFAOYSA-N tert-butyl n-[2-amino-5-(cyanomethyl)-4-iodophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CC#N)=C(I)C=C1N YVLSWRDCRIHEOK-UHFFFAOYSA-N 0.000 description 4
• YIIBSYFRWRSAFI-UHFFFAOYSA-N tert-butyl n-[2-amino-5-fluoro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(F)=C(C(F)(F)F)C=C1N YIIBSYFRWRSAFI-UHFFFAOYSA-N 0.000 description 4
• VNRFJJBEWQURRA-UHFFFAOYSA-N tert-butyl n-[2-nitro-5-thiomorpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=CC(N2CCSCC2)=C1C(F)(F)F VNRFJJBEWQURRA-UHFFFAOYSA-N 0.000 description 4
• AALDGFHVPXXYRJ-UHFFFAOYSA-N tert-butyl n-[4-(2-tert-butylpyrrol-1-yl)-5-methoxy-2-nitrophenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1N1C(C(C)(C)C)=CC=C1 AALDGFHVPXXYRJ-UHFFFAOYSA-N 0.000 description 4
• XYVPFXRLRVEDQA-UHFFFAOYSA-N tert-butyl n-[4-cyano-5-morpholin-4-yl-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]amino]phenyl]carbamate Chemical compound N#CC=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C(=CN=N2)COC2OCCCC2)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 XYVPFXRLRVEDQA-UHFFFAOYSA-N 0.000 description 4
• DPXYWAQPWQVGSO-UHFFFAOYSA-N tert-butyl n-[5-(2-methoxyethoxy)-2-nitro-4-pyrrol-1-ylphenyl]carbamate Chemical compound COCCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1N1C=CC=C1 DPXYWAQPWQVGSO-UHFFFAOYSA-N 0.000 description 4
• DZEJVEBCQXJSCG-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(Cl)=C(C=2)C(F)(F)F)NC(=O)OC(C)(C)C)=C1 DZEJVEBCQXJSCG-UHFFFAOYSA-N 0.000 description 4
• VWTCBWGUOVOCQT-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-oxo-3-[3-(1,2,4-triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1NC(=O)CC(=O)C1=CC=CC(N2N=CN=C2)=C1 VWTCBWGUOVOCQT-UHFFFAOYSA-N 0.000 description 4
• WDIAMDMEFPLYPI-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 WDIAMDMEFPLYPI-UHFFFAOYSA-N 0.000 description 4
• MLWFVBYPWMHJLJ-UHFFFAOYSA-N tert-butyl n-[5-cyano-2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-4-morpholin-4-ylphenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(C#N)=C(N2CCOCC2)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 MLWFVBYPWMHJLJ-UHFFFAOYSA-N 0.000 description 4
• HRGLKCIUKONKSX-UHFFFAOYSA-N tert-butyl n-[5-ethoxy-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OCC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 HRGLKCIUKONKSX-UHFFFAOYSA-N 0.000 description 4
• IWYNYIRMZJXRJQ-UHFFFAOYSA-N tert-butyl n-[5-ethoxy-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CCOC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C(F)(F)F IWYNYIRMZJXRJQ-UHFFFAOYSA-N 0.000 description 4
• BLVPRFICUXIWNZ-UHFFFAOYSA-N tert-butyl n-[5-methoxy-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 BLVPRFICUXIWNZ-UHFFFAOYSA-N 0.000 description 4
• NGJIIVWYRMAPRQ-UHFFFAOYSA-N tert-butyl n-[5-methoxy-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C(F)(F)F NGJIIVWYRMAPRQ-UHFFFAOYSA-N 0.000 description 4
• GVMBEUACJMKRGW-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-[[3-oxo-3-[3-(1,2,4-triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=CN=C2)=C1 GVMBEUACJMKRGW-UHFFFAOYSA-N 0.000 description 4
• HMBLOASJUYQYAH-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=NC=C2)=C1 HMBLOASJUYQYAH-UHFFFAOYSA-N 0.000 description 4
• ZVGANEZTONXZBD-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-nitro-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C([N+]([O-])=O)C=C1C(F)(F)F ZVGANEZTONXZBD-UHFFFAOYSA-N 0.000 description 4
• YAFHSTUCZFADJJ-UHFFFAOYSA-N tert-butyl n-[5-morpholin-4-yl-2-[[3-oxo-3-(3-pyrazol-1-ylphenyl)propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2N=CC=C2)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 YAFHSTUCZFADJJ-UHFFFAOYSA-N 0.000 description 4
• BLLBAINVOMUMEG-UHFFFAOYSA-N tert-butyl n-[5-morpholin-4-yl-2-[[3-oxo-3-[3-(1,2,4-triazol-4-yl)phenyl]propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C=NN=C2)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 BLLBAINVOMUMEG-UHFFFAOYSA-N 0.000 description 4
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 3
• SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 3
• RVPSMVOSOBSKDL-UHFFFAOYSA-N 3-(3-cyanophenyl)-n-[5-[2-(methoxymethyl)pyrrol-1-yl]-2-nitrophenyl]-3-oxopropanamide Chemical compound COCC1=CC=CN1C1=CC=C([N+]([O-])=O)C(NC(=O)CC(=O)C=2C=C(C=CC=2)C#N)=C1 RVPSMVOSOBSKDL-UHFFFAOYSA-N 0.000 description 3
• WAROBBFEHKGCMC-UHFFFAOYSA-N 4-iodo-2-nitro-5-pyrrol-1-ylaniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC(N2C=CC=C2)=C1I WAROBBFEHKGCMC-UHFFFAOYSA-N 0.000 description 3
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 3
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 229920002261 Corn starch Polymers 0.000 description 3
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 101001071429 Homo sapiens Metabotropic glutamate receptor 2 Proteins 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
• 208000018737 Parkinson disease Diseases 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000004703 alkoxides Chemical class 0.000 description 3
• 235000019270 ammonium chloride Nutrition 0.000 description 3
• 235000011114 ammonium hydroxide Nutrition 0.000 description 3
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
• 229910000024 caesium carbonate Inorganic materials 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 210000003169 central nervous system Anatomy 0.000 description 3
• 150000001805 chlorine compounds Chemical class 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 239000008120 corn starch Substances 0.000 description 3
• HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 3
• ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• ONFVYWWDQALCKD-UHFFFAOYSA-N ethyl 2-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 ONFVYWWDQALCKD-UHFFFAOYSA-N 0.000 description 3
• RYULTLSTUFZTBL-UHFFFAOYSA-N ethyl 5-[3-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)phenyl]-1,3-thiazole-2-carboxylate Chemical compound S1C(C(=O)OCC)=NC=C1C1=CC=CC(C=2OC(C)(C)OC(=O)C=2)=C1 RYULTLSTUFZTBL-UHFFFAOYSA-N 0.000 description 3
