ZA200408057B - Heterocyclic amide derivatives for the treatment of diabetes and other diseases - Google Patents

Info

Publication number

ZA200408057B

ZA200408057B ZA200408057A ZA200408057A ZA200408057B ZA 200408057 B ZA200408057 B ZA 200408057B ZA 200408057 A ZA200408057 A ZA 200408057A ZA 200408057 A ZA200408057 A ZA 200408057A ZA 200408057 B ZA200408057 B ZA 200408057B

Authority

ZA

South Africa

Prior art keywords

compound

substituted

trimethyl

carbon atoms

tetrahydro

Prior art date

2002-03-08

Links

• Espacenet
• Global Dossier
• Discuss

• -1 Heterocyclic amide Chemical class 0.000 title claims description 204
• 238000011282 treatment Methods 0.000 title claims description 66
• 206010012601 diabetes mellitus Diseases 0.000 title claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 31
• 201000010099 disease Diseases 0.000 title description 25
• 150000001875 compounds Chemical class 0.000 claims description 260
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 93
• 125000004432 carbon atom Chemical group C* 0.000 claims description 88
• 229910052739 hydrogen Inorganic materials 0.000 claims description 76
• 239000000203 mixture Substances 0.000 claims description 69
• 238000000034 method Methods 0.000 claims description 64
• 125000000217 alkyl group Chemical group 0.000 claims description 60
• 239000001257 hydrogen Substances 0.000 claims description 50
• 150000003839 salts Chemical class 0.000 claims description 48
• 125000003118 aryl group Chemical group 0.000 claims description 45
• 125000001072 heteroaryl group Chemical group 0.000 claims description 43
• 125000001424 substituent group Chemical group 0.000 claims description 42
• 229910052736 halogen Inorganic materials 0.000 claims description 39
• 150000002367 halogens Chemical class 0.000 claims description 39
• 241000699670 Mus sp. Species 0.000 claims description 34
• 210000004027 cell Anatomy 0.000 claims description 34
• 210000002966 serum Anatomy 0.000 claims description 34
• 150000001408 amides Chemical group 0.000 claims description 32
• 230000037356 lipid metabolism Effects 0.000 claims description 32
• 125000003545 alkoxy group Chemical group 0.000 claims description 30
• 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 30
• 229910052796 boron Inorganic materials 0.000 claims description 30
• 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 30
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 30
• 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 claims description 29
• 239000008103 glucose Substances 0.000 claims description 29
• 150000002632 lipids Chemical class 0.000 claims description 28
• 206010028980 Neoplasm Diseases 0.000 claims description 27
• 230000023852 carbohydrate metabolic process Effects 0.000 claims description 27
• 230000004069 differentiation Effects 0.000 claims description 27
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 27
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims description 25
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 25
• 235000021256 carbohydrate metabolism Nutrition 0.000 claims description 24
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
• 241000124008 Mammalia Species 0.000 claims description 21
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
• 210000001789 adipocyte Anatomy 0.000 claims description 20
• 230000007423 decrease Effects 0.000 claims description 20
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 20
• 206010006187 Breast cancer Diseases 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 125000001188 haloalkyl group Chemical group 0.000 claims description 18
• 239000002243 precursor Substances 0.000 claims description 18
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 17
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 17
• 238000005859 coupling reaction Methods 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 16
• 125000003107 substituted aryl group Chemical group 0.000 claims description 16
• 125000004423 acyloxy group Chemical group 0.000 claims description 15
• 201000001320 Atherosclerosis Diseases 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000004001 thioalkyl group Chemical group 0.000 claims description 13
• 238000010168 coupling process Methods 0.000 claims description 12
• 210000000229 preadipocyte Anatomy 0.000 claims description 12
• 208000026310 Breast neoplasm Diseases 0.000 claims description 11
• 210000004369 blood Anatomy 0.000 claims description 11
• 239000008280 blood Substances 0.000 claims description 11
• 201000011510 cancer Diseases 0.000 claims description 11
• 230000008878 coupling Effects 0.000 claims description 11
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 9
• 125000003342 alkenyl group Chemical group 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 8
• 241000699666 Mus <mouse, genus> Species 0.000 claims description 8
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• CHBRHODLKOZEPZ-UHFFFAOYSA-N Clotiazepam Chemical compound S1C(CC)=CC2=C1N(C)C(=O)CN=C2C1=CC=CC=C1Cl CHBRHODLKOZEPZ-UHFFFAOYSA-N 0.000 claims description 7
• 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 7
• 150000001768 cations Chemical class 0.000 claims description 7
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 7
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 7
• 125000004421 aryl sulphonamide group Chemical group 0.000 claims description 6
• 150000001450 anions Chemical class 0.000 claims description 5
