TWI507406B - Ｎ１／ｎ２-內醯胺乙醯輔酶ａ羧酶抑制劑類 - Google Patents

Info

Publication number

TWI507406B

TWI507406B TW103102453A TW103102453A TWI507406B TW I507406 B TWI507406 B TW I507406B TW 103102453 A TW103102453 A TW 103102453A TW 103102453 A TW103102453 A TW 103102453A TW I507406 B TWI507406 B TW I507406B

Authority

TW

Taiwan

Prior art keywords

mmol

reaction

carboxylic acid

etoac

nmr

Prior art date

2010-10-29

Links

• Espacenet
• Global Dossier
• Discuss

• 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 title description 8
• 150000001875 compounds Chemical class 0.000 claims description 231
• 150000003839 salts Chemical class 0.000 claims description 47
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• 239000003085 diluting agent Substances 0.000 claims description 9
• QBOPNKUYWIBAEP-UHFFFAOYSA-N 2-tert-butyl-1'-(1-methoxyisoquinoline-7-carbonyl)spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2C(OC)=NC=CC2=CC=C1C(=O)N(CC1)CCC1(NC1=O)CC2=C1NN(C(C)(C)C)C2 QBOPNKUYWIBAEP-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 523
• 235000019439 ethyl acetate Nutrition 0.000 description 219
• 238000006243 chemical reaction Methods 0.000 description 201
• 239000000203 mixture Substances 0.000 description 159
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 154
• 238000005481 NMR spectroscopy Methods 0.000 description 146
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
• 239000000243 solution Substances 0.000 description 117
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 112
• 239000000543 intermediate Substances 0.000 description 107
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 97
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 90
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
• 238000000034 method Methods 0.000 description 74
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 73
• -1 pyrazolopyridyl Chemical group 0.000 description 73
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 51
• 239000003112 inhibitor Substances 0.000 description 51
• 239000010410 layer Substances 0.000 description 49
• 239000002904 solvent Substances 0.000 description 49
• 238000002360 preparation method Methods 0.000 description 40
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
• 238000003818 flash chromatography Methods 0.000 description 36
• 238000003756 stirring Methods 0.000 description 36
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 35
• 239000007787 solid Substances 0.000 description 35
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 34
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
• 229910052938 sodium sulfate Inorganic materials 0.000 description 34
• 235000011152 sodium sulphate Nutrition 0.000 description 34
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
• 239000011541 reaction mixture Substances 0.000 description 30
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
• 239000012267 brine Substances 0.000 description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
• 239000007864 aqueous solution Substances 0.000 description 25
• 241001465754 Metazoa Species 0.000 description 24
• 239000012044 organic layer Substances 0.000 description 24
• 239000002585 base Substances 0.000 description 23
• 201000010099 disease Diseases 0.000 description 22
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 21
• JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical class C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 description 20
• 101000677540 Homo sapiens Acetyl-CoA carboxylase 2 Proteins 0.000 description 20
• 230000015572 biosynthetic process Effects 0.000 description 20
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 20
• 238000010992 reflux Methods 0.000 description 19
• 102100021641 Acetyl-CoA carboxylase 2 Human genes 0.000 description 18
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
• 239000000556 agonist Substances 0.000 description 18
• 239000005516 coenzyme A Substances 0.000 description 18
• 229940093530 coenzyme a Drugs 0.000 description 18
• 230000002829 reductive effect Effects 0.000 description 18
• 229920006395 saturated elastomer Polymers 0.000 description 18
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 17
• 239000002244 precipitate Substances 0.000 description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 16
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
• 208000008589 Obesity Diseases 0.000 description 16
• 239000003795 chemical substances by application Substances 0.000 description 16
• 235000020824 obesity Nutrition 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 15
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
• 238000004128 high performance liquid chromatography Methods 0.000 description 15
• 238000000746 purification Methods 0.000 description 15
• 239000000725 suspension Substances 0.000 description 15
• 238000003786 synthesis reaction Methods 0.000 description 15
• 101000894929 Homo sapiens Bcl-2-related protein A1 Proteins 0.000 description 14
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
• 235000019341 magnesium sulphate Nutrition 0.000 description 14
• 239000012071 phase Substances 0.000 description 14
• 239000007858 starting material Substances 0.000 description 14
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
• 102000004190 Enzymes Human genes 0.000 description 13
• 108090000790 Enzymes Proteins 0.000 description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
• 229940088598 enzyme Drugs 0.000 description 13
• 230000005764 inhibitory process Effects 0.000 description 13
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 13
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• 102100039164 Acetyl-CoA carboxylase 1 Human genes 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
• 206010022489 Insulin Resistance Diseases 0.000 description 11
• 238000004458 analytical method Methods 0.000 description 11
• 239000005557 antagonist Substances 0.000 description 11
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 11
• QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 11
• 125000001072 heteroaryl group Chemical group 0.000 description 11
• 239000001257 hydrogen Substances 0.000 description 11
• 229910052739 hydrogen Inorganic materials 0.000 description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 235000019198 oils Nutrition 0.000 description 11
• 101710190443 Acetyl-CoA carboxylase 1 Proteins 0.000 description 10
• RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 10
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 239000003472 antidiabetic agent Substances 0.000 description 10
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 10
• 150000001733 carboxylic acid esters Chemical class 0.000 description 10
• RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 10
• 230000008878 coupling Effects 0.000 description 10
• 238000010168 coupling process Methods 0.000 description 10
• 238000005859 coupling reaction Methods 0.000 description 10
• KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 10
• 125000005843 halogen group Chemical group 0.000 description 10
• 210000004185 liver Anatomy 0.000 description 10
• 235000017557 sodium bicarbonate Nutrition 0.000 description 10
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
• 238000010561 standard procedure Methods 0.000 description 10
• 125000001424 substituent group Chemical group 0.000 description 10
• BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 9
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
• 229960000583 acetic acid Drugs 0.000 description 9
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 9
• 238000010511 deprotection reaction Methods 0.000 description 9
• 206010012601 diabetes mellitus Diseases 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 230000002440 hepatic effect Effects 0.000 description 9
• 239000012948 isocyanate Substances 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 229940125708 antidiabetic agent Drugs 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
• 125000001624 naphthyl group Chemical group 0.000 description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 210000001519 tissue Anatomy 0.000 description 8
• 239000003643 water by type Substances 0.000 description 8
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 7
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• 239000012190 activator Substances 0.000 description 7
• 125000000217 alkyl group Chemical group 0.000 description 7
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 235000014113 dietary fatty acids Nutrition 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 239000000194 fatty acid Substances 0.000 description 7
• 229930195729 fatty acid Natural products 0.000 description 7
• 150000004665 fatty acids Chemical class 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 238000007254 oxidation reaction Methods 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 239000000523 sample Substances 0.000 description 7
• 239000012453 solvate Substances 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 6
• QDXQAOGNBCOEQX-UHFFFAOYSA-N 1-methylcyclohexa-1,4-diene Chemical compound CC1=CCC=CC1 QDXQAOGNBCOEQX-UHFFFAOYSA-N 0.000 description 6
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 6
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 101000963424 Homo sapiens Acetyl-CoA carboxylase 1 Proteins 0.000 description 6
• 241000124008 Mammalia Species 0.000 description 6
• KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• 235000019270 ammonium chloride Nutrition 0.000 description 6
• 239000012491 analyte Substances 0.000 description 6
• 239000000010 aprotic solvent Substances 0.000 description 6
• 229910002091 carbon monoxide Inorganic materials 0.000 description 6
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 6
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 6
• 208000035475 disorder Diseases 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 239000012458 free base Substances 0.000 description 6
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 6
• 230000014759 maintenance of location Effects 0.000 description 6
• 238000004519 manufacturing process Methods 0.000 description 6
• 230000003647 oxidation Effects 0.000 description 6
• 229960005489 paracetamol Drugs 0.000 description 6
• 108090000765 processed proteins & peptides Proteins 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 6
• 241000894007 species Species 0.000 description 6
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
• 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 6
• 239000003039 volatile agent Substances 0.000 description 6
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 5
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 5
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
• 239000007821 HATU Substances 0.000 description 5
• 208000001145 Metabolic Syndrome Diseases 0.000 description 5
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
• 102000001708 Protein Isoforms Human genes 0.000 description 5
• 108010029485 Protein Isoforms Proteins 0.000 description 5
• 239000007983 Tris buffer Substances 0.000 description 5
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 5
• 239000000908 ammonium hydroxide Substances 0.000 description 5
• 239000000883 anti-obesity agent Substances 0.000 description 5
• 229940125710 antiobesity agent Drugs 0.000 description 5
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 239000012141 concentrate Substances 0.000 description 5
• 235000008504 concentrate Nutrition 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 238000002425 crystallisation Methods 0.000 description 5
• 230000008025 crystallization Effects 0.000 description 5
• 238000010828 elution Methods 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 102000047784 human ACACB Human genes 0.000 description 5