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
• 229930195712 glutamate Natural products 0.000 description 3
• 150000004678 hydrides Chemical class 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 239000012948 isocyanate Substances 0.000 description 3
• 150000002513 isocyanates Chemical class 0.000 description 3
• XFYPJAPDFKSOIC-UHFFFAOYSA-N methyl 3-(5-methyl-1,3-oxazol-4-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(OC=N2)C)=C1 XFYPJAPDFKSOIC-UHFFFAOYSA-N 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• OZSGLUMHUYPXTN-UHFFFAOYSA-N n-[5-[3-(2-chlorophenyl)-4-cyanopyrrol-1-yl]-2-nitrophenyl]-3-(3-cyanophenyl)-3-oxopropanamide Chemical compound [O-][N+](=O)C1=CC=C(N2C=C(C(C#N)=C2)C=2C(=CC=CC=2)Cl)C=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 OZSGLUMHUYPXTN-UHFFFAOYSA-N 0.000 description 3
• 229910017604 nitric acid Inorganic materials 0.000 description 3
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• QVBPZZKELHNMDZ-UHFFFAOYSA-M potassium;3-[(2-methylpropan-2-yl)oxy]-3-oxopropanoate Chemical class [K+].CC(C)(C)OC(=O)CC([O-])=O QVBPZZKELHNMDZ-UHFFFAOYSA-M 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Substances [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 239000000454 talc Substances 0.000 description 3
• 229910052623 talc Inorganic materials 0.000 description 3
• MMUFWRNJOBPGMV-UHFFFAOYSA-N tert-butyl 3-[3-[5-[(dimethylamino)methyl]triazol-1-yl]phenyl]-3-oxopropanoate Chemical compound CN(C)CC1=CN=NN1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 MMUFWRNJOBPGMV-UHFFFAOYSA-N 0.000 description 3
• KCZFBLNQOSFGSH-UHFFFAOYSA-N tert-butyl n-(2-aminophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=C1N KCZFBLNQOSFGSH-UHFFFAOYSA-N 0.000 description 3
• LBYWOOGCOYSUOC-UHFFFAOYSA-N tert-butyl n-(5-hydroxy-2-nitrophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(O)=CC=C1[N+]([O-])=O LBYWOOGCOYSUOC-UHFFFAOYSA-N 0.000 description 3
• KCNGHTZCIGTALY-UHFFFAOYSA-N tert-butyl n-[5-morpholin-4-yl-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)N2C(=CN=N2)COC2OCCCC2)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 KCNGHTZCIGTALY-UHFFFAOYSA-N 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 3
• FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• QMIGEDXMDGEZSR-UHFFFAOYSA-N 2,5-dimethoxyoxolane-3-carbaldehyde Chemical compound COC1CC(C=O)C(OC)O1 QMIGEDXMDGEZSR-UHFFFAOYSA-N 0.000 description 2
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
• JJCDQNVFUDSIGM-UHFFFAOYSA-N 2-nitro-5-pyrrol-1-ylaniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC(N2C=CC=C2)=C1 JJCDQNVFUDSIGM-UHFFFAOYSA-N 0.000 description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
• QKEFOVJZNPELQH-UHFFFAOYSA-N 3-(2-bromoacetyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)CBr)=C1 QKEFOVJZNPELQH-UHFFFAOYSA-N 0.000 description 2
• XWWYILJMLBSTMW-UHFFFAOYSA-N 3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzenecarbothioamide Chemical compound NC(=S)C1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 XWWYILJMLBSTMW-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• NDILQXVACSSLIV-UHFFFAOYSA-N 3-(triazol-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(N2N=NC=C2)=C1 NDILQXVACSSLIV-UHFFFAOYSA-N 0.000 description 2
• CRRVZRDISHOQQL-UHFFFAOYSA-N 3-fluoro-4-(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(F)F)C(F)=C1 CRRVZRDISHOQQL-UHFFFAOYSA-N 0.000 description 2
• NWHOAXHJVDBUCD-UHFFFAOYSA-N 3-prop-2-enoxycarbonylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)OCC=C)=C1 NWHOAXHJVDBUCD-UHFFFAOYSA-N 0.000 description 2
• GEWCXMLSRUQIDQ-UHFFFAOYSA-N 4-(2-chlorophenyl)-1h-pyrrole-3-carbonitrile Chemical compound ClC1=CC=CC=C1C1=CNC=C1C#N GEWCXMLSRUQIDQ-UHFFFAOYSA-N 0.000 description 2
• OCKZBJNDXAQTSU-UHFFFAOYSA-N 4-[3-[4-(chloromethyl)-1,3-thiazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound ClCC1=CSC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 OCKZBJNDXAQTSU-UHFFFAOYSA-N 0.000 description 2
• BMMCNKYHQAKJBN-UHFFFAOYSA-N 4-phenyl-1h-pyrrole-3-carbonitrile Chemical compound N#CC1=CNC=C1C1=CC=CC=C1 BMMCNKYHQAKJBN-UHFFFAOYSA-N 0.000 description 2
• UTRVMCDXCUQEEJ-UHFFFAOYSA-N 5-fluoro-2-nitro-4-(trifluoromethyl)aniline Chemical compound NC1=CC(F)=C(C(F)(F)F)C=C1[N+]([O-])=O UTRVMCDXCUQEEJ-UHFFFAOYSA-N 0.000 description 2
• YKBOYHGKNPBPJI-UHFFFAOYSA-N 7-chloro-4-[3-[5-(hydroxymethyl)triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=CN=NN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(Cl)C=C3N=2)C(F)(F)F)=C1 YKBOYHGKNPBPJI-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• 208000030507 AIDS Diseases 0.000 description 2
• 208000019901 Anxiety disease Diseases 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 239000007848 Bronsted acid Substances 0.000 description 2
• 239000003341 Bronsted base Substances 0.000 description 2
• 208000000094 Chronic Pain Diseases 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• 206010012289 Dementia Diseases 0.000 description 2
• 208000012661 Dyskinesia Diseases 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-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
• 206010019196 Head injury Diseases 0.000 description 2
• 208000010496 Heart Arrest Diseases 0.000 description 2
• 208000023105 Huntington disease Diseases 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• 208000013016 Hypoglycemia Diseases 0.000 description 2
• 206010021143 Hypoxia Diseases 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• 208000019695 Migraine disease Diseases 0.000 description 2
• 208000007101 Muscle Cramp Diseases 0.000 description 2
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
• 206010057852 Nicotine dependence Diseases 0.000 description 2
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
• 240000007817 Olea europaea Species 0.000 description 2
• 208000026251 Opioid-Related disease Diseases 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
• 208000017442 Retinal disease Diseases 0.000 description 2
