CA2662449A1 - Compounds and methods for 18f labeled agents - Google Patents

Info

Publication number

CA2662449A1

CA2662449A1 CA002662449A CA2662449A CA2662449A1 CA 2662449 A1 CA2662449 A1 CA 2662449A1 CA 002662449 A CA002662449 A CA 002662449A CA 2662449 A CA2662449 A CA 2662449A CA 2662449 A1 CA2662449 A1 CA 2662449A1

Authority

CA

Canada

Prior art keywords

ala

val

trp

cndot

gln

Prior art date

2006-09-08

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 274
• 238000000034 method Methods 0.000 title claims abstract description 75
• 238000002059 diagnostic imaging Methods 0.000 claims abstract description 13
• 229910052757 nitrogen Inorganic materials 0.000 claims description 191
• 229910052731 fluorine Inorganic materials 0.000 claims description 177
• 229910052739 hydrogen Inorganic materials 0.000 claims description 169
• 239000000203 mixture Substances 0.000 claims description 141
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 131
• 239000000126 substance Substances 0.000 claims description 123
• -1 -O-(C1-C4 alkyl) Chemical group 0.000 claims description 100
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 66
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 59
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 59
• 239000003795 chemical substances by application Substances 0.000 claims description 52
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 50
• 239000011737 fluorine Substances 0.000 claims description 50
• 230000008685 targeting Effects 0.000 claims description 44
• 150000001413 amino acids Chemical group 0.000 claims description 41
• 235000001014 amino acid Nutrition 0.000 claims description 39
• 125000000217 alkyl group Chemical group 0.000 claims description 36
• 238000003384 imaging method Methods 0.000 claims description 34
• 229940002612 prodrug Drugs 0.000 claims description 34
• 239000000651 prodrug Substances 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 33
• 150000007524 organic acids Chemical class 0.000 claims description 32
• 150000002148 esters Chemical class 0.000 claims description 31
• 150000001408 amides Chemical class 0.000 claims description 30
• 150000007522 mineralic acids Chemical class 0.000 claims description 30
• 230000008878 coupling Effects 0.000 claims description 29
• 238000010168 coupling process Methods 0.000 claims description 29
• 238000005859 coupling reaction Methods 0.000 claims description 29
• 125000001153 fluoro group Chemical group F* 0.000 claims description 28
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 239000012453 solvate Substances 0.000 claims description 26
• 125000000539 amino acid group Chemical group 0.000 claims description 22
• 108091034117 Oligonucleotide Proteins 0.000 claims description 21
• 239000012216 imaging agent Substances 0.000 claims description 20
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 238000002600 positron emission tomography Methods 0.000 claims description 18
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
• 150000003384 small molecules Chemical class 0.000 claims description 16
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
• 238000004519 manufacturing process Methods 0.000 claims description 15
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
• 108010051479 Bombesin Proteins 0.000 claims description 14
• 102000013585 Bombesin Human genes 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 12
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
• 239000001257 hydrogen Substances 0.000 claims description 12
• 125000006850 spacer group Chemical group 0.000 claims description 12
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 11
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 10
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 10
• 101710151321 Melanostatin Proteins 0.000 claims description 9
• 102400000064 Neuropeptide Y Human genes 0.000 claims description 9
• 201000010099 disease Diseases 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 9
• URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 claims description 9
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
• 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 claims description 8
• 102400000015 Vasoactive intestinal peptide Human genes 0.000 claims description 8
• 239000002671 adjuvant Substances 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 claims description 8
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 239000000816 peptidomimetic Substances 0.000 claims description 7
• 101800001982 Cholecystokinin Proteins 0.000 claims description 6
• 102100025841 Cholecystokinin Human genes 0.000 claims description 6
• 102000004862 Gastrin releasing peptide Human genes 0.000 claims description 6
• 108090001053 Gastrin releasing peptide Proteins 0.000 claims description 6
• 102000005157 Somatostatin Human genes 0.000 claims description 6
• 108010056088 Somatostatin Proteins 0.000 claims description 6
• 229940107137 cholecystokinin Drugs 0.000 claims description 6
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
• IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 claims description 6
• 229960000553 somatostatin Drugs 0.000 claims description 6
• 229910019142 PO4 Inorganic materials 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 210000004027 cell Anatomy 0.000 claims description 5
• PUBCCFNQJQKCNC-XKNFJVFFSA-N gastrin-releasingpeptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C1=CNC=N1 PUBCCFNQJQKCNC-XKNFJVFFSA-N 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims description 4
• 108050001286 Somatostatin Receptor Proteins 0.000 claims description 4
• 102000011096 Somatostatin receptor Human genes 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 239000005557 antagonist Substances 0.000 claims description 4
• XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 claims description 4
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
• 102000004877 Insulin Human genes 0.000 claims description 3
• 108090001061 Insulin Proteins 0.000 claims description 3
• 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 3
• 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 3
• 230000003213 activating effect Effects 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 125000004104 aryloxy group Chemical group 0.000 claims description 3
• 239000003112 inhibitor Substances 0.000 claims description 3
• 229940125396 insulin Drugs 0.000 claims description 3
• KIWSYRHAAPLJFJ-DNZSEPECSA-N n-[(e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enyl]pyridine-3-carboxamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/CNC(=O)C1=CC=CN=C1 KIWSYRHAAPLJFJ-DNZSEPECSA-N 0.000 claims description 3
• 239000010452 phosphate Substances 0.000 claims description 3
• DFVFTMTWCUHJBL-BQBZGAKWSA-N statine Chemical class CC(C)C[C@H](N)[C@@H](O)CC(O)=O DFVFTMTWCUHJBL-BQBZGAKWSA-N 0.000 claims description 3
• 108010064733 Angiotensins Proteins 0.000 claims description 2
• 102000015427 Angiotensins Human genes 0.000 claims description 2
• IJYZHIOOBGIINM-WDSKDSINSA-N Arg-Ser Chemical group OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N IJYZHIOOBGIINM-WDSKDSINSA-N 0.000 claims description 2
• XNSKSTRGQIPTSE-ACZMJKKPSA-N Arg-Thr Chemical compound C[C@@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O XNSKSTRGQIPTSE-ACZMJKKPSA-N 0.000 claims description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
• 102000019034 Chemokines Human genes 0.000 claims description 2
• 108010012236 Chemokines Proteins 0.000 claims description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
• 102000004859 Cholecystokinin Receptors Human genes 0.000 claims description 2
• 108090001085 Cholecystokinin Receptors Proteins 0.000 claims description 2
• 102000009024 Epidermal Growth Factor Human genes 0.000 claims description 2
• 102400001368 Epidermal growth factor Human genes 0.000 claims description 2
• 101800003838 Epidermal growth factor Proteins 0.000 claims description 2
• 102400000921 Gastrin Human genes 0.000 claims description 2
• 108010052343 Gastrins Proteins 0.000 claims description 2
• 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 claims description 2
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 2
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 2
• 102000014150 Interferons Human genes 0.000 claims description 2
• 108010050904 Interferons Proteins 0.000 claims description 2
• 108010002352 Interleukin-1 Proteins 0.000 claims description 2
• 108010002350 Interleukin-2 Proteins 0.000 claims description 2