• 235000009200 high fat diet Nutrition 0.000 claims description 5
• 229910052744 lithium Inorganic materials 0.000 claims description 5
• KIWUVOGUEXMXSV-UHFFFAOYSA-N rhodanine Chemical compound O=C1CSC(=S)N1 KIWUVOGUEXMXSV-UHFFFAOYSA-N 0.000 claims description 5
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 4
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 4
• 229910052782 aluminium Inorganic materials 0.000 claims description 4
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• UGWULZWUXSCWPX-UHFFFAOYSA-N 2-sulfanylideneimidazolidin-4-one Chemical group O=C1CNC(=S)N1 UGWULZWUXSCWPX-UHFFFAOYSA-N 0.000 claims description 3
• ZCFXFIHRHWRKAY-UHFFFAOYSA-N 5-[[3-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)-4-(trifluoromethoxy)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O ZCFXFIHRHWRKAY-UHFFFAOYSA-N 0.000 claims description 3
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
• 239000011575 calcium Substances 0.000 claims description 3
• 230000006372 lipid accumulation Effects 0.000 claims description 3
• 239000011777 magnesium Substances 0.000 claims description 3
• 229910052749 magnesium Inorganic materials 0.000 claims description 3
• 229910052700 potassium Inorganic materials 0.000 claims description 3
• IGHXENSMRWDRKA-UHFFFAOYSA-N 5-[[2,5-difluoro-4-methoxy-3-(1,4,4,6-tetramethyl-2-oxo-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound FC1=C(C=2C(=CC=3C(C)(C)CC(=O)N(C)C=3C=2)C)C(OC)=C(F)C=C1C=C1SC(=O)NC1=O IGHXENSMRWDRKA-UHFFFAOYSA-N 0.000 claims description 2
• GTWRJNHQYADCSI-UHFFFAOYSA-N 5-[[4-(dimethylamino)-3-(1,4,7-trimethyl-2,3-dioxoquinoxalin-6-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C(C=2C(=CC=3N(C)C(=O)C(=O)N(C)C=3C=2)C)C(N(C)C)=CC=C1C=C1SC(=O)NC1=O GTWRJNHQYADCSI-UHFFFAOYSA-N 0.000 claims description 2
• FQHFXXCZTRYANX-UHFFFAOYSA-N 5-[[4-(ethylamino)-3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C(C=2C(=CC=3C(C)(C)CC(=O)N(CC)C=3C=2)C)C(NCC)=CC=C1C=C1SC(=O)NC1=O FQHFXXCZTRYANX-UHFFFAOYSA-N 0.000 claims description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims 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 claims description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 2
• 229910052791 calcium Inorganic materials 0.000 claims description 2
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 claims description 2
• 229960002023 chloroprocaine Drugs 0.000 claims description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 2
• 229960001231 choline Drugs 0.000 claims description 2
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
• 229940043237 diethanolamine Drugs 0.000 claims description 2
• 229940012017 ethylenediamine Drugs 0.000 claims description 2
• 125000001905 inorganic group Chemical group 0.000 claims description 2
• 229960003194 meglumine Drugs 0.000 claims description 2
• 235000019371 penicillin G benzathine Nutrition 0.000 claims description 2
• 239000011591 potassium Substances 0.000 claims description 2
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
• 229960004919 procaine Drugs 0.000 claims description 2
• 229910052708 sodium Inorganic materials 0.000 claims description 2
• 239000011734 sodium Substances 0.000 claims description 2
• 229910052725 zinc Inorganic materials 0.000 claims description 2
• 239000011701 zinc Substances 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 9
• 238000004519 manufacturing process Methods 0.000 claims 7
• RPBRNECKATZCRH-UHFFFAOYSA-N 5-[[4-(trifluoromethoxy)-3-(3,3,5-trimethyl-2-oxo-1-propylindol-6-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(CCC)C(=O)C(C)(C)C2=CC(C)=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O RPBRNECKATZCRH-UHFFFAOYSA-N 0.000 claims 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical class [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
• 150000001457 metallic cations Chemical class 0.000 claims 1
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 129
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
• 239000000243 solution Substances 0.000 description 84
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
• 235000019439 ethyl acetate Nutrition 0.000 description 67
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 66
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
• 238000005481 NMR spectroscopy Methods 0.000 description 62
• 150000003254 radicals Chemical class 0.000 description 62
• 229940093499 ethyl acetate Drugs 0.000 description 58
• 239000012267 brine Substances 0.000 description 54
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 54
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
• 239000011541 reaction mixture Substances 0.000 description 37
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
• 241001465754 Metazoa Species 0.000 description 34
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 34
• 229910052786 argon Inorganic materials 0.000 description 33
• 239000000741 silica gel Substances 0.000 description 33
• 229910002027 silica gel Inorganic materials 0.000 description 33
• 235000012000 cholesterol Nutrition 0.000 description 32
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
• 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 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
• 229940125846 compound 25 Drugs 0.000 description 30
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• 230000000694 effects Effects 0.000 description 24
• 239000000543 intermediate Substances 0.000 description 23
• 238000005160 1H NMR spectroscopy Methods 0.000 description 22