• 206010038923 Retinopathy Diseases 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• 208000005392 Spasm Diseases 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
• 208000025569 Tobacco Use disease Diseases 0.000 description 2
• 206010046543 Urinary incontinence Diseases 0.000 description 2
• 206010047700 Vomiting Diseases 0.000 description 2
• JYHSQZMKMIWLED-UHFFFAOYSA-N [2-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazol-4-yl]methyl acetate Chemical compound CC(=O)OCC1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 JYHSQZMKMIWLED-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 208000005298 acute pain Diseases 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 150000004645 aluminates Chemical class 0.000 description 2
• 230000036506 anxiety Effects 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
• 230000027455 binding Effects 0.000 description 2
• 239000012148 binding buffer Substances 0.000 description 2
• 230000036770 blood supply Effects 0.000 description 2
• 230000003925 brain function Effects 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 230000036461 convulsion Effects 0.000 description 2
• 238000007257 deesterification reaction Methods 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 2
• HZIKYLAZZZSYKF-UHFFFAOYSA-N ethyl 2-cyanopyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC(C#N)=C1 HZIKYLAZZZSYKF-UHFFFAOYSA-N 0.000 description 2
• VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 2
• 231100000040 eye damage Toxicity 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000003825 glutamate receptor antagonist Substances 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 230000002218 hypoglycaemic effect Effects 0.000 description 2
• 230000007954 hypoxia Effects 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 230000026045 iodination Effects 0.000 description 2
• 238000006192 iodination reaction Methods 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
• YUDUYCUJCQMCCJ-UHFFFAOYSA-N methyl 2,5-dimethoxyoxolane-2-carboxylate Chemical compound COC1CCC(OC)(C(=O)OC)O1 YUDUYCUJCQMCCJ-UHFFFAOYSA-N 0.000 description 2
• LVRJAFUTXDBMCM-UHFFFAOYSA-N methyl 3-(2-bromopropanoyl)benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)C(C)Br)=C1 LVRJAFUTXDBMCM-UHFFFAOYSA-N 0.000 description 2
• KYEBGXQJMRBXGX-UHFFFAOYSA-N methyl 3-[2-(hydroxymethyl)-5-methyl-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(SC(CO)=N2)C)=C1 KYEBGXQJMRBXGX-UHFFFAOYSA-N 0.000 description 2
• GCRVOUCLHCAJSR-UHFFFAOYSA-N methyl 3-[4-(hydroxymethyl)-1,3-thiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2SC=C(CO)N=2)=C1 GCRVOUCLHCAJSR-UHFFFAOYSA-N 0.000 description 2
• GGRYEDQOBPIMKX-UHFFFAOYSA-N methyl 3-[4-(oxan-2-yloxymethyl)-1,3-thiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2SC=C(COC3OCCCC3)N=2)=C1 GGRYEDQOBPIMKX-UHFFFAOYSA-N 0.000 description 2
• IEQAKGLBTYFPEP-UHFFFAOYSA-N methyl 3-[5-methyl-2-(oxan-2-yloxymethyl)-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=C(SC(COC3OCCCC3)=N2)C)=C1 IEQAKGLBTYFPEP-UHFFFAOYSA-N 0.000 description 2
• XPBHWSMZTSSEJE-UHFFFAOYSA-N methyl 3-cyanobenzoate Chemical compound COC(=O)C1=CC=CC(C#N)=C1 XPBHWSMZTSSEJE-UHFFFAOYSA-N 0.000 description 2
• FNFWFAVDUMMRJN-UHFFFAOYSA-N methyl 3-pyrazol-1-ylbenzoate Chemical compound COC(=O)C1=CC=CC(N2N=CC=C2)=C1 FNFWFAVDUMMRJN-UHFFFAOYSA-N 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 239000002858 neurotransmitter agent Substances 0.000 description 2
• 201000005040 opiate dependence Diseases 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 235000015497 potassium bicarbonate Nutrition 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 230000035935 pregnancy Effects 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 238000007127 saponification reaction Methods 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 235000017550 sodium carbonate Nutrition 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 159000000000 sodium salts Chemical class 0.000 description 2
• ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 2
• 208000020431 spinal cord injury Diseases 0.000 description 2
• 235000011150 stannous chloride Nutrition 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• NYFCOKUDSSHZCE-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-methyl-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=NC(C#N)=C1 NYFCOKUDSSHZCE-UHFFFAOYSA-N 0.000 description 2
• HMAZWMUYIKCQQZ-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-morpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(N=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 HMAZWMUYIKCQQZ-UHFFFAOYSA-N 0.000 description 2
• JSFSELOLAWYUBJ-UHFFFAOYSA-N tert-butyl n-[2-[[3-(2-cyanopyridin-4-yl)-3-oxopropanoyl]amino]-5-thiomorpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(N=CC=2)C#N)C(NC(=O)OC(C)(C)C)=CC=1N1CCSCC1 JSFSELOLAWYUBJ-UHFFFAOYSA-N 0.000 description 2
• NJEDSZJNYRSQSF-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-methoxy-4-pyrrol-1-ylphenyl]carbamate Chemical compound C1=C(N2C=CC=C2)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 NJEDSZJNYRSQSF-UHFFFAOYSA-N 0.000 description 2
• SYVXWHZIZOYSJD-UHFFFAOYSA-N tert-butyl n-[2-[[3-[3-(2-methylpyrazol-3-yl)phenyl]-3-oxopropanoyl]amino]-5-morpholin-4-yl-4-(trifluoromethyl)phenyl]carbamate Chemical compound CN1N=CC=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(=C(C=2)C(F)(F)F)N2CCOCC2)NC(=O)OC(C)(C)C)=C1 SYVXWHZIZOYSJD-UHFFFAOYSA-N 0.000 description 2
• NHFRKTUQCATLRK-UHFFFAOYSA-N tert-butyl n-[2-[[3-oxo-3-[3-(triazol-1-yl)phenyl]propanoyl]amino]-4-pyrrol-1-ylphenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(N2C=CC=C2)C=C1NC(=O)CC(=O)C(C=1)=CC=CC=1N1C=CN=N1 NHFRKTUQCATLRK-UHFFFAOYSA-N 0.000 description 2
• IHBAJMOUDHLFLJ-UHFFFAOYSA-N tert-butyl n-[4-(2-tert-butylpyrrol-1-yl)-2-[[3-(3-cyanophenyl)-3-oxopropanoyl]amino]-5-methoxyphenyl]carbamate Chemical compound C1=C(N2C(=CC=C2)C(C)(C)C)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C#N)=C1 IHBAJMOUDHLFLJ-UHFFFAOYSA-N 0.000 description 2
