TW201109313A - Derivatives of 2H pyridazin-3-ones, their preparation and their application in human therapy - Google Patents

Info

Publication number

TW201109313A

TW201109313A TW099124897A TW99124897A TW201109313A TW 201109313 A TW201109313 A TW 201109313A TW 099124897 A TW099124897 A TW 099124897A TW 99124897 A TW99124897 A TW 99124897A TW 201109313 A TW201109313 A TW 201109313A

Authority

TW

Taiwan

Prior art keywords

phenoxy

methyl

oxo

trifluoromethyl

ethylamino

Prior art date

2009-08-05

Links

• Espacenet
• Global Dossier
• Discuss

• 238000002360 preparation method Methods 0.000 title claims description 8
• 238000002560 therapeutic procedure Methods 0.000 title claims description 6
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 86
• 239000002253 acid Substances 0.000 claims abstract description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
• 239000001257 hydrogen Substances 0.000 claims abstract description 22
• 239000000203 mixture Substances 0.000 claims abstract description 21
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 19
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 13
• 239000001301 oxygen Substances 0.000 claims abstract description 13
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
• 150000003839 salts Chemical class 0.000 claims abstract description 12
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
• 150000002367 halogens Chemical class 0.000 claims abstract description 10
• 229910052731 fluorine Inorganic materials 0.000 claims abstract description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
• 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 120
• -1 nitro, trifluoromethoxy, ethenyl Chemical group 0.000 claims description 101
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 57
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 51
• 239000002585 base Substances 0.000 claims description 48
• 238000000034 method Methods 0.000 claims description 41
• OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 34
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 28
• 229910052757 nitrogen Inorganic materials 0.000 claims description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 21
• 150000002576 ketones Chemical class 0.000 claims description 17
• 230000037361 pathway Effects 0.000 claims description 16
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
• 102000004190 Enzymes Human genes 0.000 claims description 14
• 108090000790 Enzymes Proteins 0.000 claims description 14
• 230000000694 effects Effects 0.000 claims description 14
• 239000003112 inhibitor Substances 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 238000011282 treatment Methods 0.000 claims description 12
• 239000007789 gas Substances 0.000 claims description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 229910052721 tungsten Inorganic materials 0.000 claims description 9
• 208000008589 Obesity Diseases 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 235000020824 obesity Nutrition 0.000 claims description 8
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims description 7
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 7
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 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
• 229940126601 medicinal product Drugs 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
• 125000000304 alkynyl group Chemical group 0.000 claims description 5
• 238000003556 assay Methods 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 238000005859 coupling reaction Methods 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• 239000002904 solvent Substances 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 4
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 4
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 4
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 4
• SZGBQZJLJFJVOU-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenoxy]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC=CC(C(F)(F)F)=C1 SZGBQZJLJFJVOU-UHFFFAOYSA-N 0.000 claims description 3
• SKQUSSGBKAJRTE-UHFFFAOYSA-N 4-[3-fluoro-5-(trifluoromethyl)phenoxy]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC(F)=CC(C(F)(F)F)=C1 SKQUSSGBKAJRTE-UHFFFAOYSA-N 0.000 claims description 3
• JCGOYSYDPUPVBS-UHFFFAOYSA-N 4-[5-fluoro-2-(trifluoromethyl)phenoxy]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC(F)=CC=C1C(F)(F)F JCGOYSYDPUPVBS-UHFFFAOYSA-N 0.000 claims description 3
• 208000002874 Acne Vulgaris Diseases 0.000 claims description 3