• 108090000978 Interleukin-4 Proteins 0.000 claims description 2
• 108090001005 Interleukin-6 Proteins 0.000 claims description 2
• 108010063738 Interleukins Proteins 0.000 claims description 2
• 102000015696 Interleukins Human genes 0.000 claims description 2
• XNSAINXGIQZQOO-UHFFFAOYSA-N L-pyroglutamyl-L-histidyl-L-proline amide Natural products NC(=O)C1CCCN1C(=O)C(NC(=O)C1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-UHFFFAOYSA-N 0.000 claims description 2
• 102400001103 Neurotensin Human genes 0.000 claims description 2
• 101800001814 Neurotensin Proteins 0.000 claims description 2
• 238000012879 PET imaging Methods 0.000 claims description 2
• 102100024028 Progonadoliberin-1 Human genes 0.000 claims description 2
• 108010057464 Prolactin Proteins 0.000 claims description 2
• 102000003946 Prolactin Human genes 0.000 claims description 2
• XZKQVQKUZMAADP-IMJSIDKUSA-N Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(O)=O XZKQVQKUZMAADP-IMJSIDKUSA-N 0.000 claims description 2
• LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 claims description 2
• 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 claims description 2
• 239000000627 Thyrotropin-Releasing Hormone Substances 0.000 claims description 2
• 102400000336 Thyrotropin-releasing hormone Human genes 0.000 claims description 2
• 101800004623 Thyrotropin-releasing hormone Proteins 0.000 claims description 2
• 108010009583 Transforming Growth Factors Proteins 0.000 claims description 2
• 102000009618 Transforming Growth Factors Human genes 0.000 claims description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
• 102000030621 adenylate cyclase Human genes 0.000 claims description 2
• 108060000200 adenylate cyclase Proteins 0.000 claims description 2
• 239000000556 agonist Substances 0.000 claims description 2
• 150000001450 anions Chemical class 0.000 claims description 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
• AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 claims description 2
• 229940116977 epidermal growth factor Drugs 0.000 claims description 2
• XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 claims description 2
• 239000003102 growth factor Substances 0.000 claims description 2
• 102000006495 integrins Human genes 0.000 claims description 2
• 108010044426 integrins Proteins 0.000 claims description 2
• 229940047124 interferons Drugs 0.000 claims description 2
• 229940047122 interleukins Drugs 0.000 claims description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 2
• PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 claims description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
• 230000001817 pituitary effect Effects 0.000 claims description 2
• 229940097325 prolactin Drugs 0.000 claims description 2
• XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 claims description 2
• 125000003107 substituted aryl group Chemical group 0.000 claims description 2
• 239000000758 substrate Substances 0.000 claims description 2
• 229940034199 thyrotropin-releasing hormone Drugs 0.000 claims description 2
• 102000003390 tumor necrosis factor Human genes 0.000 claims description 2
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims description 2
• XZWXFWBHYRFLEF-FSPLSTOPSA-N Ala-His Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 XZWXFWBHYRFLEF-FSPLSTOPSA-N 0.000 claims 12
• 108010070944 alanylhistidine Proteins 0.000 claims 12
• DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 claims 3
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
• VWKIJBOCUCLBCH-IPMKNSEASA-N 3-cyano-4-fluoro-n-[2-[2-[3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]ethylsulfanyl]ethyl]benzamide Chemical compound O=C1N(CCSCCNC(=O)C=2C=C(C(F)=CC=2)C#N)C(=O)C(C)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 VWKIJBOCUCLBCH-IPMKNSEASA-N 0.000 claims 1
• XVHPAHJCCOUCLL-AXOPYWAMSA-N 3-cyano-4-fluoro-n-[2-[2-[3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]ethylsulfinyl]ethyl]benzamide Chemical compound O=C1N(CCS(=O)CCNC(=O)C=2C=C(C(F)=CC=2)C#N)C(=O)C(C)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 XVHPAHJCCOUCLL-AXOPYWAMSA-N 0.000 claims 1
• YIHREDIYKVRSKZ-LZLYRXPVSA-N 3-cyano-4-fluoro-n-[3-[[3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]amino]-3-oxopropyl]benzamide Chemical compound O=C1N(NC(=O)CCNC(=O)C=2C=C(C(F)=CC=2)C#N)C(=O)C(C)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 YIHREDIYKVRSKZ-LZLYRXPVSA-N 0.000 claims 1
• DYGMRLQZDJYQTE-NLWGTHIKSA-N 3-cyano-4-fluoro-n-[5-[[3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]amino]-5-oxopentyl]benzamide Chemical compound O=C1N(NC(=O)CCCCNC(=O)C=2C=C(C(F)=CC=2)C#N)C(=O)C(C)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 DYGMRLQZDJYQTE-NLWGTHIKSA-N 0.000 claims 1
• HUPNSELYLQRXHY-XUVXKRRUSA-N 3-cyano-4-fluoro-n-[6-[3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,6-dioxo-5-(trifluoromethyl)pyrimidin-1-yl]hexyl]benzamide Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N(CCCCCCNC(=O)C=2C=C(C(F)=CC=2)C#N)C(=O)C(C(F)(F)F)=C1 HUPNSELYLQRXHY-XUVXKRRUSA-N 0.000 claims 1
• 102000003797 Neuropeptides Human genes 0.000 claims 1
• 108090000189 Neuropeptides Proteins 0.000 claims 1
• 229910004679 ONO2 Inorganic materials 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 489
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 285
• 229910001868 water Inorganic materials 0.000 description 263
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 255
• 239000000243 solution Substances 0.000 description 215
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 180
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 170
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 144
• 239000002904 solvent Substances 0.000 description 141
• 239000007787 solid Substances 0.000 description 137
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 118
• 239000011541 reaction mixture Substances 0.000 description 113
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 102
• 229960004132 diethyl ether Drugs 0.000 description 95
• 239000011347 resin Substances 0.000 description 79
• 229920005989 resin Polymers 0.000 description 79
• 238000004458 analytical method Methods 0.000 description 78
• 230000015572 biosynthetic process Effects 0.000 description 76
• 239000000047 product Substances 0.000 description 75
• 238000003786 synthesis reaction Methods 0.000 description 74
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 62
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 59
• 238000004128 high performance liquid chromatography Methods 0.000 description 56
• 239000012071 phase Substances 0.000 description 52
• 229910000027 potassium carbonate Inorganic materials 0.000 description 51
• KRHYYFGTRYWZRS-BJUDXGSMSA-N ac1l2y5h Chemical compound [18FH] KRHYYFGTRYWZRS-BJUDXGSMSA-N 0.000 description 49
• 238000004440 column chromatography Methods 0.000 description 47
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 44
• 238000010438 heat treatment Methods 0.000 description 44
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 42
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 42
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 40
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 40
• 229940024606 amino acid Drugs 0.000 description 39
• 238000002372 labelling Methods 0.000 description 39
• 206010028980 Neoplasm Diseases 0.000 description 37
• 238000000746 purification Methods 0.000 description 36
• QXZBMSIDSOZZHK-DOPDSADYSA-N 31362-50-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CNC=N1 QXZBMSIDSOZZHK-DOPDSADYSA-N 0.000 description 35
• 230000002285 radioactive effect Effects 0.000 description 32
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 31
• 235000017557 sodium bicarbonate Nutrition 0.000 description 31
• 229910052938 sodium sulfate Inorganic materials 0.000 description 30
• 235000011152 sodium sulphate Nutrition 0.000 description 30
• OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 28
• AUFVJZSDSXXFOI-UHFFFAOYSA-N 2.2.2-cryptand Chemical group C1COCCOCCN2CCOCCOCCN1CCOCCOCC2 AUFVJZSDSXXFOI-UHFFFAOYSA-N 0.000 description 27
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 26
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 25
• 238000002347 injection Methods 0.000 description 25
• 239000007924 injection Substances 0.000 description 25
• 102000005962 receptors Human genes 0.000 description 24
• 108020003175 receptors Proteins 0.000 description 24
• 239000002244 precipitate Substances 0.000 description 23