• HAIBBPOJTJTMEK-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethyl)-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-4-iodophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CC#N)=C(I)C=C1NC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 HAIBBPOJTJTMEK-UHFFFAOYSA-N 0.000 description 2
• LXIKZPJLNNIMSY-UHFFFAOYSA-N tert-butyl n-[5-(cyanomethyl)-4-iodo-2-nitrophenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CC#N)=C(I)C=C1[N+]([O-])=O LXIKZPJLNNIMSY-UHFFFAOYSA-N 0.000 description 2
• CZXMHYRMBJKHAC-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1NC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 CZXMHYRMBJKHAC-UHFFFAOYSA-N 0.000 description 2
• WEKDJSNYDQWUFG-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-[3-[5-(oxan-2-yloxymethyl)-1,2,4-triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1NC(=O)CC(=O)C1=CC=CC(N2C(=NC=N2)COC2OCCCC2)=C1 WEKDJSNYDQWUFG-UHFFFAOYSA-N 0.000 description 2
• YYGVXQHLJAEIBI-UHFFFAOYSA-N tert-butyl n-[5-chloro-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(C(F)(F)F)C=C1NC(=O)CC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 YYGVXQHLJAEIBI-UHFFFAOYSA-N 0.000 description 2
• OBEKNVNJCZWZPG-UHFFFAOYSA-N tert-butyl n-[5-ethoxy-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OCC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 OBEKNVNJCZWZPG-UHFFFAOYSA-N 0.000 description 2
• KOIIOXOOKGPWKM-UHFFFAOYSA-N tert-butyl n-[5-fluoro-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(F)=C(C(F)(F)F)C=C1NC(=O)CC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 KOIIOXOOKGPWKM-UHFFFAOYSA-N 0.000 description 2
• MSWSXATZCFSMHP-UHFFFAOYSA-N tert-butyl n-[5-methoxy-2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(C=2ON=C(C)C=2)=C1 MSWSXATZCFSMHP-UHFFFAOYSA-N 0.000 description 2
• BXWIAIYZRHSWSC-UHFFFAOYSA-N tert-butyl n-[5-methoxy-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(OC)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 BXWIAIYZRHSWSC-UHFFFAOYSA-N 0.000 description 2
• XRFWKHHRUYJYEE-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-[[3-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound O1N=C(C)C=C1C1=CC=CC(C(=O)CC(=O)NC=2C(=CC(C)=C(C=2)C(F)(F)F)NC(=O)OC(C)(C)C)=C1 XRFWKHHRUYJYEE-UHFFFAOYSA-N 0.000 description 2
• PFSORCJVVGFPRM-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-[[3-[3-[5-(oxan-2-yloxymethyl)triazol-1-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 PFSORCJVVGFPRM-UHFFFAOYSA-N 0.000 description 2
• GVSAVVQHRLNXJU-UHFFFAOYSA-N tert-butyl n-[5-methyl-2-[[3-oxo-3-(3-pyrazol-1-ylphenyl)propanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2N=CC=C2)=C1 GVSAVVQHRLNXJU-UHFFFAOYSA-N 0.000 description 2
• HVTDEMRBTBYDRA-UHFFFAOYSA-N tert-butyl n-[5-morpholin-4-yl-2-[[3-[3-[3-(oxan-2-yloxymethyl)-1,2-oxazol-5-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C=2ON=C(COC3OCCCC3)C=2)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 HVTDEMRBTBYDRA-UHFFFAOYSA-N 0.000 description 2
• ZJLNALGANVUBHB-UHFFFAOYSA-N tert-butyl n-[5-morpholin-4-yl-2-[[3-[3-[5-(oxan-2-yloxymethyl)-1,2-oxazol-3-yl]phenyl]-3-oxopropanoyl]amino]-4-(trifluoromethyl)phenyl]carbamate Chemical compound FC(F)(F)C=1C=C(NC(=O)CC(=O)C=2C=C(C=CC=2)C2=NOC(COC3OCCCC3)=C2)C(NC(=O)OC(C)(C)C)=CC=1N1CCOCC1 ZJLNALGANVUBHB-UHFFFAOYSA-N 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 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
• 238000002054 transplantation Methods 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 230000008673 vomiting Effects 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• 239000008096 xylene Substances 0.000 description 2
• NHGAIGDDBFHIKX-UHFFFAOYSA-N (2,5-dimethoxyoxolan-3-yl)methanol Chemical compound COC1CC(CO)C(OC)O1 NHGAIGDDBFHIKX-UHFFFAOYSA-N 0.000 description 1
• COULAOZTCJTHOX-UHFFFAOYSA-N (2-amino-2-sulfanylideneethyl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCC(N)=S COULAOZTCJTHOX-UHFFFAOYSA-N 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
• VQGBMMKZALZKMQ-UHFFFAOYSA-N 1-[4-(3-cyanophenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-8-yl]-4-phenylpyrrole-3-carbonitrile Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=C1N(C=1)C=C(C#N)C=1C1=CC=CC=C1 VQGBMMKZALZKMQ-UHFFFAOYSA-N 0.000 description 1
• JRVZITODZAQRQM-UHFFFAOYSA-N 1-isocyanato-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1N=C=O JRVZITODZAQRQM-UHFFFAOYSA-N 0.000 description 1
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
• KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
• MQVCSABWYYPLBY-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)propanedioic acid Chemical class C[Si](C)(C)C(C(O)=O)(C(O)=O)[Si](C)(C)C MQVCSABWYYPLBY-UHFFFAOYSA-N 0.000 description 1
• QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
• GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
• DYOSAFQUIFEGSK-UHFFFAOYSA-N 2,5-dimethoxy-2,3-dihydrofuran Chemical class COC1CC=C(OC)O1 DYOSAFQUIFEGSK-UHFFFAOYSA-N 0.000 description 1
• ZZKCXXBAGQTVSD-UHFFFAOYSA-N 2,5-dimethoxy-2-(methoxymethyl)oxolane Chemical compound COCC1(OC)CCC(OC)O1 ZZKCXXBAGQTVSD-UHFFFAOYSA-N 0.000 description 1
• QWCWAWARCOQEHU-UHFFFAOYSA-N 2,5-dimethoxy-3-(methoxymethyl)oxolane Chemical compound COCC1CC(OC)OC1OC QWCWAWARCOQEHU-UHFFFAOYSA-N 0.000 description 1
• FUYICGSJBLULDW-UHFFFAOYSA-N 2,5-dimethoxy-3-phenyloxolane Chemical compound COC1OC(OC)CC1C1=CC=CC=C1 FUYICGSJBLULDW-UHFFFAOYSA-N 0.000 description 1
• AIZQKZQVAXDAHQ-UHFFFAOYSA-N 2-(5-amino-2-iodo-4-nitrophenyl)acetonitrile Chemical compound NC1=CC(CC#N)=C(I)C=C1[N+]([O-])=O AIZQKZQVAXDAHQ-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• CEGFADRHLIZQIP-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]phenol Chemical class CC(C)(C)OC1=CC=CC=C1O CEGFADRHLIZQIP-UHFFFAOYSA-N 0.000 description 1
• UQPXTPDDBGAWGJ-UHFFFAOYSA-N 2-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 UQPXTPDDBGAWGJ-UHFFFAOYSA-N 0.000 description 1