• 238000005984 hydrogenation reaction Methods 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• 239000012026 peptide coupling reagents‎ Substances 0.000 description 5
• 230000002441 reversible effect Effects 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 5
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 4
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• 125000003341 7 membered heterocyclic group Chemical group 0.000 description 4
• 102000004276 BCL2-related protein A1 Human genes 0.000 description 4
• 229910021590 Copper(II) bromide Inorganic materials 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• 102000016267 Leptin Human genes 0.000 description 4
• 108010092277 Leptin Proteins 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 206010033307 Overweight Diseases 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 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 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• 125000006242 amine protecting group Chemical group 0.000 description 4
• 229910052786 argon Inorganic materials 0.000 description 4
• 125000003118 aryl group Chemical group 0.000 description 4
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
• 239000003638 chemical reducing agent Substances 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 238000004090 dissolution Methods 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• FDVUSOCZVZVIIW-UHFFFAOYSA-N ethyl 1-oxidoquinolin-1-ium-7-carboxylate Chemical compound C1=CC=[N+]([O-])C2=CC(C(=O)OCC)=CC=C21 FDVUSOCZVZVIIW-UHFFFAOYSA-N 0.000 description 4
• 230000005284 excitation Effects 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 125000001153 fluoro group Chemical group F* 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
• 201000001421 hyperglycemia Diseases 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 150000002513 isocyanates Chemical class 0.000 description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 4
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
• 229910052744 lithium Inorganic materials 0.000 description 4
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 125000002971 oxazolyl group Chemical group 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 239000012047 saturated solution Substances 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
• AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 4
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 3
• NMJZMLLMUJTGPB-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methylamino]isoquinoline-6-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CNC1=NC=CC2=CC(C(O)=O)=CC=C12 NMJZMLLMUJTGPB-UHFFFAOYSA-N 0.000 description 3
• QFIKYWRUQBMZTL-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methylamino]isoquinoline-7-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CNC1=NC=CC2=CC=C(C(O)=O)C=C12 QFIKYWRUQBMZTL-UHFFFAOYSA-N 0.000 description 3
• YGEAVRLLVLRDFR-UHFFFAOYSA-N 1-chloroisoquinoline-7-carboxylic acid Chemical compound C1=CN=C(Cl)C2=CC(C(=O)O)=CC=C21 YGEAVRLLVLRDFR-UHFFFAOYSA-N 0.000 description 3
• WPBNZXQXFGWTHV-UHFFFAOYSA-N 1-o-ethyl 5-o-methyl 2-methyl-3-oxoindazole-1,5-dicarboxylate Chemical compound COC(=O)C1=CC=C2N(C(=O)OCC)N(C)C(=O)C2=C1 WPBNZXQXFGWTHV-UHFFFAOYSA-N 0.000 description 3
• JMYHAUFFRDHDQS-UHFFFAOYSA-N 2-chloroquinoline-7-carboxylic acid Chemical compound C1=CC(Cl)=NC2=CC(C(=O)O)=CC=C21 JMYHAUFFRDHDQS-UHFFFAOYSA-N 0.000 description 3
• ZPWKLSSETKSKAL-UHFFFAOYSA-N 3,7-dimethyl-2h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(C)=NNC2=C1C ZPWKLSSETKSKAL-UHFFFAOYSA-N 0.000 description 3
• FZZLWWNOYMHSIS-UHFFFAOYSA-N 5-bromo-2-methyl-3-nitropyridine Chemical compound CC1=NC=C(Br)C=C1[N+]([O-])=O FZZLWWNOYMHSIS-UHFFFAOYSA-N 0.000 description 3
• IDFHMSTXYPMMIJ-UHFFFAOYSA-N 5-bromo-4-(bromomethyl)-1-propan-2-ylpyrazole Chemical compound CC(C)N1N=CC(CBr)=C1Br IDFHMSTXYPMMIJ-UHFFFAOYSA-N 0.000 description 3
• ZDYXSEQHOVSTPA-UHFFFAOYSA-N 6-bromo-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C=2C1=CC(Br)=CC=2 ZDYXSEQHOVSTPA-UHFFFAOYSA-N 0.000 description 3
• PQKLBIXLXFRNKT-UHFFFAOYSA-N 6-bromoisoquinolin-3-amine Chemical compound BrC1=CC=C2C=NC(N)=CC2=C1 PQKLBIXLXFRNKT-UHFFFAOYSA-N 0.000 description 3
• UMSWWSIVPWVJOX-UHFFFAOYSA-N 7-bromo-1-chloroisoquinoline Chemical compound C1=C(Br)C=C2C(Cl)=NC=CC2=C1 UMSWWSIVPWVJOX-UHFFFAOYSA-N 0.000 description 3
• GPICPAIKTJPYEE-UHFFFAOYSA-N 7-bromo-3-chloroisoquinoline Chemical compound C1=C(Br)C=C2C=NC(Cl)=CC2=C1 GPICPAIKTJPYEE-UHFFFAOYSA-N 0.000 description 3
• 102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 3
• 108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 3
• 108010018763 Biotin carboxylase Proteins 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 208000002705 Glucose Intolerance Diseases 0.000 description 3
• 206010020772 Hypertension Diseases 0.000 description 3
• PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 3
• 239000007832 Na2SO4 Substances 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 3
• 210000000577 adipose tissue Anatomy 0.000 description 3
• 150000001335 aliphatic alkanes Chemical class 0.000 description 3
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
• 239000002220 antihypertensive agent Substances 0.000 description 3
• 229940030600 antihypertensive agent Drugs 0.000 description 3
• 239000003524 antilipemic agent Substances 0.000 description 3
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 239000004305 biphenyl Substances 0.000 description 3
• 235000010290 biphenyl Nutrition 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 210000004027 cell Anatomy 0.000 description 3
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 150000001924 cycloalkanes Chemical class 0.000 description 3
• 235000005911 diet Nutrition 0.000 description 3
• 230000037213 diet Effects 0.000 description 3
• VEKRNIZRQVEQAC-UHFFFAOYSA-N ethyl 1-chloroisoquinoline-7-carboxylate Chemical compound C1=CN=C(Cl)C2=CC(C(=O)OCC)=CC=C21 VEKRNIZRQVEQAC-UHFFFAOYSA-N 0.000 description 3
• ATACLLRCZAKMCP-UHFFFAOYSA-N ethyl 3-bromo-1-cyclobutylpyrazole-4-carboxylate Chemical compound N1=C(Br)C(C(=O)OCC)=CN1C1CCC1 ATACLLRCZAKMCP-UHFFFAOYSA-N 0.000 description 3
• OKUIOPJULAYJDU-UHFFFAOYSA-N ethyl 3-iodo-1-propan-2-ylpyrazole-4-carboxylate Chemical compound CCOC(=O)C1=CN(C(C)C)N=C1I OKUIOPJULAYJDU-UHFFFAOYSA-N 0.000 description 3
• HMONTLMXUZERMC-UHFFFAOYSA-N ethyl 5-bromo-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C1=CNN=C1Br HMONTLMXUZERMC-UHFFFAOYSA-N 0.000 description 3
• GCZGLIKEVZAURZ-UHFFFAOYSA-N ethyl 5-iodo-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1I GCZGLIKEVZAURZ-UHFFFAOYSA-N 0.000 description 3
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 235000013305 food Nutrition 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
• 238000000099 in vitro assay Methods 0.000 description 3
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 3
• SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 3
• 125000005956 isoquinolyl group Chemical group 0.000 description 3
• 229940039781 leptin Drugs 0.000 description 3
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• 230000004060 metabolic process Effects 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• AQDFNXASXNIENA-UHFFFAOYSA-N methyl 1h-pyrazolo[4,3-b]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN=C2C=NNC2=C1 AQDFNXASXNIENA-UHFFFAOYSA-N 0.000 description 3
• POZSZUBOUIBITK-UHFFFAOYSA-N methyl 3-cyano-1h-indazole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NN=C(C#N)C2=C1 POZSZUBOUIBITK-UHFFFAOYSA-N 0.000 description 3
• 229940050176 methyl chloride Drugs 0.000 description 3
• 238000002552 multiple reaction monitoring Methods 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 3
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 3
• 229960001243 orlistat Drugs 0.000 description 3
• 229910052760 oxygen Inorganic materials 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 108010029667 pramlintide Proteins 0.000 description 3
• NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 3
• 201000009104 prediabetes syndrome Diseases 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 239000003586 protic polar solvent Substances 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 238000007363 ring formation reaction Methods 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 239000013638 trimer Substances 0.000 description 3
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 3
• 239000010455 vermiculite Substances 0.000 description 3
• 229910052902 vermiculite Inorganic materials 0.000 description 3
• 235000019354 vermiculite Nutrition 0.000 description 3
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• GMTJCNWOYRYSMJ-UHFFFAOYSA-N (3-bromo-1-cyclobutylpyrazol-4-yl)methanol Chemical compound N1=C(Br)C(CO)=CN1C1CCC1 GMTJCNWOYRYSMJ-UHFFFAOYSA-N 0.000 description 2
• APDSKCAZBCGPNR-UHFFFAOYSA-N (3-iodo-1-propan-2-ylpyrazol-4-yl)methanol Chemical compound CC(C)N1C=C(CO)C(I)=N1 APDSKCAZBCGPNR-UHFFFAOYSA-N 0.000 description 2
• SPTPJHNYNZXHPX-UHFFFAOYSA-N (5-bromo-1-propan-2-ylpyrazol-4-yl)methanol Chemical compound CC(C)N1N=CC(CO)=C1Br SPTPJHNYNZXHPX-UHFFFAOYSA-N 0.000 description 2
• JOEAUSIVCWMQOT-UHFFFAOYSA-N 1'-(1-aminoisoquinoline-7-carbonyl)-2-tert-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CN=C(N)C2=CC(C(=O)N3CCC4(CC5=CN(N=C5C(=O)N4)C(C)(C)C)CC3)=CC=C21 JOEAUSIVCWMQOT-UHFFFAOYSA-N 0.000 description 2
• YPCAMYLSFZSXLS-UHFFFAOYSA-N 1'-(2-methylindazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CC2=NN(C)C=C2C=C1C(=O)N(CC1)CCC11CC(C=NN2C(C)C)=C2C(=O)N1 YPCAMYLSFZSXLS-UHFFFAOYSA-N 0.000 description 2
• UYUARKZGQUFSSK-UHFFFAOYSA-N 1'-(3,7-dimethyl-2h-indazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound CC1=C2NN=C(C)C2=CC(C(=O)N2CCC3(CC=4C=NN(C=4C(=O)N3)C(C)C)CC2)=C1 UYUARKZGQUFSSK-UHFFFAOYSA-N 0.000 description 2
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 2
• RABZYUWMIDILPP-UHFFFAOYSA-N 1,3-bis(sulfanyl)propane-1,2,3-triol Chemical compound SC(C(C(O)S)O)O RABZYUWMIDILPP-UHFFFAOYSA-N 0.000 description 2
• HXISGRVKWJITSF-UHFFFAOYSA-N 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanol Chemical compound FC(F)(F)C(O)C1=CC=C(Br)C=C1F HXISGRVKWJITSF-UHFFFAOYSA-N 0.000 description 2
• XUICLFCSWJGMIT-UHFFFAOYSA-N 1-(methylamino)isoquinoline-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(NC)=NC=CC2=C1 XUICLFCSWJGMIT-UHFFFAOYSA-N 0.000 description 2
• DQSGUBIOYRMJAQ-UHFFFAOYSA-N 1-(methylamino)isoquinoline-7-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(NC)=NC=CC2=C1 DQSGUBIOYRMJAQ-UHFFFAOYSA-N 0.000 description 2
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
• LFGZADOVHWQOSB-UHFFFAOYSA-N 1-methoxyisoquinoline-7-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(OC)=NC=CC2=C1 LFGZADOVHWQOSB-UHFFFAOYSA-N 0.000 description 2
• SPIIWFUICXZAKV-UHFFFAOYSA-N 1-o-ethyl 5-o-methyl 3-oxo-2h-indazole-1,5-dicarboxylate Chemical compound COC(=O)C1=CC=C2N(C(=O)OCC)N=C(O)C2=C1 SPIIWFUICXZAKV-UHFFFAOYSA-N 0.000 description 2
• KPDJFZOQLAFTSL-UHFFFAOYSA-N 1-o-ethyl 6-o-methyl 3-methoxyindazole-1,6-dicarboxylate Chemical compound C1=C(C(=O)OC)C=C2N(C(=O)OCC)N=C(OC)C2=C1 KPDJFZOQLAFTSL-UHFFFAOYSA-N 0.000 description 2
• VATYKCRPUNUKSE-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN=C2C=NNC2=C1 VATYKCRPUNUKSE-UHFFFAOYSA-N 0.000 description 2
• KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 2
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
• LHQWFZHYCBKYGD-UHFFFAOYSA-N 2-(2,2,2-trifluoroethylamino)quinoline-7-carboxylic acid Chemical compound C1=CC(NCC(F)(F)F)=NC2=CC(C(=O)O)=CC=C21 LHQWFZHYCBKYGD-UHFFFAOYSA-N 0.000 description 2
• STZFNUKQFCVIQM-UHFFFAOYSA-N 2-(methylamino)-3h-benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC(NC)=NC2=C1 STZFNUKQFCVIQM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• UUJCLULZZFVJER-UHFFFAOYSA-N 2-methoxyquinoline-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=CC2=NC(OC)=CC=C21 UUJCLULZZFVJER-UHFFFAOYSA-N 0.000 description 2