• 238000006243 chemical reaction Methods 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
• 238000003682 fluorination reaction Methods 0.000 description 21
• 235000005985 organic acids Nutrition 0.000 description 21
• 238000005119 centrifugation Methods 0.000 description 20
• 239000006184 cosolvent Substances 0.000 description 20
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 20
• 238000011068 loading method Methods 0.000 description 20
• 239000006228 supernatant Substances 0.000 description 20
• ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 20
• 239000012043 crude product Substances 0.000 description 19
• 125000004093 cyano group Chemical group *C#N 0.000 description 19
• 239000012153 distilled water Substances 0.000 description 18
• 238000000163 radioactive labelling Methods 0.000 description 18
• 150000004677 hydrates Chemical class 0.000 description 17
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
• 238000002360 preparation method Methods 0.000 description 15
• 239000012217 radiopharmaceutical Substances 0.000 description 14
• 229940121896 radiopharmaceutical Drugs 0.000 description 14
• 230000002799 radiopharmaceutical effect Effects 0.000 description 14
• 239000002253 acid Substances 0.000 description 13
• 239000002243 precursor Substances 0.000 description 13
• 125000001424 substituent group Chemical group 0.000 description 13
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
• 229910052799 carbon Inorganic materials 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 239000002773 nucleotide Substances 0.000 description 12
• 125000003729 nucleotide group Chemical group 0.000 description 12
• 229930182852 proteinogenic amino acid Natural products 0.000 description 11
• 108091023037 Aptamer Proteins 0.000 description 10
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 10
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 10
• 230000000694 effects Effects 0.000 description 9
• 238000001727 in vivo Methods 0.000 description 9
• 239000003446 ligand Substances 0.000 description 9
• 238000010647 peptide synthesis reaction Methods 0.000 description 9
• 239000007790 solid phase Substances 0.000 description 9
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 8
• 150000007513 acids Chemical class 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 239000000700 radioactive tracer Substances 0.000 description 8
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 7
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
• 206010027476 Metastases Diseases 0.000 description 7
• 230000009401 metastasis Effects 0.000 description 7
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
• 101001071515 Homo sapiens Gastrin-releasing peptide Proteins 0.000 description 6
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 6
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
• 125000003275 alpha amino acid group Chemical group 0.000 description 6
• 125000003277 amino group Chemical group 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 238000011161 development Methods 0.000 description 6
• 230000018109 developmental process Effects 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• 125000005647 linker group Chemical group 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
• MOFRJTLODZILCR-UHFFFAOYSA-N 2-fluoro-5-formylbenzonitrile Chemical compound FC1=CC=C(C=O)C=C1C#N MOFRJTLODZILCR-UHFFFAOYSA-N 0.000 description 5
• 206010006187 Breast cancer Diseases 0.000 description 5
• 208000026310 Breast neoplasm Diseases 0.000 description 5
• 101100455752 Caenorhabditis elegans lys-3 gene Proteins 0.000 description 5
• 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 description 5
• 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 description 5
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 5
• 102100030671 Gastrin-releasing peptide receptor Human genes 0.000 description 5
• 101001010479 Homo sapiens Gastrin-releasing peptide receptor Proteins 0.000 description 5
• 101000841490 Homo sapiens Unique cartilage matrix-associated protein Proteins 0.000 description 5
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
• 239000012346 acetyl chloride Substances 0.000 description 5
• 238000013459 approach Methods 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 230000000975 bioactive effect Effects 0.000 description 5
• 150000005829 chemical entities Chemical class 0.000 description 5
• 239000000032 diagnostic agent Substances 0.000 description 5
• 229940039227 diagnostic agent Drugs 0.000 description 5
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 5
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 5
• 102000056782 human Ucma Human genes 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
• 239000011698 potassium fluoride Substances 0.000 description 5
• 235000003270 potassium fluoride Nutrition 0.000 description 5
• 208000023958 prostate neoplasm Diseases 0.000 description 5
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 5
• HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 4
• JYSLFQTWNRYWJT-UHFFFAOYSA-N 8-(3,5-dichlorophenyl)sulfanyl-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC(Cl)=CC(Cl)=C1 JYSLFQTWNRYWJT-UHFFFAOYSA-N 0.000 description 4
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• 239000012131 assay buffer Substances 0.000 description 4
• IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 4
• 239000011324 bead Substances 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 4
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 238000001035 drying Methods 0.000 description 4
• 229940093499 ethyl acetate Drugs 0.000 description 4
• 235000019439 ethyl acetate Nutrition 0.000 description 4
• PYLWMHQQBFSUBP-JZRMKITLSA-N fluoranylbenzene Chemical class [18F]C1=CC=CC=C1 PYLWMHQQBFSUBP-JZRMKITLSA-N 0.000 description 4
• KRHYYFGTRYWZRS-BJUDXGSMSA-M fluorine-18(1-) Chemical compound [18F-] KRHYYFGTRYWZRS-BJUDXGSMSA-M 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• LREHGRMLSDSXFN-UHFFFAOYSA-N methyl 4-(dimethylamino)-2-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C=C1C(F)(F)F LREHGRMLSDSXFN-UHFFFAOYSA-N 0.000 description 4
• QJNVVJGYRQJUSQ-UHFFFAOYSA-N methyl 4-(dimethylamino)-3-fluorobenzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C(F)=C1 QJNVVJGYRQJUSQ-UHFFFAOYSA-N 0.000 description 4
• UHUDTAQUGQEPRL-UHFFFAOYSA-N methyl 4-(dimethylamino)-3-nitrobenzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C([N+]([O-])=O)=C1 UHUDTAQUGQEPRL-UHFFFAOYSA-N 0.000 description 4
• 230000020477 pH reduction Effects 0.000 description 4
• 235000021317 phosphate Nutrition 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 235000018102 proteins Nutrition 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• 210000002966 serum Anatomy 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 210000001685 thyroid gland Anatomy 0.000 description 4
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
• UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 3
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• 239000004952 Polyamide Substances 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 230000033115 angiogenesis Effects 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 238000004166 bioassay Methods 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 238000009835 boiling Methods 0.000 description 3
• 230000015556 catabolic process Effects 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 3
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 3
• 235000019797 dipotassium phosphate Nutrition 0.000 description 3
• 150000002367 halogens Chemical class 0.000 description 3
• 150000002431 hydrogen Chemical class 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000011503 in vivo imaging Methods 0.000 description 3
• 208000027866 inflammatory disease Diseases 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• QBBPCOSJWMCMPG-UHFFFAOYSA-N methyl 2-bromo-4-(dimethylamino)benzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C=C1Br QBBPCOSJWMCMPG-UHFFFAOYSA-N 0.000 description 3
• DLSMZBNKKTUSHI-UHFFFAOYSA-N methyl 2-bromo-5-(dimethylamino)benzoate Chemical compound COC(=O)C1=CC(N(C)C)=CC=C1Br DLSMZBNKKTUSHI-UHFFFAOYSA-N 0.000 description 3
• SVDLDBZMTKFPTM-UHFFFAOYSA-N methyl 2-chloro-4-(dimethylamino)-5-methylsulfonylbenzoate Chemical compound COC(=O)C1=CC(S(C)(=O)=O)=C(N(C)C)C=C1Cl SVDLDBZMTKFPTM-UHFFFAOYSA-N 0.000 description 3
• DUBJZBQCZFLZQH-UHFFFAOYSA-N methyl 2-chloro-4-(dimethylamino)benzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C=C1Cl DUBJZBQCZFLZQH-UHFFFAOYSA-N 0.000 description 3