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
• 102000004877 Insulin Human genes 0.000 claims description 3
• 108090001061 Insulin Proteins 0.000 claims description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 3
• 206010000496 acne Diseases 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 3
• 229940125396 insulin Drugs 0.000 claims description 3
• PFBSOANQDDTNGJ-YNHQPCIGSA-N morphinone Chemical compound O([C@H]1C(C=C[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O PFBSOANQDDTNGJ-YNHQPCIGSA-N 0.000 claims description 3
• 125000005825 oxyethoxy group Chemical group [H]C([H])(O[*:1])C([H])([H])O[*:2] 0.000 claims description 3
• 230000001225 therapeutic effect Effects 0.000 claims description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
• KVGKFRJNCLJWQN-UHFFFAOYSA-N 2-methyl-1,2-dihydroindol-3-one Chemical compound C1=CC=C2C(=O)C(C)NC2=C1 KVGKFRJNCLJWQN-UHFFFAOYSA-N 0.000 claims description 2
• NZNIWGUHHXQCKU-UHFFFAOYSA-N 4-(2-bromo-4,5-difluorophenoxy)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC(F)=C(F)C=C1Br NZNIWGUHHXQCKU-UHFFFAOYSA-N 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 239000005944 Chlorpyrifos Substances 0.000 claims description 2
• 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 2
• 206010015150 Erythema Diseases 0.000 claims description 2
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
• 206010020772 Hypertension Diseases 0.000 claims description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 239000004480 active ingredient Substances 0.000 claims description 2
• 239000002168 alkylating agent Substances 0.000 claims description 2
• 229940100198 alkylating agent Drugs 0.000 claims description 2
• 239000003054 catalyst Substances 0.000 claims description 2
• 239000003153 chemical reaction reagent Substances 0.000 claims description 2
• SBPBAQFWLVIOKP-UHFFFAOYSA-N chlorpyrifos Chemical group CCOP(=S)(OCC)OC1=NC(Cl)=C(Cl)C=C1Cl SBPBAQFWLVIOKP-UHFFFAOYSA-N 0.000 claims description 2
• 231100000321 erythema Toxicity 0.000 claims description 2
• 239000007788 liquid Substances 0.000 claims description 2
• 201000007270 liver cancer Diseases 0.000 claims description 2
• 208000014018 liver neoplasm Diseases 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
• 210000002374 sebum Anatomy 0.000 claims description 2
• 238000006467 substitution reaction Methods 0.000 claims description 2
• 239000001384 succinic acid Substances 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• 206010028980 Neoplasm Diseases 0.000 claims 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 3
• 201000004624 Dermatitis Diseases 0.000 claims 2
• 208000017170 Lipid metabolism disease Diseases 0.000 claims 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims 2
• 229940088710 antibiotic agent Drugs 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 claims 1
• KGUGJAPPQDPQHB-UHFFFAOYSA-N 3-(4-nitrophenyl)phthalic acid Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)C1=C(C(C(=O)O)=CC=C1)C(=O)O KGUGJAPPQDPQHB-UHFFFAOYSA-N 0.000 claims 1
• VGCKBZMYKUWJRU-UHFFFAOYSA-N 4-(2,4-dichlorophenoxy)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC=C(Cl)C=C1Cl VGCKBZMYKUWJRU-UHFFFAOYSA-N 0.000 claims 1
• JBNOYNPVKVSADM-UHFFFAOYSA-N 4-(2,5-dimethylphenoxy)piperidine-1-carboxylic acid Chemical compound CC1=CC=C(C)C(OC2CCN(CC2)C(O)=O)=C1 JBNOYNPVKVSADM-UHFFFAOYSA-N 0.000 claims 1
• JTNGXZCBRTZFAA-UHFFFAOYSA-N 4-(3,4-dichlorophenoxy)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC=C(Cl)C(Cl)=C1 JTNGXZCBRTZFAA-UHFFFAOYSA-N 0.000 claims 1
• MBZJEIRMMYDAFD-UHFFFAOYSA-N 4-[2-(trifluoromethyl)phenoxy]piperidine Chemical compound FC(F)(F)C1=CC=CC=C1OC1CCNCC1 MBZJEIRMMYDAFD-UHFFFAOYSA-N 0.000 claims 1
• 229940123208 Biguanide Drugs 0.000 claims 1
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims 1
• 208000003174 Brain Neoplasms Diseases 0.000 claims 1
• OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 claims 1
• NWMDMRWOXWXQEY-UHFFFAOYSA-N CC(C)[N]C(C)C Chemical compound CC(C)[N]C(C)C NWMDMRWOXWXQEY-UHFFFAOYSA-N 0.000 claims 1
• 206010009944 Colon cancer Diseases 0.000 claims 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
• 241000219112 Cucumis Species 0.000 claims 1
• 235000015510 Cucumis melo subsp melo Nutrition 0.000 claims 1
• 102000051325 Glucagon Human genes 0.000 claims 1
• 108060003199 Glucagon Proteins 0.000 claims 1
• 102000004366 Glucosidases Human genes 0.000 claims 1
• 108010056771 Glucosidases Proteins 0.000 claims 1