• IGLVDZUZTBJSNC-UHFFFAOYSA-N 2-methyl-3-oxo-1h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(=O)N(C)NC2=C1 IGLVDZUZTBJSNC-UHFFFAOYSA-N 0.000 description 2
• GZHWABCBKGMLIE-UHFFFAOYSA-N 2-methyl-3h-benzimidazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2NC(C)=NC2=C1 GZHWABCBKGMLIE-UHFFFAOYSA-N 0.000 description 2
• HNFGGBMTWQVAED-UHFFFAOYSA-N 2-methylindazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=NN(C)C=C21 HNFGGBMTWQVAED-UHFFFAOYSA-N 0.000 description 2
• LFZDQWVIOIYHBD-UHFFFAOYSA-N 2-tert-butyl-1'-(1-chloroisoquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CN=C(Cl)C2=CC(C(=O)N3CCC4(CC5=CN(N=C5C(=O)N4)C(C)(C)C)CC3)=CC=C21 LFZDQWVIOIYHBD-UHFFFAOYSA-N 0.000 description 2
• MSKXXSVWOVMZOL-UHFFFAOYSA-N 2-tert-butyl-1'-(2-chloroquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CC(Cl)=NC2=CC(C(=O)N3CCC4(CC5=CN(N=C5C(=O)N4)C(C)(C)C)CC3)=CC=C21 MSKXXSVWOVMZOL-UHFFFAOYSA-N 0.000 description 2
• NYVKGEAZGMXJOW-UHFFFAOYSA-N 2-tert-butyl-1'-[1-[(4-methoxyphenyl)methylamino]isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CC(OC)=CC=C1CNC1=NC=CC2=CC=C(C(=O)N3CCC4(CC3)NC(=O)C3=NN(C=C3C4)C(C)(C)C)C=C12 NYVKGEAZGMXJOW-UHFFFAOYSA-N 0.000 description 2
• WEUHMBVHNLAESA-UHFFFAOYSA-N 2-tert-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one;hydrochloride Chemical compound Cl.N1C(=O)C2=NN(C(C)(C)C)C=C2CC21CCNCC2 WEUHMBVHNLAESA-UHFFFAOYSA-N 0.000 description 2
• QCMATQUYIYCWCW-UHFFFAOYSA-N 3,4-diamino-5-chlorobenzoic acid Chemical compound NC1=CC(C(O)=O)=CC(Cl)=C1N QCMATQUYIYCWCW-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• QFLTUWMGALSANJ-UHFFFAOYSA-N 3-(methylamino)-1h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(NC)=NNC2=C1 QFLTUWMGALSANJ-UHFFFAOYSA-N 0.000 description 2
• BSJRJLNYCMQMRY-UHFFFAOYSA-N 3-(methylamino)-1h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(NC)=NNC2=C1 BSJRJLNYCMQMRY-UHFFFAOYSA-N 0.000 description 2
• WITFNXANFWSVLS-UHFFFAOYSA-N 3-(methylamino)isoquinoline-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=NC(NC)=CC2=C1 WITFNXANFWSVLS-UHFFFAOYSA-N 0.000 description 2
• PNISNYPMYATRFP-UHFFFAOYSA-N 3-(methylamino)isoquinoline-7-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C=NC(NC)=CC2=C1 PNISNYPMYATRFP-UHFFFAOYSA-N 0.000 description 2
• IQHAOAJOMLUVEF-UHFFFAOYSA-N 3-(trifluoromethyl)-2h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(C(F)(F)F)=NNC2=C1 IQHAOAJOMLUVEF-UHFFFAOYSA-N 0.000 description 2
• IAPDANAEZMNOEP-UHFFFAOYSA-N 3-chloro-1h-pyrrolo[3,2-b]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN=C2C(Cl)=CNC2=C1 IAPDANAEZMNOEP-UHFFFAOYSA-N 0.000 description 2
• FPWDNADXYRGXRR-UHFFFAOYSA-N 3-cyano-1h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(C#N)=NNC2=C1 FPWDNADXYRGXRR-UHFFFAOYSA-N 0.000 description 2
• YOQXHBSCVRWJAC-UHFFFAOYSA-N 3-methoxy-1h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(OC)=NNC2=C1 YOQXHBSCVRWJAC-UHFFFAOYSA-N 0.000 description 2
• JJENYJMSQOWKJN-UHFFFAOYSA-N 3-methoxyisoquinoline-7-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C=NC(OC)=CC2=C1 JJENYJMSQOWKJN-UHFFFAOYSA-N 0.000 description 2
• JAPGBCYHMJSRNG-UHFFFAOYSA-N 3-oxo-1,2-dihydroindazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NN=C(O)C2=C1 JAPGBCYHMJSRNG-UHFFFAOYSA-N 0.000 description 2
• YPFZNQWLNDDXEJ-UHFFFAOYSA-N 4,8-dimethoxyquinoline-2-carboxylic acid Chemical compound C1=C(C(O)=O)N=C2C(OC)=CC=CC2=C1OC YPFZNQWLNDDXEJ-UHFFFAOYSA-N 0.000 description 2
• QKEYRQOKUAAKBF-UHFFFAOYSA-N 4-(bromomethyl)-3-iodo-1-propan-2-ylpyrazole Chemical compound CC(C)N1C=C(CBr)C(I)=N1 QKEYRQOKUAAKBF-UHFFFAOYSA-N 0.000 description 2
• ORJRNMSPYLCYQE-UHFFFAOYSA-N 4-[(5-bromo-1-propan-2-ylpyrazol-4-yl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)N1N=CC(CC2(CCN(CC2)C(=O)OC(C)(C)C)C(O)=O)=C1Br ORJRNMSPYLCYQE-UHFFFAOYSA-N 0.000 description 2
• BAJCFNRLEJHPTQ-UHFFFAOYSA-N 4-bromo-2-fluoro-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(Br)C=C1F BAJCFNRLEJHPTQ-UHFFFAOYSA-N 0.000 description 2
• MUFLKMJJPJVLST-UHFFFAOYSA-N 4-bromo-2-fluoro-n-methylbenzenecarbothioamide Chemical compound CNC(=S)C1=CC=C(Br)C=C1F MUFLKMJJPJVLST-UHFFFAOYSA-N 0.000 description 2
• WEIDCCQGPKGAKJ-UHFFFAOYSA-N 4-bromo-2-methyl-6-(trifluoromethyl)aniline Chemical compound CC1=CC(Br)=CC(C(F)(F)F)=C1N WEIDCCQGPKGAKJ-UHFFFAOYSA-N 0.000 description 2
• IAJRTGABDFKUSX-UHFFFAOYSA-N 5-amino-1-propan-2-ylpyrazole-4-carboxylic acid Chemical compound CC(C)N1N=CC(C(O)=O)=C1N IAJRTGABDFKUSX-UHFFFAOYSA-N 0.000 description 2
• VIEWWZLMNKKIGQ-UHFFFAOYSA-N 5-bromo-2-fluoro-n-methylbenzamide Chemical compound CNC(=O)C1=CC(Br)=CC=C1F VIEWWZLMNKKIGQ-UHFFFAOYSA-N 0.000 description 2
• GUEWHDRZVMZATD-UHFFFAOYSA-N 5-bromo-2-fluoro-n-methylbenzenecarbothioamide Chemical compound CNC(=S)C1=CC(Br)=CC=C1F GUEWHDRZVMZATD-UHFFFAOYSA-N 0.000 description 2
• CBAXYISWNGGXOZ-UHFFFAOYSA-N 5-bromo-2-methylpyridin-3-amine Chemical compound CC1=NC=C(Br)C=C1N CBAXYISWNGGXOZ-UHFFFAOYSA-N 0.000 description 2
• OGFDEOWHCWNHQQ-UHFFFAOYSA-N 5-bromo-3-(trifluoromethyl)-1H-carbazole Chemical compound BrC1=C2C3=CC(=CCC3=NC2=CC=C1)C(F)(F)F OGFDEOWHCWNHQQ-UHFFFAOYSA-N 0.000 description 2
• IXCLPEJUNPPZOJ-UHFFFAOYSA-N 5-bromo-n-methyl-1h-indazol-3-amine Chemical compound C1=C(Br)C=C2C(NC)=NNC2=C1 IXCLPEJUNPPZOJ-UHFFFAOYSA-N 0.000 description 2
• FONNZZMIJPHSJP-UHFFFAOYSA-N 6-bromo-1h-pyrazolo[4,3-b]pyridine Chemical compound BrC1=CN=C2C=NNC2=C1 FONNZZMIJPHSJP-UHFFFAOYSA-N 0.000 description 2
• MZXOHGOCNRWAPY-UHFFFAOYSA-N 6-bromo-2h-isoquinolin-3-one Chemical compound BrC1=CC=C2C=NC(O)=CC2=C1 MZXOHGOCNRWAPY-UHFFFAOYSA-N 0.000 description 2
• JVMUEAIOOCTKKJ-UHFFFAOYSA-N 6-bromo-3-methoxyisoquinoline Chemical compound BrC1=CC=C2C=NC(OC)=CC2=C1 JVMUEAIOOCTKKJ-UHFFFAOYSA-N 0.000 description 2
• JOAJLTRLSSFKJV-UHFFFAOYSA-N 6-bromo-n-methyl-1h-indazol-3-amine Chemical compound BrC1=CC=C2C(NC)=NNC2=C1 JOAJLTRLSSFKJV-UHFFFAOYSA-N 0.000 description 2
• BZJLCRDLJFMJAF-UHFFFAOYSA-N 6-bromo-n-methylisoquinolin-3-amine Chemical compound BrC1=CC=C2C=NC(NC)=CC2=C1 BZJLCRDLJFMJAF-UHFFFAOYSA-N 0.000 description 2
• RDTKFZONKRNVBL-UHFFFAOYSA-N 7-(trifluoromethyl)-1h-indazole-5-carboxylic acid Chemical compound OC(=O)C1=CC(C(F)(F)F)=C2NN=CC2=C1 RDTKFZONKRNVBL-UHFFFAOYSA-N 0.000 description 2
• RNZQCNYQATWREI-UHFFFAOYSA-N 7-bromo-1-methoxyisoquinoline Chemical compound C1=C(Br)C=C2C(OC)=NC=CC2=C1 RNZQCNYQATWREI-UHFFFAOYSA-N 0.000 description 2
• DSOKREQUHLPVFR-UHFFFAOYSA-N 7-bromo-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C2=CC(Br)=CC=C21 DSOKREQUHLPVFR-UHFFFAOYSA-N 0.000 description 2
• UUOPCILVZYFPAA-UHFFFAOYSA-N 7-bromo-3-methoxyisoquinoline Chemical compound C1=C(Br)C=C2C=NC(OC)=CC2=C1 UUOPCILVZYFPAA-UHFFFAOYSA-N 0.000 description 2
• BYVMHDODQSGSOI-UHFFFAOYSA-N 7-bromo-n-methylisoquinolin-3-amine Chemical compound C1=C(Br)C=C2C=NC(NC)=CC2=C1 BYVMHDODQSGSOI-UHFFFAOYSA-N 0.000 description 2
• FBTKUAFGTDENLW-UHFFFAOYSA-N 7-bromoisoquinolin-3-amine Chemical compound C1=C(Br)C=C2C=NC(N)=CC2=C1 FBTKUAFGTDENLW-UHFFFAOYSA-N 0.000 description 2
• XYBSZCUHOLWQQU-UHFFFAOYSA-N 7-bromoquinoline Chemical compound C1=CC=NC2=CC(Br)=CC=C21 XYBSZCUHOLWQQU-UHFFFAOYSA-N 0.000 description 2
• OGAXJAGKIRCCLN-UHFFFAOYSA-N 7-methoxy-1-(oxan-2-yl)indazole-5-carboxylic acid Chemical compound C1=2C(OC)=CC(C(O)=O)=CC=2C=NN1C1CCCCO1 OGAXJAGKIRCCLN-UHFFFAOYSA-N 0.000 description 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 2
• ROWKJAVDOGWPAT-UHFFFAOYSA-N Acetoin Chemical compound CC(O)C(C)=O ROWKJAVDOGWPAT-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• HNIPEKMFLGMOMG-UHFFFAOYSA-N C(C)(C)(C)OC(=O)N1CC(C(CC1)N=C=O)CC=1C(=NN(C1)C(C)C)I Chemical compound C(C)(C)(C)OC(=O)N1CC(C(CC1)N=C=O)CC=1C(=NN(C1)C(C)C)I HNIPEKMFLGMOMG-UHFFFAOYSA-N 0.000 description 2
• ZNPJIYNABXPBRN-UHFFFAOYSA-N C1C(C(=O)O)CC2CCC1N2C(O)=O Chemical compound C1C(C(=O)O)CC2CCC1N2C(O)=O ZNPJIYNABXPBRN-UHFFFAOYSA-N 0.000 description 2
• NKPNWWFEMGRRPU-UHFFFAOYSA-N C1C=C(C=C2C1=NC3=C2C=C(C=C3)Br)C(F)(F)F Chemical compound C1C=C(C=C2C1=NC3=C2C=C(C=C3)Br)C(F)(F)F NKPNWWFEMGRRPU-UHFFFAOYSA-N 0.000 description 2
• VZWFYXLSCLCSGX-UHFFFAOYSA-N CC(C)N(C=C1CC(CC2)(CCN2C(O)=O)C(O)=O)N=C1I Chemical compound CC(C)N(C=C1CC(CC2)(CCN2C(O)=O)C(O)=O)N=C1I VZWFYXLSCLCSGX-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 2
• 101710150887 Cholecystokinin A Proteins 0.000 description 2
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
• 208000032928 Dyslipidaemia Diseases 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 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
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 102100025353 G-protein coupled bile acid receptor 1 Human genes 0.000 description 2
• 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 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000857733 Homo sapiens G-protein coupled bile acid receptor 1 Proteins 0.000 description 2
• 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 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
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• 208000031773 Insulin resistance syndrome Diseases 0.000 description 2
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 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
• 208000017170 Lipid metabolism disease Diseases 0.000 description 2
• 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 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
• 101710151321 Melanostatin Proteins 0.000 description 2
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical group CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
• 102400000064 Neuropeptide Y Human genes 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• 108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• 102000002512 Orexin Human genes 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
• 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 2
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
• 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• IMIPDPVHGGHVNH-YWVHRCQQSA-N [(8r,9s,13s,14s)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-3-yl] (z)-octadec-9-enoate Chemical compound C1C[C@]2(C)C(=O)CC[C@H]2[C@@H]2CCC3=CC(OC(=O)CCCCCCC\C=C/CCCCCCCC)=CC=C3[C@H]21 IMIPDPVHGGHVNH-YWVHRCQQSA-N 0.000 description 2
• SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 229960004733 albiglutide Drugs 0.000 description 2
• OGWAVGNOAMXIIM-UHFFFAOYSA-N albiglutide Chemical compound O=C(O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)CNC(=O)C(N)CC=1(N=CNC=1))CCC(=O)O)C(O)C)CC2(=CC=CC=C2))C(O)C)CO)CC(=O)O)C(C)C)CO)CO)CC3(=CC=C(O)C=C3))CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCN)CCC(=O)O)CC4(=CC=CC=C4))C(CC)C)C)CC=6(C5(=C(C=CC=C5)NC=6)))CC(C)C)C(C)C)CCCCN)CCCNC(=N)N OGWAVGNOAMXIIM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 229960001667 alogliptin Drugs 0.000 description 2
• 239000003888 alpha glucosidase inhibitor Substances 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 239000002830 appetite depressant Substances 0.000 description 2
• 239000003125 aqueous solvent Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 238000003149 assay kit Methods 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 239000002876 beta blocker Substances 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 229960002685 biotin Drugs 0.000 description 2
• 235000020958 biotin Nutrition 0.000 description 2
• 239000011616 biotin Substances 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
• OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 2
• 229960002802 bromocriptine Drugs 0.000 description 2
• 229940045348 brown mixture Drugs 0.000 description 2
• SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
• 229960001058 bupropion Drugs 0.000 description 2
• WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
• GXXOBXPRDUPYEJ-UHFFFAOYSA-N butylhydrazine;hydron;chloride Chemical group Cl.CCCCNN GXXOBXPRDUPYEJ-UHFFFAOYSA-N 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 2