• PQXJXWHRTKTFAJ-UHFFFAOYSA-N methyl 2-chloro-5-(dimethylamino)benzoate Chemical compound COC(=O)C1=CC(N(C)C)=CC=C1Cl PQXJXWHRTKTFAJ-UHFFFAOYSA-N 0.000 description 3
• HZIZJQYULLDSRV-UHFFFAOYSA-N methyl 2-cyano-4-(dimethylamino)benzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C=C1C#N HZIZJQYULLDSRV-UHFFFAOYSA-N 0.000 description 3
• DLHBZNDZKLXVOG-UHFFFAOYSA-N methyl 4-(dimethylamino)-2,3-difluorobenzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C(F)=C1F DLHBZNDZKLXVOG-UHFFFAOYSA-N 0.000 description 3
• ZELUMYFXHSKXPB-UHFFFAOYSA-N methyl 4-(dimethylamino)-2,6-difluorobenzoate Chemical compound COC(=O)C1=C(F)C=C(N(C)C)C=C1F ZELUMYFXHSKXPB-UHFFFAOYSA-N 0.000 description 3
• TXVOCFPZXUJZQH-UHFFFAOYSA-N methyl 4-(dimethylamino)-2-fluorobenzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C=C1F TXVOCFPZXUJZQH-UHFFFAOYSA-N 0.000 description 3
• SGFSPEHQIATLLK-UHFFFAOYSA-N methyl 4-(dimethylamino)-2-nitrobenzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C=C1[N+]([O-])=O SGFSPEHQIATLLK-UHFFFAOYSA-N 0.000 description 3
• OHWHNDWJHMPFDR-UHFFFAOYSA-N methyl 4-(dimethylamino)-3-(trifluoromethoxy)benzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C(OC(F)(F)F)=C1 OHWHNDWJHMPFDR-UHFFFAOYSA-N 0.000 description 3
• DCARBLUAUUNSJS-UHFFFAOYSA-N methyl 4-(dimethylamino)-3-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C(C(F)(F)F)=C1 DCARBLUAUUNSJS-UHFFFAOYSA-N 0.000 description 3
• OYMFKCBASIXODY-UHFFFAOYSA-N methyl 4-(dimethylamino)-3-methylsulfonylbenzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C(S(C)(=O)=O)=C1 OYMFKCBASIXODY-UHFFFAOYSA-N 0.000 description 3
• MCILWQJVQABHJC-UHFFFAOYSA-N methyl 5-(dimethylamino)-2-nitrobenzoate Chemical compound COC(=O)C1=CC(N(C)C)=CC=C1[N+]([O-])=O MCILWQJVQABHJC-UHFFFAOYSA-N 0.000 description 3
• 150000004702 methyl esters Chemical class 0.000 description 3
• 201000006417 multiple sclerosis Diseases 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 108020004707 nucleic acids Proteins 0.000 description 3
• 102000039446 nucleic acids Human genes 0.000 description 3
• 230000000269 nucleophilic effect Effects 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 239000008194 pharmaceutical composition Substances 0.000 description 3
• 210000002381 plasma Anatomy 0.000 description 3
• 229920002647 polyamide Polymers 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 description 3
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 3
• 238000002821 scintillation proximity assay Methods 0.000 description 3
• UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 3
• 229960002218 sodium chlorite Drugs 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 3
• 229930004006 tropane Natural products 0.000 description 3
• LSSQMISUDUUZCC-DWSYCVKZSA-N (2,5-dioxopyrrolidin-1-yl) 4-fluoranylbenzoate Chemical compound C1=CC([18F])=CC=C1C(=O)ON1C(=O)CCC1=O LSSQMISUDUUZCC-DWSYCVKZSA-N 0.000 description 2
• UWTXJLHYJRFMOD-UHFFFAOYSA-M (2-fluoro-4-methoxycarbonylphenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.COC(=O)C1=CC=C([N+](C)(C)C)C(F)=C1 UWTXJLHYJRFMOD-UHFFFAOYSA-M 0.000 description 2
• RZYBZQCZGHTDDV-UHFFFAOYSA-M (3-chloro-4-methoxycarbonylphenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.COC(=O)C1=CC=C([N+](C)(C)C)C=C1Cl RZYBZQCZGHTDDV-UHFFFAOYSA-M 0.000 description 2
• IFJCQKBPVNPHSF-UHFFFAOYSA-M (3-fluoro-4-methoxycarbonylphenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.COC(=O)C1=CC=C([N+](C)(C)C)C=C1F IFJCQKBPVNPHSF-UHFFFAOYSA-M 0.000 description 2
• DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical class C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
• PBLZLIFKVPJDCO-UHFFFAOYSA-N 12-aminododecanoic acid Chemical compound NCCCCCCCCCCCC(O)=O PBLZLIFKVPJDCO-UHFFFAOYSA-N 0.000 description 2
• FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 2
• ZJFWCELATJMDNO-LMANFOLPSA-N 2-bromo-1-(4-fluoranylphenyl)ethanone Chemical compound [18F]C1=CC=C(C(=O)CBr)C=C1 ZJFWCELATJMDNO-LMANFOLPSA-N 0.000 description 2
• WAOQONBSWFLFPE-VIFPVBQESA-N 3,5-dichloro-N-[[(2S)-1-ethyl-2-pyrrolidinyl]methyl]-2-hydroxy-6-methoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(Cl)=CC(Cl)=C1OC WAOQONBSWFLFPE-VIFPVBQESA-N 0.000 description 2
• HRILPEMWERJNRC-AWDFDDCISA-N 3-(2,5-dioxopyrrol-1-yl)-N-[(4-(18F)fluoranylphenyl)methyl]benzamide Chemical compound C1(C=CC(N1C=1C=C(C(=O)NCC2=CC=C(C=C2)[18F])C=CC=1)=O)=O HRILPEMWERJNRC-AWDFDDCISA-N 0.000 description 2
• JMHGATOBRPWPBZ-UHFFFAOYSA-N 3-cyano-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(C#N)=C1 JMHGATOBRPWPBZ-UHFFFAOYSA-N 0.000 description 2
• KFJCXIOVAGJCKB-UHFFFAOYSA-N 4-(3-amino-1h-indazol-5-yl)-n-tert-butylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC(C)(C)C)=CC=C1C1=CC=C(NN=C2N)C2=C1 KFJCXIOVAGJCKB-UHFFFAOYSA-N 0.000 description 2
• JJMDCOVWQOJGCB-UHFFFAOYSA-N 5-aminopentanoic acid Chemical compound [NH3+]CCCCC([O-])=O JJMDCOVWQOJGCB-UHFFFAOYSA-N 0.000 description 2
• SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 108010009685 Cholinergic Receptors Proteins 0.000 description 2
• 101150049660 DRD2 gene Proteins 0.000 description 2
• 102000005915 GABA Receptors Human genes 0.000 description 2
• 108010005551 GABA Receptors Proteins 0.000 description 2
• 102000004300 GABA-A Receptors Human genes 0.000 description 2
• 108090000839 GABA-A Receptors Proteins 0.000 description 2
• MBZXSJWDBIIBLL-GDVGLLTNSA-N Homoisoleucine Chemical compound CCC(C)C[C@H](N)C(O)=O MBZXSJWDBIIBLL-GDVGLLTNSA-N 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• AGPKZVBTJJNPAG-UHNVWZDZSA-N L-allo-Isoleucine Chemical compound CC[C@@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-UHNVWZDZSA-N 0.000 description 2
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
• FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 2
• 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 2
• SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 2
• 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 2
• 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• SBPRIAGPYFYCRT-UHFFFAOYSA-N N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCN(C(=O)C2CCCCC2)C=2N=CC=CC=2)CC1 SBPRIAGPYFYCRT-UHFFFAOYSA-N 0.000 description 2
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 206010060862 Prostate cancer Diseases 0.000 description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• 201000010208 Seminoma Diseases 0.000 description 2
• 206010041067 Small cell lung cancer Diseases 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N THREONINE Chemical compound CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
• 108700026614 Tyr(3)- octreotate Proteins 0.000 description 2
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
• 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 2
• 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 2
• BPHVNYAITJOGCW-UHFFFAOYSA-M [2-chloro-5-[2-(dimethylcarbamoyl)phenyl]sulfanyl-4-nitrophenyl]-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.CN(C)C(=O)C1=CC=CC=C1SC1=CC([N+](C)(C)C)=C(Cl)C=C1[N+]([O-])=O BPHVNYAITJOGCW-UHFFFAOYSA-M 0.000 description 2
• 102000034337 acetylcholine receptors Human genes 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 229950009005 altanserin Drugs 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• IKADZPYEPSHGPY-UHFFFAOYSA-N benzene;n,n-dimethylmethanamine Chemical class CN(C)C.C1=CC=CC=C1 IKADZPYEPSHGPY-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 230000036983 biotransformation Effects 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 210000003679 cervix uteri Anatomy 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 2
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• KDQPSPMLNJTZAL-UHFFFAOYSA-L disodium hydrogenphosphate dihydrate Chemical compound O.O.[Na+].[Na+].OP([O-])([O-])=O KDQPSPMLNJTZAL-UHFFFAOYSA-L 0.000 description 2
• 229960003638 dopamine Drugs 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 210000003238 esophagus Anatomy 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 230000002349 favourable effect Effects 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 2
• 229960004381 flumazenil Drugs 0.000 description 2
• 230000003325 follicular Effects 0.000 description 2
• 210000000232 gallbladder Anatomy 0.000 description 2
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 229910052500 inorganic mineral Inorganic materials 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 229960004592 isopropanol Drugs 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• DWPCPZJAHOETAG-UHFFFAOYSA-N meso-lanthionine Natural products OC(=O)C(N)CSCC(N)C(O)=O DWPCPZJAHOETAG-UHFFFAOYSA-N 0.000 description 2