• 238000006243 chemical reaction Methods 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 17
• 150000005347 biaryls Chemical group 0.000 description 16
• 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 description 16
• 229910052757 nitrogen Inorganic materials 0.000 description 16
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 16
• 229910000027 potassium carbonate Inorganic materials 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• 239000004480 active ingredient Substances 0.000 description 15
• 239000010410 layer Substances 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• 229940125782 compound 2 Drugs 0.000 description 14
• CNBHOGNVZIMKAQ-UHFFFAOYSA-N 7-bromo-1,4,4,6-tetramethyl-3h-quinolin-2-one Chemical compound CC1=C(Br)C=C2N(C)C(=O)CC(C)(C)C2=C1 CNBHOGNVZIMKAQ-UHFFFAOYSA-N 0.000 description 13
• SSIVEDPNMAMSDY-UHFFFAOYSA-N 7-bromo-1-ethyl-4,4,6-trimethyl-3h-quinolin-2-one Chemical compound CC1=C(Br)C=C2N(CC)C(=O)CC(C)(C)C2=C1 SSIVEDPNMAMSDY-UHFFFAOYSA-N 0.000 description 13
• 235000005911 diet Nutrition 0.000 description 13
• 230000037213 diet Effects 0.000 description 13
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 12
• 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 12
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 12
• 229910052799 carbon Inorganic materials 0.000 description 12
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 12
• 229940125961 compound 24 Drugs 0.000 description 12
• 230000002829 reductive effect Effects 0.000 description 11
• PJAKAPWOIDACRK-UHFFFAOYSA-N 7-bromo-4,4,6-trimethyl-1,3-dihydroquinolin-2-one Chemical compound C1=C(Br)C(C)=CC2=C1NC(=O)CC2(C)C PJAKAPWOIDACRK-UHFFFAOYSA-N 0.000 description 10
• 125000004429 atom Chemical group 0.000 description 10
• 230000015572 biosynthetic process Effects 0.000 description 10
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 10
• 239000003981 vehicle Substances 0.000 description 10
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 9
• 229910052794 bromium Inorganic materials 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000008159 sesame oil Substances 0.000 description 9
• 235000011803 sesame oil Nutrition 0.000 description 9
• 102000004877 Insulin Human genes 0.000 description 8
• 108090001061 Insulin Proteins 0.000 description 8
• 210000000497 foam cell Anatomy 0.000 description 8
• 230000000977 initiatory effect Effects 0.000 description 8
• 229940125396 insulin Drugs 0.000 description 8
• 229910052740 iodine Inorganic materials 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• 238000012453 sprague-dawley rat model Methods 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• 241000283984 Rodentia Species 0.000 description 7
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
• 230000004071 biological effect Effects 0.000 description 7
• 229910052801 chlorine Inorganic materials 0.000 description 7
• 239000012044 organic layer Substances 0.000 description 7
• 239000001301 oxygen Substances 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical compound C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 description 7
• 238000001953 recrystallisation Methods 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• 241000282412 Homo Species 0.000 description 6
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
• 229940123464 Thiazolidinedione Drugs 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• 208000035475 disorder Diseases 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 239000003480 eluent Substances 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 210000002540 macrophage Anatomy 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 229910052751 metal Inorganic materials 0.000 description 6
• XGOQDFJVDHMBKQ-UHFFFAOYSA-N n-(2-bromo-5-methoxy-4-methylphenyl)-2-methylpropanamide Chemical compound COC1=CC(NC(=O)C(C)C)=C(Br)C=C1C XGOQDFJVDHMBKQ-UHFFFAOYSA-N 0.000 description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
• IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical class CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 6
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 6
• JUQPMGSSKZAASF-UHFFFAOYSA-N 3-bromo-2,5-difluoro-4-methoxybenzaldehyde Chemical compound COC1=C(F)C=C(C=O)C(F)=C1Br JUQPMGSSKZAASF-UHFFFAOYSA-N 0.000 description 5
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
• 208000031226 Hyperlipidaemia Diseases 0.000 description 5
• 238000008214 LDL Cholesterol Methods 0.000 description 5
• 238000006069 Suzuki reaction reaction Methods 0.000 description 5
• 125000003277 amino group Chemical group 0.000 description 5
• 125000003710 aryl alkyl group Chemical group 0.000 description 5
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• 230000004663 cell proliferation Effects 0.000 description 5
• 238000009833 condensation Methods 0.000 description 5
• 230000005494 condensation Effects 0.000 description 5
• 230000003247 decreasing effect Effects 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 230000006870 function Effects 0.000 description 5
• 230000001939 inductive effect Effects 0.000 description 5
• 230000004060 metabolic process Effects 0.000 description 5
• 239000002184 metal Substances 0.000 description 5
• 238000003305 oral gavage Methods 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 230000001105 regulatory effect Effects 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 5
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