• 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 2
• 238000004440 column chromatography Methods 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 239000012468 concentrated sample Substances 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• YWDRRHINJWKDTJ-UHFFFAOYSA-N diethyl 2-(5-bromo-3-nitropyridin-2-yl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=NC=C(Br)C=C1[N+]([O-])=O YWDRRHINJWKDTJ-UHFFFAOYSA-N 0.000 description 2
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 238000007876 drug discovery Methods 0.000 description 2
• 230000009977 dual effect Effects 0.000 description 2
• 229950000269 emiglitate Drugs 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 125000004185 ester group Chemical group 0.000 description 2
• MLFIXLDZQGSOAX-UHFFFAOYSA-N ethyl 1-(methylamino)isoquinoline-6-carboxylate Chemical compound CNC1=NC=CC2=CC(C(=O)OCC)=CC=C21 MLFIXLDZQGSOAX-UHFFFAOYSA-N 0.000 description 2
• YKFOBSKZGNOLGA-UHFFFAOYSA-N ethyl 1-(methylamino)isoquinoline-7-carboxylate Chemical compound C1=CN=C(NC)C2=CC(C(=O)OCC)=CC=C21 YKFOBSKZGNOLGA-UHFFFAOYSA-N 0.000 description 2
• ISQUZJJGKPPHKB-UHFFFAOYSA-N ethyl 1-[(4-methoxyphenyl)methylamino]isoquinoline-7-carboxylate Chemical compound C12=CC(C(=O)OCC)=CC=C2C=CN=C1NCC1=CC=C(OC)C=C1 ISQUZJJGKPPHKB-UHFFFAOYSA-N 0.000 description 2
• MJHWJISKIWUXES-UHFFFAOYSA-N ethyl 1-chloroisoquinoline-6-carboxylate Chemical compound ClC1=NC=CC2=CC(C(=O)OCC)=CC=C21 MJHWJISKIWUXES-UHFFFAOYSA-N 0.000 description 2
• ZWJSAXUONDRCOV-UHFFFAOYSA-N ethyl 1-oxidoquinolin-1-ium-6-carboxylate Chemical compound [O-][N+]1=CC=CC2=CC(C(=O)OCC)=CC=C21 ZWJSAXUONDRCOV-UHFFFAOYSA-N 0.000 description 2
• UQCQMEQQIMBMSM-UHFFFAOYSA-N ethyl 1-tert-butyl-3-iodopyrazole-4-carboxylate Chemical compound CCOC(=O)C1=CN(C(C)(C)C)N=C1I UQCQMEQQIMBMSM-UHFFFAOYSA-N 0.000 description 2
• FPABHYIKKMHYMT-UHFFFAOYSA-N ethyl 1-tert-butyl-4-(hydroxymethyl)pyrazole-3-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)(C)C)C=C1CO FPABHYIKKMHYMT-UHFFFAOYSA-N 0.000 description 2
• RBFSKWFUQVVBLR-UHFFFAOYSA-N ethyl 2-(methylamino)quinoline-6-carboxylate Chemical compound N1=C(NC)C=CC2=CC(C(=O)OCC)=CC=C21 RBFSKWFUQVVBLR-UHFFFAOYSA-N 0.000 description 2
• PWBLMBXLGXIVHF-UHFFFAOYSA-N ethyl 2-chloroquinoline-7-carboxylate Chemical compound C1=CC(Cl)=NC2=CC(C(=O)OCC)=CC=C21 PWBLMBXLGXIVHF-UHFFFAOYSA-N 0.000 description 2
• LAYNFJHYMIMKIE-UHFFFAOYSA-N ethyl 2-methoxyquinoline-7-carboxylate Chemical compound C1=CC(OC)=NC2=CC(C(=O)OCC)=CC=C21 LAYNFJHYMIMKIE-UHFFFAOYSA-N 0.000 description 2
• PTCFZHKVKXXEQU-UHFFFAOYSA-N ethyl 4-(bromomethyl)-1-tert-butylpyrazole-3-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)(C)C)C=C1CBr PTCFZHKVKXXEQU-UHFFFAOYSA-N 0.000 description 2
• NWWORXYTJRPSMC-QKPAOTATSA-N ethyl 4-[2-[(2r,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 NWWORXYTJRPSMC-QKPAOTATSA-N 0.000 description 2
• YPXGHKWOJXQLQU-UHFFFAOYSA-N ethyl 5-amino-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1N YPXGHKWOJXQLQU-UHFFFAOYSA-N 0.000 description 2
• KZDVIRXJSBNRTK-UHFFFAOYSA-N ethyl 7-methoxy-1-(oxan-2-yl)indazole-5-carboxylate Chemical compound N1=CC2=CC(C(=O)OCC)=CC(OC)=C2N1C1CCCCO1 KZDVIRXJSBNRTK-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 230000004136 fatty acid synthesis Effects 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 238000001030 gas--liquid chromatography Methods 0.000 description 2
• 229960004580 glibenclamide Drugs 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 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 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 229940125396 insulin Drugs 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
• QUFUUBBLCOBJPH-UHFFFAOYSA-N isoquinoline-7-carboxylic acid Chemical compound C1=CN=CC2=CC(C(=O)O)=CC=C21 QUFUUBBLCOBJPH-UHFFFAOYSA-N 0.000 description 2
• 238000011813 knockout mouse model Methods 0.000 description 2
• 229940099584 lactobionate Drugs 0.000 description 2
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 229960002397 linagliptin Drugs 0.000 description 2
• 230000006372 lipid accumulation Effects 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 238000004811 liquid chromatography Methods 0.000 description 2
• 238000001819 mass spectrum Methods 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
• 229960003105 metformin Drugs 0.000 description 2
• FYXVHJJZGRTONS-AATRIKPKSA-N methyl (e)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(/C#N)C(=O)OC FYXVHJJZGRTONS-AATRIKPKSA-N 0.000 description 2
• HUKGAIBUMOKLHZ-UHFFFAOYSA-N methyl 1-oxidoquinolin-1-ium-7-carboxylate Chemical compound C1=CC=[N+]([O-])C2=CC(C(=O)OC)=CC=C21 HUKGAIBUMOKLHZ-UHFFFAOYSA-N 0.000 description 2
• JZFTWMGTLMPFEL-UHFFFAOYSA-N methyl 1h-pyrrolo[3,2-b]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN=C2C=CNC2=C1 JZFTWMGTLMPFEL-UHFFFAOYSA-N 0.000 description 2
• WIGUKGNWZNYFHE-UHFFFAOYSA-N methyl 2-(methylamino)-3h-benzimidazole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC(NC)=NC2=C1 WIGUKGNWZNYFHE-UHFFFAOYSA-N 0.000 description 2
• HHWIDMOVARJDLR-UHFFFAOYSA-N methyl 3-(methylamino)-1h-indazole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=C2C(NC)=NNC2=C1 HHWIDMOVARJDLR-UHFFFAOYSA-N 0.000 description 2
• PGTDLJVBQZRNJK-UHFFFAOYSA-N methyl 3-(methylamino)-1h-indazole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C(NC)=NNC2=C1 PGTDLJVBQZRNJK-UHFFFAOYSA-N 0.000 description 2
• NBCMXSJIQKNDCJ-UHFFFAOYSA-N methyl 3-chloro-1h-pyrrolo[3,2-b]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN=C2C(Cl)=CNC2=C1 NBCMXSJIQKNDCJ-UHFFFAOYSA-N 0.000 description 2
• ROBGLDDGCODEOT-UHFFFAOYSA-N methyl 3-cyano-1h-indazole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C(C#N)=NNC2=C1 ROBGLDDGCODEOT-UHFFFAOYSA-N 0.000 description 2
• JQHYEHRKSDHNFC-UHFFFAOYSA-N methyl 3-iodo-2h-indazole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=CC2=NNC(I)=C21 JQHYEHRKSDHNFC-UHFFFAOYSA-N 0.000 description 2
• VSXHXVGWOSYULI-UHFFFAOYSA-N methyl 3-iodo-2h-indazole-6-carboxylate Chemical compound C1=C(C(=O)OC)C=CC2=C(I)NN=C21 VSXHXVGWOSYULI-UHFFFAOYSA-N 0.000 description 2
• MZGHHXKIAMNUHR-UHFFFAOYSA-N methyl 3-oxo-1,2-dihydroindazole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NN=C(O)C2=C1 MZGHHXKIAMNUHR-UHFFFAOYSA-N 0.000 description 2
• MERFKJILADBKQU-UHFFFAOYSA-N methyl 3-oxo-1,2-dihydroindazole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C(O)=NNC2=C1 MERFKJILADBKQU-UHFFFAOYSA-N 0.000 description 2
• GTMRDKCXGHWYDB-UHFFFAOYSA-N methyl 7-(trifluoromethyl)-1h-indazole-5-carboxylate Chemical compound COC(=O)C1=CC(C(F)(F)F)=C2NN=CC2=C1 GTMRDKCXGHWYDB-UHFFFAOYSA-N 0.000 description 2
• ZTZCGCCFJZVRTO-UHFFFAOYSA-N methyl quinoline-7-carboxylate Chemical compound C1=CC=NC2=CC(C(=O)OC)=CC=C21 ZTZCGCCFJZVRTO-UHFFFAOYSA-N 0.000 description 2
• NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• RVTYXFKKBCBRPZ-UHFFFAOYSA-N n-(5-bromo-2-methylpyridin-3-yl)acetamide Chemical compound CC(=O)NC1=CC(Br)=CN=C1C RVTYXFKKBCBRPZ-UHFFFAOYSA-N 0.000 description 2
• DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 2
• 229960003086 naltrexone Drugs 0.000 description 2
• 239000003887 narcotic antagonist Substances 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 108060005714 orexin Proteins 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
• AZUIUVJESCFSLJ-UHFFFAOYSA-N phenyl 6-[[3-methoxy-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C=1C=C(C(F)(F)F)C=CC=1C=1C(OC)=CC=CC=1C(=O)NC(C=C1CC2)=CC=C1CN2C(=O)OC1=CC=CC=C1 AZUIUVJESCFSLJ-UHFFFAOYSA-N 0.000 description 2
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 150000003053 piperidines Chemical class 0.000 description 2
• 239000004033 plastic Substances 0.000 description 2
• 229920003023 plastic Polymers 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• 239000001508 potassium citrate Substances 0.000 description 2
• QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 2
• 229960003611 pramlintide Drugs 0.000 description 2
• 239000001294 propane Substances 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 238000003908 quality control method Methods 0.000 description 2
• VXGYRCVTBHVXMZ-UHFFFAOYSA-N quinoline-6-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CC=C21 VXGYRCVTBHVXMZ-UHFFFAOYSA-N 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 108700027806 rGLP-1 Proteins 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 229960004586 rosiglitazone Drugs 0.000 description 2
• 229960004937 saxagliptin Drugs 0.000 description 2
• 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 2
• 108010033693 saxagliptin Proteins 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000002485 serotonin 2C agonist Substances 0.000 description 2
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 2
• 229960004425 sibutramine Drugs 0.000 description 2
• 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 2
• 229960004034 sitagliptin Drugs 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 235000010288 sodium nitrite Nutrition 0.000 description 2
• BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 2
• 229910001488 sodium perchlorate Inorganic materials 0.000 description 2
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 229960002277 tolazamide Drugs 0.000 description 2
• OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 2
• 229960005371 tolbutamide Drugs 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 150000003626 triacylglycerols Chemical class 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
• 235000015870 tripotassium citrate Nutrition 0.000 description 2
• 238000001323 two-dimensional chromatography Methods 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
• 229960001254 vildagliptin Drugs 0.000 description 2
• DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 2
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
• DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-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
• FOZFSEMFCIPOSZ-SPCKQMHLSA-N (2r,3r,4r,5s)-2-(hydroxymethyl)-1-[[(2r,3s,4s,5r,6s)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]methyl]piperidine-3,4,5-triol;trihydrate Chemical compound O.O.O.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 FOZFSEMFCIPOSZ-SPCKQMHLSA-N 0.000 description 1
• AMNXBQPRODZJQR-DITALETJSA-N (2s)-2-cyclopentyl-2-[3-[(2,4-dimethylpyrido[2,3-b]indol-9-yl)methyl]phenyl]-n-[(1r)-2-hydroxy-1-phenylethyl]acetamide Chemical compound C1([C@@H](C=2C=CC=C(C=2)CN2C3=CC=CC=C3C3=C(C)C=C(N=C32)C)C(=O)N[C@@H](CO)C=2C=CC=CC=2)CCCC1 AMNXBQPRODZJQR-DITALETJSA-N 0.000 description 1
• IRAAJHYKQDFNFO-SFHVURJKSA-N (2s)-3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-(2,2,2-trifluoroethoxy)propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC1=CC=C(C[C@H](OCC(F)(F)F)C(O)=O)C=C1 IRAAJHYKQDFNFO-SFHVURJKSA-N 0.000 description 1
• PUTJFIQGLGDLIT-RNDOZLNUSA-N (2s,3s,3ar,5as,9as,9br)-3-[(2s)-2-(furan-3-yl)-2-hydroxyethyl]-2,3a,6,6,9a-pentamethyl-3,4,5,5a,7,8,9,9b-octahydro-1h-cyclopenta[a]naphthalene-2-carbaldehyde Chemical compound C=1([C@@H](O)C[C@H]2[C@@]3(C)[C@@H]([C@]4(CCCC(C)(C)[C@@H]4CC3)C)C[C@]2(C)C=O)C=COC=1 PUTJFIQGLGDLIT-RNDOZLNUSA-N 0.000 description 1
• NPBCMXATLRCCLF-IRRLEISYSA-N (2s,4r)-4-[(3r,5s,6r,7r,8r,9s,10s,12s,13r,14s,17r)-6-ethyl-3,7,12-trihydroxy-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]2C[C@H](O)[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 NPBCMXATLRCCLF-IRRLEISYSA-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
• PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 1
• NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 1
• URJPEAYLOXTYED-UHFFFAOYSA-N (5-bromo-1-tert-butylpyrazol-4-yl)methanol Chemical compound CC(C)(C)N1N=CC(CO)=C1Br URJPEAYLOXTYED-UHFFFAOYSA-N 0.000 description 1