• DWRVHDWKWKFSAI-UHFFFAOYSA-N methyl 3,4-difluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C(F)=C1 DWRVHDWKWKFSAI-UHFFFAOYSA-N 0.000 description 2
• MAJPSIMHGFFUTE-UHFFFAOYSA-N methyl 3-cyano-4-(dimethylamino)benzoate Chemical compound COC(=O)C1=CC=C(N(C)C)C(C#N)=C1 MAJPSIMHGFFUTE-UHFFFAOYSA-N 0.000 description 2
• UCOJKDQJOVWXRE-UHFFFAOYSA-N methyl 3-cyano-4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C(C#N)=C1 UCOJKDQJOVWXRE-UHFFFAOYSA-N 0.000 description 2
• BNUYNCHJMOWGOH-UHFFFAOYSA-N methyl 4-fluoro-2-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(F)C=C1C(F)(F)F BNUYNCHJMOWGOH-UHFFFAOYSA-N 0.000 description 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
• 235000010755 mineral Nutrition 0.000 description 2
• 239000011707 mineral Substances 0.000 description 2
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 239000002858 neurotransmitter agent Substances 0.000 description 2
• 150000007523 nucleic acids Chemical class 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 201000008968 osteosarcoma Diseases 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 230000007030 peptide scission Effects 0.000 description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
• 210000001428 peripheral nervous system Anatomy 0.000 description 2
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 229950001518 raclopride Drugs 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 230000035484 reaction time Effects 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 208000000587 small cell lung carcinoma Diseases 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 229950000244 sulfanilic acid Drugs 0.000 description 2
• 208000001608 teratocarcinoma Diseases 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 150000003573 thiols Chemical class 0.000 description 2
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
• 238000003325 tomography Methods 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 210000003932 urinary bladder Anatomy 0.000 description 2
• RWPYOAUYOSFJQV-UHFFFAOYSA-N (1-methylpiperidin-4-yl) acetate Chemical compound CN1CCC(OC(C)=O)CC1 RWPYOAUYOSFJQV-UHFFFAOYSA-N 0.000 description 1
• GNWBLLYJQXKPIP-ZOGIJGBBSA-N (1s,3as,3bs,5ar,9ar,9bs,11as)-n,n-diethyl-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinoline-1-carboxamide Chemical compound CN([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)N(CC)CC)[C@@]2(C)CC1 GNWBLLYJQXKPIP-ZOGIJGBBSA-N 0.000 description 1
• AQKBVSICZIOFAA-UHFFFAOYSA-M (2,2-dimethyl-1,3-dioxoinden-5-yl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C1=C([N+](C)(C)C)C=C2C(=O)C(C)(C)C(=O)C2=C1 AQKBVSICZIOFAA-UHFFFAOYSA-M 0.000 description 1
• PGMNUZZMJLHSML-UHFFFAOYSA-M (2-bromo-4-nitrophenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[N+](C)(C)C1=CC=C([N+]([O-])=O)C=C1Br PGMNUZZMJLHSML-UHFFFAOYSA-M 0.000 description 1
• OIYMZVALCGOKCJ-UHFFFAOYSA-M (2-chloro-4-nitrophenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[N+](C)(C)C1=CC=C([N+]([O-])=O)C=C1Cl OIYMZVALCGOKCJ-UHFFFAOYSA-M 0.000 description 1
• ZRMFNEFNQCRYLR-UHFFFAOYSA-M (2-cyano-4-methoxycarbonylphenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.COC(=O)C1=CC=C([N+](C)(C)C)C(C#N)=C1 ZRMFNEFNQCRYLR-UHFFFAOYSA-M 0.000 description 1
• RWNUHIUVCMIKMQ-UHFFFAOYSA-M (2-formyl-5-methoxyphenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.COC1=CC=C(C=O)C([N+](C)(C)C)=C1 RWNUHIUVCMIKMQ-UHFFFAOYSA-M 0.000 description 1
• SHAPQBYCPZRQIP-RXMQYKEDSA-N (2r)-2-(thiophen-2-ylamino)propanoic acid Chemical compound OC(=O)[C@@H](C)NC1=CC=CS1 SHAPQBYCPZRQIP-RXMQYKEDSA-N 0.000 description 1
• QUOGESRFPZDMMT-RXMQYKEDSA-N (2r)-2-amino-6-(diaminomethylideneamino)hexanoic acid Chemical compound OC(=O)[C@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-RXMQYKEDSA-N 0.000 description 1
• FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
• MSECZMWQBBVGEN-ZCFIWIBFSA-N (2r)-2-azaniumyl-4-(1h-imidazol-5-yl)butanoate Chemical compound [O-]C(=O)[C@H]([NH3+])CCC1=CN=CN1 MSECZMWQBBVGEN-ZCFIWIBFSA-N 0.000 description 1
• ADJZXDVMJPTFKT-SNVBAGLBSA-N (2r)-2-azaniumyl-4-(1h-indol-3-yl)butanoate Chemical compound C1=CC=C2C(CC[C@@H](N)C(O)=O)=CNC2=C1 ADJZXDVMJPTFKT-SNVBAGLBSA-N 0.000 description 1
• JTTHKOPSMAVJFE-SECBINFHSA-N (2r)-2-azaniumyl-4-phenylbutanoate Chemical compound [O-]C(=O)[C@H]([NH3+])CCC1=CC=CC=C1 JTTHKOPSMAVJFE-SECBINFHSA-N 0.000 description 1
• FMUMEWVNYMUECA-ZCFIWIBFSA-N (2r)-2-azaniumyl-5-methylhexanoate Chemical compound CC(C)CC[C@@H](N)C(O)=O FMUMEWVNYMUECA-ZCFIWIBFSA-N 0.000 description 1
• BFNDLDRNJFLIKE-ROLXFIACSA-N (2s)-2,6-diamino-6-hydroxyhexanoic acid Chemical compound NC(O)CCC[C@H](N)C(O)=O BFNDLDRNJFLIKE-ROLXFIACSA-N 0.000 description 1
• NMDDZEVVQDPECF-LURJTMIESA-N (2s)-2,7-diaminoheptanoic acid Chemical compound NCCCCC[C@H](N)C(O)=O NMDDZEVVQDPECF-LURJTMIESA-N 0.000 description 1
• IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
• RWLSBXBFZHDHHX-VIFPVBQESA-N (2s)-2-(naphthalen-2-ylamino)propanoic acid Chemical compound C1=CC=CC2=CC(N[C@@H](C)C(O)=O)=CC=C21 RWLSBXBFZHDHHX-VIFPVBQESA-N 0.000 description 1
• KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
• MSECZMWQBBVGEN-LURJTMIESA-N (2s)-2-azaniumyl-4-(1h-imidazol-5-yl)butanoate Chemical compound OC(=O)[C@@H](N)CCC1=CN=CN1 MSECZMWQBBVGEN-LURJTMIESA-N 0.000 description 1
• ADJZXDVMJPTFKT-JTQLQIEISA-N (2s)-2-azaniumyl-4-(1h-indol-3-yl)butanoate Chemical compound C1=CC=C2C(CC[C@H](N)C(O)=O)=CNC2=C1 ADJZXDVMJPTFKT-JTQLQIEISA-N 0.000 description 1
• FMUMEWVNYMUECA-LURJTMIESA-N (2s)-2-azaniumyl-5-methylhexanoate Chemical compound CC(C)CC[C@H](N)C(O)=O FMUMEWVNYMUECA-LURJTMIESA-N 0.000 description 1
• JMDCRDOIPYCSCH-LURJTMIESA-N (2s)-3-(3,4-dihydroxyphenyl)-2-(fluoroamino)propanoic acid Chemical compound OC(=O)[C@@H](NF)CC1=CC=C(O)C(O)=C1 JMDCRDOIPYCSCH-LURJTMIESA-N 0.000 description 1
• RPGVFTUDMMGULT-UHFFFAOYSA-N (3-carboxy-4-chlorophenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[N+](C)(C)C1=CC=C(Cl)C(C(O)=O)=C1 RPGVFTUDMMGULT-UHFFFAOYSA-N 0.000 description 1
• VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 1
• ZTEJJZFXUYWTGA-UHFFFAOYSA-N (4-carboxy-2-fluorophenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[N+](C)(C)C1=CC=C(C(O)=O)C=C1F ZTEJJZFXUYWTGA-UHFFFAOYSA-N 0.000 description 1
• WNWGXNBQCXGVAU-UHFFFAOYSA-N (4-carboxy-3-chlorophenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[N+](C)(C)C1=CC=C(C(O)=O)C(Cl)=C1 WNWGXNBQCXGVAU-UHFFFAOYSA-N 0.000 description 1
• XUXTXSVLPIWZRS-UHFFFAOYSA-N (4-carboxy-3-fluorophenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[N+](C)(C)C1=CC=C(C(O)=O)C(F)=C1 XUXTXSVLPIWZRS-UHFFFAOYSA-N 0.000 description 1
• CQXMKHWQQNZMSQ-UHFFFAOYSA-M (4-chloro-3-methoxycarbonylphenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.COC(=O)C1=CC([N+](C)(C)C)=CC=C1Cl CQXMKHWQQNZMSQ-UHFFFAOYSA-M 0.000 description 1
• QVAYBTQAQYWEOZ-UHFFFAOYSA-M (4-fluoro-3-nitrophenyl)-trimethylazanium;iodide Chemical compound [I-].C[N+](C)(C)C1=CC=C(F)C([N+]([O-])=O)=C1 QVAYBTQAQYWEOZ-UHFFFAOYSA-M 0.000 description 1
• FUIUNTKTXOTDGV-UHFFFAOYSA-M (4-formyl-2-phenylmethoxyphenyl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[N+](C)(C)C1=CC=C(C=O)C=C1OCC1=CC=CC=C1 FUIUNTKTXOTDGV-UHFFFAOYSA-M 0.000 description 1
• FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 1
• KPYXMALABCDPGN-HYOZMBHHSA-N (4s)-5-[[(2s)-6-amino-1-[[(2s,3s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[2-[[2-[[(1s)-3-amino-1-carboxy-3-oxopropyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]a Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN)CC1=CC=C(O)C=C1 KPYXMALABCDPGN-HYOZMBHHSA-N 0.000 description 1
• CVIAHOXXRLQHHL-UHFFFAOYSA-N (5-chloro-8-hydroxyquinolin-7-yl)-trimethylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C1=CC=NC2=C(O)C([N+](C)(C)C)=CC(Cl)=C21 CVIAHOXXRLQHHL-UHFFFAOYSA-N 0.000 description 1
• YVKDUIAAPBKHMJ-MOPGFXCFSA-N (6R,10bS)-6-[4-(methylthio)phenyl]-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline Chemical compound C1=CC(SC)=CC=C1[C@@H]1C2=CC=CC=C2[C@@H]2CCCN2C1 YVKDUIAAPBKHMJ-MOPGFXCFSA-N 0.000 description 1
• VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 1
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
• DPRJPRMZJGWLHY-HNGSOEQISA-N (e,3r,5s)-7-[5-(4-fluorophenyl)-3-propan-2-yl-1-pyrazin-2-ylpyrazol-4-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)/C=C/C=1C(C(C)C)=NN(C=2N=CC=NC=2)C=1C1=CC=C(F)C=C1 DPRJPRMZJGWLHY-HNGSOEQISA-N 0.000 description 1