• WGDYFGFEQGIYQC-UHFFFAOYSA-N 2-[4-(3-imidazol-1-ylphenyl)-8-iodo-2-oxo-1,3-dihydro-1,5-benzodiazepin-7-yl]acetonitrile Chemical compound N=1C=2C=C(CC#N)C(I)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1N1C=CN=C1 WGDYFGFEQGIYQC-UHFFFAOYSA-N 0.000 description 1
• TZGPACAKMCUCKX-UHFFFAOYSA-N 2-hydroxyacetamide Chemical class NC(=O)CO TZGPACAKMCUCKX-UHFFFAOYSA-N 0.000 description 1
• HQAXHIGPGBPPFU-UHFFFAOYSA-N 2-prop-2-ynoxyoxane Chemical compound C#CCOC1CCCCO1 HQAXHIGPGBPPFU-UHFFFAOYSA-N 0.000 description 1
• ZBWZEFLYRWANSY-UHFFFAOYSA-N 2-quinoxalin-2-ylsulfanylacetic acid Chemical compound C1=CC=CC2=NC(SCC(=O)O)=CN=C21 ZBWZEFLYRWANSY-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• IMAITKPPSLYKDS-UHFFFAOYSA-N 3-(1,3-oxazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2OC=CN=2)=C1 IMAITKPPSLYKDS-UHFFFAOYSA-N 0.000 description 1
• FQEHTHUZUNTZFD-UHFFFAOYSA-N 3-(1,3-oxazol-2-yl)benzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C=2OC=CN=2)=C1 FQEHTHUZUNTZFD-UHFFFAOYSA-N 0.000 description 1
• RHHQMJRBXPMZAL-UHFFFAOYSA-N 3-(2-bromopropanoyl)benzoic acid Chemical compound CC(Br)C(=O)C1=CC=CC(C(O)=O)=C1 RHHQMJRBXPMZAL-UHFFFAOYSA-N 0.000 description 1
• FPXMBUCYKWIUOK-UHFFFAOYSA-N 3-(2-ethoxycarbonyl-1,3-thiazol-4-yl)benzoic acid Chemical compound S1C(C(=O)OCC)=NC(C=2C=C(C=CC=2)C(O)=O)=C1 FPXMBUCYKWIUOK-UHFFFAOYSA-N 0.000 description 1
• RKFZOINNIJWOEZ-UHFFFAOYSA-N 3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzamide Chemical compound NC(=O)C1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 RKFZOINNIJWOEZ-UHFFFAOYSA-N 0.000 description 1
• XFODIAHSXPAKCW-UHFFFAOYSA-N 3-(3-cyanophenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(C#N)=C1 XFODIAHSXPAKCW-UHFFFAOYSA-N 0.000 description 1
• QSIJJFJVURXYMN-UHFFFAOYSA-N 3-(3-imidazol-1-ylphenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 QSIJJFJVURXYMN-UHFFFAOYSA-N 0.000 description 1
• MDHICEGQTXCLTJ-UHFFFAOYSA-N 3-(3-iodophenyl)-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(I)=C1 MDHICEGQTXCLTJ-UHFFFAOYSA-N 0.000 description 1
• VBONQYXZNRRESH-UHFFFAOYSA-N 3-(4-ethoxycarbonyl-1,3-oxazol-5-yl)benzoic acid Chemical compound N1=COC(C=2C=C(C=CC=2)C(O)=O)=C1C(=O)OCC VBONQYXZNRRESH-UHFFFAOYSA-N 0.000 description 1
• SWACMTBZYVTEGK-UHFFFAOYSA-N 3-(4-methoxycarbonyl-1,3-oxazol-2-yl)benzoic acid Chemical compound COC(=O)C1=COC(C=2C=C(C=CC=2)C(O)=O)=N1 SWACMTBZYVTEGK-UHFFFAOYSA-N 0.000 description 1
• XFAAMURUPKGCEC-UHFFFAOYSA-N 3-(7-iodo-2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzonitrile Chemical compound IC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1N1C=CC=C1 XFAAMURUPKGCEC-UHFFFAOYSA-N 0.000 description 1
• URORLVFFDOBESS-UHFFFAOYSA-N 3-(7-methoxy-2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)benzonitrile Chemical compound COC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1N1C=CC=C1 URORLVFFDOBESS-UHFFFAOYSA-N 0.000 description 1
• PMULQRSPXDDXRR-UHFFFAOYSA-N 3-[3-(1,3-oxazol-2-yl)phenyl]-3-oxopropanoic acid Chemical compound OC(=O)CC(=O)C1=CC=CC(C=2OC=CN=2)=C1 PMULQRSPXDDXRR-UHFFFAOYSA-N 0.000 description 1
• KHXLLVDTOKSDGU-UHFFFAOYSA-N 3-[3-(2-ethoxycarbonyl-1,3-thiazol-4-yl)phenyl]-3-oxopropanoic acid Chemical compound S1C(C(=O)OCC)=NC(C=2C=C(C=CC=2)C(=O)CC(O)=O)=C1 KHXLLVDTOKSDGU-UHFFFAOYSA-N 0.000 description 1
• ITOKZQLRGOYAAD-UHFFFAOYSA-N 3-[3-(4-ethoxycarbonyl-1,3-oxazol-5-yl)phenyl]-3-oxopropanoic acid Chemical compound N1=COC(C=2C=C(C=CC=2)C(=O)CC(O)=O)=C1C(=O)OCC ITOKZQLRGOYAAD-UHFFFAOYSA-N 0.000 description 1
• AXVAUDKOJFRVSG-UHFFFAOYSA-N 3-[3-(4-methoxycarbonyl-1,3-oxazol-2-yl)phenyl]-3-oxopropanoic acid Chemical compound COC(=O)C1=COC(C=2C=C(C=CC=2)C(=O)CC(O)=O)=N1 AXVAUDKOJFRVSG-UHFFFAOYSA-N 0.000 description 1
• FZDUKFGCCAIWCH-UHFFFAOYSA-N 3-[7-(2-methoxyethoxy)-2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound COCCOC1=CC=2N=C(C=3C=C(C=CC=3)C#N)CC(=O)NC=2C=C1N1C=CC=C1 FZDUKFGCCAIWCH-UHFFFAOYSA-N 0.000 description 1
• ABCMSDVRIOZDTA-UHFFFAOYSA-N 3-[8-[3-(hydroxymethyl)pyrrol-1-yl]-2-oxo-1,3-dihydro-1,5-benzodiazepin-4-yl]benzonitrile Chemical compound C1=C(CO)C=CN1C1=CC=C(N=C(CC(=O)N2)C=3C=C(C=CC=3)C#N)C2=C1 ABCMSDVRIOZDTA-UHFFFAOYSA-N 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
• OHFLNNVKHIOKKU-UHFFFAOYSA-N 3-carbonochloridoylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C(Cl)=O)=C1 OHFLNNVKHIOKKU-UHFFFAOYSA-N 0.000 description 1
• RPESZQVUWMFBEO-UHFFFAOYSA-N 3-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(C#N)=C1 RPESZQVUWMFBEO-UHFFFAOYSA-N 0.000 description 1
• VKJZLGSUMISODO-UHFFFAOYSA-N 3-imidazol-1-ylbenzoyl chloride;hydrochloride Chemical compound Cl.ClC(=O)C1=CC=CC(N2C=NC=C2)=C1 VKJZLGSUMISODO-UHFFFAOYSA-N 0.000 description 1
• DTELTOREECFDBC-UHFFFAOYSA-N 3-iodobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(I)=C1 DTELTOREECFDBC-UHFFFAOYSA-N 0.000 description 1
• WLABMYNWZJOAOU-UHFFFAOYSA-N 3-methoxy-2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenyl]-3-oxopropanoic acid Chemical compound COC(=O)C(C(O)=O)C1=CC=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=C1 WLABMYNWZJOAOU-UHFFFAOYSA-N 0.000 description 1
• WMZNGTSLFSJHMZ-UHFFFAOYSA-N 3-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=CC(C(O)=O)=C1 WMZNGTSLFSJHMZ-UHFFFAOYSA-N 0.000 description 1
• ZVKOWQCEVFTISF-UHFFFAOYSA-N 4-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)pyridine-2-carbonitrile Chemical compound O1C(C)(C)OC(=O)C=C1C1=CC=NC(C#N)=C1 ZVKOWQCEVFTISF-UHFFFAOYSA-N 0.000 description 1
• OMPSOUDKKRRXSI-UHFFFAOYSA-N 4-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)pyridine-2-carbonitrile Chemical compound C1=C2NC(=O)CC(C=3C=C(N=CC=3)C#N)=NC2=CC=C1N1C=CC=C1 OMPSOUDKKRRXSI-UHFFFAOYSA-N 0.000 description 1
• FNEJMJMDFCTEQZ-UHFFFAOYSA-N 4-(3-cyanophenyl)-7-morpholin-4-yl-2-oxo-1,3-dihydro-1,5-benzodiazepine-8-carbonitrile Chemical compound N#CC=1C=C2NC(=O)CC(C=3C=C(C=CC=3)C#N)=NC2=CC=1N1CCOCC1 FNEJMJMDFCTEQZ-UHFFFAOYSA-N 0.000 description 1