• 210000003462 vein Anatomy 0.000 description 5
• DMTYZWDMNXEIDM-UHFFFAOYSA-N (2-formylquinolin-4-yl) trifluoromethanesulfonate Chemical compound C1=CC=C2C(OS(=O)(=O)C(F)(F)F)=CC(C=O)=NC2=C1 DMTYZWDMNXEIDM-UHFFFAOYSA-N 0.000 description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
• KZRXNWKQSSTNPU-UHFFFAOYSA-N 2-fluoro-3-iodo-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(F)=C1I KZRXNWKQSSTNPU-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• 108010007622 LDL Lipoproteins Proteins 0.000 description 4
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 239000007983 Tris buffer Substances 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 150000001720 carbohydrates Chemical class 0.000 description 4
• 235000014633 carbohydrates Nutrition 0.000 description 4
• 239000001768 carboxy methyl cellulose Substances 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 4
• 229940105329 carboxymethylcellulose Drugs 0.000 description 4
• 239000003183 carcinogenic agent Substances 0.000 description 4
• 229940125904 compound 1 Drugs 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 150000004820 halides Chemical class 0.000 description 4
• 150000002391 heterocyclic compounds Chemical class 0.000 description 4
• 150000002430 hydrocarbons Chemical group 0.000 description 4
• 239000005457 ice water Substances 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 235000019341 magnesium sulphate Nutrition 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
• 229910052698 phosphorus Inorganic materials 0.000 description 4
• 239000011574 phosphorus Substances 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
• 230000003068 static effect Effects 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 230000002194 synthesizing effect Effects 0.000 description 4
• 150000003626 triacylglycerols Chemical class 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
• 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
• ZDYZXDMSXMJOEV-UHFFFAOYSA-N 1,4,6-trimethylquinoxaline-2,3-dione Chemical compound CN1C(=O)C(=O)N(C)C2=CC(C)=CC=C21 ZDYZXDMSXMJOEV-UHFFFAOYSA-N 0.000 description 3
• ARUFMVSDUAMBFY-UHFFFAOYSA-N 1-benzyl-6-hydroxy-3,3,5-trimethylindol-2-one Chemical compound C1=C(O)C(C)=CC(C(C2=O)(C)C)=C1N2CC1=CC=CC=C1 ARUFMVSDUAMBFY-UHFFFAOYSA-N 0.000 description 3
• WGVJMLYQPNCPSD-UHFFFAOYSA-N 2-bromo-5-methoxy-4-methylaniline Chemical compound COC1=CC(N)=C(Br)C=C1C WGVJMLYQPNCPSD-UHFFFAOYSA-N 0.000 description 3
• TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 3
• VWOYSIGIEVHTRQ-UHFFFAOYSA-N 3-bromo-4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1Br VWOYSIGIEVHTRQ-UHFFFAOYSA-N 0.000 description 3
• XUBRIMJGYHSDAR-UHFFFAOYSA-N 3-bromo-4-(ethylamino)benzaldehyde Chemical compound CCNC1=CC=C(C=O)C=C1Br XUBRIMJGYHSDAR-UHFFFAOYSA-N 0.000 description 3
• GRXMMIBZRMKADT-UHFFFAOYSA-N 3-bromo-4-methylaniline Chemical compound CC1=CC=C(N)C=C1Br GRXMMIBZRMKADT-UHFFFAOYSA-N 0.000 description 3
• ONADZNBSLRAJFW-UHFFFAOYSA-N 3-methoxy-4-methylaniline Chemical compound COC1=CC(N)=CC=C1C ONADZNBSLRAJFW-UHFFFAOYSA-N 0.000 description 3
• LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 3
• HGNFGAFGLAHEDK-UHFFFAOYSA-N 6-bromo-1,4,7-trimethylquinoxaline-2,3-dione Chemical compound CN1C(=O)C(=O)N(C)C2=C1C=C(C)C(Br)=C2 HGNFGAFGLAHEDK-UHFFFAOYSA-N 0.000 description 3
• HOHZZPCLZWZMOM-UHFFFAOYSA-N 6-methyl-1,4-dihydroquinoxaline-2,3-dione Chemical compound N1C(=O)C(=O)NC2=CC(C)=CC=C21 HOHZZPCLZWZMOM-UHFFFAOYSA-N 0.000 description 3
• QBRKQYMAWUFRDT-UHFFFAOYSA-N 7-bromo-4,4,6-trimethyl-1-propyl-3h-quinolin-2-one Chemical compound CC1=C(Br)C=C2N(CCC)C(=O)CC(C)(C)C2=C1 QBRKQYMAWUFRDT-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 3
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 125000002252 acyl group Chemical group 0.000 description 3
• 125000003368 amide group Chemical group 0.000 description 3
• 230000003178 anti-diabetic effect Effects 0.000 description 3
• 150000001502 aryl halides Chemical class 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 125000001246 bromo group Chemical group Br* 0.000 description 3
• 230000000711 cancerogenic effect Effects 0.000 description 3
• 231100000357 carcinogen Toxicity 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000013626 chemical specie Substances 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 230000015271 coagulation Effects 0.000 description 3
• 238000005345 coagulation Methods 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 239000012894 fetal calf serum Substances 0.000 description 3
• 239000012634 fragment Substances 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 125000002346 iodo group Chemical group I* 0.000 description 3
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• HZGRQOIWBSRYTI-UHFFFAOYSA-N n-(3-bromo-4-methylphenyl)-3-methylbut-2-enamide Chemical compound CC(C)=CC(=O)NC1=CC=C(C)C(Br)=C1 HZGRQOIWBSRYTI-UHFFFAOYSA-N 0.000 description 3
• DNNTYPWUKXSDCR-UHFFFAOYSA-N n-(3-hydroxy-4-methylphenyl)-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=C(C)C(O)=C1 DNNTYPWUKXSDCR-UHFFFAOYSA-N 0.000 description 3
• ZBGRNWYPTUDFTE-UHFFFAOYSA-N n-(3-methoxy-4-methylphenyl)-2-methylpropanamide Chemical compound COC1=CC(NC(=O)C(C)C)=CC=C1C ZBGRNWYPTUDFTE-UHFFFAOYSA-N 0.000 description 3
• YYDMGLLIVHEAFK-UHFFFAOYSA-N n-benzyl-n-(2-bromo-5-methoxy-4-methylphenyl)-2-methylpropanamide Chemical compound C1=C(C)C(OC)=CC(N(CC=2C=CC=CC=2)C(=O)C(C)C)=C1Br YYDMGLLIVHEAFK-UHFFFAOYSA-N 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
