BR112019019868A2 - derivados de tetra-hidro-benzo[d]azepina como moduladores gpr120 - Google Patents

Info

Publication number

BR112019019868A2

BR112019019868A2 BR112019019868A BR112019019868A BR112019019868A2 BR 112019019868 A2 BR112019019868 A2 BR 112019019868A2 BR 112019019868 A BR112019019868 A BR 112019019868A BR 112019019868 A BR112019019868 A BR 112019019868A BR 112019019868 A2 BR112019019868 A2 BR 112019019868A2

Authority

BR

Brazil

Prior art keywords

optionally substituted

alkyl

halo

cio

compound according

Prior art date

2017-03-24

Links

• Espacenet
• Global Dossier
• Discuss

• MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical class C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 233
• 239000000203 mixture Substances 0.000 claims abstract description 135
• 238000000034 method Methods 0.000 claims abstract description 109
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract description 62
• 102000004877 Insulin Human genes 0.000 claims abstract description 31
• 108090001061 Insulin Proteins 0.000 claims abstract description 31
• 229940125396 insulin Drugs 0.000 claims abstract description 31
• 238000011282 treatment Methods 0.000 claims abstract description 27
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 24
• 208000008589 Obesity Diseases 0.000 claims abstract description 20
• 235000020824 obesity Nutrition 0.000 claims abstract description 20
• -1 R 21 Chemical compound 0.000 claims description 324
• 125000005843 halogen group Chemical group 0.000 claims description 179
• 125000000217 alkyl group Chemical group 0.000 claims description 117
• 125000003118 aryl group Chemical group 0.000 claims description 108
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 78
• 239000002253 acid Substances 0.000 claims description 73
• 125000001424 substituent group Chemical group 0.000 claims description 68
• 101000890672 Homo sapiens Free fatty acid receptor 4 Proteins 0.000 claims description 59
• 125000001072 heteroaryl group Chemical group 0.000 claims description 49
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 47
• 229910052739 hydrogen Inorganic materials 0.000 claims description 44
• 239000001257 hydrogen Substances 0.000 claims description 44
• 238000002360 preparation method Methods 0.000 claims description 42
• 201000010099 disease Diseases 0.000 claims description 41
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 41
• 239000000651 prodrug Substances 0.000 claims description 39
• 229940002612 prodrug Drugs 0.000 claims description 39
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
• 239000003814 drug Substances 0.000 claims description 38
• 102100040134 Free fatty acid receptor 4 Human genes 0.000 claims description 37
• 125000001153 fluoro group Chemical group F* 0.000 claims description 34
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 34
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 31
• 125000000304 alkynyl group Chemical group 0.000 claims description 29
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 29
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 28
• 229910052805 deuterium Inorganic materials 0.000 claims description 28
• 125000000623 heterocyclic group Chemical group 0.000 claims description 28
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 28
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 27
• 125000003545 alkoxy group Chemical group 0.000 claims description 27
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 27
• 235000019260 propionic acid Nutrition 0.000 claims description 27
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 26
• 150000002431 hydrogen Chemical class 0.000 claims description 26
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 25
• 125000003342 alkenyl group Chemical group 0.000 claims description 25
• 125000001188 haloalkyl group Chemical group 0.000 claims description 25
• 125000003107 substituted aryl group Chemical group 0.000 claims description 25
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
• 150000002148 esters Chemical class 0.000 claims description 22
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 21
• 125000004414 alkyl thio group Chemical group 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
• 230000000694 effects Effects 0.000 claims description 19
• 208000017169 kidney disease Diseases 0.000 claims description 19
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 19
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 17
• 206010020772 Hypertension Diseases 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 206010022489 Insulin Resistance Diseases 0.000 claims description 16
• 150000001204 N-oxides Chemical class 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 239000012453 solvate Substances 0.000 claims description 15
• 201000001320 Atherosclerosis Diseases 0.000 claims description 14
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 14
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 13
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 12
• 208000002705 Glucose Intolerance Diseases 0.000 claims description 12
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 12
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 12
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
• 230000001225 therapeutic effect Effects 0.000 claims description 12
• 229910052721 tungsten Inorganic materials 0.000 claims description 12
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 11
• 201000001421 hyperglycemia Diseases 0.000 claims description 11
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 10
• 206010023379 Ketoacidosis Diseases 0.000 claims description 10
• 208000007976 Ketosis Diseases 0.000 claims description 10
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 10
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 9
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 9
• 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 9
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 9
• 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 9
• 208000013016 Hypoglycemia Diseases 0.000 claims description 9
• 206010030113 Oedema Diseases 0.000 claims description 9
• 208000007536 Thrombosis Diseases 0.000 claims description 9
• 201000006549 dyspepsia Diseases 0.000 claims description 9
• 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 9
• 201000008980 hyperinsulinism Diseases 0.000 claims description 9
• 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 9
• 208000006575 hypertriglyceridemia Diseases 0.000 claims description 9
• 230000002218 hypoglycaemic effect Effects 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 208000011580 syndromic disease Diseases 0.000 claims description 9
• 206010028980 Neoplasm Diseases 0.000 claims description 8
• 201000011510 cancer Diseases 0.000 claims description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 7
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 7
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 5
• 230000008569 process Effects 0.000 claims description 5
• 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 4
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 2
• MZBVNYACSSGXID-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1-benzazepine Chemical class N1CCCCC2=CC=CC=C21 MZBVNYACSSGXID-UHFFFAOYSA-N 0.000 abstract description 4