• 101100041816 Homo sapiens SCD gene Proteins 0.000 claims 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
• 206010025323 Lymphomas Diseases 0.000 claims 1
• 241000283973 Oryctolagus cuniculus Species 0.000 claims 1
• 206010033128 Ovarian cancer Diseases 0.000 claims 1
• 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
• 101710176384 Peptide 1 Proteins 0.000 claims 1
• 239000001888 Peptone Substances 0.000 claims 1
• 108010080698 Peptones Proteins 0.000 claims 1
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims 1
• 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
• 206010036790 Productive cough Diseases 0.000 claims 1
• 101150097713 SCD1 gene Proteins 0.000 claims 1
• 108091006269 SLC5A2 Proteins 0.000 claims 1
• 208000015390 Sebaceous gland disease Diseases 0.000 claims 1
• 102000058081 Sodium-Glucose Transporter 2 Human genes 0.000 claims 1
• 102100028897 Stearoyl-CoA desaturase Human genes 0.000 claims 1
• 229940100389 Sulfonylurea Drugs 0.000 claims 1
• MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 claims 1
• 241000863480 Vinca Species 0.000 claims 1
• AEDMQUAPBVOJNN-UHFFFAOYSA-N [3-[2-[4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl]-1,3-thiazol-5-yl]-1,2,4-oxadiazol-5-yl]methanol Chemical compound O1C(CO)=NC(C=2SC(=NC=2)N2CCC(CC2)OC=2C(=CC=CC=2)C(F)(F)F)=N1 AEDMQUAPBVOJNN-UHFFFAOYSA-N 0.000 claims 1
• FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 claims 1
• 150000001412 amines Chemical class 0.000 claims 1
• RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 claims 1
• 239000003242 anti bacterial agent Substances 0.000 claims 1
• 230000002280 anti-androgenic effect Effects 0.000 claims 1
• 230000000844 anti-bacterial effect Effects 0.000 claims 1
• 239000000883 anti-obesity agent Substances 0.000 claims 1
• 239000000051 antiandrogen Substances 0.000 claims 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims 1
• 238000011394 anticancer treatment Methods 0.000 claims 1
• 229940125708 antidiabetic agent Drugs 0.000 claims 1
• 239000003472 antidiabetic agent Substances 0.000 claims 1
• 229940125710 antiobesity agent Drugs 0.000 claims 1
• 208000010668 atopic eczema Diseases 0.000 claims 1
• 210000000481 breast Anatomy 0.000 claims 1
• 239000003984 copper intrauterine device Substances 0.000 claims 1
• 239000000824 cytostatic agent Substances 0.000 claims 1
• 230000001085 cytostatic effect Effects 0.000 claims 1
• 231100000433 cytotoxic Toxicity 0.000 claims 1
• 230000001472 cytotoxic effect Effects 0.000 claims 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 claims 1
• 230000006806 disease prevention Effects 0.000 claims 1
• 210000003238 esophagus Anatomy 0.000 claims 1
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims 1
• 229960004666 glucagon Drugs 0.000 claims 1
• 208000019622 heart disease Diseases 0.000 claims 1
• 208000032839 leukemia Diseases 0.000 claims 1
• 238000007443 liposuction Methods 0.000 claims 1
• 201000005202 lung cancer Diseases 0.000 claims 1
• 208000020816 lung neoplasm Diseases 0.000 claims 1
• 229940127554 medical product Drugs 0.000 claims 1
• 201000001441 melanoma Diseases 0.000 claims 1
• 201000000050 myeloid neoplasm Diseases 0.000 claims 1
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims 1
• 229960001243 orlistat Drugs 0.000 claims 1
• 235000019319 peptone Nutrition 0.000 claims 1
• 239000000825 pharmaceutical preparation Substances 0.000 claims 1
• 229940127557 pharmaceutical product Drugs 0.000 claims 1
• 108090000765 processed proteins & peptides Proteins 0.000 claims 1
• 210000002307 prostate Anatomy 0.000 claims 1
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims 1
• 239000011347 resin Substances 0.000 claims 1
• 229920005989 resin Polymers 0.000 claims 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
• 230000028327 secretion Effects 0.000 claims 1
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 claims 1
• 229960004425 sibutramine Drugs 0.000 claims 1
• 208000017520 skin disease Diseases 0.000 claims 1
• 210000003802 sputum Anatomy 0.000 claims 1
• 208000024794 sputum Diseases 0.000 claims 1
• 210000002784 stomach Anatomy 0.000 claims 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 1
• 210000003932 urinary bladder Anatomy 0.000 claims 1
• 210000004291 uterus Anatomy 0.000 claims 1
• 150000007513 acids Chemical class 0.000 abstract description 4
• 239000000543 intermediate Substances 0.000 description 214
• 239000007787 solid Substances 0.000 description 93
• 239000012429 reaction media Substances 0.000 description 78