• BWKMGYQJPOAASG-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CNC(C(=O)O)CC2=C1 BWKMGYQJPOAASG-UHFFFAOYSA-N 0.000 description 1
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• SBKKXWSZVVDOLR-KXMUYVCJSA-N 1-(4-fluoranylphenyl)pyrrole-2,5-dione Chemical compound C1=CC([18F])=CC=C1N1C(=O)C=CC1=O SBKKXWSZVVDOLR-KXMUYVCJSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• FJZNNKJZHQFMCK-LRDDRELGSA-N 1-[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]-3-phenylurea Chemical compound C1(=CC(=CC(=C1[C@H]1[C@@H](C(=O)NC1)NC(=O)NC1=CC=CC=C1)F)OC)F FJZNNKJZHQFMCK-LRDDRELGSA-N 0.000 description 1
• YCGQPIRMLGEWMW-UHFFFAOYSA-N 1-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,8-naphthyridin-3-yl]-3-[4-[(dimethylamino)methyl]-2,6-di(propan-2-yl)phenyl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN(C)C)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OC)=C1 YCGQPIRMLGEWMW-UHFFFAOYSA-N 0.000 description 1
• XPJCWJSVPBMPOX-SQZVAGKESA-N 1-[2-(4-chloro-5-fluoranyl-2-methylphenyl)sulfanylphenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC=C1SC1=CC([18F])=C(Cl)C=C1C XPJCWJSVPBMPOX-SQZVAGKESA-N 0.000 description 1
• YKYWUHHZZRBGMG-JWTNVVGKSA-N 1-methyl-2-[[(1r,5s)-6-[[5-(trifluoromethyl)pyridin-2-yl]methoxymethyl]-3-azabicyclo[3.1.0]hexan-3-yl]methyl]benzimidazole Chemical compound C1([C@@H]2CN(C[C@@H]21)CC=1N(C2=CC=CC=C2N=1)C)COCC1=CC=C(C(F)(F)F)C=N1 YKYWUHHZZRBGMG-JWTNVVGKSA-N 0.000 description 1
• XAUQWYHSQICPAZ-UHFFFAOYSA-N 10-amino-decanoic acid Chemical compound NCCCCCCCCCC(O)=O XAUQWYHSQICPAZ-UHFFFAOYSA-N 0.000 description 1
• NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
• OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• CJLZUKCACMUYFP-GOSISDBHSA-N 2-[(5R)-4-[2-[3-(3-methylbutanoyloxy)phenyl]acetyl]-8-(trifluoromethyl)-1,2,3,5-tetrahydropyrido[2,3-e][1,4]diazepin-5-yl]acetic acid Chemical compound CC(C)CC(=O)OC1=CC=CC(CC(=O)N2[C@@H](C3=CC=C(N=C3NCC2)C(F)(F)F)CC(O)=O)=C1 CJLZUKCACMUYFP-GOSISDBHSA-N 0.000 description 1
• RUVRGYVESPRHSZ-UHFFFAOYSA-N 2-[2-(2-azaniumylethoxy)ethoxy]acetate Chemical compound NCCOCCOCC(O)=O RUVRGYVESPRHSZ-UHFFFAOYSA-N 0.000 description 1
• UABIXNSHHIMZEP-UHFFFAOYSA-N 2-[2-[(dimethylamino)methyl]phenyl]sulfanyl-5-methylaniline Chemical compound CN(C)CC1=CC=CC=C1SC1=CC=C(C)C=C1N UABIXNSHHIMZEP-UHFFFAOYSA-N 0.000 description 1
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
• NJZSQTMICFLABM-COJKEBBMSA-N 2-chloro-1-(18F)fluoranyl-3-nitrobenzene Chemical compound ClC=1C(=CC=CC=1[18F])[N+](=O)[O-] NJZSQTMICFLABM-COJKEBBMSA-N 0.000 description 1
• MUQWLBDSRBARGV-UHFFFAOYSA-N 2-cyano-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1C#N MUQWLBDSRBARGV-UHFFFAOYSA-N 0.000 description 1
• ASJSAQIRZKANQN-UHFFFAOYSA-N 2-deoxypentose Chemical compound OCC(O)C(O)CC=O ASJSAQIRZKANQN-UHFFFAOYSA-N 0.000 description 1
• IBBYQNVXKFMSSI-LMANFOLPSA-N 2-fluoranyl-4,5-dimethoxybenzaldehyde Chemical compound COC1=CC([18F])=C(C=O)C=C1OC IBBYQNVXKFMSSI-LMANFOLPSA-N 0.000 description 1
• ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 1
• QIQDJNUUWYCZFZ-COJKEBBMSA-N 3-(18F)fluoranyl-5-nitrobenzamide Chemical compound C1=C(C=C(C=C1[N+](=O)[O-])[18F])C(=O)N QIQDJNUUWYCZFZ-COJKEBBMSA-N 0.000 description 1
• MNARAEXGMVEFDO-UHFFFAOYSA-N 3-(2-fluoroethyl)-8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(CCCC(=O)C=2C=CC(F)=CC=2)CCC21C(=O)N(CCF)CN2C1=CC=CC=C1 MNARAEXGMVEFDO-UHFFFAOYSA-N 0.000 description 1
• FHNLXNKFRGMOPW-UHFFFAOYSA-N 3-amino-2-sulfanylpropanoic acid Chemical compound NCC(S)C(O)=O FHNLXNKFRGMOPW-UHFFFAOYSA-N 0.000 description 1
• PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 1
• MWDVCHRYCKXEBY-LBPRGKRZSA-N 3-chloro-n-[2-oxo-2-[[(1s)-1-phenylethyl]amino]ethyl]benzamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(Cl)=C1 MWDVCHRYCKXEBY-LBPRGKRZSA-N 0.000 description 1
• HULGXUWGLHFHLE-IPMKNSEASA-N 3-cyano-4-fluoro-n-[2-[2-[3-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]ethylsulfonyl]ethyl]benzamide Chemical compound O=C1N(CCS(=O)(=O)CCNC(=O)C=2C=C(C(F)=CC=2)C#N)C(=O)C(C)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 HULGXUWGLHFHLE-IPMKNSEASA-N 0.000 description 1
• OVDGUTHABMXVMI-UHFFFAOYSA-N 3-nitro-4-(propylamino)benzoic acid Chemical compound CCCNC1=CC=C(C(O)=O)C=C1[N+]([O-])=O OVDGUTHABMXVMI-UHFFFAOYSA-N 0.000 description 1
• FZTIWOBQQYPTCJ-UHFFFAOYSA-N 4-[4-(4-carboxyphenyl)phenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(O)=O)C=C1 FZTIWOBQQYPTCJ-UHFFFAOYSA-N 0.000 description 1
• UVGYSEIWAOOIJR-RVRFMXCPSA-N 4-chloro-2-(18F)fluoranylbenzaldehyde Chemical compound ClC1=CC(=C(C=O)C=C1)[18F] UVGYSEIWAOOIJR-RVRFMXCPSA-N 0.000 description 1
• UOQXIWFBQSVDPP-COJKEBBMSA-N 4-fluoranylbenzaldehyde Chemical compound [18F]C1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-COJKEBBMSA-N 0.000 description 1
• PTPKGMXRSREZFB-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(F)C(OC(F)(F)F)=C1 PTPKGMXRSREZFB-UHFFFAOYSA-N 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
• 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 1
• KUZSBKJSGSKPJH-VXGBXAGGSA-N 5-[(9R)-6-[(3R)-3-methylmorpholin-4-yl]-11-oxa-1,3,5-triazatricyclo[7.4.0.02,7]trideca-2,4,6-trien-4-yl]pyrazin-2-amine Chemical compound C[C@@H]1COCCN1c1nc(nc2N3CCOC[C@H]3Cc12)-c1cnc(N)cn1 KUZSBKJSGSKPJH-VXGBXAGGSA-N 0.000 description 1
• 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 1
• 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 1
• 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• RRELDGDKULRRDM-UHFFFAOYSA-N 6-[2-chloro-4-nitro-5-(oxan-4-yloxy)anilino]-3,4-dihydro-1H-quinolin-2-one Chemical compound [O-][N+](=O)c1cc(Cl)c(Nc2ccc3NC(=O)CCc3c2)cc1OC1CCOCC1 RRELDGDKULRRDM-UHFFFAOYSA-N 0.000 description 1
• FCBOUJYKAGWYQM-DEOSSOPVSA-N 6-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-n-(2-phenoxyethyl)-2-(3,4,5-trimethoxyphenyl)pyridine-3-carboxamide Chemical compound COC1=C(OC)C(OC)=CC(C=2C(=CC=C(N[C@H](CO)CC=3C=CC=CC=3)N=2)C(=O)NCCOC=2C=CC=CC=2)=C1 FCBOUJYKAGWYQM-DEOSSOPVSA-N 0.000 description 1
• RGDOXQAJXVTNRP-UHFFFAOYSA-N 8-(dicyclopropylmethyl)-1-methyl-3-propyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(C)C(=O)N(CCC)C=2N=C1C(C1CC1)C1CC1 RGDOXQAJXVTNRP-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• UQXNEWQGGVUVQA-UHFFFAOYSA-N 8-aminooctanoic acid Chemical compound NCCCCCCCC(O)=O UQXNEWQGGVUVQA-UHFFFAOYSA-N 0.000 description 1
• GGGMDKJPUXTDAW-SJPDSGJFSA-N 8-cyclopentyl-3-(3-fluoranylpropyl)-1-propyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC[18F])C=2N=C1C1CCCC1 GGGMDKJPUXTDAW-SJPDSGJFSA-N 0.000 description 1
• VWPQCOZMXULHDM-UHFFFAOYSA-N 9-aminononanoic acid Chemical compound NCCCCCCCCC(O)=O VWPQCOZMXULHDM-UHFFFAOYSA-N 0.000 description 1
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
• 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
• ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 102000009346 Adenosine receptors Human genes 0.000 description 1
• 108050000203 Adenosine receptors Proteins 0.000 description 1
• 241001136792 Alle Species 0.000 description 1
• SMYALUSCZJXWHG-UHFFFAOYSA-N Altanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=S)=O)CC1 SMYALUSCZJXWHG-UHFFFAOYSA-N 0.000 description 1
• IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• ODFIRPLYRUOKIP-UHFFFAOYSA-N C(C)(C)C1(CCC(CC1)N=C=N)C(C)C Chemical compound C(C)(C)C1(CCC(CC1)N=C=N)C(C)C ODFIRPLYRUOKIP-UHFFFAOYSA-N 0.000 description 1
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• QUMCIHKVKQYNPA-RUZDIDTESA-N C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC Chemical compound C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC QUMCIHKVKQYNPA-RUZDIDTESA-N 0.000 description 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
• XMWRBQBLMFGWIX-UHFFFAOYSA-N C60 fullerene Chemical class C12=C3C(C4=C56)=C7C8=C5C5=C9C%10=C6C6=C4C1=C1C4=C6C6=C%10C%10=C9C9=C%11C5=C8C5=C8C7=C3C3=C7C2=C1C1=C2C4=C6C4=C%10C6=C9C9=C%11C5=C5C8=C3C3=C7C1=C1C2=C4C6=C2C9=C5C3=C12 XMWRBQBLMFGWIX-UHFFFAOYSA-N 0.000 description 1
• WUZBOJXXYMKMMF-UHFFFAOYSA-N COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F Chemical compound COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F WUZBOJXXYMKMMF-UHFFFAOYSA-N 0.000 description 1
• 101100180402 Caenorhabditis elegans jun-1 gene Proteins 0.000 description 1
• 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
• 102000055006 Calcitonin Human genes 0.000 description 1
• 108060001064 Calcitonin Proteins 0.000 description 1
• 108010089448 Cholecystokinin B Receptor Proteins 0.000 description 1
• VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 1