• 206010061218 Inflammation Diseases 0.000 abstract description 4
• 230000004054 inflammatory process Effects 0.000 abstract description 4
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 abstract description 3
• 238000001727 in vivo Methods 0.000 abstract description 2
• 208000030159 metabolic disease Diseases 0.000 abstract description 2
• 102000004169 proteins and genes Human genes 0.000 abstract description 2
• 108090000623 proteins and genes Proteins 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
• 239000000243 solution Substances 0.000 description 97
• 235000019439 ethyl acetate Nutrition 0.000 description 94
• 238000005481 NMR spectroscopy Methods 0.000 description 93
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 81
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 70
• 239000000047 product Substances 0.000 description 66
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 53
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 50
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 50
• 238000004587 chromatography analysis Methods 0.000 description 50
• 239000011734 sodium Substances 0.000 description 47
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 42
• 239000000741 silica gel Substances 0.000 description 41
• 229910002027 silica gel Inorganic materials 0.000 description 41
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 229910052757 nitrogen Inorganic materials 0.000 description 29
• 239000012267 brine Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• 239000007787 solid Substances 0.000 description 28
• 239000003208 petroleum Substances 0.000 description 26
• 229910052786 argon Inorganic materials 0.000 description 25
• 239000012230 colorless oil Substances 0.000 description 25
• 102000056353 human FFAR4 Human genes 0.000 description 21
• 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 description 20
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 19
• 239000000556 agonist Substances 0.000 description 18
• 229940079593 drug Drugs 0.000 description 18
• 239000003921 oil Substances 0.000 description 18
• 235000019198 oils Nutrition 0.000 description 18
• 239000012074 organic phase Substances 0.000 description 18
• 239000007858 starting material Substances 0.000 description 18
• 229910052731 fluorine Inorganic materials 0.000 description 17
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 17
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
• 238000006243 chemical reaction Methods 0.000 description 16
• 239000011737 fluorine Substances 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
• 210000004027 cell Anatomy 0.000 description 15
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 15
• 239000011541 reaction mixture Substances 0.000 description 15
• 229940124597 therapeutic agent Drugs 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 14
• 239000000377 silicon dioxide Substances 0.000 description 14
• 239000003472 antidiabetic agent Substances 0.000 description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 125000004432 carbon atom Chemical group C* 0.000 description 12
• 125000005842 heteroatom Chemical group 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 11
• 239000004480 active ingredient Substances 0.000 description 11
• 239000008103 glucose Substances 0.000 description 11
• 238000004519 manufacturing process Methods 0.000 description 11
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 229940125708 antidiabetic agent Drugs 0.000 description 10
• 229910052799 carbon Inorganic materials 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 0 CCC(CC1)C(CCC*C(C)(C)*(C)(C)*)C*1[C@]1(C)CCICC*(C)CCC1 Chemical compound CCC(CC1)C(CCC*C(C)(C)*(C)(C)*)C*1[C@]1(C)CCICC*(C)CCC1 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• 108010007622 LDL Lipoproteins Proteins 0.000 description 8
• 102000007330 LDL Lipoproteins Human genes 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
• 125000004429 atom Chemical group 0.000 description 8
• 210000004204 blood vessel Anatomy 0.000 description 8
• 239000004615 ingredient Substances 0.000 description 8
• 239000003112 inhibitor Substances 0.000 description 8
• 210000004185 liver Anatomy 0.000 description 8
• 210000002381 plasma Anatomy 0.000 description 8
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
• FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 8
• 102000004895 Lipoproteins Human genes 0.000 description 7
• 108090001030 Lipoproteins Proteins 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 7
• 210000004369 blood Anatomy 0.000 description 7
• 239000008280 blood Substances 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 235000012000 cholesterol Nutrition 0.000 description 7
• 235000014113 dietary fatty acids Nutrition 0.000 description 7
• 239000000194 fatty acid Substances 0.000 description 7
• 229930195729 fatty acid Natural products 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 230000002209 hydrophobic effect Effects 0.000 description 7
• 229910052760 oxygen Inorganic materials 0.000 description 7
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 7
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 238000006467 substitution reaction Methods 0.000 description 7
• VVVFPEJORKPEST-UHFFFAOYSA-N 2-bromo-1-fluoro-4-(trifluoromethoxy)benzene Chemical compound FC1=CC=C(OC(F)(F)F)C=C1Br VVVFPEJORKPEST-UHFFFAOYSA-N 0.000 description 6
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 6
• 102100039994 Gastric inhibitory polypeptide Human genes 0.000 description 6
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 108010010234 HDL Lipoproteins Proteins 0.000 description 6
• 102000015779 HDL Lipoproteins Human genes 0.000 description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 238000010521 absorption reaction Methods 0.000 description 6
• 238000000225 bioluminescence resonance energy transfer Methods 0.000 description 6
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
• 229910000024 caesium carbonate Inorganic materials 0.000 description 6
• 208000035475 disorder Diseases 0.000 description 6
• 150000004665 fatty acids Chemical class 0.000 description 6
• 239000000796 flavoring agent Substances 0.000 description 6
• 235000013355 food flavoring agent Nutrition 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 230000003647 oxidation Effects 0.000 description 6
• 238000007254 oxidation reaction Methods 0.000 description 6
• 230000036961 partial effect Effects 0.000 description 6
• 239000012041 precatalyst Substances 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 229910052717 sulfur Inorganic materials 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• HLYYXICXUZUTQP-UHFFFAOYSA-N 2-[2-(5-cyclobutyloxy-2-fluorophenyl)-3,4-dihydro-1H-isoquinolin-6-yl]cyclopropane-1-carboxylic acid Chemical compound C1(CCC1)OC=1C=CC(=C(C=1)N1CC2=CC=C(C=C2CC1)C1C(C1)C(=O)O)F HLYYXICXUZUTQP-UHFFFAOYSA-N 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• 239000004215 Carbon black (E152) Substances 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 5
• 108010001831 LDL receptors Proteins 0.000 description 5
• 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 5
• 101100227062 Mus musculus Ffar4 gene Proteins 0.000 description 5
• 102100040918 Pro-glucagon Human genes 0.000 description 5
• 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 5