• KJFSUONZDZKWIS-UHFFFAOYSA-N 4-(3-imidazol-1-ylphenyl)-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=C1 KJFSUONZDZKWIS-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• ULLLAUKRHNEPQZ-UHFFFAOYSA-N 4-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-thiazole-2-carboxamide Chemical compound S1C(C(=O)N)=NC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1 ULLLAUKRHNEPQZ-UHFFFAOYSA-N 0.000 description 1
• URMKMTNXWBIFGV-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-2-oxo-7-thiomorpholin-4-yl-1,3-dihydro-1,5-benzodiazepine-8-carbonitrile Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCSCC4)C=C3N=2)C#N)=C1 URMKMTNXWBIFGV-UHFFFAOYSA-N 0.000 description 1
• CQZNGBCEKUYLSD-UHFFFAOYSA-N 4-[3-(3-methyl-1,2-oxazol-5-yl)phenyl]-7-morpholin-4-yl-2-oxo-1,3-dihydro-1,5-benzodiazepine-8-carbonitrile Chemical compound O1N=C(C)C=C1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C#N)=C1 CQZNGBCEKUYLSD-UHFFFAOYSA-N 0.000 description 1
• ZAWKJIXKKSXYGW-UHFFFAOYSA-N 4-[3-[4-(methylaminomethyl)-1,3-oxazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CNCC1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 ZAWKJIXKKSXYGW-UHFFFAOYSA-N 0.000 description 1
• NZDQHLCPVSAWHD-UHFFFAOYSA-N 4-[3-[4-(morpholin-4-ylmethyl)-1,3-oxazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=C2NC(=O)CC(C=3C=C(C=CC=3)C=3OC=C(CN4CCOCC4)N=3)=NC2=CC=C1N1C=CC=C1 NZDQHLCPVSAWHD-UHFFFAOYSA-N 0.000 description 1
• USGINUHJUVAHDB-UHFFFAOYSA-N 4-[3-[4-[(dimethylamino)methyl]-1,3-thiazol-2-yl]phenyl]-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CN(C)CC1=CSC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 USGINUHJUVAHDB-UHFFFAOYSA-N 0.000 description 1
• ZARZKZKOXPVVDS-UHFFFAOYSA-N 4-[3-[5-(hydroxymethyl)triazol-1-yl]phenyl]-7-morpholin-4-yl-2-oxo-1,3-dihydro-1,5-benzodiazepine-8-carbonitrile Chemical compound OCC1=CN=NN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C#N)=C1 ZARZKZKOXPVVDS-UHFFFAOYSA-N 0.000 description 1
• ZXXMAZVBWSYFIZ-UHFFFAOYSA-N 4-[3-[5-(hydroxymethyl)triazol-1-yl]phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=CN=NN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 ZXXMAZVBWSYFIZ-UHFFFAOYSA-N 0.000 description 1
• NGSLOBQJDOYYKT-UHFFFAOYSA-N 4-[3-[5-[(dimethylamino)methyl]triazol-1-yl]phenyl]-7-morpholin-4-yl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CN(C)CC1=CN=NN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(N4CCOCC4)C=C3N=2)C(F)(F)F)=C1 NGSLOBQJDOYYKT-UHFFFAOYSA-N 0.000 description 1
• OXQWBRXAPDHAKJ-UHFFFAOYSA-N 4-[7-methoxy-2-oxo-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-4-yl]pyridine-2-carbonitrile Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OC)=CC=2N=C1C1=CC=NC(C#N)=C1 OXQWBRXAPDHAKJ-UHFFFAOYSA-N 0.000 description 1
• XAHREBHCCFVAHU-UHFFFAOYSA-N 4-amino-2-fluoro-5-nitrobenzonitrile Chemical compound NC1=CC(F)=C(C#N)C=C1[N+]([O-])=O XAHREBHCCFVAHU-UHFFFAOYSA-N 0.000 description 1
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
• CKYFLHSFEILNMK-UHFFFAOYSA-N 7-chloro-4-[3-[5-[(cyclopropylamino)methyl]-1,2,4-triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1N1N=CN=C1CNC1CC1 CKYFLHSFEILNMK-UHFFFAOYSA-N 0.000 description 1
• PKZVAKSSIZASBZ-UHFFFAOYSA-N 7-chloro-4-[3-[5-[(cyclopropylamino)methyl]triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1N1N=NC=C1CNC1CC1 PKZVAKSSIZASBZ-UHFFFAOYSA-N 0.000 description 1
• PCRZQVSQRACKNP-UHFFFAOYSA-N 7-fluoro-4-[3-[5-(hydroxymethyl)triazol-1-yl]phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound OCC1=CN=NN1C1=CC=CC(C=2CC(=O)NC3=CC(=C(F)C=C3N=2)C(F)(F)F)=C1 PCRZQVSQRACKNP-UHFFFAOYSA-N 0.000 description 1
• JKPOSJYDJHAYMP-UHFFFAOYSA-N 7-methyl-4-(3-pyrazol-1-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1N1C=CC=N1 JKPOSJYDJHAYMP-UHFFFAOYSA-N 0.000 description 1
• VQEKZQDRWAQGTF-UHFFFAOYSA-N 7-methyl-4-[3-(5-methyl-1,3-oxazol-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound O1C=NC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1C VQEKZQDRWAQGTF-UHFFFAOYSA-N 0.000 description 1
• JOYIPFAAAYEHOM-UHFFFAOYSA-N 7-methyl-4-[3-(triazol-1-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1N1C=CN=N1 JOYIPFAAAYEHOM-UHFFFAOYSA-N 0.000 description 1
• VXRZKYPJKBBKRA-UHFFFAOYSA-N 7-morpholin-4-yl-4-(3-pyrazol-1-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC(F)(F)C1=CC=2NC(=O)CC(C=3C=C(C=CC=3)N3N=CC=C3)=NC=2C=C1N1CCOCC1 VXRZKYPJKBBKRA-UHFFFAOYSA-N 0.000 description 1
• FWTMLOBJUZKEAY-UHFFFAOYSA-N 7-morpholin-4-yl-4-[3-(1,2,4-triazol-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC(F)(F)C1=CC=2NC(=O)CC(C=3C=C(C=CC=3)N3C=NN=C3)=NC=2C=C1N1CCOCC1 FWTMLOBJUZKEAY-UHFFFAOYSA-N 0.000 description 1
• 125000006847 BOC protecting group Chemical group 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 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
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
• 241000400611 Eucalyptus deanei Species 0.000 description 1
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 229930195714 L-glutamate Natural products 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• 229910010084 LiAlH4 Inorganic materials 0.000 description 1
• 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
• 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
• 102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 description 1
• 102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
• 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 1
• 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 1
• 102100038300 Metabotropic glutamate receptor 6 Human genes 0.000 description 1
• 102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 1
• 102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
• LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 101150003085 Pdcl gene Proteins 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 238000003428 Staudinger Azide reduction reaction Methods 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
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 1
• 108010006785 Taq Polymerase Proteins 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
• QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