• 210000002381 plasma Anatomy 0.000 description 3
• 229920000728 polyester Polymers 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 230000002250 progressing effect Effects 0.000 description 3
• 238000007363 ring formation reaction Methods 0.000 description 3
• 229960005322 streptomycin Drugs 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 238000010189 synthetic method Methods 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 3
• KHNIBLSPHKTIAE-UHFFFAOYSA-N 1,4,4,6-tetramethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3h-quinolin-2-one Chemical compound C1=C2N(C)C(=O)CC(C)(C)C2=CC(C)=C1B1OC(C)(C)C(C)(C)O1 KHNIBLSPHKTIAE-UHFFFAOYSA-N 0.000 description 2
• FXOWNWCPCUXUCM-UHFFFAOYSA-N 1-benzyl-6-methoxy-3,3,5-trimethylindol-2-one Chemical compound O=C1C(C)(C)C=2C=C(C)C(OC)=CC=2N1CC1=CC=CC=C1 FXOWNWCPCUXUCM-UHFFFAOYSA-N 0.000 description 2
• XANVIFOBBVAKCY-UHFFFAOYSA-N 1-bromo-2-fluoro-4-methoxybenzene Chemical compound COC1=CC=C(Br)C(F)=C1 XANVIFOBBVAKCY-UHFFFAOYSA-N 0.000 description 2
• FFPHRYLGIPAZBL-UHFFFAOYSA-N 2,5-difluoro-4-hydroxybenzaldehyde Chemical compound OC1=CC(F)=C(C=O)C=C1F FFPHRYLGIPAZBL-UHFFFAOYSA-N 0.000 description 2
• UWEZBKLLMKVIPI-UHFFFAOYSA-N 2,5-dinitrophenol Chemical compound OC1=CC([N+]([O-])=O)=CC=C1[N+]([O-])=O UWEZBKLLMKVIPI-UHFFFAOYSA-N 0.000 description 2
• NZIRPRNRDXSPAP-UHFFFAOYSA-N 2-(2-fluoro-4-methoxyphenyl)-1,3-dioxolane Chemical compound FC1=CC(OC)=CC=C1C1OCCO1 NZIRPRNRDXSPAP-UHFFFAOYSA-N 0.000 description 2
• UNWQNFJBBWXFBG-UHFFFAOYSA-N 2-fluoro-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(F)=C1 UNWQNFJBBWXFBG-UHFFFAOYSA-N 0.000 description 2
• LZHLMTIYRMCYPZ-UHFFFAOYSA-N 3-bromo-2,5-difluoro-4-hydroxybenzaldehyde Chemical compound OC1=C(F)C=C(C=O)C(F)=C1Br LZHLMTIYRMCYPZ-UHFFFAOYSA-N 0.000 description 2
• AKDABJGHOOCVKX-UHFFFAOYSA-N 3-bromo-4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Br AKDABJGHOOCVKX-UHFFFAOYSA-N 0.000 description 2
• QQSOKNIUOFMGHE-UHFFFAOYSA-N 3-bromo-5-fluoro-4-methoxybenzaldehyde Chemical compound COC1=C(F)C=C(C=O)C=C1Br QQSOKNIUOFMGHE-UHFFFAOYSA-N 0.000 description 2
• PSFYFMXVPVBVNK-UHFFFAOYSA-N 4-(dimethylamino)-3-(1,4,7-trimethyl-2,3-dioxoquinoxalin-6-yl)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1C(C(=C1)C)=CC2=C1N(C)C(=O)C(=O)N2C PSFYFMXVPVBVNK-UHFFFAOYSA-N 0.000 description 2
• VOZPBSXWLDIHGY-UHFFFAOYSA-N 4-(trifluoromethoxy)-3-(3,3,5-trimethyl-2-oxo-1-propylindol-6-yl)benzaldehyde Chemical compound C1=C2N(CCC)C(=O)C(C)(C)C2=CC(C)=C1C1=CC(C=O)=CC=C1OC(F)(F)F VOZPBSXWLDIHGY-UHFFFAOYSA-N 0.000 description 2
• ZMZSNUROGZUHAW-UHFFFAOYSA-N 6-hydroxy-3,3,5-trimethyl-1h-indol-2-one Chemical compound C1=C(O)C(C)=CC2=C1NC(=O)C2(C)C ZMZSNUROGZUHAW-UHFFFAOYSA-N 0.000 description 2
• UODCBMPAVVLWGY-UHFFFAOYSA-N 7-bromo-4,4,6-trimethyl-1-propan-2-yl-3h-quinolin-2-one Chemical compound CC1=C(Br)C=C2N(C(C)C)C(=O)CC(C)(C)C2=C1 UODCBMPAVVLWGY-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 229920000858 Cyclodextrin Polymers 0.000 description 2
• XYWDPYKBIRQXQS-UHFFFAOYSA-N Diisopropyl sulfide Chemical compound CC(C)SC(C)C XYWDPYKBIRQXQS-UHFFFAOYSA-N 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• 239000002841 Lewis acid Substances 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical compound NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
• GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical class ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 2
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 150000001448 anilines Chemical class 0.000 description 2
• 125000000129 anionic group Chemical group 0.000 description 2
• 239000003472 antidiabetic agent Substances 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• QYVVUXPJFQZLSY-UHFFFAOYSA-N argon;n,n-diethylethanamine Chemical compound [Ar].CCN(CC)CC QYVVUXPJFQZLSY-UHFFFAOYSA-N 0.000 description 2
• 150000001491 aromatic compounds Chemical class 0.000 description 2
• 150000005840 aryl radicals Chemical class 0.000 description 2
• 230000003143 atherosclerotic effect Effects 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
• 239000012455 biphasic mixture Substances 0.000 description 2
• 230000036765 blood level Effects 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• 230000031709 bromination Effects 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
• 150000001718 carbodiimides Chemical class 0.000 description 2
• 230000024245 cell differentiation Effects 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 230000000052 comparative effect Effects 0.000 description 2
• 239000007822 coupling agent Substances 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 150000001924 cycloalkanes Chemical class 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 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 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 230000002939 deleterious effect Effects 0.000 description 2
• 239000003599 detergent Substances 0.000 description 2
• 239000012954 diazonium Substances 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
• VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 2
• LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical group C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 description 2
• 150000004683 dihydrates Chemical class 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 235000019197 fats Nutrition 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 208000019622 heart disease Diseases 0.000 description 2