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 5
• 108010062497 VLDL Lipoproteins Proteins 0.000 description 5
• 239000007900 aqueous suspension Substances 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 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 5
• 230000006378 damage Effects 0.000 description 5
• 235000003599 food sweetener Nutrition 0.000 description 5
• 150000002367 halogens Chemical class 0.000 description 5
• 229930195733 hydrocarbon Natural products 0.000 description 5
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 229920000728 polyester Polymers 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 230000028327 secretion Effects 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• KXLPARPVNCJKPG-UHFFFAOYSA-N 2-[2-(3-phenoxyphenyl)-3,4-dihydro-1H-isoquinolin-6-yl]cyclopropane-1-carboxylic acid Chemical compound O(C1=CC=CC=C1)C=1C=C(C=CC=1)N1CC2=CC=C(C=C2CC1)C1C(C1)C(=O)O KXLPARPVNCJKPG-UHFFFAOYSA-N 0.000 description 4
• CVOMTGPYFHADJZ-UHFFFAOYSA-N 3-[2-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound FC1=C(C=C(C=C1)OC(F)(F)F)N1CC2=CC=C(C=C2CC1)CCC(=O)O CVOMTGPYFHADJZ-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 4
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 210000000577 adipose tissue Anatomy 0.000 description 4
• KXVUSQIDCZRUKF-UHFFFAOYSA-N bromocyclobutane Chemical compound BrC1CCC1 KXVUSQIDCZRUKF-UHFFFAOYSA-N 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• 230000007547 defect Effects 0.000 description 4
• 230000007812 deficiency Effects 0.000 description 4
• MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical compound CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 235000019197 fats Nutrition 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 230000003914 insulin secretion Effects 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• 235000019341 magnesium sulphate Nutrition 0.000 description 4
• 229960003105 metformin Drugs 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 239000000080 wetting agent Substances 0.000 description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 3
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 3
• FVZLXIARAAOVCZ-UHFFFAOYSA-N 1h-azepine-3-carboxylic acid Chemical compound OC(=O)C1=CNC=CC=C1 FVZLXIARAAOVCZ-UHFFFAOYSA-N 0.000 description 3
• BWXXPDPOLZNOLQ-UHFFFAOYSA-N 3-[2-(6-cyclobutyloxy-3,5-difluoropyridin-2-yl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C1(CCC1)OC1=C(C=C(C(=N1)N1CC2=CC=C(C=C2CC1)CCC(=O)O)F)F BWXXPDPOLZNOLQ-UHFFFAOYSA-N 0.000 description 3
• JMIOODLINTVCIJ-UHFFFAOYSA-N 3-[2-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-methylpropanoic acid Chemical compound FC1=C(C=C(C=C1)OC(F)(F)F)N1CC2=CC=C(C=C2CC1)CC(C(=O)O)C JMIOODLINTVCIJ-UHFFFAOYSA-N 0.000 description 3
• QWTULQLVGNZMLF-UHFFFAOYSA-N 3-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C(Br)=C1 QWTULQLVGNZMLF-UHFFFAOYSA-N 0.000 description 3
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
• ZTEATMVVGQUULZ-UHFFFAOYSA-N 6-bromoisoquinoline Chemical compound C1=NC=CC2=CC(Br)=CC=C21 ZTEATMVVGQUULZ-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 3
• YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 3
• 108010046315 IDL Lipoproteins Proteins 0.000 description 3
• 235000019483 Peanut oil Nutrition 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 108010052090 Renilla Luciferases Proteins 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 3
• 229940100389 Sulfonylurea Drugs 0.000 description 3
• 229940123464 Thiazolidinedione Drugs 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 230000005856 abnormality Effects 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 229940127003 anti-diabetic drug Drugs 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 125000005605 benzo group Chemical group 0.000 description 3
• 238000005415 bioluminescence Methods 0.000 description 3
• 230000029918 bioluminescence Effects 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 208000029078 coronary artery disease Diseases 0.000 description 3
• KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 229960003834 dapagliflozin Drugs 0.000 description 3
• 235000005911 diet Nutrition 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• YIJPGYIGIACKPA-UHFFFAOYSA-N ethyl 3-(1,2,3,4-tetrahydroisoquinolin-6-yl)propanoate hydrochloride Chemical compound Cl.C1NCCC2=CC(=CC=C12)CCC(=O)OCC YIJPGYIGIACKPA-UHFFFAOYSA-N 0.000 description 3
• 239000012091 fetal bovine serum Substances 0.000 description 3
• 238000003818 flash chromatography Methods 0.000 description 3
• 230000002496 gastric effect Effects 0.000 description 3
• 210000001035 gastrointestinal tract Anatomy 0.000 description 3
• 208000004104 gestational diabetes Diseases 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• 229940088597 hormone Drugs 0.000 description 3
• 239000005556 hormone Substances 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 239000000312 peanut oil Substances 0.000 description 3
• 239000000813 peptide hormone Substances 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
• 229960005095 pioglitazone Drugs 0.000 description 3
• 235000015320 potassium carbonate Nutrition 0.000 description 3
• 201000009104 prediabetes syndrome Diseases 0.000 description 3
• 230000009257 reactivity Effects 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
• 125000004434 sulfur atom Chemical group 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 3
• 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• 238000001890 transfection Methods 0.000 description 3
• BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• 239000003643 water by type Substances 0.000 description 3
• 238000009736 wetting Methods 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 2
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
• DRAFPQXZQPSXRI-UHFFFAOYSA-N (3-methoxycyclobutyl)oxymethylbenzene Chemical compound COC1CC(C1)OCc1ccccc1 DRAFPQXZQPSXRI-UHFFFAOYSA-N 0.000 description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
• AOGCIOQQBKDEHN-UHFFFAOYSA-N 1-cyclobutyloxy-4,5-difluoro-2-nitrobenzene Chemical compound C1(CCC1)OC1=C(C=C(C(=C1)F)F)[N+](=O)[O-] AOGCIOQQBKDEHN-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• NXWZDQUUCHVDMW-UHFFFAOYSA-N 2-[2-(6-cyclobutyloxy-3-fluoropyridin-2-yl)-3,4-dihydro-1H-isoquinolin-6-yl]cyclopropane-1-carboxylic acid Chemical compound C1(CCC1)OC1=CC=C(C(=N1)N1CC2=CC=C(C=C2CC1)C1C(C1)C(=O)O)F NXWZDQUUCHVDMW-UHFFFAOYSA-N 0.000 description 2
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
• GNJLAKNGFNVOOF-UHFFFAOYSA-N 2-cyclobutyloxy-4,5-difluoroaniline Chemical compound C1(CCC1)OC1=C(N)C=C(C(=C1)F)F GNJLAKNGFNVOOF-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• MJNDBMVJHWUXPI-UHFFFAOYSA-N 3-[2-(2-phenoxyphenyl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound O(C1=CC=CC=C1)C1=C(C=CC=C1)N1CC2=CC=C(C=C2CC1)CCC(=O)O MJNDBMVJHWUXPI-UHFFFAOYSA-N 0.000 description 2
• QJGFJGVDKUBXFY-UHFFFAOYSA-N 3-[2-(3,5-dimethylphenyl)-3,4-dihydro-1H-isoquinolin-7-yl]propanoic acid Chemical compound CC=1C=C(C=C(C=1)C)N1CC2=CC(=CC=C2CC1)CCC(=O)O QJGFJGVDKUBXFY-UHFFFAOYSA-N 0.000 description 2
• UTWNXYMRAKYNMB-UHFFFAOYSA-N 3-[2-(3-cyclobutyloxy-5-fluorophenyl)-7-fluoro-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C1(CCC1)OC=1C=C(C=C(C=1)F)N1CC2=CC(=C(C=C2CC1)CCC(=O)O)F UTWNXYMRAKYNMB-UHFFFAOYSA-N 0.000 description 2