• OYIFNHCXNCRBQI-SCSAIBSYSA-N D-2-aminoadipic acid Chemical compound OC(=O)[C@H](N)CCCC(O)=O OYIFNHCXNCRBQI-SCSAIBSYSA-N 0.000 description 1
• FFFHZYDWPBMWHY-GSVOUGTGSA-N D-Homocysteine Chemical compound OC(=O)[C@H](N)CCS FFFHZYDWPBMWHY-GSVOUGTGSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
• SFSJZXMDTNDWIX-RXMQYKEDSA-N D-homomethionine Chemical compound CSCCC[C@@H](N)C(O)=O SFSJZXMDTNDWIX-RXMQYKEDSA-N 0.000 description 1
• UQBOJOOOTLPNST-UHFFFAOYSA-N Dehydroalanine Chemical compound NC(=C)C(O)=O UQBOJOOOTLPNST-UHFFFAOYSA-N 0.000 description 1
• 206010012289 Dementia Diseases 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
• 108010016626 Dipeptides Proteins 0.000 description 1
• OIJXLIIMXHRJJH-KNLIIKEYSA-N Diprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)C(C)(C)O)OC)CN2CC1CC1 OIJXLIIMXHRJJH-KNLIIKEYSA-N 0.000 description 1
• 108050004812 Dopamine receptor Proteins 0.000 description 1
• 102000015554 Dopamine receptor Human genes 0.000 description 1
• 108060002716 Exonuclease Proteins 0.000 description 1
• 101100295741 Gallus gallus COR4 gene Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 101000631929 Homo sapiens Sodium-dependent serotonin transporter Proteins 0.000 description 1
• YZJSUQQZGCHHNQ-UHFFFAOYSA-N Homoglutamine Chemical compound OC(=O)C(N)CCCC(N)=O YZJSUQQZGCHHNQ-UHFFFAOYSA-N 0.000 description 1
• STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
• 102100037644 Kelch-like protein 41 Human genes 0.000 description 1
• 108050003242 Kelch-like protein 41 Proteins 0.000 description 1
• OYIFNHCXNCRBQI-BYPYZUCNSA-N L-2-aminoadipic acid Chemical compound OC(=O)[C@@H](N)CCCC(O)=O OYIFNHCXNCRBQI-BYPYZUCNSA-N 0.000 description 1
• SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
• QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
• LOOZZTFGSTZNRX-VIFPVBQESA-N L-Homotyrosine Chemical compound OC(=O)[C@@H](N)CCC1=CC=C(O)C=C1 LOOZZTFGSTZNRX-VIFPVBQESA-N 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• QWCKQJZIFLGMSD-VKHMYHEASA-N L-alpha-aminobutyric acid Chemical compound CC[C@H](N)C(O)=O QWCKQJZIFLGMSD-VKHMYHEASA-N 0.000 description 1
• QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
• SFSJZXMDTNDWIX-YFKPBYRVSA-N L-homomethionine Chemical compound CSCCC[C@H](N)C(O)=O SFSJZXMDTNDWIX-YFKPBYRVSA-N 0.000 description 1
• UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
• DWPCPZJAHOETAG-IMJSIDKUSA-N L-lanthionine Chemical compound OC(=O)[C@@H](N)CSC[C@H](N)C(O)=O DWPCPZJAHOETAG-IMJSIDKUSA-N 0.000 description 1
• HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
• STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
• QHJLPOSPWKZACG-UHFFFAOYSA-N N-Methylspiperone Chemical compound C1CN(CCCC(=O)C=2C=CC(F)=CC=2)CCC21C(=O)N(C)CN2C1=CC=CC=C1 QHJLPOSPWKZACG-UHFFFAOYSA-N 0.000 description 1
• CAHKINHBCWCHCF-UHFFFAOYSA-N N-acetyltyrosine Chemical compound CC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 CAHKINHBCWCHCF-UHFFFAOYSA-N 0.000 description 1
• 238000007126 N-alkylation reaction Methods 0.000 description 1
• TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
• NPKSPKHJBVJUKB-UHFFFAOYSA-N N-phenylglycine Chemical compound OC(=O)CNC1=CC=CC=C1 NPKSPKHJBVJUKB-UHFFFAOYSA-N 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• 102000003840 Opioid Receptors Human genes 0.000 description 1
• 108090000137 Opioid Receptors Proteins 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• 229910003873 O—P—O Inorganic materials 0.000 description 1
• 108091093037 Peptide nucleic acid Proteins 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
• 229940125907 SJ995973 Drugs 0.000 description 1
• 108010077895 Sarcosine Proteins 0.000 description 1
• 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 1
• 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 1
• 102100028874 Sodium-dependent serotonin transporter Human genes 0.000 description 1
• 102000006601 Thymidine Kinase Human genes 0.000 description 1
• 108020004440 Thymidine kinase Proteins 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical class CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 125000002723 alicyclic group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 125000005529 alkyleneoxy group Chemical group 0.000 description 1
• QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 1
• 229960002684 aminocaproic acid Drugs 0.000 description 1
• 239000001099 ammonium carbonate Substances 0.000 description 1
• 235000012501 ammonium carbonate Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
• XFILPEOLDIKJHX-QYZOEREBSA-N batimastat Chemical compound C([C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)[C@H](CSC=1SC=CC=1)C(=O)NO)C1=CC=CC=C1 XFILPEOLDIKJHX-QYZOEREBSA-N 0.000 description 1
• 229950001858 batimastat Drugs 0.000 description 1
• 150000003936 benzamides Chemical class 0.000 description 1
• GIJXKZJWITVLHI-PMOLBWCYSA-N benzatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(C=1C=CC=CC=1)C1=CC=CC=C1 GIJXKZJWITVLHI-PMOLBWCYSA-N 0.000 description 1
• 229960001081 benzatropine Drugs 0.000 description 1
• 150000001555 benzenes Chemical group 0.000 description 1
• 150000008038 benzoazepines Chemical class 0.000 description 1
• MWZCDAOUROKGLW-UHFFFAOYSA-N benzoic acid;n,n-dimethylmethanamine Chemical class CN(C)C.OC(=O)C1=CC=CC=C1 MWZCDAOUROKGLW-UHFFFAOYSA-N 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 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
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• JCZLABDVDPYLRZ-AWEZNQCLSA-N biphenylalanine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C1=CC=CC=C1 JCZLABDVDPYLRZ-AWEZNQCLSA-N 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
• 229960004015 calcitonin Drugs 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000004623 carbolinyl group Chemical group 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• YDSDEBIZUNNPOB-UHFFFAOYSA-N carfentanil Chemical group C1CN(CCC=2C=CC=CC=2)CCC1(C(=O)OC)N(C(=O)CC)C1=CC=CC=C1 YDSDEBIZUNNPOB-UHFFFAOYSA-N 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 229910052804 chromium Inorganic materials 0.000 description 1
• 239000011651 chromium Substances 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 238000003759 clinical diagnosis Methods 0.000 description 1
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
• 229960004170 clozapine Drugs 0.000 description 1
• 229960003920 cocaine Drugs 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940127206 compound 14d Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940125851 compound 27 Drugs 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 125000004122 cyclic 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
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
• 229940104302 cytosine Drugs 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 239000000412 dendrimer Substances 0.000 description 1
• 229920000736 dendritic polymer Polymers 0.000 description 1
• 239000012351 deprotecting agent Substances 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• MQUBEBJFHBANKV-UHFFFAOYSA-N di(propan-2-yl)silicon Chemical compound CC(C)[Si]C(C)C MQUBEBJFHBANKV-UHFFFAOYSA-N 0.000 description 1
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 229950002494 diprenorphine Drugs 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000002612 dispersion medium Substances 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
• 125000006575 electron-withdrawing group Chemical group 0.000 description 1
• 239000002532 enzyme inhibitor Substances 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 102000013165 exonuclease Human genes 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 125000001207 fluorophenyl group Chemical group 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 229910003472 fullerene Inorganic materials 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• SFSJZXMDTNDWIX-UHFFFAOYSA-N homomethionine Natural products CSCCCC(N)C(O)=O SFSJZXMDTNDWIX-UHFFFAOYSA-N 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• XGCKLPDYTQRDTR-UHFFFAOYSA-H indium(iii) sulfate Chemical compound [In+3].[In+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O XGCKLPDYTQRDTR-UHFFFAOYSA-H 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 125000006303 iodophenyl group Chemical group 0.000 description 1
• CANPFCFJURGKAX-JTQLQIEISA-N iolopride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(I)=CC=C1OC CANPFCFJURGKAX-JTQLQIEISA-N 0.000 description 1
• 229940084651 iressa Drugs 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 1