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
• 230000000260 hypercholesteremic effect Effects 0.000 description 2
• 201000001421 hyperglycemia Diseases 0.000 description 2
• 208000006575 hypertriglyceridemia Diseases 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 230000028709 inflammatory response Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 150000003951 lactams Chemical class 0.000 description 2
• 150000007517 lewis acids Chemical class 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 239000012452 mother liquor Substances 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• FSJPJQTYBADMOU-UHFFFAOYSA-N n-(2-bromo-5-methoxy-4-methylphenyl)-n-[(4-methoxyphenyl)methyl]-2-methylpropanamide Chemical compound C1=CC(OC)=CC=C1CN(C(=O)C(C)C)C1=CC(OC)=C(C)C=C1Br FSJPJQTYBADMOU-UHFFFAOYSA-N 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 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 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 230000002335 preservative effect Effects 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 2
• 229940070891 pyridium Drugs 0.000 description 2
• 239000011669 selenium Substances 0.000 description 2
• 239000004017 serum-free culture medium Substances 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 238000013222 sprague-dawley male rat Methods 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• SFLXUZPXEWWQNH-UHFFFAOYSA-K tetrabutylazanium;tribromide Chemical compound [Br-].[Br-].[Br-].CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC SFLXUZPXEWWQNH-UHFFFAOYSA-K 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 150000003852 triazoles Chemical class 0.000 description 2
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 2
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
• QYYZXEPEVBXNNA-QGZVFWFLSA-N (1R)-2-acetyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-methylsulfonyl-1,3-dihydroisoindole-1-carboxamide Chemical compound C(C)(=O)N1[C@H](C2=CC=C(C=C2C1)S(=O)(=O)C)C(=O)NC1=CC=C(C=C1)C(C(F)(F)F)(C(F)(F)F)O QYYZXEPEVBXNNA-QGZVFWFLSA-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
• 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
• 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
• 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
• 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
• FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
• MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-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
• AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• MFJNOXOAIFNSBX-UHFFFAOYSA-N 1-fluoro-3-methoxybenzene Chemical compound COC1=CC=CC(F)=C1 MFJNOXOAIFNSBX-UHFFFAOYSA-N 0.000 description 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
• AHPNFDUORGLKLN-UHFFFAOYSA-N 2-(2-fluoro-3-iodo-4-methoxyphenyl)-1,3-dioxolane Chemical compound FC1=C(I)C(OC)=CC=C1C1OCCO1 AHPNFDUORGLKLN-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
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• XFZFJQHXWJIBQV-UHFFFAOYSA-N 2-bromo-1-methyl-4-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1Br XFZFJQHXWJIBQV-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• 125000006040 2-hexenyl group Chemical group 0.000 description 1
• WVQGZNRUEVFXKR-UHFFFAOYSA-N 2-methoxy-1-methyl-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1C WVQGZNRUEVFXKR-UHFFFAOYSA-N 0.000 description 1
• DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
• 125000006024 2-pentenyl group Chemical group 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• CYKREIUNECUPJV-UHFFFAOYSA-N 3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)-2-fluoro-4-methoxybenzaldehyde Chemical compound C1=C2N(CC)C(=O)CC(C)(C)C2=CC(C)=C1C1=C(F)C(C=O)=CC=C1OC CYKREIUNECUPJV-UHFFFAOYSA-N 0.000 description 1
• WELPCQAOQVBHOX-UHFFFAOYSA-N 3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)-5-fluoro-4-methoxybenzaldehyde Chemical compound C1=C2N(CC)C(=O)CC(C)(C)C2=CC(C)=C1C1=CC(C=O)=CC(F)=C1OC WELPCQAOQVBHOX-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• OCIAOFZMQWTYNX-UHFFFAOYSA-N 3-bromo-4-(trifluoromethoxy)benzaldehyde Chemical compound FC(F)(F)OC1=CC=C(C=O)C=C1Br OCIAOFZMQWTYNX-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• SOQCZBSZZLWDGU-UHFFFAOYSA-N 3-fluoro-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1F SOQCZBSZZLWDGU-UHFFFAOYSA-N 0.000 description 1
• 125000006041 3-hexenyl group Chemical group 0.000 description 1
• BDUBTLFQHNYXPC-UHFFFAOYSA-N 3-methylbut-2-enoyl chloride Chemical compound CC(C)=CC(Cl)=O BDUBTLFQHNYXPC-UHFFFAOYSA-N 0.000 description 1
• MNFZZNNFORDXSV-UHFFFAOYSA-N 4-(diethylamino)benzaldehyde Chemical compound CCN(CC)C1=CC=C(C=O)C=C1 MNFZZNNFORDXSV-UHFFFAOYSA-N 0.000 description 1
• BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
• KZVSSYOBRMRKAW-UHFFFAOYSA-N 4-(ethylamino)-3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)benzaldehyde Chemical compound CCNC1=CC=C(C=O)C=C1C(C(=C1)C)=CC2=C1C(C)(C)CC(=O)N2CC KZVSSYOBRMRKAW-UHFFFAOYSA-N 0.000 description 1
• HHFADIWGIXULNU-UHFFFAOYSA-N 4-(trifluoromethylsulfonyl)quinoline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC(S(=O)(=O)C(F)(F)F)=C21 HHFADIWGIXULNU-UHFFFAOYSA-N 0.000 description 1
• LSKRWPRFCQDQRI-UHFFFAOYSA-N 4-chloro-3-(1,4,4,6-tetramethyl-2-oxo-3h-quinolin-7-yl)benzaldehyde Chemical compound C1=C2N(C)C(=O)CC(C)(C)C2=CC(C)=C1C1=CC(C=O)=CC=C1Cl LSKRWPRFCQDQRI-UHFFFAOYSA-N 0.000 description 1
• AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
• 125000006042 4-hexenyl group Chemical group 0.000 description 1
• DGRGLKZMKWPMOH-UHFFFAOYSA-N 4-methylbenzene-1,2-diamine Chemical compound CC1=CC=C(N)C(N)=C1 DGRGLKZMKWPMOH-UHFFFAOYSA-N 0.000 description 1
• 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
• ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical compound OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 description 1
• OVGKEHDDXLFCLP-UHFFFAOYSA-N 5-[[4-(dimethylamino)-3-(1,4,4,6-tetramethyl-2-oxo-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C(C=2C(=CC=3C(C)(C)CC(=O)N(C)C=3C=2)C)C(N(C)C)=CC=C1C=C1SC(=O)NC1=O OVGKEHDDXLFCLP-UHFFFAOYSA-N 0.000 description 1
• NDSWOANBUNAJAY-UHFFFAOYSA-N 5-[[4-(dimethylamino)-3-(4,4,6-trimethyl-2-oxo-1-propan-2-yl-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(C(C)C)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)N(C)C)=CC=1C=C1SC(=O)NC1=O NDSWOANBUNAJAY-UHFFFAOYSA-N 0.000 description 1
• RXSDNKZJROLXLW-UHFFFAOYSA-N 5-[[4-(trifluoromethoxy)-3-(4,4,6-trimethyl-2-oxo-1-propan-2-yl-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(C(C)C)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O RXSDNKZJROLXLW-UHFFFAOYSA-N 0.000 description 1
• DBFYESDCPWWCHN-UHFFFAOYSA-N 5-amino-2-methylphenol Chemical compound CC1=CC=C(N)C=C1O DBFYESDCPWWCHN-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• BSFODEXXVBBYOC-UHFFFAOYSA-N 8-[4-(dimethylamino)butan-2-ylamino]quinolin-6-ol Chemical compound C1=CN=C2C(NC(CCN(C)C)C)=CC(O)=CC2=C1 BSFODEXXVBBYOC-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
• 102000005666 Apolipoprotein A-I Human genes 0.000 description 1
• 108010059886 Apolipoprotein A-I Proteins 0.000 description 1
• OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 description 1
• 241001249193 Artemisia campestris Species 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• RZSUFWRGUUUUFO-UHFFFAOYSA-N BrC1C(N(C2=CC=C(C=C2C1(C)C)C)CC)=O Chemical compound BrC1C(N(C2=CC=C(C=C2C1(C)C)C)CC)=O RZSUFWRGUUUUFO-UHFFFAOYSA-N 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
• KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
• 238000006364 Duff aldehyde synthesis reaction Methods 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
• GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
• 238000007107 Gatterman reaction Methods 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 238000007164 Haack reaction Methods 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 229940122355 Insulin sensitizer Drugs 0.000 description 1
• 208000031942 Late Onset disease Diseases 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 206010054805 Macroangiopathy Diseases 0.000 description 1
• 101100046991 Mus musculus Trim46 gene Proteins 0.000 description 1
• ZRKWMRDKSOPRRS-UHFFFAOYSA-N N-Methyl-N-nitrosourea Chemical compound O=NN(C)C(N)=O ZRKWMRDKSOPRRS-UHFFFAOYSA-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
• 206010061309 Neoplasm progression Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 101100450138 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) hat-2 gene Proteins 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 206010033307 Overweight Diseases 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 241000287127 Passeridae Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 239000012979 RPMI medium Substances 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• 238000007013 Reimer-Tiemann formylation reaction Methods 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical group C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 238000007239 Wittig reaction Methods 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
• XPIVOYOQXKNYHA-RGDJUOJXSA-N [(2r,3s,4s,5r,6s)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]methyl n-heptylcarbamate Chemical compound CCCCCCCNC(=O)OC[C@H]1O[C@H](OC)[C@H](O)[C@@H](O)[C@@H]1O XPIVOYOQXKNYHA-RGDJUOJXSA-N 0.000 description 1
• ZZWABYQKBLDNHJ-UHFFFAOYSA-N [C]=Cc1ccccc1 Chemical compound [C]=Cc1ccccc1 ZZWABYQKBLDNHJ-UHFFFAOYSA-N 0.000 description 1
• 159000000021 acetate salts Chemical class 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 108010022164 acetyl-LDL Proteins 0.000 description 1
• 229910052768 actinide Inorganic materials 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 125000005360 alkyl sulfoxide group Chemical group 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
• 229960003942 amphotericin b Drugs 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 229940125708 antidiabetic agent Drugs 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 108010068380 arginylarginine Proteins 0.000 description 1
• UBOIOTWHERUBJL-UHFFFAOYSA-N argon;pyridine Chemical compound [Ar].C1=CC=NC=C1 UBOIOTWHERUBJL-UHFFFAOYSA-N 0.000 description 1
• 229910052785 arsenic Inorganic materials 0.000 description 1
• RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 230000000923 atherogenic effect Effects 0.000 description 1
• ZUDYPQRUOYEARG-UHFFFAOYSA-L barium(2+);dihydroxide;octahydrate Chemical compound O.O.O.O.O.O.O.O.[OH-].[OH-].[Ba+2] ZUDYPQRUOYEARG-UHFFFAOYSA-L 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 125000001743 benzylic group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229910052792 caesium Inorganic materials 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000019522 cellular metabolic process Effects 0.000 description 1
• 230000004700 cellular uptake Effects 0.000 description 1