• GDYPJFRFZPCYAV-UHFFFAOYSA-N 3-[2-(5-cyclobutyloxy-2-fluorophenyl)-3,4-dihydro-1H-isoquinolin-6-yl]-2-methylpropanoic acid Chemical compound C1(CCC1)OC=1C=CC(=C(C=1)N1CC2=CC=C(C=C2CC1)CC(C(=O)O)C)F GDYPJFRFZPCYAV-UHFFFAOYSA-N 0.000 description 2
• LTWACFZTWKUWHM-UHFFFAOYSA-N 3-[2-[3-(trifluoromethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound FC(OC=1C=C(C=CC=1)N1CC2=CC=C(C=C2CC1)CCC(=O)O)(F)F LTWACFZTWKUWHM-UHFFFAOYSA-N 0.000 description 2
• LPGBXHWIQNZEJB-UHFFFAOYSA-N 3-[4-[[5-fluoro-2-(4-methylphenyl)phenyl]methoxy]phenyl]propanoic acid Chemical compound C1=CC(C)=CC=C1C1=CC=C(F)C=C1COC1=CC=C(CCC(O)=O)C=C1 LPGBXHWIQNZEJB-UHFFFAOYSA-N 0.000 description 2
• ZGSDRBWWICYJBU-UHFFFAOYSA-N 3-phenylmethoxycyclobutan-1-ol Chemical compound C1C(O)CC1OCC1=CC=CC=C1 ZGSDRBWWICYJBU-UHFFFAOYSA-N 0.000 description 2
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• SEHPXAKLMRODLS-UHFFFAOYSA-N 6-bromo-7-fluoroisoquinoline Chemical compound N1=CC=C2C=C(Br)C(F)=CC2=C1 SEHPXAKLMRODLS-UHFFFAOYSA-N 0.000 description 2
• ULCYLVITTXFZCK-UHFFFAOYSA-N 6-bromo-8-fluoroisoquinoline Chemical compound C1=NC=C2C(F)=CC(Br)=CC2=C1 ULCYLVITTXFZCK-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 2
• SRHSUCQTLMTVKY-WCCKRBBISA-N COC([C@@H](C[Zn])C)=O Chemical compound COC([C@@H](C[Zn])C)=O SRHSUCQTLMTVKY-WCCKRBBISA-N 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 229940127007 Compound 39 Drugs 0.000 description 2
• 208000002249 Diabetes Complications Diseases 0.000 description 2
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 2
• 108010011459 Exenatide Proteins 0.000 description 2
• 201000001376 Familial Combined Hyperlipidemia Diseases 0.000 description 2
• 101150108864 Ffar1 gene Proteins 0.000 description 2
• 108010088406 Glucagon-Like Peptides Proteins 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
• 239000012981 Hank's balanced salt solution Substances 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 206010020710 Hyperphagia Diseases 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 208000026350 Inborn Genetic disease Diseases 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 2
• 239000004367 Lipase Substances 0.000 description 2
• 102000004882 Lipase Human genes 0.000 description 2
• 108090001060 Lipase Proteins 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
• AWAPAFOTUVGLGQ-UHFFFAOYSA-N N-[(4-bromo-2-fluorophenyl)methyl]-N-(2,2-dimethoxyethyl)-4-methylbenzenesulfonamide Chemical compound BrC1=CC(=C(CN(S(=O)(=O)C2=CC=C(C=C2)C)CC(OC)OC)C=C1)F AWAPAFOTUVGLGQ-UHFFFAOYSA-N 0.000 description 2
• SLYPEPKCAKVRAM-UHFFFAOYSA-N N-[(4-bromo-3-fluorophenyl)methyl]-N-(2,2-dimethoxyethyl)-4-methylbenzenesulfonamide Chemical compound BrC1=C(C=C(CN(S(=O)(=O)C2=CC=C(C=C2)C)CC(OC)OC)C=C1)F SLYPEPKCAKVRAM-UHFFFAOYSA-N 0.000 description 2
• SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
• 239000000006 Nitroglycerin Substances 0.000 description 2
• 208000018262 Peripheral vascular disease Diseases 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 229920002873 Polyethylenimine Polymers 0.000 description 2
• 208000004880 Polyuria Diseases 0.000 description 2
• 208000017442 Retinal disease Diseases 0.000 description 2
• 206010038923 Retinopathy Diseases 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
• 229930006000 Sucrose Natural products 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 101100264077 Xenopus laevis wrn gene Proteins 0.000 description 2
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 239000000305 astragalus gummifer gum Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 230000004071 biological effect Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 208000015114 central nervous system disease Diseases 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 230000001906 cholesterol absorption Effects 0.000 description 2
• 229940125904 compound 1 Drugs 0.000 description 2
• 229940125773 compound 10 Drugs 0.000 description 2
• 229940127573 compound 38 Drugs 0.000 description 2
• 230000021615 conjugation Effects 0.000 description 2
• RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• 230000000378 dietary effect Effects 0.000 description 2
• 239000006274 endogenous ligand Substances 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• HKJSYKUSQDSTRX-UHFFFAOYSA-N ethyl 3-(7-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)propanoate hydrochloride Chemical compound Cl.FC1=C(C=C2CCNCC2=C1)CCC(=O)OCC HKJSYKUSQDSTRX-UHFFFAOYSA-N 0.000 description 2
• LDDOSDVZPSGLFZ-UHFFFAOYSA-N ethyl cyclopropanecarboxylate Chemical compound CCOC(=O)C1CC1 LDDOSDVZPSGLFZ-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 235000013305 food Nutrition 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• 208000016361 genetic disease Diseases 0.000 description 2
• 230000014101 glucose homeostasis Effects 0.000 description 2
• 229960003711 glyceryl trinitrate Drugs 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
• 239000012442 inert solvent Substances 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 description 2
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 229960002397 linagliptin Drugs 0.000 description 2
• 235000019421 lipase Nutrition 0.000 description 2
• 230000004130 lipolysis Effects 0.000 description 2
• 108010022197 lipoprotein cholesterol Proteins 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
• 239000002324 mouth wash Substances 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 125000005429 oxyalkyl group Chemical group 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 238000003359 percent control normalization Methods 0.000 description 2
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
• 206010036067 polydipsia Diseases 0.000 description 2
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 208000022530 polyphagia Diseases 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
• 125000005493 quinolyl group Chemical group 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 239000013557 residual solvent Substances 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 229960004586 rosiglitazone Drugs 0.000 description 2
• 230000000580 secretagogue effect Effects 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 229960004034 sitagliptin Drugs 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 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 2
• 238000012799 strong cation exchange Methods 0.000 description 2
• 125000005415 substituted alkoxy group Chemical group 0.000 description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• CTEOEMPYRPQTDU-UHFFFAOYSA-N tert-butyl 1h-azepine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CNC=CC=C1 CTEOEMPYRPQTDU-UHFFFAOYSA-N 0.000 description 2
• IYEKKKPZDSSCCE-UHFFFAOYSA-N tert-butyl 7-bromo-1,3,4,5-tetrahydro-2-benzazepine-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC2=CC(Br)=CC=C21 IYEKKKPZDSSCCE-UHFFFAOYSA-N 0.000 description 2
• JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 2
• NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 150000003626 triacylglycerols Chemical class 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 229960001641 troglitazone Drugs 0.000 description 2
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
• 238000000825 ultraviolet detection Methods 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 229960001254 vildagliptin Drugs 0.000 description 2