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
• 229920001296 polysiloxane Polymers 0.000 description 58
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
• 238000003818 flash chromatography Methods 0.000 description 48
• 239000000243 solution Substances 0.000 description 48
• 239000012074 organic phase Substances 0.000 description 46
• 238000001035 drying Methods 0.000 description 42
• 239000003921 oil Substances 0.000 description 41
• 235000019198 oils Nutrition 0.000 description 41
• 238000001308 synthesis method Methods 0.000 description 41
• IYGZSLRPKFUJMR-UHFFFAOYSA-N 4-amino-2-methylpyridazin-3-one Chemical compound CN1N=CC=C(N)C1=O IYGZSLRPKFUJMR-UHFFFAOYSA-N 0.000 description 40
• 239000000741 silica gel Substances 0.000 description 35
• 229910002027 silica gel Inorganic materials 0.000 description 35
• 238000010189 synthetic method Methods 0.000 description 35
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• CELPHAGZKFMOMR-UHFFFAOYSA-N azanium;dichloromethane;methanol;hydroxide Chemical compound [NH4+].[OH-].OC.ClCCl CELPHAGZKFMOMR-UHFFFAOYSA-N 0.000 description 33
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 28
• 235000018553 tannin Nutrition 0.000 description 27
• 229920001864 tannin Polymers 0.000 description 27
• 239000001648 tannin Substances 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
• 239000000706 filtrate Substances 0.000 description 22
• 101710159293 Acyl-CoA desaturase 1 Proteins 0.000 description 20
• 230000015572 biosynthetic process Effects 0.000 description 20
• 238000003786 synthesis reaction Methods 0.000 description 20
• 239000003208 petroleum Substances 0.000 description 19
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
• ZCLSQRQRWNDNLV-UHFFFAOYSA-N acetic acid;dichloromethane;methanol Chemical compound OC.ClCCl.CC(O)=O ZCLSQRQRWNDNLV-UHFFFAOYSA-N 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 15
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• 239000002244 precipitate Substances 0.000 description 12
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 239000012298 atmosphere Substances 0.000 description 9
• 239000012230 colorless oil Substances 0.000 description 9
• 150000002923 oximes Chemical class 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• JOKPOVVMRWSRAT-UHFFFAOYSA-N 5-[[2-[4-[2-chloro-5-(trifluoromethyl)phenoxy]piperidin-1-yl]-2-oxoethyl]amino]-1h-pyridazin-6-one Chemical compound FC(F)(F)C1=CC=C(Cl)C(OC2CCN(CC2)C(=O)CNC=2C(NN=CC=2)=O)=C1 JOKPOVVMRWSRAT-UHFFFAOYSA-N 0.000 description 6
• 101150041968 CDC13 gene Proteins 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 6
• 229960002449 glycine Drugs 0.000 description 6
• 150000002632 lipids Chemical class 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 239000012071 phase Substances 0.000 description 6
• 229910001220 stainless steel Inorganic materials 0.000 description 6
• 239000010935 stainless steel Substances 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• OGHGGBMXRUJBAF-UHFFFAOYSA-N 4-chloro-5-methoxy-2-methylpyridazin-3-one Chemical compound COC=1C=NN(C)C(=O)C=1Cl OGHGGBMXRUJBAF-UHFFFAOYSA-N 0.000 description 5
• 239000004471 Glycine Substances 0.000 description 5
• 235000021355 Stearic acid Nutrition 0.000 description 5
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 235000014113 dietary fatty acids Nutrition 0.000 description 5
• 229930195729 fatty acid Natural products 0.000 description 5
• 239000000194 fatty acid Substances 0.000 description 5
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 239000008117 stearic acid Substances 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• NITHEPQEHPCCKD-UHFFFAOYSA-N 6-amino-2-methylpyridazin-3-one Chemical compound CN1NC(=N)C=CC1=O NITHEPQEHPCCKD-UHFFFAOYSA-N 0.000 description 4
• 239000005909 Kieselgur Substances 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 150000004665 fatty acids Chemical class 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
• SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 4
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 3
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 3
• CCPJHBSYXWLXCU-UHFFFAOYSA-N 3-[[2-chloro-5-(trifluoromethyl)phenoxy]methyl]azetidine;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=C(Cl)C(OCC2CNC2)=C1 CCPJHBSYXWLXCU-UHFFFAOYSA-N 0.000 description 3
• SJHXUZIUQVZYRP-UHFFFAOYSA-N 4-[2-chloro-5-(trifluoromethyl)phenoxy]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC(C(F)(F)F)=CC=C1Cl SJHXUZIUQVZYRP-UHFFFAOYSA-N 0.000 description 3