• 208000019065 cervical carcinoma Diseases 0.000 description 1
• 230000012085 chronic inflammatory response Effects 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004040 coloring Methods 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
• 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
• 229940126214 compound 3 Drugs 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 238000006482 condensation reaction Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 235000019784 crude fat Nutrition 0.000 description 1
• 210000004748 cultured cell Anatomy 0.000 description 1
• 150000001923 cyclic compounds Chemical class 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
• 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• 150000001993 dienes Chemical class 0.000 description 1
• LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• WAMUUPMTZJJGAW-UHFFFAOYSA-N ethyl 4-(trifluoromethylsulfonyl)quinoline-2-carboxylate Chemical compound C1=CC=CC2=NC(C(=O)OCC)=CC(S(=O)(=O)C(F)(F)F)=C21 WAMUUPMTZJJGAW-UHFFFAOYSA-N 0.000 description 1
• QYWDBSSGPAVTJX-UHFFFAOYSA-N ethyl 4-(trifluoromethylsulfonyloxy)quinoline-2-carboxylate Chemical compound C1=CC=CC2=NC(C(=O)OCC)=CC(OS(=O)(=O)C(F)(F)F)=C21 QYWDBSSGPAVTJX-UHFFFAOYSA-N 0.000 description 1
• UACLREXZGKWWIC-UHFFFAOYSA-N ethyl 4-oxo-1h-quinoline-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC(=O)C2=C1 UACLREXZGKWWIC-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000013213 extrapolation Methods 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 235000021588 free fatty acids Nutrition 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 229910052733 gallium Inorganic materials 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000003349 gelling agent Substances 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 229910052732 germanium Inorganic materials 0.000 description 1
• GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 231100000304 hepatotoxicity Toxicity 0.000 description 1
• 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229920001477 hydrophilic polymer Polymers 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• GVONPBONFIJAHJ-UHFFFAOYSA-N imidazolidin-4-one Chemical group O=C1CNCN1 GVONPBONFIJAHJ-UHFFFAOYSA-N 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 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
• 229940047889 isobutyramide Drugs 0.000 description 1
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 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
• 150000002576 ketones Chemical class 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 229910052747 lanthanoid Inorganic materials 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• SQEHCNOBYLQFTG-UHFFFAOYSA-M lithium;thiophene-2-carboxylate Chemical compound [Li+].[O-]C(=O)C1=CC=CS1 SQEHCNOBYLQFTG-UHFFFAOYSA-M 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 230000007056 liver toxicity Effects 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 229910052987 metal hydride Inorganic materials 0.000 description 1
• 150000004681 metal hydrides Chemical class 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 229910052752 metalloid Inorganic materials 0.000 description 1
• 150000002738 metalloids Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• OTHBCWKTCXJYAW-UHFFFAOYSA-N n,n-dibenzylformamide Chemical compound C=1C=CC=CC=1CN(C=O)CC1=CC=CC=C1 OTHBCWKTCXJYAW-UHFFFAOYSA-N 0.000 description 1
• ACVHDOLKAPAIGB-UHFFFAOYSA-N n-benzyl-n-methylformamide Chemical compound O=CN(C)CC1=CC=CC=C1 ACVHDOLKAPAIGB-UHFFFAOYSA-N 0.000 description 1
• FJLHLDBEZKTSOK-UHFFFAOYSA-N n-ethyl-n-methylformamide Chemical compound CCN(C)C=O FJLHLDBEZKTSOK-UHFFFAOYSA-N 0.000 description 1
• KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 1
• KVTGAKFJRLBHLU-UHFFFAOYSA-N n-propan-2-ylformamide Chemical compound CC(C)NC=O KVTGAKFJRLBHLU-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 229910052756 noble gas Inorganic materials 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
• 150000004986 phenylenediamines Chemical class 0.000 description 1
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 208000030761 polycystic kidney disease Diseases 0.000 description 1
• 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 230000004853 protein function Effects 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229910052711 selenium Inorganic materials 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229940054269 sodium pyruvate Drugs 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
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 238000013223 sprague-dawley female rat Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229910052714 tellurium Inorganic materials 0.000 description 1
• PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• LBUJPTNKIBCYBY-UHFFFAOYSA-N tetrahydroquinoline Natural products C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• 229910052718 tin Inorganic materials 0.000 description 1
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 150000005671 trienes Chemical class 0.000 description 1
• 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
• 150000008648 triflates Chemical class 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
• 229960001641 troglitazone Drugs 0.000 description 1
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
• 230000005751 tumor progression Effects 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000011787 zinc oxide Substances 0.000 description 1