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 2
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 2
• JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
• WLWNRAWQDZRXMB-YLFCFFPRSA-N (2r,3r,4r,5s)-n,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 WLWNRAWQDZRXMB-YLFCFFPRSA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
• PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
• OEFSDPTZUXBHBT-PUUKEUDRSA-N (4S)-3-[2-[2-(5-cyclobutyloxy-2-fluorophenyl)-3,4-dihydro-1H-isoquinolin-6-yl]cyclopropanecarbonyl]-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound C1(CCC1)OC=1C=CC(=C(C=1)N1CC2=CC=C(C=C2CC1)C1C(C1)C(=O)N1C(OC[C@@H]1C(C)C)=O)F OEFSDPTZUXBHBT-PUUKEUDRSA-N 0.000 description 1
• YBUPWRYTXGAWJX-RXMQYKEDSA-N (4s)-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)[C@H]1COC(=O)N1 YBUPWRYTXGAWJX-RXMQYKEDSA-N 0.000 description 1
• RBCOYOYDYNXAFA-UHFFFAOYSA-L (5-hydroxy-4,6-dimethylpyridin-3-yl)methyl phosphate Chemical compound CC1=NC=C(COP([O-])([O-])=O)C(C)=C1O RBCOYOYDYNXAFA-UHFFFAOYSA-L 0.000 description 1
• RWIUTHWKQHRQNP-ZDVGBALWSA-N (9e,12e)-n-(1-phenylethyl)octadeca-9,12-dienamide Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(=O)NC(C)C1=CC=CC=C1 RWIUTHWKQHRQNP-ZDVGBALWSA-N 0.000 description 1
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
• LAPUCTDQSOSDRH-UHFFFAOYSA-N 1,1-dimethoxyethanamine Chemical compound COC(C)(N)OC LAPUCTDQSOSDRH-UHFFFAOYSA-N 0.000 description 1
• OXFGRWIKQDSSLY-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-2-ium-1-carboxylate Chemical compound C1=CC=C2C(C(=O)O)NCCC2=C1 OXFGRWIKQDSSLY-UHFFFAOYSA-N 0.000 description 1
• HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
• 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
• LMFRTSBQRLSJHC-UHFFFAOYSA-N 1-bromo-3,5-dimethylbenzene Chemical compound CC1=CC(C)=CC(Br)=C1 LMFRTSBQRLSJHC-UHFFFAOYSA-N 0.000 description 1
• WVUDHWBCPSXAFN-UHFFFAOYSA-N 1-bromo-3-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=CC(Br)=C1 WVUDHWBCPSXAFN-UHFFFAOYSA-N 0.000 description 1
• WRTZKPSRGUXBOM-UHFFFAOYSA-N 1-bromo-3-chloro-5-cyclobutyloxybenzene Chemical compound BrC1=CC(=CC(=C1)OC1CCC1)Cl WRTZKPSRGUXBOM-UHFFFAOYSA-N 0.000 description 1
• HPQQLBGOMYSPFF-UHFFFAOYSA-N 1-bromo-3-cyclobutyloxy-5-fluorobenzene Chemical compound BrC1=CC(=CC(=C1)F)OC1CCC1 HPQQLBGOMYSPFF-UHFFFAOYSA-N 0.000 description 1
• AHDAKFFMKLQPTD-UHFFFAOYSA-N 1-bromo-3-phenoxybenzene Chemical compound BrC1=CC=CC(OC=2C=CC=CC=2)=C1 AHDAKFFMKLQPTD-UHFFFAOYSA-N 0.000 description 1
• JYWJZIQSPRFCDB-UHFFFAOYSA-N 1-bromo-3-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=CC(Br)=C1 JYWJZIQSPRFCDB-UHFFFAOYSA-N 0.000 description 1
• VWQDSNNJAIQCBE-UHFFFAOYSA-N 1-bromo-5-cyclobutyloxy-2,3-difluorobenzene Chemical compound BrC1=C(C(=CC(=C1)OC1CCC1)F)F VWQDSNNJAIQCBE-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
• HWIPMBCMGVXOKN-UHFFFAOYSA-N 2,3,5,6-tetrafluoropyridine Chemical compound FC1=CC(F)=C(F)N=C1F HWIPMBCMGVXOKN-UHFFFAOYSA-N 0.000 description 1
• WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 1
• MGTUVUVRFJVHAL-UHFFFAOYSA-N 2,8-dibenzyl-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3-ol Chemical compound Oc1c(Cc2ccccc2)nc2c(Cc3ccccc3)nc(cn12)-c1ccc(O)cc1 MGTUVUVRFJVHAL-UHFFFAOYSA-N 0.000 description 1
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
• ACHYVWSZKWHZBB-UHFFFAOYSA-N 2-[2-(5-cyclobutyloxy-2,3-difluorophenyl)-3,4-dihydro-1H-isoquinolin-6-yl]cyclopropane-1-carboxylic acid Chemical compound C1(CCC1)OC=1C=C(C(=C(C=1)N1CC2=CC=C(C=C2CC1)C1C(C1)C(=O)O)F)F ACHYVWSZKWHZBB-UHFFFAOYSA-N 0.000 description 1
• FXOFOQAQRNJSFK-UHFFFAOYSA-N 2-[2-(5-cyclobutyloxy-2-fluorophenyl)-3,4-dihydro-1H-isoquinolin-6-yl]cyclopropane-1-carbonyl chloride Chemical compound C1(CCC1)OC=1C=CC(=C(C=1)N1CC2=CC=C(C=C2CC1)C1C(C1)C(=O)Cl)F FXOFOQAQRNJSFK-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
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• INMCANPWMNHTRQ-UHFFFAOYSA-N 2-bromo-1-chloro-4-cyclobutyloxybenzene Chemical compound Clc1ccc(OC2CCC2)cc1Br INMCANPWMNHTRQ-UHFFFAOYSA-N 0.000 description 1
• URCUHTMNVBERAZ-UHFFFAOYSA-N 2-bromo-1-fluoro-4-phenoxybenzene Chemical compound C1=C(Br)C(F)=CC=C1OC1=CC=CC=C1 URCUHTMNVBERAZ-UHFFFAOYSA-N 0.000 description 1
• YRCAVOAGAXGSOV-UHFFFAOYSA-N 2-bromo-4-cyclobutyloxy-1-methylbenzene Chemical compound BrC1=C(C=CC(=C1)OC1CCC1)C YRCAVOAGAXGSOV-UHFFFAOYSA-N 0.000 description 1
• CHAXYQWWKNXGDM-UHFFFAOYSA-N 2-bromo-4-cyclopropyloxy-1-fluorobenzene Chemical compound C1=C(Br)C(F)=CC=C1OC1CC1 CHAXYQWWKNXGDM-UHFFFAOYSA-N 0.000 description 1
• IQVITMLWLHGMBS-UHFFFAOYSA-N 2-bromo-6-cyclobutyloxy-3,4-difluoroaniline Chemical compound BrC1=C(N)C(=CC(=C1F)F)OC1CCC1 IQVITMLWLHGMBS-UHFFFAOYSA-N 0.000 description 1
• APUYEPKEAQVHKI-UHFFFAOYSA-N 2-chloro-4-cyclobutyloxy-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1OC1CCC1 APUYEPKEAQVHKI-UHFFFAOYSA-N 0.000 description 1
• PTQDACFIBHUBBD-UHFFFAOYSA-N 2-cyclobutyloxy-3,5,6-trifluoropyridine Chemical compound C1(CCC1)OC1=NC(=C(C=C1F)F)F PTQDACFIBHUBBD-UHFFFAOYSA-N 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 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
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 1
• RZLAMDICDZNMKW-UHFFFAOYSA-N 3-[2-(2-cyclobutyloxypyridin-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C1(CCC1)OC1=NC=CC=C1N1CC2=CC=C(C=C2CC1)CCC(=O)O RZLAMDICDZNMKW-UHFFFAOYSA-N 0.000 description 1
• KSBXNBUNAJOTBO-UHFFFAOYSA-N 3-[2-(3-chloro-5-cyclobutyloxyphenyl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound ClC=1C=C(C=C(C=1)OC1CCC1)N1CC2=CC=C(C=C2CC1)CCC(=O)O KSBXNBUNAJOTBO-UHFFFAOYSA-N 0.000 description 1
• WXNKJXUFHJYMNC-UHFFFAOYSA-N 3-[2-(3-chloro-5-methoxyphenyl)-3,4-dihydro-1H-isoquinolin-7-yl]propanoic acid Chemical compound ClC=1C=C(C=C(C=1)OC)N1CC2=CC(=CC=C2CC1)CCC(=O)O WXNKJXUFHJYMNC-UHFFFAOYSA-N 0.000 description 1
• WHRYDXWFLGWLEQ-UHFFFAOYSA-N 3-[2-(3-phenoxyphenyl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound O(C1=CC=CC=C1)C=1C=C(C=CC=1)N1CC2=CC=C(C=C2CC1)CCC(=O)O WHRYDXWFLGWLEQ-UHFFFAOYSA-N 0.000 description 1
• JOLPNNZTRXNFGL-UHFFFAOYSA-N 3-[2-(3-propan-2-yloxyphenyl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C(C)(C)OC=1C=C(C=CC=1)N1CC2=CC=C(C=C2CC1)CCC(=O)O JOLPNNZTRXNFGL-UHFFFAOYSA-N 0.000 description 1
• LQCGAIAMNOXMAI-UHFFFAOYSA-N 3-[2-(4-cyclobutyloxy-5-fluoropyrimidin-2-yl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C1(CCC1)OC1=NC(=NC=C1F)N1CC2=CC=C(C=C2CC1)CCC(=O)O LQCGAIAMNOXMAI-UHFFFAOYSA-N 0.000 description 1
• LRYCBGXMRLAYOU-UHFFFAOYSA-N 3-[2-(5-chloro-2,2-dimethyl-3H-1-benzofuran-7-yl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound ClC=1C=C(C2=C(CC(O2)(C)C)C=1)N1CC2=CC=C(C=C2CC1)CCC(=O)O LRYCBGXMRLAYOU-UHFFFAOYSA-N 0.000 description 1
• KHCLLZCPKUMMIY-UHFFFAOYSA-N 3-[2-(5-cyclobutyloxy-2-fluorophenyl)-7-fluoro-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C1(CCC1)OC=1C=CC(=C(C=1)N1CC2=CC(=C(C=C2CC1)CCC(=O)O)F)F KHCLLZCPKUMMIY-UHFFFAOYSA-N 0.000 description 1
• OPIYWFHIETYQFM-UHFFFAOYSA-N 3-[2-(5-cyclobutyloxy-2-methylphenyl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C1(CCC1)OC=1C=CC(=C(C=1)N1CC2=CC=C(C=C2CC1)CCC(=O)O)C OPIYWFHIETYQFM-UHFFFAOYSA-N 0.000 description 1
• WLKUONQYDSGCRG-UHFFFAOYSA-N 3-[2-(6-cyclobutyloxypyridin-2-yl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound C1(CCC1)OC1=CC=CC(=N1)N1CC2=CC=C(C=C2CC1)CCC(=O)O WLKUONQYDSGCRG-UHFFFAOYSA-N 0.000 description 1