• QJLPWVUZFKETMK-LLVKDONJSA-N (5r)-1,5,7,9,11,14-hexahydroxy-3-methyl-8,13-dioxo-5,6-dihydrobenzo[a]tetracene-2-carboxylic acid Chemical compound O=C1C2=C(O)C=C(O)C=C2C(=O)C2=C1C(O)=C1C[C@@H](O)C(C=C(C(=C3O)C(O)=O)C)=C3C1=C2O QJLPWVUZFKETMK-LLVKDONJSA-N 0.000 description 1
• DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
• 229940095131 (r)- propylene glycol Drugs 0.000 description 1
• 229960004463 (s)- propylene glycol Drugs 0.000 description 1
• IJLUPPUCKMKAKX-UHFFFAOYSA-N 1'-(2-aminoquinoline-7-carbonyl)-2-tert-butylspiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CC(N)=NC2=CC(C(=O)N3CCC4(NC(=O)C5=C(C4)CN(N5)C(C)(C)C)CC3)=CC=C21 IJLUPPUCKMKAKX-UHFFFAOYSA-N 0.000 description 1
• LEOPENMCGPJGTF-UHFFFAOYSA-N 1'-(2-methyl-3h-benzimidazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2NC(C)=NC2=CC(C(=O)N2CCC3(CC=4C=NN(C=4C(=O)N3)C(C)C)CC2)=C1 LEOPENMCGPJGTF-UHFFFAOYSA-N 0.000 description 1
• QCXBBRKJDISZRM-UHFFFAOYSA-N 1'-(4-methoxy-1h-indazole-6-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C=2NN=CC=2C(OC)=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1N(C(C)C)N=C2 QCXBBRKJDISZRM-UHFFFAOYSA-N 0.000 description 1
• UFBFUXKIRMFBIJ-UHFFFAOYSA-N 1'-(7-chloro-1h-indazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound ClC1=C2NN=CC2=CC(C(=O)N2CCC3(CC=4C=NN(C=4C(=O)N3)C(C)C)CC2)=C1 UFBFUXKIRMFBIJ-UHFFFAOYSA-N 0.000 description 1
• GRXDVGBIFLDTMB-UHFFFAOYSA-N 1'-(7-ethyl-1h-indazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C=2C=NNC=2C(CC)=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1N(C(C)C)N=C2 GRXDVGBIFLDTMB-UHFFFAOYSA-N 0.000 description 1
• NKFJONYGBJGHDD-UHFFFAOYSA-N 1'-(7-methyl-1h-indazole-5-carbonyl)-2-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound CC1=C2NN=CC2=CC(C(=O)N2CCC3(CC4=CN(N=C4C(=O)N3)C(C)C)CC2)=C1 NKFJONYGBJGHDD-UHFFFAOYSA-N 0.000 description 1
• YDCCEMINNAHUCT-UHFFFAOYSA-N 1'-(isoquinoline-6-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=NC=CC2=CC(C(=O)N3CCC4(CC=5C=NN(C=5C(=O)N4)C(C)C)CC3)=CC=C21 YDCCEMINNAHUCT-UHFFFAOYSA-N 0.000 description 1
• RZESKAYUIYZXNK-UHFFFAOYSA-N 1'-(isoquinoline-7-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CN=CC2=CC(C(=O)N3CCC4(CC=5C=NN(C=5C(=O)N4)C(C)C)CC3)=CC=C21 RZESKAYUIYZXNK-UHFFFAOYSA-N 0.000 description 1
• SBVYADOWSDORRO-UHFFFAOYSA-N 1'-[2-(methylamino)quinoline-7-carbonyl]-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C2=NC(NC)=CC=C2C=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1N(C(C)C)N=C2 SBVYADOWSDORRO-UHFFFAOYSA-N 0.000 description 1
• UXMBUNWOVWTIFH-UHFFFAOYSA-N 1,1,1-trifluoro-11,11-dimethyldodecane Chemical compound CC(CCCCCCCCCC(F)(F)F)(C)C UXMBUNWOVWTIFH-UHFFFAOYSA-N 0.000 description 1
• NIIPNAJXERMYOG-UHFFFAOYSA-N 1,1,2-trimethylhydrazine Chemical compound CNN(C)C NIIPNAJXERMYOG-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• NOXOVDSZFKJWSB-UHFFFAOYSA-N 1-(tert-butylamino)isoquinoline-7-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(NC(C)(C)C)=NC=CC2=C1 NOXOVDSZFKJWSB-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
• XPZXCUSYVUOLPT-UHFFFAOYSA-N 1-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C(CCC)N1N=CC2=C1C(NC1(C2)CCNCC1)=O XPZXCUSYVUOLPT-UHFFFAOYSA-N 0.000 description 1
• XGDBADPYOLJEKU-UHFFFAOYSA-N 1-chloroisoquinoline-7-carbonyl chloride Chemical compound C1=CN=C(Cl)C2=CC(C(=O)Cl)=CC=C21 XGDBADPYOLJEKU-UHFFFAOYSA-N 0.000 description 1
• LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 description 1
• LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
• BTUGGGLMQBJCBN-UHFFFAOYSA-N 1-iodo-2-methylpropane Chemical compound CC(C)CI BTUGGGLMQBJCBN-UHFFFAOYSA-N 0.000 description 1
• FDUYXXPQMKLEAZ-UHFFFAOYSA-N 1-methoxyisoquinoline-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(OC)=NC=CC2=C1 FDUYXXPQMKLEAZ-UHFFFAOYSA-N 0.000 description 1
• VWIWCHCBXWBREL-UHFFFAOYSA-N 1-methylindazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(C)N=CC2=C1 VWIWCHCBXWBREL-UHFFFAOYSA-N 0.000 description 1
• XQEUZCLDUSDIFQ-UHFFFAOYSA-N 1-o-ethyl 5-o-methyl 3-methoxyindazole-1,5-dicarboxylate Chemical compound COC(=O)C1=CC=C2N(C(=O)OCC)N=C(OC)C2=C1 XQEUZCLDUSDIFQ-UHFFFAOYSA-N 0.000 description 1
• CJZHQWLTASOXSF-UHFFFAOYSA-N 1-o-ethyl 6-o-methyl 2-methyl-3-oxoindazole-1,6-dicarboxylate Chemical compound C1=C(C(=O)OC)C=C2N(C(=O)OCC)N(C)C(=O)C2=C1 CJZHQWLTASOXSF-UHFFFAOYSA-N 0.000 description 1
• VQXCFJSKJUHISI-UHFFFAOYSA-N 1-o-ethyl 6-o-methyl 3-oxo-2h-indazole-1,6-dicarboxylate Chemical compound C1=C(C(=O)OC)C=C2N(C(=O)OCC)N=C(O)C2=C1 VQXCFJSKJUHISI-UHFFFAOYSA-N 0.000 description 1
• WYHBWJNFGZOCCU-UHFFFAOYSA-N 1-propan-2-yl-1'-(1h-pyrrolo[2,3-b]pyridine-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound N1=C2NC=CC2=CC(C(=O)N2CCC3(CC=4C=NN(C=4C(=O)N3)C(C)C)CC2)=C1 WYHBWJNFGZOCCU-UHFFFAOYSA-N 0.000 description 1
• IOBQZXIUUDKZNT-UHFFFAOYSA-N 1-propan-2-yl-1'-(1h-pyrrolo[3,2-b]pyridine-2-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=CC=C2NC(C(=O)N3CCC4(CC=5C=NN(C=5C(=O)N4)C(C)C)CC3)=CC2=N1 IOBQZXIUUDKZNT-UHFFFAOYSA-N 0.000 description 1
• ZKSKVYJIPOOHTQ-UHFFFAOYSA-N 1-propan-2-ylspiro[4,6-dihydro-2H-pyrazolo[3,4-c]pyridine-5,4'-piperidine] Chemical compound C(C)(C)N1NC=C2C1=CNC1(C2)CCNCC1 ZKSKVYJIPOOHTQ-UHFFFAOYSA-N 0.000 description 1
• VUPPGECTCYOIJR-UHFFFAOYSA-N 1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound N1C(=O)C=2N(C(C)C)N=CC=2CC21CCNCC2 VUPPGECTCYOIJR-UHFFFAOYSA-N 0.000 description 1
• CPYQAPRHOQDIPQ-UHFFFAOYSA-N 1-tert-butyl-1'-(7-methyl-1h-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C=2C=NNC=2C(C)=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1N(C(C)(C)C)N=C2 CPYQAPRHOQDIPQ-UHFFFAOYSA-N 0.000 description 1
• DVWIBDRVVPEGMY-UHFFFAOYSA-N 1-tert-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one;hydrochloride Chemical compound Cl.N1C(=O)C=2N(C(C)(C)C)N=CC=2CC21CCNCC2 DVWIBDRVVPEGMY-UHFFFAOYSA-N 0.000 description 1
• 102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 description 1
• 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 description 1
• ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 1
• MAVGBUDLHOOROM-UHFFFAOYSA-N 1h-indazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NN=CC2=C1 MAVGBUDLHOOROM-UHFFFAOYSA-N 0.000 description 1
• DNCVTVVLMRHJCJ-UHFFFAOYSA-N 1h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=NNC2=C1 DNCVTVVLMRHJCJ-UHFFFAOYSA-N 0.000 description 1
• SINFYKZXNIJIEU-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C2NC=CC2=C1 SINFYKZXNIJIEU-UHFFFAOYSA-N 0.000 description 1
• KBHQUFPZXCNYKN-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=N1 KBHQUFPZXCNYKN-UHFFFAOYSA-N 0.000 description 1
• QLGJLBPWOCDQQM-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine-6-carboxylic acid Chemical compound OC(=O)C1=CN=C2C=CNC2=C1 QLGJLBPWOCDQQM-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
• IANXAXNUNBAWBA-UHFFFAOYSA-N 2,2,3-trimethylundecane Chemical compound CCCCCCCCC(C)C(C)(C)C IANXAXNUNBAWBA-UHFFFAOYSA-N 0.000 description 1
• OVRWUZYZECPJOB-UHFFFAOYSA-N 2,2-difluoroethanamine Chemical compound NCC(F)F OVRWUZYZECPJOB-UHFFFAOYSA-N 0.000 description 1
• QBRDYRZYMKDWNT-UHFFFAOYSA-N 2,4-bis(4-bromo-2-fluorophenyl)-1,1,1,5,5,5-hexafluoropentan-3-one Chemical compound BrC1=CC(=C(C=C1)C(C(F)(F)F)C(=O)C(C(F)(F)F)C1=C(C=C(C=C1)Br)F)F QBRDYRZYMKDWNT-UHFFFAOYSA-N 0.000 description 1
• CNOOTVLHXJLFMF-UHFFFAOYSA-N 2,6,6-trimethyloxaborinane Chemical compound CB1CCCC(C)(C)O1 CNOOTVLHXJLFMF-UHFFFAOYSA-N 0.000 description 1
• XLRLFJFPQNKAFC-UHFFFAOYSA-N 2-(2,2-difluoropropylamino)quinoline-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=CC2=NC(NCC(F)(F)C)=CC=C21 XLRLFJFPQNKAFC-UHFFFAOYSA-N 0.000 description 1
• YXEUGPLRNSLCKC-UHFFFAOYSA-N 2-(methylamino)-1H-isoquinoline-6-carboxylic acid Chemical compound CNN1CC2=CC=C(C=C2C=C1)C(=O)O YXEUGPLRNSLCKC-UHFFFAOYSA-N 0.000 description 1
• XZKVIOBCXWXCIU-UHFFFAOYSA-N 2-(methylamino)quinoline-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=NC(NC)=CC=C21 XZKVIOBCXWXCIU-UHFFFAOYSA-N 0.000 description 1
• WYLBCXSEHOFOGE-UHFFFAOYSA-N 2-(methylamino)quinoline-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=CC2=NC(NC)=CC=C21 WYLBCXSEHOFOGE-UHFFFAOYSA-N 0.000 description 1
• HQSRVYUCBOCBLY-XOOFNSLWSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2s,4r)-2-(4-chlorophenyl)-2-[(4-methyl-1,2,4-triazol-3-yl)sulfanylmethyl]-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3O[C@@](CSC=4N(C=NN=4)C)(OC3)C=3C=CC(Cl)=CC=3)=CC=2)C=C1 HQSRVYUCBOCBLY-XOOFNSLWSA-N 0.000 description 1
• FOFXXEHXOCAJIW-GNAFDRTKSA-N 2-[(3s)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid;hydrate Chemical compound O.CC1=CC(OCCCS(C)(=O)=O)=CC(C)=C1C1=CC=CC(COC=2C=C3OC[C@@H](CC(O)=O)C3=CC=2)=C1 FOFXXEHXOCAJIW-GNAFDRTKSA-N 0.000 description 1
• NFTMKHWBOINJGM-UHFFFAOYSA-N 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-4-[[4-(tetrazol-1-yl)phenoxy]methyl]-1,3-thiazole Chemical compound N1=CC(CC)=CN=C1N1CCC(C=2SC=C(COC=3C=CC(=CC=3)N3N=NN=C3)N=2)CC1 NFTMKHWBOINJGM-UHFFFAOYSA-N 0.000 description 1
• YMWJDWJXIXITMD-UHFFFAOYSA-N 2-[4-[3-[2-(2-chloro-6-fluorophenyl)ethyl-[(2,3-dichlorophenyl)carbamoyl]amino]propyl]phenoxy]-2-methylpropanoic acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCCN(C(=O)NC=1C(=C(Cl)C=CC=1)Cl)CCC1=C(F)C=CC=C1Cl YMWJDWJXIXITMD-UHFFFAOYSA-N 0.000 description 1
• YXFNPRHZMOGREC-UHFFFAOYSA-N 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl]acetic acid Chemical compound N1=C(C(N)=O)C(C)=NC(C)=C1C1=CC=C(C2CCC(CC(O)=O)CC2)C=C1 YXFNPRHZMOGREC-UHFFFAOYSA-N 0.000 description 1
• GXALXAKNHIROPE-UHFFFAOYSA-N 2-[4-[4-[5-[[6-(trifluoromethyl)pyridin-3-yl]amino]pyridin-2-yl]phenyl]cyclohexyl]acetic acid Chemical compound C1CC(CC(=O)O)CCC1C1=CC=C(C=2N=CC(NC=3C=NC(=CC=3)C(F)(F)F)=CC=2)C=C1 GXALXAKNHIROPE-UHFFFAOYSA-N 0.000 description 1
• AYKLXGCULGWUJX-UHFFFAOYSA-N 2-[5-chloro-2-[[1-[(3,4-difluorophenyl)methyl]-4-[(4-methylsulfonylphenyl)methyl]pyrrole-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CC1=CN(CC=2C=C(F)C(F)=CC=2)C(C(=O)NC=2SC(Cl)=C(CC(O)=O)N=2)=C1 AYKLXGCULGWUJX-UHFFFAOYSA-N 0.000 description 1
• HPGJSAAUJGAMLV-UHFFFAOYSA-N 2-[[2-[[cyclohexyl-(4-propoxycyclohexyl)carbamoyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetic acid Chemical compound C1CC(OCCC)CCC1N(C(=O)NC=1SC(SCC(O)=O)=CN=1)C1CCCCC1 HPGJSAAUJGAMLV-UHFFFAOYSA-N 0.000 description 1
• QNBMELTXPLGIMF-UHFFFAOYSA-N 2-amino-3h-benzimidazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2NC(N)=NC2=C1 QNBMELTXPLGIMF-UHFFFAOYSA-N 0.000 description 1
• RGFNYRASTCKUCA-UHFFFAOYSA-N 2-aminoquinoline-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=CC2=NC(N)=CC=C21 RGFNYRASTCKUCA-UHFFFAOYSA-N 0.000 description 1
• ZPMHZVQNFAFZEK-UHFFFAOYSA-N 2-aminoquinoline-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=CC2=NC(N)=CC=C21 ZPMHZVQNFAFZEK-UHFFFAOYSA-N 0.000 description 1
• NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
• RFAUJISEYXFHCF-UHFFFAOYSA-N 2-cyclobutylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1C2=CN(C3CCC3)N=C2C(=O)NC21CCNCC2 RFAUJISEYXFHCF-UHFFFAOYSA-N 0.000 description 1
• ORVCATCRRUXRCE-UHFFFAOYSA-N 2-iodooxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OI ORVCATCRRUXRCE-UHFFFAOYSA-N 0.000 description 1
• WLVOVUGXWQEERM-UHFFFAOYSA-N 2-methyl-3-oxo-1h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(=O)N(C)NC2=C1 WLVOVUGXWQEERM-UHFFFAOYSA-N 0.000 description 1
• LXPCTHRQJVSSIQ-UHFFFAOYSA-N 2-methyl-6-(trifluoromethyl)aniline Chemical compound CC1=CC=CC(C(F)(F)F)=C1N LXPCTHRQJVSSIQ-UHFFFAOYSA-N 0.000 description 1
• MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
• CYWZDXFWCGZVHM-UHFFFAOYSA-N 2-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one;hydrochloride Chemical compound Cl.N1C(=O)C2=NN(C(C)C)C=C2CC21CCNCC2 CYWZDXFWCGZVHM-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• UYALYOQTUSXACU-UHFFFAOYSA-N 2-tert-butyl-1'-(1h-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2NN=CC2=CC(C(=O)N2CCC3(CC4=CN(N=C4C(=O)N3)C(C)(C)C)CC2)=C1 UYALYOQTUSXACU-UHFFFAOYSA-N 0.000 description 1