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 3
• 108010087894 Fatty acid desaturases Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 102000016267 Leptin Human genes 0.000 description 3
• 108010092277 Leptin Proteins 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 239000007832 Na2SO4 Substances 0.000 description 3
• 239000005642 Oleic acid Substances 0.000 description 3
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 3
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
• 102000016553 Stearoyl-CoA Desaturase Human genes 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 238000010908 decantation Methods 0.000 description 3
• 238000006911 enzymatic reaction Methods 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 3
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 3
• 229940039781 leptin Drugs 0.000 description 3
• 210000001589 microsome Anatomy 0.000 description 3
• 235000013336 milk Nutrition 0.000 description 3
• 239000008267 milk Substances 0.000 description 3
• 210000004080 milk Anatomy 0.000 description 3
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 3
• 239000010455 vermiculite Substances 0.000 description 3
• 235000019354 vermiculite Nutrition 0.000 description 3
• 229910052902 vermiculite Inorganic materials 0.000 description 3
• QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
• SLVVMPLOQDFREV-UHFFFAOYSA-N 4,5-dibromo-2-methylpyridazin-3-one Chemical compound CN1N=CC(Br)=C(Br)C1=O SLVVMPLOQDFREV-UHFFFAOYSA-N 0.000 description 2
• OTLODDFZRJIDET-UHFFFAOYSA-N 4-(2-chloro-5-fluorophenoxy)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC(F)=CC=C1Cl OTLODDFZRJIDET-UHFFFAOYSA-N 0.000 description 2
• HUBCPEYEJSRXFU-UHFFFAOYSA-N 4-(2-chlorophenoxy)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC=CC=C1Cl HUBCPEYEJSRXFU-UHFFFAOYSA-N 0.000 description 2
• CLVBAJRLFCKYLH-UHFFFAOYSA-N 4-(2-methyl-5-propan-2-ylphenoxy)piperidine Chemical compound CC(C)C1=CC=C(C)C(OC2CCNCC2)=C1 CLVBAJRLFCKYLH-UHFFFAOYSA-N 0.000 description 2
• NQOZDUSXMVDAIP-UHFFFAOYSA-N 4-(2-methylphenoxy)piperidine-1-carboxylic acid Chemical compound CC1=CC=CC=C1OC1CCN(C(O)=O)CC1 NQOZDUSXMVDAIP-UHFFFAOYSA-N 0.000 description 2
• NMAKJOWVEDTHOA-UHFFFAOYSA-N 4-(chloromethyl)-1,3-thiazol-2-amine;hydron;chloride Chemical compound Cl.NC1=NC(CCl)=CS1 NMAKJOWVEDTHOA-UHFFFAOYSA-N 0.000 description 2
• HXUIXFWGSQHYPQ-UHFFFAOYSA-N 4-[4-fluoro-3-(trifluoromethyl)phenoxy]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC=C(F)C(C(F)(F)F)=C1 HXUIXFWGSQHYPQ-UHFFFAOYSA-N 0.000 description 2
• QCLPXDPYUVXJOZ-UHFFFAOYSA-N 4-[5-fluoro-2-(trifluoromethyl)phenoxy]piperidine Chemical compound FC1=CC=C(C(F)(F)F)C(OC2CCNCC2)=C1 QCLPXDPYUVXJOZ-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 235000021319 Palmitoleic acid Nutrition 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 108010077895 Sarcosine Proteins 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• PQRKPYLNZGDCFH-UHFFFAOYSA-N Sterculic-saeure Natural products CCCCCCCCC1=C(CCCCCCCC(O)=O)C1 PQRKPYLNZGDCFH-UHFFFAOYSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 2
• ZKHVSNDPPPJHTM-UHFFFAOYSA-N [5-fluoro-2-(trifluoromethyl)phenyl]-piperazin-1-ylmethanone Chemical compound FC1=CC=C(C(F)(F)F)C(C(=O)N2CCNCC2)=C1 ZKHVSNDPPPJHTM-UHFFFAOYSA-N 0.000 description 2
• 230000004888 barrier function Effects 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
• SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 2
• 229940125846 compound 25 Drugs 0.000 description 2
• 229940126179 compound 72 Drugs 0.000 description 2
• MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• 235000019439 ethyl acetate Nutrition 0.000 description 2
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• 230000002440 hepatic effect Effects 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• 208000006575 hypertriglyceridemia Diseases 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 235000021281 monounsaturated fatty acids Nutrition 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 229940043230 sarcosine Drugs 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 210000002027 skeletal muscle Anatomy 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 239000004575 stone Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 238000001291 vacuum drying Methods 0.000 description 2
• 230000004580 weight loss Effects 0.000 description 2
• GEFUGGQLCNKIQP-UHFFFAOYSA-N (1-benzhydrylazetidin-3-yl)methanol Chemical compound C1C(CO)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 GEFUGGQLCNKIQP-UHFFFAOYSA-N 0.000 description 1