• YXKBEIZHAOKWOD-UHFFFAOYSA-N 3-[2-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-7-yl]propanoic acid Chemical compound C(=O)(CCC1=CC=2CN(CCC=2C=C1)C1=C(F)C=CC(OC(F)(F)F)=C1)O YXKBEIZHAOKWOD-UHFFFAOYSA-N 0.000 description 1
• JWOJCDCOKUTQFY-UHFFFAOYSA-N 3-[8-fluoro-2-(3-phenoxyphenyl)-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound FC=1C=C(C=C2CCN(CC=12)C1=CC(=CC=C1)OC1=CC=CC=C1)CCC(=O)O JWOJCDCOKUTQFY-UHFFFAOYSA-N 0.000 description 1
• ADUDCEYSAAKMNT-UHFFFAOYSA-N 3-[8-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-6-yl]propanoic acid Chemical compound OC(=O)CCC1=CC2=C(CN(CC2)C2=C(F)C=CC(OC(F)(F)F)=C2)C(F)=C1 ADUDCEYSAAKMNT-UHFFFAOYSA-N 0.000 description 1
• OUAZPCKRSSEQKB-UHFFFAOYSA-N 3-bromo-2-fluorobenzaldehyde Chemical compound FC1=C(Br)C=CC=C1C=O OUAZPCKRSSEQKB-UHFFFAOYSA-N 0.000 description 1
• JLFFHIKASCUQRL-UHFFFAOYSA-N 3-bromo-4-chlorophenol Chemical compound OC1=CC=C(Cl)C(Br)=C1 JLFFHIKASCUQRL-UHFFFAOYSA-N 0.000 description 1
• GMZKNRDHSHYMHG-UHFFFAOYSA-N 3-bromo-4-methylphenol Chemical compound CC1=CC=C(O)C=C1Br GMZKNRDHSHYMHG-UHFFFAOYSA-N 0.000 description 1
• GMGWXLPFRHYWAS-UHFFFAOYSA-N 3-bromo-5-chlorophenol Chemical compound OC1=CC(Cl)=CC(Br)=C1 GMGWXLPFRHYWAS-UHFFFAOYSA-N 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• GPPSQLLIFNWNSB-UHFFFAOYSA-N 3-phenylmethoxycyclobutan-1-one Chemical compound C1C(=O)CC1OCC1=CC=CC=C1 GPPSQLLIFNWNSB-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KZODZOGGCQZLNF-UHFFFAOYSA-N 4,5-difluoro-2-nitrophenol Chemical compound OC1=CC(F)=C(F)C=C1[N+]([O-])=O KZODZOGGCQZLNF-UHFFFAOYSA-N 0.000 description 1
• WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
• SWHUROFMIMHWKS-UHFFFAOYSA-N 4-bromo-3-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC=C1Br SWHUROFMIMHWKS-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
• CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
• YRTYJMFONWTUCC-UHFFFAOYSA-N 7-bromo-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid Chemical compound C1CN(C(=O)O)CCC2=CC=C(Br)C=C21 YRTYJMFONWTUCC-UHFFFAOYSA-N 0.000 description 1
• VVIBDGNBSRRQEC-UHFFFAOYSA-N 7-bromo-1,2-dihydronaphthalene Chemical compound C1=CCCC2=CC(Br)=CC=C21 VVIBDGNBSRRQEC-UHFFFAOYSA-N 0.000 description 1
• ZVNFJSFIRKPMES-UHFFFAOYSA-N 7-bromo-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC(Br)=CC=C21 ZVNFJSFIRKPMES-UHFFFAOYSA-N 0.000 description 1
• KABRXLINDSPGDF-UHFFFAOYSA-N 7-bromoisoquinoline Chemical compound C1=CN=CC2=CC(Br)=CC=C21 KABRXLINDSPGDF-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• 208000004611 Abdominal Obesity Diseases 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
• OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical compound ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 108010058207 Anistreplase Proteins 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 229940123208 Biguanide Drugs 0.000 description 1
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 239000004135 Bone phosphate Substances 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• DYKKXGBVRXBCDD-UHFFFAOYSA-N BrC1=C(C=CC(=C1)OC1CCC1)F Chemical compound BrC1=C(C=CC(=C1)OC1CCC1)F DYKKXGBVRXBCDD-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• VNXNRYYBAVLABR-UHFFFAOYSA-N C(C=CC)CC(C)(C)P(C(C)(C)C)C(C)(C)C.[Cl] Chemical compound C(C=CC)CC(C)(C)P(C(C)(C)C)C(C)(C)C.[Cl] VNXNRYYBAVLABR-UHFFFAOYSA-N 0.000 description 1
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 description 1
• YUZANMKFPDQQQT-UHFFFAOYSA-N CC(C)(C)OC(C(C1)C1C1=CC2C=CN=CC2C=C1)=O Chemical compound CC(C)(C)OC(C(C1)C1C1=CC2C=CN=CC2C=C1)=O YUZANMKFPDQQQT-UHFFFAOYSA-N 0.000 description 1
• JZEIRXRGCZYQKT-UHFFFAOYSA-N CC(CN(Cc(cc1)cc(F)c1Br)I)OC Chemical compound CC(CN(Cc(cc1)cc(F)c1Br)I)OC JZEIRXRGCZYQKT-UHFFFAOYSA-N 0.000 description 1
• JLWXZNUGZXHXEE-MRVPVSSYSA-N CCC(CC[C@@H](C)N)=C Chemical compound CCC(CC[C@@H](C)N)=C JLWXZNUGZXHXEE-MRVPVSSYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• XTNGUQKDFGDXSJ-ZXGKGEBGSA-N Canagliflozin Chemical compound CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 XTNGUQKDFGDXSJ-ZXGKGEBGSA-N 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 206010065941 Central obesity Diseases 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 108010004103 Chylomicrons Proteins 0.000 description 1
• 229920002911 Colestipol Polymers 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 208000014311 Cushing syndrome Diseases 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
• 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 1
• OBWASQILIWPZMG-UHFFFAOYSA-N Empagliflozin Chemical compound OC1C(O)C(O)C(CO)OC1C1=CC=C(Cl)C(CC=2C=CC(OC3COCC3)=CC=2)=C1 OBWASQILIWPZMG-UHFFFAOYSA-N 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
• 206010059183 Familial hypertriglyceridaemia Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
• 102000051325 Glucagon Human genes 0.000 description 1
• 108060003199 Glucagon Proteins 0.000 description 1
• 102000004366 Glucosidases Human genes 0.000 description 1
• 108010056771 Glucosidases Proteins 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 241000463109 Haloprofundus marisrubri Species 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
• 206010019837 Hepatocellular injury Diseases 0.000 description 1
• 102000007625 Hirudins Human genes 0.000 description 1
• 108010007267 Hirudins Proteins 0.000 description 1
• 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
• 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 1
• 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 description 1
• 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 1
• 201000010252 Hyperlipoproteinemia Type III Diseases 0.000 description 1
• 231100001131 Idiosyncratic toxicity Toxicity 0.000 description 1
• 102000003746 Insulin Receptor Human genes 0.000 description 1
• 108010001127 Insulin Receptor Proteins 0.000 description 1
• 229940122199 Insulin secretagogue Drugs 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
• 108010019598 Liraglutide Proteins 0.000 description 1
• XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 description 1
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• RELIERHAQBBBQO-UHFFFAOYSA-N N-[(4-bromo-3-fluorophenyl)methyl]-2,2-dimethoxyethanamine Chemical compound COC(OC)CNCC1=CC=C(Br)C(F)=C1 RELIERHAQBBBQO-UHFFFAOYSA-N 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• 208000028389 Nerve injury Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• 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 1
• 102000015731 Peptide Hormones Human genes 0.000 description 1
• 108010038988 Peptide Hormones Proteins 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 206010036049 Polycystic ovaries Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 101710150451 Protein Bel-1 Proteins 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 101001032756 Rattus norvegicus Granzyme-like protein 1 Proteins 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 102000005782 Squalene Monooxygenase Human genes 0.000 description 1
• 108020003891 Squalene monooxygenase Proteins 0.000 description 1
• 206010041925 Staphylococcal infections Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 1
• 108010054082 Sterol O-acyltransferase Proteins 0.000 description 1