• BDYVWDMHYNGVGE-UHFFFAOYSA-N [2-(aminomethyl)cyclohexyl]methanamine Chemical compound NCC1CCCCC1CN BDYVWDMHYNGVGE-UHFFFAOYSA-N 0.000 description 1
• OBDSITLACDGNMC-UHFFFAOYSA-N [Rh+] Chemical class [Rh+] OBDSITLACDGNMC-UHFFFAOYSA-N 0.000 description 1
• 150000008061 acetanilides Chemical class 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
• 125000000746 allylic group Chemical group 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000011609 ammonium molybdate Substances 0.000 description 1
• 235000018660 ammonium molybdate Nutrition 0.000 description 1
• APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
• 229940010552 ammonium molybdate Drugs 0.000 description 1
• 238000005915 ammonolysis reaction Methods 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• RLECCBFNWDXKPK-UHFFFAOYSA-N bis(trimethylsilyl)sulfide Chemical compound C[Si](C)(C)S[Si](C)(C)C RLECCBFNWDXKPK-UHFFFAOYSA-N 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 244000309464 bull Species 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
• 239000006227 byproduct Substances 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 235000011148 calcium chloride Nutrition 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000006482 condensation reaction Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000006352 cycloaddition reaction Methods 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
• 238000007405 data analysis Methods 0.000 description 1
• MATPZHBYOVDBLI-JJYYJPOSSA-N dcg-iv Chemical compound OC(=O)[C@@H](N)C1[C@@H](C(O)=O)[C@@H]1C(O)=O MATPZHBYOVDBLI-JJYYJPOSSA-N 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 238000004925 denaturation Methods 0.000 description 1
• 230000036425 denaturation Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000005828 desilylation reaction Methods 0.000 description 1
• 239000012973 diazabicyclooctane Substances 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• YMBMCMOZIGSBOA-UHFFFAOYSA-N ethyl 2-amino-2-sulfanylideneacetate Chemical compound CCOC(=O)C(N)=S YMBMCMOZIGSBOA-UHFFFAOYSA-N 0.000 description 1
• FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 1
• RDYVOLQRIFEJAZ-UHFFFAOYSA-N ethyl 3-(3-methyl-1,2-oxazol-5-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2ON=C(C)C=2)=C1 RDYVOLQRIFEJAZ-UHFFFAOYSA-N 0.000 description 1
• PGNHYEASYXBVHG-UHFFFAOYSA-N ethyl 3-oxo-3-[3-(1,2,4-triazol-4-yl)phenyl]propanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC(N2C=NN=C2)=C1 PGNHYEASYXBVHG-UHFFFAOYSA-N 0.000 description 1
• KEHJWELPDWMNRB-UHFFFAOYSA-N ethyl 4-(3-bromophenyl)-2,4-dioxobutanoate Chemical compound CCOC(=O)C(=O)CC(=O)C1=CC=CC(Br)=C1 KEHJWELPDWMNRB-UHFFFAOYSA-N 0.000 description 1
• GIRPBJCYTYQKNA-UHFFFAOYSA-N ethyl 4-(3-carbonochloridoylphenyl)-1,3-thiazole-2-carboxylate Chemical compound S1C(C(=O)OCC)=NC(C=2C=C(C=CC=2)C(Cl)=O)=C1 GIRPBJCYTYQKNA-UHFFFAOYSA-N 0.000 description 1
• HUFAYDVERGDYNL-UHFFFAOYSA-N ethyl 4-[3-(2,2-dimethyl-6-oxo-1,3-dioxin-4-yl)phenyl]-1,3-thiazole-2-carboxylate Chemical compound S1C(C(=O)OCC)=NC(C=2C=C(C=CC=2)C=2OC(C)(C)OC(=O)C=2)=C1 HUFAYDVERGDYNL-UHFFFAOYSA-N 0.000 description 1
• MZFCGLBMWQOIMK-UHFFFAOYSA-N ethyl 5-(3-carbonochloridoylphenyl)-1,3-oxazole-4-carboxylate Chemical compound N1=COC(C=2C=C(C=CC=2)C(Cl)=O)=C1C(=O)OCC MZFCGLBMWQOIMK-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• MGJURKDLIJVDEO-UHFFFAOYSA-N formaldehyde;hydrate Chemical compound O.O=C MGJURKDLIJVDEO-UHFFFAOYSA-N 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 150000002240 furans Chemical class 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229960004903 invert sugar Drugs 0.000 description 1
• 238000006317 isomerization reaction Methods 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 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
• 150000002690 malonic acid derivatives Chemical class 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
• 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
• 108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 1
• 108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
• 108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
• 108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• NDBQJIBNNUJNHA-DFWYDOINSA-N methyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CO NDBQJIBNNUJNHA-DFWYDOINSA-N 0.000 description 1
• LJBDQARGRBNGLE-UHFFFAOYSA-N methyl 1-[4-(3-cyanophenyl)-2-oxo-1,3-dihydro-1,5-benzodiazepin-8-yl]pyrrole-2-carboxylate Chemical compound COC(=O)C1=CC=CN1C1=CC=C(N=C(CC(=O)N2)C=3C=C(C=CC=3)C#N)C2=C1 LJBDQARGRBNGLE-UHFFFAOYSA-N 0.000 description 1
• SRLROYBBFDQUJL-UHFFFAOYSA-N methyl 2-(3-carbonochloridoylphenyl)-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(C=2C=C(C=CC=2)C(Cl)=O)=N1 SRLROYBBFDQUJL-UHFFFAOYSA-N 0.000 description 1
• OIQHKKSYHZIDLX-UHFFFAOYSA-N methyl 2-(3-methyl-1,2-oxazol-5-yl)pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C=2ON=C(C)C=2)=C1 OIQHKKSYHZIDLX-UHFFFAOYSA-N 0.000 description 1
• KYIORMVOQPQUEK-UHFFFAOYSA-N methyl 2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-nitrophenyl]acetate Chemical compound COC(=O)CC1=CC=C([N+]([O-])=O)C(NC(=O)OC(C)(C)C)=C1 KYIORMVOQPQUEK-UHFFFAOYSA-N 0.000 description 1
• XXOKMYMXDALOEN-UHFFFAOYSA-N methyl 2-iodopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(I)=C1 XXOKMYMXDALOEN-UHFFFAOYSA-N 0.000 description 1
• PKFNYIJQJRDTKG-UHFFFAOYSA-N methyl 3-(1,3-oxazol-2-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC=CN=2)=C1 PKFNYIJQJRDTKG-UHFFFAOYSA-N 0.000 description 1
• JKNYFEXHKRIDTA-UHFFFAOYSA-N methyl 3-(2,2-dimethoxyethylcarbamoyl)benzoate Chemical compound COC(OC)CNC(=O)C1=CC=CC(C(=O)OC)=C1 JKNYFEXHKRIDTA-UHFFFAOYSA-N 0.000 description 1
• LEIJXXQQGMEHKW-UHFFFAOYSA-N methyl 3-(2-methylpyrazol-3-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2N(N=CC=2)C)=C1 LEIJXXQQGMEHKW-UHFFFAOYSA-N 0.000 description 1
• IYFCPKFXJHLORW-UHFFFAOYSA-N methyl 3-(2-oxoethylcarbamoyl)benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)NCC=O)=C1 IYFCPKFXJHLORW-UHFFFAOYSA-N 0.000 description 1