• 229960005417 ketanserin Drugs 0.000 description 1
• HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
• 150000002605 large molecules Chemical class 0.000 description 1
• 229960004502 levodopa Drugs 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
• JHPAOEXOUXURFL-UHFFFAOYSA-N methyl 2,3,4-trifluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C(F)=C1F JHPAOEXOUXURFL-UHFFFAOYSA-N 0.000 description 1
• YQUHULOBTDYMAG-UHFFFAOYSA-N methyl 2,4-difluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1F YQUHULOBTDYMAG-UHFFFAOYSA-N 0.000 description 1
• JENBPOJAZCPSEW-UHFFFAOYSA-N methyl 2-bromo-4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1Br JENBPOJAZCPSEW-UHFFFAOYSA-N 0.000 description 1
• FCMQMRAFVRTHCR-UHFFFAOYSA-N methyl 2-bromo-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1Br FCMQMRAFVRTHCR-UHFFFAOYSA-N 0.000 description 1
• SUHCMLBOLPHTHV-UHFFFAOYSA-N methyl 2-chloro-4-fluoro-5-methylsulfonylbenzoate Chemical compound COC(=O)C1=CC(S(C)(=O)=O)=C(F)C=C1Cl SUHCMLBOLPHTHV-UHFFFAOYSA-N 0.000 description 1
• YZDLPZNWBRBZMZ-UHFFFAOYSA-N methyl 2-chloro-4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1Cl YZDLPZNWBRBZMZ-UHFFFAOYSA-N 0.000 description 1
• NRKMNOPYHIGOKT-UHFFFAOYSA-N methyl 2-chloro-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1Cl NRKMNOPYHIGOKT-UHFFFAOYSA-N 0.000 description 1
• BCYCPVRVZPDHEC-UHFFFAOYSA-N methyl 2-cyano-4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1C#N BCYCPVRVZPDHEC-UHFFFAOYSA-N 0.000 description 1
• MDEIAFRKJRPGHY-UHFFFAOYSA-N methyl 2-cyano-5-(dimethylamino)benzoate Chemical compound COC(=O)C1=CC(N(C)C)=CC=C1C#N MDEIAFRKJRPGHY-UHFFFAOYSA-N 0.000 description 1
• CVFHFKWDNDKBOV-UHFFFAOYSA-N methyl 2-cyano-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1C#N CVFHFKWDNDKBOV-UHFFFAOYSA-N 0.000 description 1
• WKXJQUHWVURHDS-UHFFFAOYSA-N methyl 3-fluoro-3-nitrocyclohexa-1,5-diene-1-carboxylate Chemical compound COC(=O)C1=CC(F)([N+]([O-])=O)CC=C1 WKXJQUHWVURHDS-UHFFFAOYSA-N 0.000 description 1
• YBAZOLISUXINHV-UHFFFAOYSA-N methyl 4-fluoro-2-nitrobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1[N+]([O-])=O YBAZOLISUXINHV-UHFFFAOYSA-N 0.000 description 1
• HOVCTMDPKALOEL-UHFFFAOYSA-N methyl 4-fluoro-3-(trifluoromethoxy)benzoate Chemical compound COC(=O)C1=CC=C(F)C(OC(F)(F)F)=C1 HOVCTMDPKALOEL-UHFFFAOYSA-N 0.000 description 1
• IRYBOHVMFKZODT-UHFFFAOYSA-N methyl 4-fluoro-3-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(F)C(C(F)(F)F)=C1 IRYBOHVMFKZODT-UHFFFAOYSA-N 0.000 description 1
• YUVSGFLZOSEKEA-UHFFFAOYSA-N methyl 4-fluoro-3-methylsulfonylbenzoate Chemical compound COC(=O)C1=CC=C(F)C(S(C)(=O)=O)=C1 YUVSGFLZOSEKEA-UHFFFAOYSA-N 0.000 description 1
• CNJJSTPBUHAEFH-UHFFFAOYSA-N methyl 4-fluoro-3-nitrobenzoate Chemical compound COC(=O)C1=CC=C(F)C([N+]([O-])=O)=C1 CNJJSTPBUHAEFH-UHFFFAOYSA-N 0.000 description 1
• DOIYGTDENDGLSP-UHFFFAOYSA-N methyl 5-(dimethylamino)-2-methylsulfonylbenzoate Chemical compound COC(=O)C1=CC(N(C)C)=CC=C1S(C)(=O)=O DOIYGTDENDGLSP-UHFFFAOYSA-N 0.000 description 1
• KGDQMNVZZNCLBF-UHFFFAOYSA-N methyl 5-fluoro-2-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC(F)=CC=C1C(F)(F)F KGDQMNVZZNCLBF-UHFFFAOYSA-N 0.000 description 1
• LDQNVGIGTJSTKK-UHFFFAOYSA-N methyl 5-fluoro-2-methylsulfonylbenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1S(C)(=O)=O LDQNVGIGTJSTKK-UHFFFAOYSA-N 0.000 description 1
• 229960001344 methylphenidate Drugs 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 239000003068 molecular probe Substances 0.000 description 1
• NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
• QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 1
• PHVXTQIROLEEDB-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-n-pyrrolidin-3-ylbenzamide Chemical compound CC1=CC=CC=C1C1CN(CC=2C=CC(=CC=2)C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CNCC2)CCC1 PHVXTQIROLEEDB-UHFFFAOYSA-N 0.000 description 1
• MUJNAWXXOJRNGK-UHFFFAOYSA-N n-[3-(6-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)propyl]cyclohexanamine Chemical compound C1=2CCCCC=2C2=CC(C)=CC=C2N1CCCNC1CCCCC1 MUJNAWXXOJRNGK-UHFFFAOYSA-N 0.000 description 1
• BODLESUVCQEUII-UHFFFAOYSA-N n-[4-[2-(hydroxyamino)-2-oxoethyl]piperidin-4-yl]-4-[(2-methylquinolin-4-yl)methoxy]benzamide Chemical compound C=12C=CC=CC2=NC(C)=CC=1COC(C=C1)=CC=C1C(=O)NC1(CC(=O)NO)CCNCC1 BODLESUVCQEUII-UHFFFAOYSA-N 0.000 description 1
• XZMHJYWMCRQSSI-UHFFFAOYSA-N n-[5-[2-(3-acetylanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]benzamide Chemical compound CC(=O)C1=CC=CC(NC=2SC=C(N=2)C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C)=C1 XZMHJYWMCRQSSI-UHFFFAOYSA-N 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• NNGHUOVQYKDIAH-UHFFFAOYSA-N nitrobenzene;trifluoromethanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)F.[O-][N+](=O)C1=CC=CC=C1 NNGHUOVQYKDIAH-UHFFFAOYSA-N 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• XXPANQJNYNUNES-UHFFFAOYSA-N nomifensine Chemical compound C12=CC=CC(N)=C2CN(C)CC1C1=CC=CC=C1 XXPANQJNYNUNES-UHFFFAOYSA-N 0.000 description 1
• 229960001073 nomifensine Drugs 0.000 description 1
• 238000009206 nuclear medicine Methods 0.000 description 1
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
• 238000007344 nucleophilic reaction Methods 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• 229920001542 oligosaccharide Polymers 0.000 description 1
• 150000002482 oligosaccharides Chemical class 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• NPKKRSHVJIQBKU-UHFFFAOYSA-N ornogenin Natural products CC(OC(=O)C=Cc1ccccc1)C2(O)CCC3(O)C4(O)CC=C5CC(O)CCC5(C)C4CC(OC(=O)C=Cc6ccccc6)C23C NPKKRSHVJIQBKU-UHFFFAOYSA-N 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• PFGVNLZDWRZPJW-OPAMFIHVSA-N otamixaban Chemical compound C([C@@H](C(=O)OC)[C@@H](C)NC(=O)C=1C=CC(=CC=1)C=1C=C[N+]([O-])=CC=1)C1=CC=CC(C(N)=N)=C1 PFGVNLZDWRZPJW-OPAMFIHVSA-N 0.000 description 1
• 229940045681 other alkylating agent in atc Drugs 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• TVIDEEHSOPHZBR-AWEZNQCLSA-N para-(benzoyl)-phenylalanine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C(=O)C1=CC=CC=C1 TVIDEEHSOPHZBR-AWEZNQCLSA-N 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 108010091742 peptide F Proteins 0.000 description 1
• RJSZPKZQGIKVAU-UXBJKDEOSA-N peptide f Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C(C)C)C(C)C)C1=CC=CC=C1 RJSZPKZQGIKVAU-UXBJKDEOSA-N 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 150000004713 phosphodiesters Chemical class 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
• 238000006068 polycondensation reaction Methods 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• 239000001120 potassium sulphate Substances 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000003223 protective agent Substances 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 150000003248 quinolines Chemical class 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 230000003439 radiotherapeutic effect Effects 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 238000001525 receptor binding assay Methods 0.000 description 1
• RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
• 238000009877 rendering Methods 0.000 description 1
• 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• TZSZZENYCISATO-WIOPSUGQSA-N rodatristat Chemical compound CCOC(=O)[C@@H]1CC2(CN1)CCN(CC2)c1cc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)nc(N)n1 TZSZZENYCISATO-WIOPSUGQSA-N 0.000 description 1
• 229940043230 sarcosine Drugs 0.000 description 1
• STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
• 229960002646 scopolamine Drugs 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229940055619 selenocysteine Drugs 0.000 description 1
• ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
• 235000016491 selenocysteine Nutrition 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 238000004793 spatially offset Raman spectroscopy Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 239000001117 sulphuric acid Substances 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
• 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 229940113082 thymine Drugs 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• AIYPFZXRUMBFGF-UHFFFAOYSA-M trifluoromethanesulfonate;trimethyl-(4-nitronaphthalen-1-yl)azanium Chemical compound [O-]S(=O)(=O)C(F)(F)F.C1=CC=C2C([N+](C)(C)C)=CC=C([N+]([O-])=O)C2=C1 AIYPFZXRUMBFGF-UHFFFAOYSA-M 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• 229940035893 uracil Drugs 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1