• 108010023197 Streptokinase Proteins 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 102000003673 Symporters Human genes 0.000 description 1
• 108090000088 Symporters Proteins 0.000 description 1
• 206010043458 Thirst Diseases 0.000 description 1
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
• 229930003270 Vitamin B Natural products 0.000 description 1
• 229930003779 Vitamin B12 Natural products 0.000 description 1
• FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
• WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
• SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
• 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 229960002632 acarbose Drugs 0.000 description 1
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 230000009858 acid secretion Effects 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 229940062328 actos Drugs 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000808 adrenergic beta-agonist Substances 0.000 description 1
• 230000008484 agonism Effects 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 229960001667 alogliptin Drugs 0.000 description 1
• ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229960003318 alteplase Drugs 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 229960000983 anistreplase Drugs 0.000 description 1
• 239000000883 anti-obesity agent Substances 0.000 description 1
• 239000003529 anticholesteremic agent Substances 0.000 description 1
• 229940127226 anticholesterol agent Drugs 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940125710 antiobesity agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 229960004676 antithrombotic agent Drugs 0.000 description 1
• 150000005840 aryl radicals Chemical class 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 229960002274 atenolol Drugs 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
• QAYPFHIZJSDUSF-UHFFFAOYSA-N azepin-3-one Chemical compound O=C1C=CC=CN=C1 QAYPFHIZJSDUSF-UHFFFAOYSA-N 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• 229940076810 beta sitosterol Drugs 0.000 description 1
• 102000007379 beta-Arrestin 2 Human genes 0.000 description 1
• 108010032967 beta-Arrestin 2 Proteins 0.000 description 1
• LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
• NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
• LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 229940084891 byetta Drugs 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229960001713 canagliflozin Drugs 0.000 description 1
• VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000004623 carbolinyl group Chemical group 0.000 description 1
• 150000001722 carbon compounds Chemical class 0.000 description 1
• STNNHWPJRRODGI-UHFFFAOYSA-N carbonic acid;n,n-diethylethanamine Chemical compound [O-]C([O-])=O.CC[NH+](CC)CC.CC[NH+](CC)CC STNNHWPJRRODGI-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 208000026106 cerebrovascular disease Diseases 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 150000001793 charged compounds Chemical class 0.000 description 1
• 238000000451 chemical ionisation Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 229960001214 clofibrate Drugs 0.000 description 1
• KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
• AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
• 229960002604 colestipol Drugs 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 229940127204 compound 29 Drugs 0.000 description 1
• 229940125936 compound 42 Drugs 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 235000000639 cyanocobalamin Nutrition 0.000 description 1
• 239000011666 cyanocobalamin Substances 0.000 description 1
• 229960002104 cyanocobalamin Drugs 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 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
• 230000034994 death Effects 0.000 description 1
• 208000029936 defective apolipoprotein b-100 Diseases 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000011903 deuterated solvents‎ Substances 0.000 description 1
• 125000004431 deuterium atom Chemical group 0.000 description 1
• 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 235000013367 dietary fats Nutrition 0.000 description 1
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
• 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
• 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
• XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 229960003345 empagliflozin Drugs 0.000 description 1
• OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• DNKQIXRITVBJDC-UHFFFAOYSA-N ethyl 3-(8-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)propanoate hydrochloride Chemical compound Cl.FC=1C=C(C=C2CCNCC12)CCC(=O)OCC DNKQIXRITVBJDC-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 229960001519 exenatide Drugs 0.000 description 1
• 201000001386 familial hypercholesterolemia Diseases 0.000 description 1
• 235000019581 fat taste sensations Nutrition 0.000 description 1
• 229960002297 fenofibrate Drugs 0.000 description 1
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
• 229940125753 fibrate Drugs 0.000 description 1
• 239000003527 fibrinolytic agent Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 125000003709 fluoroalkyl group Chemical group 0.000 description 1
• 125000001207 fluorophenyl group Chemical group 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 230000002538 fungal effect Effects 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 230000030136 gastric emptying Effects 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960003627 gemfibrozil Drugs 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 229960004580 glibenclamide Drugs 0.000 description 1
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
• 229960004346 glimepiride Drugs 0.000 description 1
• 229960001381 glipizide Drugs 0.000 description 1
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
• 229960004666 glucagon Drugs 0.000 description 1
• 229940095884 glucophage Drugs 0.000 description 1
• 230000009229 glucose formation Effects 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
• 208000018914 glucose metabolism disease Diseases 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 150000002308 glutamine derivatives Chemical class 0.000 description 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 230000002650 habitual effect Effects 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 235000004280 healthy diet Nutrition 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
• FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
• WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
• 229940006607 hirudin Drugs 0.000 description 1
• 235000012907 honey Nutrition 0.000 description 1
• 235000003642 hunger Nutrition 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 208000020887 hyperlipoproteinemia type 3 Diseases 0.000 description 1
• 208000000522 hyperlipoproteinemia type IV Diseases 0.000 description 1
• 208000003532 hypothyroidism Diseases 0.000 description 1
• 230000002989 hypothyroidism Effects 0.000 description 1
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical group C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
• 239000000859 incretin Substances 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• VBCVPMMZEGZULK-NRFANRHFSA-N indoxacarb Chemical compound C([C@@]1(OC2)C(=O)OC)C3=CC(Cl)=CC=C3C1=NN2C(=O)N(C(=O)OC)C1=CC=C(OC(F)(F)F)C=C1 VBCVPMMZEGZULK-NRFANRHFSA-N 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 229940121068 invokana Drugs 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 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