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
• ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• RNKOUSCCPHSCFE-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanol Chemical compound COC1=CC=C(CO)C(OC)=C1 RNKOUSCCPHSCFE-UHFFFAOYSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
• IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
• YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
• ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
• IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
• OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
• MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
• NDYMQOUYJJXCKJ-UHFFFAOYSA-N (4-fluorophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CCOCC1 NDYMQOUYJJXCKJ-UHFFFAOYSA-N 0.000 description 1
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
• STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
• DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
• KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
• QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
• LNNXOEHOXSYWLD-UHFFFAOYSA-N 1-bromobut-2-yne Chemical compound CC#CCBr LNNXOEHOXSYWLD-UHFFFAOYSA-N 0.000 description 1
• BRSRUYVJULRMRQ-UHFFFAOYSA-N 1-phenylanthracene Chemical group C1=CC=CC=C1C1=CC=CC2=CC3=CC=CC=C3C=C12 BRSRUYVJULRMRQ-UHFFFAOYSA-N 0.000 description 1
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
• FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
• HZDLKGMXXMJTJE-UHFFFAOYSA-N 2-(9,9,9-trifluorononyl)phenol Chemical compound FC(CCCCCCCCC1=C(C=CC=C1)O)(F)F HZDLKGMXXMJTJE-UHFFFAOYSA-N 0.000 description 1
• MXIUWSYTQJLIKE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC=C1C(Cl)=O MXIUWSYTQJLIKE-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• DKCOMYBLBQPCNU-UHFFFAOYSA-N 2-[(1-methyl-6-oxopyridazin-4-yl)amino]acetic acid Chemical compound CN1N=CC(NCC(O)=O)=CC1=O DKCOMYBLBQPCNU-UHFFFAOYSA-N 0.000 description 1
• WOJKSJHHLQYBOQ-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-5-yl)amino]acetic acid Chemical compound OC(=O)CNC1=CC=NNC1=O WOJKSJHHLQYBOQ-UHFFFAOYSA-N 0.000 description 1
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
• GMTAOJMPNXLKJI-UHFFFAOYSA-N 2-[[1-cyclopentyl-5-[1-(oxetan-3-yl)piperidin-4-yl]pyrazol-3-yl]amino]pyridine-4-carbonitrile Chemical compound C1(CCCC1)N1N=C(C=C1C1CCN(CC1)C1COC1)NC=1C=C(C#N)C=CN=1 GMTAOJMPNXLKJI-UHFFFAOYSA-N 0.000 description 1
• FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
• VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
• NRRWGZXBTDGOCW-UHFFFAOYSA-N 2-amino-1-[4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)CN)CCC1OC1=CC=CC=C1C(F)(F)F NRRWGZXBTDGOCW-UHFFFAOYSA-N 0.000 description 1
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-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
• ITIIKYCTJXXJHV-UHFFFAOYSA-N 2-but-2-ynyl-4-[[2-[4-[2-chloro-5-(trifluoromethyl)phenoxy]piperidin-1-yl]-2-oxoethyl]amino]pyridazin-3-one Chemical compound O=C1N(CC#CC)N=CC=C1NCC(=O)N1CCC(OC=2C(=CC=C(C=2)C(F)(F)F)Cl)CC1 ITIIKYCTJXXJHV-UHFFFAOYSA-N 0.000 description 1
• YZBOVSFWWNVKRJ-UHFFFAOYSA-M 2-butoxycarbonylbenzoate Chemical compound CCCCOC(=O)C1=CC=CC=C1C([O-])=O YZBOVSFWWNVKRJ-UHFFFAOYSA-M 0.000 description 1
• LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
• NXGURAZHMLZTAV-UHFFFAOYSA-N 2-methyl-4-[[2-oxo-2-[3-[2-(trifluoromethyl)phenoxy]azetidin-1-yl]ethyl]amino]pyridazin-3-one Chemical compound O=C1N(C)N=CC=C1NCC(=O)N1CC(OC=2C(=CC=CC=2)C(F)(F)F)C1 NXGURAZHMLZTAV-UHFFFAOYSA-N 0.000 description 1
• IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
• TYEYBOSBBBHJIV-UHFFFAOYSA-M 2-oxobutanoate Chemical compound CCC(=O)C([O-])=O TYEYBOSBBBHJIV-UHFFFAOYSA-M 0.000 description 1
• GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
• UMRYPVYCXBBOJV-UHFFFAOYSA-N 3-[2-(trifluoromethyl)phenoxy]azetidine Chemical compound FC(F)(F)C1=CC=CC=C1OC1CNC1 UMRYPVYCXBBOJV-UHFFFAOYSA-N 0.000 description 1
• VNTKPYNBATZMSV-UHFFFAOYSA-N 3-fluoro-5-(trifluoromethyl)phenol Chemical compound OC1=CC(F)=CC(C(F)(F)F)=C1 VNTKPYNBATZMSV-UHFFFAOYSA-N 0.000 description 1
• ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 1
• KSTFWHGADZMXAS-UHFFFAOYSA-N 4-(2,4-dichlorophenoxy)piperidine;hydrochloride Chemical compound Cl.ClC1=CC(Cl)=CC=C1OC1CCNCC1 KSTFWHGADZMXAS-UHFFFAOYSA-N 0.000 description 1
• VEMQTTQDABETNM-UHFFFAOYSA-N 4-(2,5-dichlorophenoxy)piperidine;hydrochloride Chemical compound Cl.ClC1=CC=C(Cl)C(OC2CCNCC2)=C1 VEMQTTQDABETNM-UHFFFAOYSA-N 0.000 description 1