• XWLDUNOJXFZZEH-UHFFFAOYSA-N 2-tert-butyl-1'-(3-chloro-7-methyl-2h-indazole-5-carbonyl)spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C=2C(Cl)=NNC=2C(C)=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1NN(C(C)(C)C)C2 XWLDUNOJXFZZEH-UHFFFAOYSA-N 0.000 description 1
• CKSGXKWTIWDGQU-UHFFFAOYSA-N 2-tert-butyl-1'-(3-methoxyisoquinoline-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1C2=CN(C(C)(C)C)N=C2C(=O)NC1(CC1)CCN1C(=O)C1=CC=C(C=NC(OC)=C2)C2=C1 CKSGXKWTIWDGQU-UHFFFAOYSA-N 0.000 description 1
• VFGLBIMIOZWHHH-UHFFFAOYSA-N 2-tert-butyl-1'-(5-methoxyquinoline-3-carbonyl)spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2C(OC)=CC=CC2=NC=C1C(=O)N(CC1)CCC1(NC1=O)CC2=C1NN(C(C)(C)C)C2 VFGLBIMIOZWHHH-UHFFFAOYSA-N 0.000 description 1
• CTABULNLJVUTKF-UHFFFAOYSA-N 2-tert-butyl-1'-(6-methoxyquinoline-3-carbonyl)spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C2=CC(OC)=CC=C2N=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1NN(C(C)(C)C)C2 CTABULNLJVUTKF-UHFFFAOYSA-N 0.000 description 1
• XIEROAVRWVMNBZ-UHFFFAOYSA-N 2-tert-butyl-1'-(7-methyl-1h-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1C2=CN(C(C)(C)C)N=C2C(=O)NC1(CC1)CCN1C(=O)C(C=C1C)=CC2=C1NN=C2 XIEROAVRWVMNBZ-UHFFFAOYSA-N 0.000 description 1
• QAFQLXQNVOFDDS-UHFFFAOYSA-N 2-tert-butyl-1'-[1-(tert-butylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1C2=CN(C(C)(C)C)N=C2C(=O)NC1(CC1)CCN1C(=O)C1=CC=C2C=CN=C(NC(C)(C)C)C2=C1 QAFQLXQNVOFDDS-UHFFFAOYSA-N 0.000 description 1
• RGBPRTWGKYKJPN-UHFFFAOYSA-N 2-tert-butyl-1'-[2-(methylamino)quinoline-7-carbonyl]spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C2=NC(NC)=CC=C2C=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1NN(C(C)(C)C)C2 RGBPRTWGKYKJPN-UHFFFAOYSA-N 0.000 description 1
• NDKNRZPWSLAZNF-UHFFFAOYSA-N 2-tert-butylpyrazol-3-amine Chemical compound CC(C)(C)N1N=CC=C1N NDKNRZPWSLAZNF-UHFFFAOYSA-N 0.000 description 1
• IMAQITWQJIXTFR-UHFFFAOYSA-N 2-tert-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical class N1C(=O)C2=NN(C(C)(C)C)C=C2CC21CCNCC2 IMAQITWQJIXTFR-UHFFFAOYSA-N 0.000 description 1
• GVIYUKXRXPXMQM-BPXGDYAESA-N 221231-10-3 Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]1C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CSSC1)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C(C)C)=O)C1=CC=C(O)C=C1 GVIYUKXRXPXMQM-BPXGDYAESA-N 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• GUOVBFFLXKJFEE-UHFFFAOYSA-N 2h-benzotriazole-5-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC2=NNN=C21 GUOVBFFLXKJFEE-UHFFFAOYSA-N 0.000 description 1
• GVYVBTFBPYRODD-UHFFFAOYSA-N 2h-pyridine-1,4-dicarboxylic acid Chemical compound OC(=O)N1CC=C(C(O)=O)C=C1 GVYVBTFBPYRODD-UHFFFAOYSA-N 0.000 description 1
• HEMGYNNCNNODNX-UHFFFAOYSA-N 3,4-diaminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1N HEMGYNNCNNODNX-UHFFFAOYSA-N 0.000 description 1
• IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 1
• LPYTWEKATXBHGQ-UHFFFAOYSA-N 3-(aminomethyl)-2H-indazole-5-carboxylic acid Chemical compound C1=CC(C(O)=O)=CC2=C(CN)NN=C21 LPYTWEKATXBHGQ-UHFFFAOYSA-N 0.000 description 1
• FHKPNGNKOMYRKN-UHFFFAOYSA-N 3-(trifluoromethyl)-2h-indazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NN=C(C(F)(F)F)C2=C1 FHKPNGNKOMYRKN-UHFFFAOYSA-N 0.000 description 1
• FJEJHJINOKKDCW-INIZCTEOSA-N 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(5-methylpyrazin-2-yl)benzamide Chemical compound C=1C(C(=O)NC=2N=CC(C)=NC=2)=CC(O[C@@H](C)COC)=CC=1OC(N=C1)=CN=C1C(=O)N1CCC1 FJEJHJINOKKDCW-INIZCTEOSA-N 0.000 description 1
• YEGQMUOUKUEJRM-UHFFFAOYSA-N 3-amino-1h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(N)=NNC2=C1 YEGQMUOUKUEJRM-UHFFFAOYSA-N 0.000 description 1
• NECZTEQDOQLSQW-UHFFFAOYSA-N 3-amino-1h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(N)=NNC2=C1 NECZTEQDOQLSQW-UHFFFAOYSA-N 0.000 description 1
• QFLMVHHJMPJLKY-UHFFFAOYSA-N 3-aminoisoquinoline-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=NC(N)=CC2=C1 QFLMVHHJMPJLKY-UHFFFAOYSA-N 0.000 description 1
• JWYMSZPSIYOAJA-UHFFFAOYSA-N 3-aminoisoquinoline-7-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C=NC(N)=CC2=C1 JWYMSZPSIYOAJA-UHFFFAOYSA-N 0.000 description 1
• APIYNLCRNDEUAJ-UHFFFAOYSA-N 3-bromo-1-cyclobutylpyrazole-4-carboxylic acid Chemical compound OC(=O)c1cn(nc1Br)C1CCC1 APIYNLCRNDEUAJ-UHFFFAOYSA-N 0.000 description 1
• MZUYNTLMQOTJOQ-UHFFFAOYSA-N 3-chloro-1h-indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=C(Cl)C2=C1 MZUYNTLMQOTJOQ-UHFFFAOYSA-N 0.000 description 1
• PZARQIQAMMARKR-UHFFFAOYSA-N 3-chloro-1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(Cl)=CNC2=C1 PZARQIQAMMARKR-UHFFFAOYSA-N 0.000 description 1
• OKTWITMFUYTPDK-UHFFFAOYSA-N 3-chloro-1h-pyrrolo[2,3-b]pyridine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C2NC=C(Cl)C2=C1 OKTWITMFUYTPDK-UHFFFAOYSA-N 0.000 description 1
• RQKVYMZENPQZMX-UHFFFAOYSA-N 3-chloro-2h-indazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NN=C(Cl)C2=C1 RQKVYMZENPQZMX-UHFFFAOYSA-N 0.000 description 1
• HRAVHSXRYSOREF-UHFFFAOYSA-N 3-chloro-7-methyl-2h-indazole-5-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC2=C1NN=C2Cl HRAVHSXRYSOREF-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• BFOULEVCZBQRIV-UHFFFAOYSA-N 3-cyano-1h-indazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NN=C(C#N)C2=C1 BFOULEVCZBQRIV-UHFFFAOYSA-N 0.000 description 1
• JMHGATOBRPWPBZ-UHFFFAOYSA-N 3-cyano-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(C#N)=C1 JMHGATOBRPWPBZ-UHFFFAOYSA-N 0.000 description 1
• HGEQQTLZQSGXFK-UHFFFAOYSA-N 3-methoxy-1h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(OC)=NNC2=C1 HGEQQTLZQSGXFK-UHFFFAOYSA-N 0.000 description 1
• BGNZTRUIXUSPDY-UHFFFAOYSA-N 3-methyl-2h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(C)=NNC2=C1 BGNZTRUIXUSPDY-UHFFFAOYSA-N 0.000 description 1
• JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 1
• DHOVADZPJIWNHE-UHFFFAOYSA-N 4-(bromomethyl)-1-propan-2-ylpyrazole Chemical compound BrCC=1C=NN(C=1)C(C)C DHOVADZPJIWNHE-UHFFFAOYSA-N 0.000 description 1
• JSGFETCAEIUIHN-UHFFFAOYSA-N 4-[(3-iodo-1-propan-2-ylpyrazol-4-yl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound IC1=NN(C(C)C)C=C1CC1(C(O)=O)CCN(C(=O)OC(C)(C)C)CC1 JSGFETCAEIUIHN-UHFFFAOYSA-N 0.000 description 1
• QYFBVKXIAZEAAI-UHFFFAOYSA-N 4-[(5-bromo-1-tert-butylpyrazol-4-yl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C(O)=O)CC1=C(Br)N(C(C)(C)C)N=C1 QYFBVKXIAZEAAI-UHFFFAOYSA-N 0.000 description 1
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
• UPCARQPLANFGQJ-UHFFFAOYSA-N 4-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC(Br)=CC=C1C=O UPCARQPLANFGQJ-UHFFFAOYSA-N 0.000 description 1
• ZWKNDLMYSLLMRF-UHFFFAOYSA-N 4-cyano-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C(F)=C1 ZWKNDLMYSLLMRF-UHFFFAOYSA-N 0.000 description 1
• RHHMAAWHLLTKQV-UHFFFAOYSA-N 4-methoxy-1h-indazole-6-carboxylic acid Chemical compound COC1=CC(C(O)=O)=CC2=C1C=NN2 RHHMAAWHLLTKQV-UHFFFAOYSA-N 0.000 description 1
• JYPDQXPGNMLIJO-UHFFFAOYSA-N 4-methoxy-7-methyl-1h-indole-2-carboxylic acid Chemical compound COC1=CC=C(C)C2=C1C=C(C(O)=O)N2 JYPDQXPGNMLIJO-UHFFFAOYSA-N 0.000 description 1
• LAMQVIQMVKWXOC-UHFFFAOYSA-N 4-methyl-n-[2-[3-(morpholin-4-ylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl]-2-pyridin-3-yl-1,3-thiazole-5-carboxamide Chemical compound CC=1N=C(C=2C=NC=CC=2)SC=1C(=O)NC1=CC=CC=C1C(N=C1SC=2)=CN1C=2CN1CCOCC1 LAMQVIQMVKWXOC-UHFFFAOYSA-N 0.000 description 1
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
• NFFXEUUOMTXWCX-UHFFFAOYSA-N 5-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-methoxy-n-[[4-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C(F)(F)F)C(OC)=CC=C1CC1SC(=O)NC1=O NFFXEUUOMTXWCX-UHFFFAOYSA-N 0.000 description 1
• QGFYFOHMBDMGBZ-UHFFFAOYSA-N 5-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol Chemical compound C1=C(O)C(CN(CC)CC)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 QGFYFOHMBDMGBZ-UHFFFAOYSA-N 0.000 description 1
• MPLLLQUZNJSVTK-UHFFFAOYSA-N 5-[3-[4-[2-(4-fluorophenyl)ethoxy]phenyl]propyl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1CCCC(C=C1)=CC=C1OCCC1=CC=C(F)C=C1 MPLLLQUZNJSVTK-UHFFFAOYSA-N 0.000 description 1
• AYJRTVVIBJSSKN-UHFFFAOYSA-N 5-[4-[[6-(4-methylsulfonylphenyl)pyridin-3-yl]oxymethyl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(COC=3C=NC(=CC=3)C=3C=CC(=CC=3)S(C)(=O)=O)CC2)=N1 AYJRTVVIBJSSKN-UHFFFAOYSA-N 0.000 description 1
• MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 1
• IETKPTYAGKZLKY-UHFFFAOYSA-N 5-[[4-[(3-methyl-4-oxoquinazolin-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2C(=O)N(C)C=1COC(C=C1)=CC=C1CC1SC(=O)NC1=O IETKPTYAGKZLKY-UHFFFAOYSA-N 0.000 description 1
• WWQQPSDIIVXFOX-UHFFFAOYSA-N 5-bromo-2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC(Br)=CN=C1Cl WWQQPSDIIVXFOX-UHFFFAOYSA-N 0.000 description 1
• PEXAZYDITWXYNJ-UHFFFAOYSA-N 5-bromo-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC=C1F PEXAZYDITWXYNJ-UHFFFAOYSA-N 0.000 description 1
• AEHWRCUKWUYGEM-UHFFFAOYSA-N 5-bromo-4-(bromomethyl)-1-tert-butylpyrazole Chemical compound CC(C)(C)N1N=CC(CBr)=C1Br AEHWRCUKWUYGEM-UHFFFAOYSA-N 0.000 description 1
• YAOKXXMTIWHAOS-UHFFFAOYSA-N 5-bromo-7-(trifluoromethyl)-1H-carbazole Chemical compound BrC1=C2C3=CC=CCC3=NC2=CC(=C1)C(F)(F)F YAOKXXMTIWHAOS-UHFFFAOYSA-N 0.000 description 1
• YLMFTTBYMVQLMH-UHFFFAOYSA-N 5-bromo-7-(trifluoromethyl)-1h-indazole Chemical compound FC(F)(F)C1=CC(Br)=CC2=C1NN=C2 YLMFTTBYMVQLMH-UHFFFAOYSA-N 0.000 description 1
• 239000003406 5-lipoxygenase-activating protein inhibitor Substances 0.000 description 1
• QDECJNWVPYZYIP-UHFFFAOYSA-N 5-methoxynaphthalene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(OC)=CC=CC2=C1 QDECJNWVPYZYIP-UHFFFAOYSA-N 0.000 description 1
• IQTWNFKXMYNHOP-UHFFFAOYSA-N 5-methoxyquinoline-3-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(OC)=CC=CC2=N1 IQTWNFKXMYNHOP-UHFFFAOYSA-N 0.000 description 1
• YZBILXXOZFORFE-UHFFFAOYSA-N 6-Methoxy-2-naphthoic acid Chemical compound C1=C(C(O)=O)C=CC2=CC(OC)=CC=C21 YZBILXXOZFORFE-UHFFFAOYSA-N 0.000 description 1
• FWEAJWWRFMELBH-UHFFFAOYSA-N 7-chloro-1h-indazole-5-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=C2NN=CC2=C1 FWEAJWWRFMELBH-UHFFFAOYSA-N 0.000 description 1
• RRSILBKAFUIMRE-UHFFFAOYSA-N 7-chloro-2h-benzotriazole-5-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=C2NN=NC2=C1 RRSILBKAFUIMRE-UHFFFAOYSA-N 0.000 description 1
• RATSXIODAZYQOS-UHFFFAOYSA-N 7-ethyl-1h-indazole-5-carboxylic acid Chemical compound CCC1=CC(C(O)=O)=CC2=C1NN=C2 RATSXIODAZYQOS-UHFFFAOYSA-N 0.000 description 1
• XBYYNTYGENEUGY-UHFFFAOYSA-N 7-methoxy-3-methyl-2h-indazole-5-carboxylic acid Chemical compound COC1=CC(C(O)=O)=CC2=C1NN=C2C XBYYNTYGENEUGY-UHFFFAOYSA-N 0.000 description 1
• JJAGLIPYTVMFTL-UHFFFAOYSA-N 7-methoxynaphthalene-2-carboxylic acid Chemical compound C1=CC(C(O)=O)=CC2=CC(OC)=CC=C21 JJAGLIPYTVMFTL-UHFFFAOYSA-N 0.000 description 1
• XMVNTKZCEKCKQD-UHFFFAOYSA-N 7-methyl-1h-indazole-5-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC2=C1NN=C2 XMVNTKZCEKCKQD-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• WVVFTEVROJKIJA-UHFFFAOYSA-N 8-methoxynaphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(OC)=CC=CC2=C1 WVVFTEVROJKIJA-UHFFFAOYSA-N 0.000 description 1
• MCODIFYTJFMYQG-UHFFFAOYSA-N 8-methoxyquinoline-3-carboxylic acid Chemical compound OC(=O)C1=CN=C2C(OC)=CC=CC2=C1 MCODIFYTJFMYQG-UHFFFAOYSA-N 0.000 description 1
• WOKQIIIYLBVUCE-UHFFFAOYSA-N 8H-carbazole-3-carboxylic acid Chemical compound C1C=CC=C2C3=CC(=CC=C3N=C12)C(=O)O WOKQIIIYLBVUCE-UHFFFAOYSA-N 0.000 description 1
• 108010070305 AOD 9604 Proteins 0.000 description 1
• 229940127110 AZD1656 Drugs 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
• 102000054930 Agouti-Related Human genes 0.000 description 1
• 101710127426 Agouti-related protein Proteins 0.000 description 1
• 102000016912 Aldehyde Reductase Human genes 0.000 description 1
• 108010053754 Aldehyde reductase Proteins 0.000 description 1
• PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
• PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
• 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
• 102000018616 Apolipoproteins B Human genes 0.000 description 1
• 108010027006 Apolipoproteins B Proteins 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 108090001008 Avidin Proteins 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
• 102100038495 Bile acid receptor Human genes 0.000 description 1
• 108010051479 Bombesin Proteins 0.000 description 1
• 102000013585 Bombesin Human genes 0.000 description 1
• 102100028628 Bombesin receptor subtype-3 Human genes 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• DJMAUQALEIEVLM-UHFFFAOYSA-N BrC1=C(C=NN1C(C)(C)C)CC1(CCN(CC1)C(=O)O)C(=O)O Chemical compound BrC1=C(C=NN1C(C)(C)C)CC1(CCN(CC1)C(=O)O)C(=O)O DJMAUQALEIEVLM-UHFFFAOYSA-N 0.000 description 1
• OLUKUVGYPBGOKJ-UHFFFAOYSA-N BrC1=C(C=NN1C(C)C)CC1(CCN(CC1)C(=O)O)C(=O)O Chemical compound BrC1=C(C=NN1C(C)C)CC1(CCN(CC1)C(=O)O)C(=O)O OLUKUVGYPBGOKJ-UHFFFAOYSA-N 0.000 description 1
• XRZKOZFRQBATHP-UHFFFAOYSA-N BrC1=C(C=NN1C(C)C)CC1(CCN(CC1)C(=O)O)[N+]#[C-] Chemical compound BrC1=C(C=NN1C(C)C)CC1(CCN(CC1)C(=O)O)[N+]#[C-] XRZKOZFRQBATHP-UHFFFAOYSA-N 0.000 description 1
• GUWKYNIRQMANJN-UHFFFAOYSA-N C(C)(C)(C)OC(=O)N1CCC2(CC3=C(CN2)NN=C3)CC1 Chemical compound C(C)(C)(C)OC(=O)N1CCC2(CC3=C(CN2)NN=C3)CC1 GUWKYNIRQMANJN-UHFFFAOYSA-N 0.000 description 1
• WFQSMZDMCSNWEK-UHFFFAOYSA-N C(C)(C)N1N=CC2=C1C(NC1(C2)CCN(CC1)C(=O)C=1C=2C3=CC=CCC3=NC2C=C(C1)C)=O Chemical compound C(C)(C)N1N=CC2=C1C(NC1(C2)CCN(CC1)C(=O)C=1C=2C3=CC=CCC3=NC2C=C(C1)C)=O WFQSMZDMCSNWEK-UHFFFAOYSA-N 0.000 description 1
• WKKFNDMZGIWYAN-UHFFFAOYSA-N C(C)C1=CCC2=NC=3C=CC=C(C3C2=C1)C(=O)O Chemical compound C(C)C1=CCC2=NC=3C=CC=C(C3C2=C1)C(=O)O WKKFNDMZGIWYAN-UHFFFAOYSA-N 0.000 description 1
• VGBZWBWJCJLCBY-UHFFFAOYSA-N C(C)OC(=O)N1N(C(C2C(C=C(C=C12)C(=O)O)=O)=O)C Chemical compound C(C)OC(=O)N1N(C(C2C(C=C(C=C12)C(=O)O)=O)=O)C VGBZWBWJCJLCBY-UHFFFAOYSA-N 0.000 description 1
• RVIUJMXQUUCSFD-UHFFFAOYSA-N C(CCC)N1N=C2C(NC3(CC2=C1)CCNCC3)=O Chemical group C(CCC)N1N=C2C(NC3(CC2=C1)CCNCC3)=O RVIUJMXQUUCSFD-UHFFFAOYSA-N 0.000 description 1
• 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
• 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
• 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
• 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
• PVAJDEVOHOZSCM-UHFFFAOYSA-N C1(CCCCC1)NC(=O)N.C(C)(=O)C1=CC=CC=C1 Chemical compound C1(CCCCC1)NC(=O)N.C(C)(=O)C1=CC=CC=C1 PVAJDEVOHOZSCM-UHFFFAOYSA-N 0.000 description 1
• OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 1
• BNECILQSPOZUFE-UHFFFAOYSA-N C1NC=CC2=CC(=CC=C12)C(=O)O.[O] Chemical compound C1NC=CC2=CC(=CC=C12)C(=O)O.[O] BNECILQSPOZUFE-UHFFFAOYSA-N 0.000 description 1
• JHVPCZWERZFZQU-UHFFFAOYSA-N C1NC=CC2=CC=C(C=C12)C(=O)O.[O] Chemical compound C1NC=CC2=CC=C(C=C12)C(=O)O.[O] JHVPCZWERZFZQU-UHFFFAOYSA-N 0.000 description 1
• 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
• PWDLDBWXTVILPC-WGAVTJJLSA-N CC(C)(N)CC1=CC=CC=C1.C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 Chemical compound CC(C)(N)CC1=CC=CC=C1.C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 PWDLDBWXTVILPC-WGAVTJJLSA-N 0.000 description 1
• IVSPLDAEVHXZOM-UHFFFAOYSA-N CC=1C=C(C=2C3=CC=CCC3=NC2C1)C(=O)O Chemical compound CC=1C=C(C=2C3=CC=CCC3=NC2C1)C(=O)O IVSPLDAEVHXZOM-UHFFFAOYSA-N 0.000 description 1
• XSGVVNHYXQQWQK-UHFFFAOYSA-N CNN(C)C.CNN(C)C.[Li] Chemical compound CNN(C)C.CNN(C)C.[Li] XSGVVNHYXQQWQK-UHFFFAOYSA-N 0.000 description 1
• YRJRXMNEMJBVPV-UHFFFAOYSA-N COC(=O)C=1C=2C3=CC(=CC(C3=NC2C=CC1)C(=O)OCC)OC Chemical compound COC(=O)C=1C=2C3=CC(=CC(C3=NC2C=CC1)C(=O)OCC)OC YRJRXMNEMJBVPV-UHFFFAOYSA-N 0.000 description 1
• SQONVOPYYFMLQG-UHFFFAOYSA-N COC(=O)C=1C=C2C3=CC(=CC(C3=NC2=CC1)C(=O)OCC)O Chemical compound COC(=O)C=1C=C2C3=CC(=CC(C3=NC2=CC1)C(=O)OCC)O SQONVOPYYFMLQG-UHFFFAOYSA-N 0.000 description 1
• DLFRDVRKUSEEQK-UHFFFAOYSA-N COC(=O)C=1C=C2C3=CC(=CC(C3=NC2=CC1)C(=O)OCC)OC Chemical compound COC(=O)C=1C=C2C3=CC(=CC(C3=NC2=CC1)C(=O)OCC)OC DLFRDVRKUSEEQK-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229940127291 Calcium channel antagonist Drugs 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 description 1
• 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 239000005944 Chlorpyrifos Substances 0.000 description 1
• VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
• 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
• 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 208000002249 Diabetes Complications Diseases 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
• 206010012655 Diabetic complications Diseases 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• DVJAMEIQRSHVKC-BDAKNGLRSA-N Dutogliptin Chemical compound OB(O)[C@@H]1CCCN1C(=O)CN[C@H]1CNCC1 DVJAMEIQRSHVKC-BDAKNGLRSA-N 0.000 description 1
• 108050009340 Endothelin Proteins 0.000 description 1
• 102000002045 Endothelin Human genes 0.000 description 1
• YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 1
• 208000010201 Exanthema Diseases 0.000 description 1
• 108010039731 Fatty Acid Synthases Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 1
• 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
• 102100026148 Free fatty acid receptor 1 Human genes 0.000 description 1
• 102100040133 Free fatty acid receptor 2 Human genes 0.000 description 1
• 102100040136 Free fatty acid receptor 3 Human genes 0.000 description 1
• 102100040134 Free fatty acid receptor 4 Human genes 0.000 description 1
• 102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
• 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 102100030280 G-protein coupled receptor 39 Human genes 0.000 description 1
• QTQMRBZOBKYXCG-MHZLTWQESA-N GW 1929 Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCN(C)C=1N=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 QTQMRBZOBKYXCG-MHZLTWQESA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 102400000321 Glucagon Human genes 0.000 description 1
• 108060003199 Glucagon Proteins 0.000 description 1
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
• 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 1
• 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 description 1
• 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
• 102100033417 Glucocorticoid receptor Human genes 0.000 description 1
• 102000030595 Glucokinase Human genes 0.000 description 1
• 108010021582 Glucokinase Proteins 0.000 description 1
• 102100033839 Glucose-dependent insulinotropic receptor Human genes 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 206010019708 Hepatic steatosis Diseases 0.000 description 1
• 101000928179 Homo sapiens Agouti-related protein Proteins 0.000 description 1
• 101000695054 Homo sapiens Bombesin receptor subtype-3 Proteins 0.000 description 1
• 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 description 1
• 101000890668 Homo sapiens Free fatty acid receptor 2 Proteins 0.000 description 1
• 101000890662 Homo sapiens Free fatty acid receptor 3 Proteins 0.000 description 1
• 101000890672 Homo sapiens Free fatty acid receptor 4 Proteins 0.000 description 1
• 101001009541 Homo sapiens G-protein coupled receptor 39 Proteins 0.000 description 1
• 101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 description 1
• 101000843810 Homo sapiens Hydroxycarboxylic acid receptor 1 Proteins 0.000 description 1
• 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
• 101001059984 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 4 Proteins 0.000 description 1
• 101001121539 Homo sapiens P2Y purinoceptor 14 Proteins 0.000 description 1
• 101100463125 Homo sapiens PDK4 gene Proteins 0.000 description 1
• 101001051777 Homo sapiens Protein kinase C alpha type Proteins 0.000 description 1
• 101001051767 Homo sapiens Protein kinase C beta type Proteins 0.000 description 1
• 101001026864 Homo sapiens Protein kinase C gamma type Proteins 0.000 description 1
• 101001093899 Homo sapiens Retinoic acid receptor RXR-alpha Proteins 0.000 description 1
• 101000829127 Homo sapiens Somatostatin receptor type 2 Proteins 0.000 description 1
• 101000829138 Homo sapiens Somatostatin receptor type 3 Proteins 0.000 description 1
• 101000829153 Homo sapiens Somatostatin receptor type 5 Proteins 0.000 description 1
• 101001117143 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 102100030642 Hydroxycarboxylic acid receptor 1 Human genes 0.000 description 1
• 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
• 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• 229940122199 Insulin secretagogue Drugs 0.000 description 1
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
• 241000764238 Isis Species 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
• 102000000853 LDL receptors Human genes 0.000 description 1
• 108010001831 LDL receptors Proteins 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 102000003960 Ligases Human genes 0.000 description 1
• 108090000364 Ligases Proteins 0.000 description 1
• 229940127470 Lipase Inhibitors Drugs 0.000 description 1
• 229940086609 Lipase inhibitor Drugs 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• 108090001030 Lipoproteins Proteins 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
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 1
• 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-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
• 102100028194 Mitogen-activated protein kinase kinase kinase kinase 4 Human genes 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• OKLUZMUKXYWEGD-UHFFFAOYSA-N N-bromobutan-1-imine Chemical compound CCCC=NBr OKLUZMUKXYWEGD-UHFFFAOYSA-N 0.000 description 1
• AHLBNYSZXLDEJQ-UHFFFAOYSA-N N-formyl-L-leucylester Natural products CCCCCCCCCCCC(OC(=O)C(CC(C)C)NC=O)CC1OC(=O)C1CCCCCC AHLBNYSZXLDEJQ-UHFFFAOYSA-N 0.000 description 1
• OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• UUUDLEHDPPHVCR-UHFFFAOYSA-N N1C(=CC2=CC=CC=C12)N1N=CC2=CC(=CC=C12)C(=O)O Chemical compound N1C(=CC2=CC=CC=C12)N1N=CC2=CC(=CC=C12)C(=O)O UUUDLEHDPPHVCR-UHFFFAOYSA-N 0.000 description 1
• SKOQJVNILGJUBA-UHFFFAOYSA-N N1N=C(C=C1)C(=O)O.C(C)C=1N(C2=CC=CC(=C2C1)C)C(C)(C)C Chemical compound N1N=C(C=C1)C(=O)O.C(C)C=1N(C2=CC=CC(=C2C1)C)C(C)(C)C SKOQJVNILGJUBA-UHFFFAOYSA-N 0.000 description 1
• GMTZUOVKTJNSQB-UHFFFAOYSA-N NC(N)=N.[Li+] Chemical compound NC(N)=N.[Li+] GMTZUOVKTJNSQB-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 239000006057 Non-nutritive feed additive Substances 0.000 description 1
• 102000008092 Norepinephrine Plasma Membrane Transport Proteins Human genes 0.000 description 1
• 108010049586 Norepinephrine Plasma Membrane Transport Proteins Proteins 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• XQAGLILCYPTEQO-UHFFFAOYSA-N OC(=O)C(C)=CC1=CC=CC=C1C(C)(C)C Chemical compound OC(=O)C(C)=CC1=CC=CC=C1C(C)(C)C XQAGLILCYPTEQO-UHFFFAOYSA-N 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 102000003840 Opioid Receptors Human genes 0.000 description 1
• 108090000137 Opioid Receptors Proteins 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 102400000319 Oxyntomodulin Human genes 0.000 description 1
• 101800001388 Oxyntomodulin Proteins 0.000 description 1
• 102100025808 P2Y purinoceptor 14 Human genes 0.000 description 1
• 102000023984 PPAR alpha Human genes 0.000 description 1
• 108010015181 PPAR delta Proteins 0.000 description 1
• 229940124754 PPAR-alpha/gamma agonist Drugs 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 101710176384 Peptide 1 Proteins 0.000 description 1
• 208000018262 Peripheral vascular disease Diseases 0.000 description 1
• 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
• 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• QJLPWVUZFKETMK-UHFFFAOYSA-N Pradimicin Q Natural products O=C1C2=C(O)C=C(O)C=C2C(=O)C2=C1C(O)=C1CC(O)C(C=C(C(=C3O)C(O)=O)C)=C3C1=C2O QJLPWVUZFKETMK-UHFFFAOYSA-N 0.000 description 1