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229940039009 isoproterenol Drugs 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 229940090473 januvia Drugs 0.000 description 1
• 229940110665 jardiance Drugs 0.000 description 1
• 235000015110 jellies Nutrition 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229960002701 liraglutide Drugs 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 231100000849 liver cell damage Toxicity 0.000 description 1
• 229960001093 lixisenatide Drugs 0.000 description 1
• 108010004367 lixisenatide Proteins 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 208000018769 loss of vision Diseases 0.000 description 1
• 231100000864 loss of vision Toxicity 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 229950004994 meglitinide Drugs 0.000 description 1
• 229950008446 melinamide Drugs 0.000 description 1
• 208000011661 metabolic syndrome X Diseases 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• RBIGOBZTICPMPV-UHFFFAOYSA-N methyl 2-methyl-3-(1,2,3,4-tetrahydroisoquinolin-6-yl)propanoate Chemical compound CC(C(=O)OC)CC=1C=C2CCNCC2=CC=1 RBIGOBZTICPMPV-UHFFFAOYSA-N 0.000 description 1
• RWYFRMZJTKFISG-UHFFFAOYSA-N methyl 3-[2-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-6-yl]-2-methylpropanoate Chemical compound FC1=C(C=C(C=C1)OC(F)(F)F)N1CC2=CC=C(C=C2CC1)CC(C(=O)OC)C RWYFRMZJTKFISG-UHFFFAOYSA-N 0.000 description 1
• ZTLVCBSBZPAPTF-UHFFFAOYSA-N methyl 3-isoquinolin-6-yl-2-methylprop-2-enoate Chemical compound C1=NC=CC2=CC(=CC=C12)C=C(C(=O)OC)C ZTLVCBSBZPAPTF-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• BHIWKHZACMWKOJ-UHFFFAOYSA-N methyl isobutyrate Chemical compound COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 229960001110 miglitol Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000006682 monohaloalkyl group Chemical group 0.000 description 1
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
• 210000000663 muscle cell Anatomy 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• OLAPPGSPBNVTRF-UHFFFAOYSA-N naphthalene-1,4,5,8-tetracarboxylic acid Chemical compound C1=CC(C(O)=O)=C2C(C(=O)O)=CC=C(C(O)=O)C2=C1C(O)=O OLAPPGSPBNVTRF-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 230000008764 nerve damage Effects 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• AIKVCUNQWYTVTO-UHFFFAOYSA-N nicardipine hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 AIKVCUNQWYTVTO-UHFFFAOYSA-N 0.000 description 1
• 229960002289 nicardipine hydrochloride Drugs 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000012053 oil suspension Substances 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 238000012261 overproduction Methods 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000001151 peptidyl group Chemical group 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000006461 physiological response Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 125000006684 polyhaloalkyl group Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates Nutrition 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
• FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
• 229960003912 probucol Drugs 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
• 235000008160 pyridoxine Nutrition 0.000 description 1
• 239000011677 pyridoxine Substances 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 239000002516 radical scavenger Substances 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 229960002917 reteplase Drugs 0.000 description 1
• 108010051412 reteplase Proteins 0.000 description 1
• 230000004141 reverse cholesterol transport Effects 0.000 description 1
• 208000004124 rheumatic heart disease Diseases 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 230000036186 satiety Effects 0.000 description 1
• 235000019627 satiety Nutrition 0.000 description 1
• 235000021003 saturated fats Nutrition 0.000 description 1
• 229960004937 saxagliptin Drugs 0.000 description 1
• QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
• 108010033693 saxagliptin Proteins 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
• 210000002966 serum Anatomy 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• DHNUAKOQUGJUGA-UHFFFAOYSA-N silicon;sulfane Chemical compound [Si].S DHNUAKOQUGJUGA-UHFFFAOYSA-N 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
• 229950005143 sitosterol Drugs 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 229940083618 sodium nitroprusside Drugs 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 1
• 239000004059 squalene synthase inhibitor Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 229960005202 streptokinase Drugs 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 208000023516 stroke disease Diseases 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229950000034 teneligliptin Drugs 0.000 description 1
• WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical compound O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 description 1
• CHXCFNZASLZVLR-UHFFFAOYSA-N tert-butyl 3-(1,2,3,4-tetrahydroisoquinolin-6-yl)propanoate Chemical compound C1=2CNCCC1=CC(CCC(=O)OC(C)(C)C)=CC=2 CHXCFNZASLZVLR-UHFFFAOYSA-N 0.000 description 1
• ZSMASAHQEGIEPI-UHFFFAOYSA-N tert-butyl 3-(1,2,3,4-tetrahydroisoquinolin-7-yl)propanoate Chemical compound O(C(C)(C)C)C(=O)CCC1=CC=2CNCCC=2C=C1 ZSMASAHQEGIEPI-UHFFFAOYSA-N 0.000 description 1
• ANNKTKCQDAEEIM-UHFFFAOYSA-N tert-butyl 7-(2-ethoxycarbonylcyclopropyl)-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate Chemical compound CCOC(=O)C1CC1c1ccc2CCN(CCc2c1)C(=O)OC(C)(C)C ANNKTKCQDAEEIM-UHFFFAOYSA-N 0.000 description 1
• UICPNVVRZYJXAM-UHFFFAOYSA-N tert-butyl 7-bromo-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC2=CC=C(Br)C=C21 UICPNVVRZYJXAM-UHFFFAOYSA-N 0.000 description 1
• ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• FODWRUPJCKASBN-UHFFFAOYSA-M tetrabutylazanium;chloride;hydrate Chemical compound O.[Cl-].CCCC[N+](CCCC)(CCCC)CCCC FODWRUPJCKASBN-UHFFFAOYSA-M 0.000 description 1
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 150000001467 thiazolidinediones Chemical class 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000005309 thioalkoxy group Chemical group 0.000 description 1
• 229960000103 thrombolytic agent Drugs 0.000 description 1
• 101150009089 tifa gene Proteins 0.000 description 1
• 231100000820 toxicity test Toxicity 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 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
• 210000002700 urine Anatomy 0.000 description 1
• 230000006441 vascular event Effects 0.000 description 1
• 229940124549 vasodilator Drugs 0.000 description 1
• 239000003071 vasodilator agent Substances 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
• 230000004393 visual impairment Effects 0.000 description 1
• 235000019156 vitamin B Nutrition 0.000 description 1
• 239000011720 vitamin B Substances 0.000 description 1
• 235000019163 vitamin B12 Nutrition 0.000 description 1
• 239000011715 vitamin B12 Substances 0.000 description 1
• 229940011671 vitamin b6 Drugs 0.000 description 1
• 229960001729 voglibose Drugs 0.000 description 1
• PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical class OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1