• FOPHVZGVLTXTBF-UHFFFAOYSA-N 4-(2,5-difluorophenoxy)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC(F)=CC=C1F FOPHVZGVLTXTBF-UHFFFAOYSA-N 0.000 description 1
• JDUHRTUCWUOSGK-UHFFFAOYSA-N 4-(2-bromo-4,5-difluorophenoxy)piperidine;hydrochloride Chemical compound Cl.C1=C(F)C(F)=CC(Br)=C1OC1CCNCC1 JDUHRTUCWUOSGK-UHFFFAOYSA-N 0.000 description 1
• ABOWEJNMSYULQQ-UHFFFAOYSA-N 4-(2-chloro-5-fluorophenoxy)piperidine;hydrochloride Chemical compound Cl.FC1=CC=C(Cl)C(OC2CCNCC2)=C1 ABOWEJNMSYULQQ-UHFFFAOYSA-N 0.000 description 1
• DQNSSLUVUXZLEO-UHFFFAOYSA-N 4-(3,4-dichlorophenoxy)piperidine Chemical compound C1=C(Cl)C(Cl)=CC=C1OC1CCNCC1 DQNSSLUVUXZLEO-UHFFFAOYSA-N 0.000 description 1
• IQWRYKVNVHNBJY-UHFFFAOYSA-N 4-(3,4-difluorophenoxy)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC=C(F)C(F)=C1 IQWRYKVNVHNBJY-UHFFFAOYSA-N 0.000 description 1
• QEUYJPUVGNZMOT-UHFFFAOYSA-N 4-(5-bromo-2-chlorophenoxy)piperidine Chemical compound ClC1=CC=C(Br)C=C1OC1CCNCC1 QEUYJPUVGNZMOT-UHFFFAOYSA-N 0.000 description 1
• XKIGYPITTSDEKB-UHFFFAOYSA-N 4-(5-bromo-2-chlorophenoxy)piperidine;hydrochloride Chemical compound Cl.ClC1=CC=C(Br)C=C1OC1CCNCC1 XKIGYPITTSDEKB-UHFFFAOYSA-N 0.000 description 1
• FIPQGQLTGWTZQZ-UHFFFAOYSA-N 4-[2-(trifluoromethyl)phenoxy]piperidine;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC=C1OC1CCNCC1 FIPQGQLTGWTZQZ-UHFFFAOYSA-N 0.000 description 1
• UKVRVGNYRYEURP-UHFFFAOYSA-N 4-[2-fluoro-5-(trifluoromethyl)phenoxy]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1OC1=CC(C(F)(F)F)=CC=C1F UKVRVGNYRYEURP-UHFFFAOYSA-N 0.000 description 1
• RSJYIBUWJRIPIJ-UHFFFAOYSA-N 4-[3-(trifluoromethoxy)phenoxy]piperidine Chemical compound FC(F)(F)OC1=CC=CC(OC2CCNCC2)=C1 RSJYIBUWJRIPIJ-UHFFFAOYSA-N 0.000 description 1
• BYJVBLFZMKBFMT-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenoxy]piperidine Chemical compound FC(F)(F)C1=CC=CC(OC2CCNCC2)=C1 BYJVBLFZMKBFMT-UHFFFAOYSA-N 0.000 description 1
• BWRMVZSDOPHLGV-UHFFFAOYSA-N 4-[3-fluoro-5-(trifluoromethyl)phenoxy]piperidine Chemical compound FC(F)(F)C1=CC(F)=CC(OC2CCNCC2)=C1 BWRMVZSDOPHLGV-UHFFFAOYSA-N 0.000 description 1
• WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
• SDEBYHVDMCQKNZ-UHFFFAOYSA-N 4-methoxy-6-piperazin-1-ylpyrimidine;hydrochloride Chemical compound Cl.C1=NC(OC)=CC(N2CCNCC2)=N1 SDEBYHVDMCQKNZ-UHFFFAOYSA-N 0.000 description 1
• DSFQYHJOHZUZNZ-UHFFFAOYSA-N 5-[[2-oxo-2-[4-[3-(trifluoromethyl)phenoxy]piperidin-1-yl]ethyl]amino]-1h-pyridazin-6-one Chemical compound FC(F)(F)C1=CC=CC(OC2CCN(CC2)C(=O)CNC=2C(NN=CC=2)=O)=C1 DSFQYHJOHZUZNZ-UHFFFAOYSA-N 0.000 description 1
• YIAQLMJPMMISNQ-UHFFFAOYSA-N 5-amino-2-methylpyridazin-3-one Chemical compound CN1N=CC(N)=CC1=O YIAQLMJPMMISNQ-UHFFFAOYSA-N 0.000 description 1
• XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
• RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
• JTWMOWRMSZZHDR-UHFFFAOYSA-N 7-(5-hydroxy-2-methylphenyl)-6-(2-methoxyphenyl)-4-methylpurino[7,8-a]imidazole-1,3-dione Chemical compound COC1=CC=CC=C1N(C(=CN12)C=3C(=CC=C(O)C=3)C)C2=NC2=C1C(=O)NC(=O)N2C JTWMOWRMSZZHDR-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
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N Acetylene Chemical compound C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• DYUSKDCBDVOBSG-UHFFFAOYSA-N C(C)(C)(C)[Ru] Chemical compound C(C)(C)(C)[Ru] DYUSKDCBDVOBSG-UHFFFAOYSA-N 0.000 description 1
• JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
• MTUKJCBQQQYYJM-UHFFFAOYSA-N C1=CC(=C(C2=C1N=CC2=O)Cl)Cl Chemical compound C1=CC(=C(C2=C1N=CC2=O)Cl)Cl MTUKJCBQQQYYJM-UHFFFAOYSA-N 0.000 description 1
• XHGZKAQBHBSXFQ-UHFFFAOYSA-N C1=CC=C(C(=C1)O)OCCCCCCCCCC(F)(F)F Chemical compound C1=CC=C(C(=C1)O)OCCCCCCCCCC(F)(F)F XHGZKAQBHBSXFQ-UHFFFAOYSA-N 0.000 description 1
• CDGPAYYJZNVUQB-UHFFFAOYSA-N C1=CC=C2C(=C1)C=C(N2)C3=C(C=C(C=C3)F)O Chemical compound C1=CC=C2C(=C1)C=C(N2)C3=C(C=C(C=C3)F)O CDGPAYYJZNVUQB-UHFFFAOYSA-N 0.000 description 1
• BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
• WABFRTVFIWTTDD-UHFFFAOYSA-N Cl.C(C)(C)(C)[SiH](C)C Chemical compound Cl.C(C)(C)(C)[SiH](C)C WABFRTVFIWTTDD-UHFFFAOYSA-N 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• 229940126639 Compound 33 Drugs 0.000 description 1
• 229940127007 Compound 39 Drugs 0.000 description 1
• 241000195493 Cryptophyta Species 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 206010019708 Hepatic steatosis Diseases 0.000 description 1
• 206010020112 Hirsutism Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