• KZGRSYGDDBGHOO-POHAHGRESA-N methyl 3-[(z)-hydroxyiminomethyl]benzoate Chemical compound COC(=O)C1=CC=CC(\C=N/O)=C1 KZGRSYGDDBGHOO-POHAHGRESA-N 0.000 description 1
• FXIPLAQQNNBNPC-UHFFFAOYSA-N methyl 3-[3-(methoxymethyl)-1,2-oxazol-5-yl]benzoate Chemical compound O1N=C(COC)C=C1C1=CC=CC(C(=O)OC)=C1 FXIPLAQQNNBNPC-UHFFFAOYSA-N 0.000 description 1
• OUEQQZHRRCUGRX-UHFFFAOYSA-N methyl 3-[3-(oxan-2-yloxymethyl)-1,2-oxazol-5-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2ON=C(COC3OCCCC3)C=2)=C1 OUEQQZHRRCUGRX-UHFFFAOYSA-N 0.000 description 1
• BDTPDPQMEHZDSZ-UHFFFAOYSA-N methyl 3-[5-(oxan-2-yloxymethyl)-1,2,4-triazol-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(=NC=N2)COC2OCCCC2)=C1 BDTPDPQMEHZDSZ-UHFFFAOYSA-N 0.000 description 1
• YKRNIIORQBLEDF-UHFFFAOYSA-N methyl 3-[5-(oxan-2-yloxymethyl)-1,2-oxazol-3-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=NOC(COC3OCCCC3)=C2)=C1 YKRNIIORQBLEDF-UHFFFAOYSA-N 0.000 description 1
• MLCIBDZPKBPFBY-UHFFFAOYSA-N methyl 3-[5-(oxan-2-yloxymethyl)triazol-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(=CN=N2)COC2OCCCC2)=C1 MLCIBDZPKBPFBY-UHFFFAOYSA-N 0.000 description 1
• DGMIWLZFGRRVIS-UHFFFAOYSA-N methyl 3-[5-[(dimethylamino)methyl]triazol-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(=CN=N2)CN(C)C)=C1 DGMIWLZFGRRVIS-UHFFFAOYSA-N 0.000 description 1
• MBBRSLODSVCTGY-UHFFFAOYSA-N methyl 3-carbamothioylbenzoate Chemical compound COC(=O)C1=CC=CC(C(N)=S)=C1 MBBRSLODSVCTGY-UHFFFAOYSA-N 0.000 description 1
• CWINGXPWIXWOBS-UHFFFAOYSA-N methyl 3-imidazol-1-ylbenzoate Chemical compound COC(=O)C1=CC=CC(N2C=NC=C2)=C1 CWINGXPWIXWOBS-UHFFFAOYSA-N 0.000 description 1
• GAKCQFDXNPITFA-UHFFFAOYSA-N methyl 3-propanoylbenzoate Chemical compound CCC(=O)C1=CC=CC(C(=O)OC)=C1 GAKCQFDXNPITFA-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
• DBAHBVORPROTOK-UHFFFAOYSA-N n,n-bis(2-hydroxyethyl)-2-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazole-4-carboxamide Chemical compound OCCN(CCO)C(=O)C1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 DBAHBVORPROTOK-UHFFFAOYSA-N 0.000 description 1
• VOZCMYDPBKVIJA-UHFFFAOYSA-N n-(2-hydroxyethyl)-2-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazole-4-carboxamide Chemical compound OCCNC(=O)C1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=N1 VOZCMYDPBKVIJA-UHFFFAOYSA-N 0.000 description 1
• RRZZNNGRCRICDV-UHFFFAOYSA-N n-(2-hydroxyethyl)-5-[3-(2-oxo-8-pyrrol-1-yl-1,3-dihydro-1,5-benzodiazepin-4-yl)phenyl]-1,3-oxazole-4-carboxamide Chemical compound N1=COC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)N2C=CC=C2)=C1C(=O)NCCO RRZZNNGRCRICDV-UHFFFAOYSA-N 0.000 description 1
• MVCQUSKTBSVSRY-UHFFFAOYSA-N n-(2-methoxyethylidene)hydroxylamine Chemical compound COCC=NO MVCQUSKTBSVSRY-UHFFFAOYSA-N 0.000 description 1
• AMOIXNOVGONYIG-UHFFFAOYSA-N n-(2-nitro-5-pyrrol-1-ylphenyl)acetamide Chemical compound C1=C([N+]([O-])=O)C(NC(=O)C)=CC(N2C=CC=C2)=C1 AMOIXNOVGONYIG-UHFFFAOYSA-N 0.000 description 1
• WSWVCZCMLQWMAB-UHFFFAOYSA-N n-[5-[3-(2-chlorophenyl)-4-cyanopyrrol-1-yl]-2-nitrophenyl]-3-(3-cyanophenyl)-2-oxopropanamide Chemical compound [O-][N+](=O)C1=CC=C(N2C=C(C(C#N)=C2)C=2C(=CC=CC=2)Cl)C=C1NC(=O)C(=O)CC1=CC=CC(C#N)=C1 WSWVCZCMLQWMAB-UHFFFAOYSA-N 0.000 description 1
• NPOLCELBYKFCMB-UHFFFAOYSA-N n-fluoro-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NF NPOLCELBYKFCMB-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• ZEJPMRKECMRICL-UHFFFAOYSA-N o-ethyl 2-amino-2-oxoethanethioate Chemical compound CCOC(=S)C(N)=O ZEJPMRKECMRICL-UHFFFAOYSA-N 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
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 150000003014 phosphoric acid esters Chemical class 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• WVUCPRGADMCTBN-UHFFFAOYSA-M potassium;3-ethoxy-3-oxopropanoate Chemical compound [K+].CCOC(=O)CC([O-])=O WVUCPRGADMCTBN-UHFFFAOYSA-M 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• OCAAZRFBJBEVPS-UHFFFAOYSA-N prop-2-enyl carbamate Chemical compound NC(=O)OCC=C OCAAZRFBJBEVPS-UHFFFAOYSA-N 0.000 description 1
• 229940080818 propionamide Drugs 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 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
• 239000002516 radical scavenger Substances 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000010839 reverse transcription Methods 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229930000044 secondary metabolite Natural products 0.000 description 1
• 210000002265 sensory receptor cell Anatomy 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000007940 sugar coated tablet Substances 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• QKUXMIVMLPOOQJ-UHFFFAOYSA-N tert-butyl 3-[2-(3-methyl-1,2-oxazol-5-yl)pyridin-4-yl]-3-oxopropanoate Chemical compound O1N=C(C)C=C1C1=CC(C(=O)CC(=O)OC(C)(C)C)=CC=N1 QKUXMIVMLPOOQJ-UHFFFAOYSA-N 0.000 description 1
• IEIAOGRUQMUPSY-UHFFFAOYSA-N tert-butyl 3-[3-[3-(methoxymethyl)-1,2-oxazol-5-yl]phenyl]-3-oxopropanoate Chemical compound O1N=C(COC)C=C1C1=CC=CC(C(=O)CC(=O)OC(C)(C)C)=C1 IEIAOGRUQMUPSY-UHFFFAOYSA-N 0.000 description 1
• WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
• GCTLUKBVSGNCCY-UHFFFAOYSA-N tert-butyl n-[2-[[3-(3-imidazol-1-ylphenyl)-3-oxopropanoyl]amino]-5-methyl-4-(trifluoromethyl)phenyl]carbamate Chemical compound C1=C(C(F)(F)F)C(C)=CC(NC(=O)OC(C)(C)C)=C1NC(=O)CC(=O)C1=CC=CC(N2C=NC=C2)=C1 GCTLUKBVSGNCCY-UHFFFAOYSA-N 0.000 description 1
• CRAJFVNFDNRPAS-UHFFFAOYSA-N tert-butyl-dimethyl-[3-(oxan-2-yloxy)prop-1-ynyl]silane Chemical compound CC(C)(C)[Si](C)(C)C#CCOC1CCCCO1 CRAJFVNFDNRPAS-UHFFFAOYSA-N 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 238000010257 thawing Methods 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
• 238000007039 two-step reaction Methods 0.000 description 1
• 239000013598 vector Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000011995 wilkinson's catalyst Substances 0.000 description 1
• UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1