• 206010029412 Nightmare Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
• AWIFXDFXQTZAPT-UHFFFAOYSA-N SN(C1CCNCC1)S Chemical compound SN(C1CCNCC1)S AWIFXDFXQTZAPT-UHFFFAOYSA-N 0.000 description 1
• PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
• 240000006394 Sorghum bicolor Species 0.000 description 1
• 235000011684 Sorghum saccharatum Nutrition 0.000 description 1
• 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 description 1
• 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 description 1
• 239000012317 TBTU Substances 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 208000035868 Vascular inflammations Diseases 0.000 description 1
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
• SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
• SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
• 210000001789 adipocyte Anatomy 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 229940037003 alum Drugs 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 239000011260 aqueous acid Substances 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
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
• 229940073608 benzyl chloride Drugs 0.000 description 1
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 238000006388 chemical passivation reaction Methods 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
• WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
• LADPCMZCENPFGV-UHFFFAOYSA-N chloromethoxymethylbenzene Chemical compound ClCOCC1=CC=CC=C1 LADPCMZCENPFGV-UHFFFAOYSA-N 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 229940125810 compound 20 Drugs 0.000 description 1
• 229940126086 compound 21 Drugs 0.000 description 1
• 229940126208 compound 22 Drugs 0.000 description 1
• 229940125833 compound 23 Drugs 0.000 description 1
• 229940125961 compound 24 Drugs 0.000 description 1
• 229940125851 compound 27 Drugs 0.000 description 1
• 229940127204 compound 29 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 229940125877 compound 31 Drugs 0.000 description 1
• 229940125878 compound 36 Drugs 0.000 description 1
• 229940125807 compound 37 Drugs 0.000 description 1
• 229940127573 compound 38 Drugs 0.000 description 1
• 229940126540 compound 41 Drugs 0.000 description 1
• 229940125936 compound 42 Drugs 0.000 description 1
• 229940125844 compound 46 Drugs 0.000 description 1
• 229940127271 compound 49 Drugs 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 229940126545 compound 53 Drugs 0.000 description 1
• 229940127113 compound 57 Drugs 0.000 description 1
• 229940125900 compound 59 Drugs 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• SRTXFRURQPIPHT-UHFFFAOYSA-N dioxan-4-one Chemical compound O=C1CCOOC1 SRTXFRURQPIPHT-UHFFFAOYSA-N 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
• LUBGFMZTGFXIIN-UHFFFAOYSA-N ethyl 4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)CC1 LUBGFMZTGFXIIN-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000009313 farming Methods 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 238000005227 gel permeation chromatography Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 239000003292 glue Substances 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 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
• 230000003520 lipogenic effect Effects 0.000 description 1
• RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 230000003228 microsomal effect Effects 0.000 description 1
• YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 1
• IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 230000036581 peripheral resistance Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 235000013824 polyphenols Nutrition 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• RWMKSKOZLCXHOK-UHFFFAOYSA-M potassium;butanoate Chemical compound [K+].CCCC([O-])=O RWMKSKOZLCXHOK-UHFFFAOYSA-M 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 230000001012 protector Effects 0.000 description 1
• 230000001337 psychedelic effect Effects 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 201000004700 rosacea Diseases 0.000 description 1
• 229910052707 ruthenium Inorganic materials 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 239000002689 soil Substances 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
• 230000001732 thrombotic effect Effects 0.000 description 1
• 150000003613 toluenes Chemical class 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
• FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
• 238000005406 washing Methods 0.000 description 1