• 102100040918 Pro-glucagon Human genes 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 108090000315 Protein Kinase C Proteins 0.000 description 1
• 102100024924 Protein kinase C alpha type Human genes 0.000 description 1
• 102100024923 Protein kinase C beta type Human genes 0.000 description 1
• 102100037314 Protein kinase C gamma type Human genes 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 102100035178 Retinoic acid receptor RXR-alpha Human genes 0.000 description 1
• 102100038246 Retinol-binding protein 4 Human genes 0.000 description 1
• 101710137011 Retinol-binding protein 4 Proteins 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• XIUMQSREFXCDGE-UHFFFAOYSA-L S(=O)(=O)([O-])O.[Na+].[Cl-].[Na+] Chemical compound S(=O)(=O)([O-])O.[Na+].[Cl-].[Na+] XIUMQSREFXCDGE-UHFFFAOYSA-L 0.000 description 1
• 108091006277 SLC5A1 Proteins 0.000 description 1
• OCTNNXHKAOLDJL-BMGYQPLYSA-N Salbostatin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)OC[C@@H]1N[C@@H]1[C@H](O)[C@@H](O)[C@H](O)C(CO)=C1 OCTNNXHKAOLDJL-BMGYQPLYSA-N 0.000 description 1
• OCTNNXHKAOLDJL-UHFFFAOYSA-N Salbostatin Natural products OC1C(O)C(CO)OCC1NC1C(O)C(O)C(O)C(CO)=C1 OCTNNXHKAOLDJL-UHFFFAOYSA-N 0.000 description 1
• DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
• 108010034546 Serratia marcescens nuclease Proteins 0.000 description 1
• 102000058090 Sodium-Glucose Transporter 1 Human genes 0.000 description 1
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
• 102100029329 Somatostatin receptor type 1 Human genes 0.000 description 1
• 102100023802 Somatostatin receptor type 2 Human genes 0.000 description 1
• 102100023803 Somatostatin receptor type 3 Human genes 0.000 description 1
• 102100023806 Somatostatin receptor type 5 Human genes 0.000 description 1
• 102000005782 Squalene Monooxygenase Human genes 0.000 description 1
• 108020003891 Squalene monooxygenase Proteins 0.000 description 1
• 102000007451 Steroid Receptors Human genes 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 229940100389 Sulfonylurea Drugs 0.000 description 1
• 239000000150 Sympathomimetic Substances 0.000 description 1
• 239000004098 Tetracycline Substances 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• ZXOCGDDVNPDRIW-NHFZGCSJSA-N Tofogliflozin Chemical compound O.C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 ZXOCGDDVNPDRIW-NHFZGCSJSA-N 0.000 description 1
• LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
• 102000004357 Transferases Human genes 0.000 description 1
• 108090000992 Transferases Proteins 0.000 description 1
• 229930186167 Trestatin Natural products 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 241000009298 Trigla lyra Species 0.000 description 1
• 102100038286 Vasoactive intestinal polypeptide receptor 2 Human genes 0.000 description 1
• 101710137651 Vasoactive intestinal polypeptide receptor 2 Proteins 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
• GRTJBNJOHNTQBO-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenyl)phenyl]-diphenylphosphane Chemical group C1=CC=CC=C1P(C=1C(=CC=CC=1)C=1C(=CC=CC=1)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 GRTJBNJOHNTQBO-UHFFFAOYSA-N 0.000 description 1
• VSYMNDBTCKIDLT-UHFFFAOYSA-N [2-(carbamoyloxymethyl)-2-ethylbutyl] carbamate Chemical compound NC(=O)OCC(CC)(CC)COC(N)=O VSYMNDBTCKIDLT-UHFFFAOYSA-N 0.000 description 1
• USDAKWQVDUFVGH-BLPRJPCASA-N [C@@H]1([C@H](O)[C@H](OP(=O)(O)O)[C@@H](COP(=O)(O)OP(=O)(O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O1)N1C=NC=2C(N)=NC=NC12.C(C)(=N)N Chemical compound [C@@H]1([C@H](O)[C@H](OP(=O)(O)O)[C@@H](COP(=O)(O)OP(=O)(O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O1)N1C=NC=2C(N)=NC=NC12.C(C)(=N)N USDAKWQVDUFVGH-BLPRJPCASA-N 0.000 description 1
• DODOHUTYOAEFNY-UHFFFAOYSA-N [Li].CC(CCCCCCCCCN)(C)C.CC(CCCCCCCCCN)(C)C Chemical compound [Li].CC(CCCCCCCCCN)(C)C.CC(CCCCCCCCCN)(C)C DODOHUTYOAEFNY-UHFFFAOYSA-N 0.000 description 1
• 102100024150 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial Human genes 0.000 description 1
• 102100034825 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial Human genes 0.000 description 1
• 238000010521 absorption reaction Methods 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
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
• PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000012042 active reagent Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000000048 adrenergic agonist Substances 0.000 description 1
• 239000000951 adrenergic alpha-1 receptor antagonist Substances 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 229960002478 aldosterone Drugs 0.000 description 1
• 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 150000001350 alkyl halides Chemical group 0.000 description 1
• 239000002160 alpha blocker Substances 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000003392 amylase inhibitor Substances 0.000 description 1
• 239000002269 analeptic agent Substances 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
• 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
• 229940125709 anorectic agent Drugs 0.000 description 1
• 229940127003 anti-diabetic drug Drugs 0.000 description 1
• 230000003579 anti-obesity Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 229940127218 antiplatelet drug Drugs 0.000 description 1
• 239000000074 antisense oligonucleotide Substances 0.000 description 1
• 238000012230 antisense oligonucleotides Methods 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 150000001499 aryl bromides Chemical class 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 108010014210 axokine Proteins 0.000 description 1
• 229950010663 balaglitazone Drugs 0.000 description 1
• ZEZFKUBILQRZCK-MJSCXXSSSA-N beloranib Chemical compound C([C@H]([C@H]([C@@H]1[C@]2(C)[C@H](O2)CC=C(C)C)OC)OC(=O)\C=C\C=2C=CC(OCCN(C)C)=CC=2)C[C@@]21CO2 ZEZFKUBILQRZCK-MJSCXXSSSA-N 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 229920000080 bile acid sequestrant Polymers 0.000 description 1
• 229940096699 bile acid sequestrants Drugs 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group 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 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000002051 biphasic effect Effects 0.000 description 1
• 229930189065 blasticidin Natural products 0.000 description 1
• DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• KXVUSQIDCZRUKF-UHFFFAOYSA-N bromocyclobutane Chemical compound BrC1CCC1 KXVUSQIDCZRUKF-UHFFFAOYSA-N 0.000 description 1
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 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
• 239000000480 calcium channel blocker Substances 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 229950001261 camiglibose Drugs 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
• 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 235000013877 carbamide Nutrition 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 238000012754 cardiac puncture Methods 0.000 description 1
• 229960004203 carnitine Drugs 0.000 description 1
• 239000008004 cell lysis buffer Substances 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• MVCQKIKWYUURMU-UHFFFAOYSA-N cetilistat Chemical compound C1=C(C)C=C2C(=O)OC(OCCCCCCCCCCCCCCCC)=NC2=C1 MVCQKIKWYUURMU-UHFFFAOYSA-N 0.000 description 1
• 229950002397 cetilistat Drugs 0.000 description 1
• WGEWUYACXPEFPO-AULYBMBSSA-N chembl2016681 Chemical compound C1C[C@@H](NS(=O)(=O)C(C)(C)C)CC[C@@H]1C(=O)NC1=CC=C(C(F)(F)F)C=N1 WGEWUYACXPEFPO-AULYBMBSSA-N 0.000 description 1
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 229930002875 chlorophyll Natural products 0.000 description 1
• 235000019804 chlorophyll Nutrition 0.000 description 1
• ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
• 229960001761 chlorpropamide Drugs 0.000 description 1
• SBPBAQFWLVIOKP-UHFFFAOYSA-N chlorpyrifos Chemical compound CCOP(=S)(OCC)OC1=NC(Cl)=C(Cl)C=C1Cl SBPBAQFWLVIOKP-UHFFFAOYSA-N 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
• 229910052804 chromium Inorganic materials 0.000 description 1
• 239000011651 chromium Substances 0.000 description 1
• YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
• 229950009226 ciglitazone Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 239000008139 complexing agent Substances 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000000498 cooling water Substances 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 108091008723 corticosteroid receptors Proteins 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 125000004093 cyano group Chemical group *C#N 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• QQKNSPHAFATFNQ-UHFFFAOYSA-N darglitazone Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=O)C(C=C1)=CC=C1CC1SC(=O)NC1=O QQKNSPHAFATFNQ-UHFFFAOYSA-N 0.000 description 1
• 229950006689 darglitazone Drugs 0.000 description 1
• DBOBAIHRZONIPT-GHCHSQRSSA-N decanedioic acid;2,2-dimethyl-3-[3-[3-methyl-4-[[5-propan-2-yl-3-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1h-pyrazol-4-yl]methyl]phenoxy]propylamino]propanamide Chemical compound OC(=O)CCCCCCCCC(O)=O.C=1C=C(OCCCNCC(C)(C)C(N)=O)C=C(C)C=1CC1=C(C(C)C)NN=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O.C=1C=C(OCCCNCC(C)(C)C(N)=O)C=C(C)C=1CC1=C(C(C)C)NN=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O DBOBAIHRZONIPT-GHCHSQRSSA-N 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000005695 dehalogenation reaction Methods 0.000 description 1
• FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
• 238000000151 deposition Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 208000033679 diabetic kidney disease Diseases 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 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 1
• WDVGNXKCFBOKDF-UHFFFAOYSA-N dicyclohexyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C1CCCCC1)C1CCCCC1 WDVGNXKCFBOKDF-UHFFFAOYSA-N 0.000 description 1
• FPUQGCOBYOXAED-UHFFFAOYSA-N diethyl 2-[[2-[3-(dimethylcarbamoyl)-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]phenyl]acetyl]oxymethyl]-2-phenylpropanedioate Chemical compound C=1C=CC=CC=1C(C(=O)OCC)(C(=O)OCC)COC(=O)CC(C=C1C(=O)N(C)C)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 FPUQGCOBYOXAED-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 238000000113 differential scanning calorimetry Methods 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• TUOSYWCFRFNJBS-BHVANESWSA-N dirlotapide Chemical compound O=C([C@@H](NC(=O)C=1N(C2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2C=1)C)C=1C=CC=CC=1)N(C)CC1=CC=CC=C1 TUOSYWCFRFNJBS-BHVANESWSA-N 0.000 description 1
• 229960002551 dirlotapide Drugs 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 229960005175 dulaglutide Drugs 0.000 description 1
• 108010005794 dulaglutide Proteins 0.000 description 1
• 229950003693 dutogliptin Drugs 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)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](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
• 229950002375 englitazone Drugs 0.000 description 1
• 239000002792 enkephalinase inhibitor Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• XDGRKQJBBYAGQA-UHFFFAOYSA-N ethyl 1-ethylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(CC)C=1 XDGRKQJBBYAGQA-UHFFFAOYSA-N 0.000 description 1
• FREGHPVLEPOIFA-UHFFFAOYSA-N ethyl 1-tert-butyl-5-iodopyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C(C)(C)C)C=1I FREGHPVLEPOIFA-UHFFFAOYSA-N 0.000 description 1
• MSPOSRHJXMILNK-UHFFFAOYSA-N ethyl 1h-pyrazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=NN1 MSPOSRHJXMILNK-UHFFFAOYSA-N 0.000 description 1
• OFSRMXPYRMMISS-UHFFFAOYSA-N ethyl 5-amino-1-propan-2-ylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C(C)C)C=1N OFSRMXPYRMMISS-UHFFFAOYSA-N 0.000 description 1
• XBFFWXCMGUSKSU-UHFFFAOYSA-N ethyl 5-bromo-1-propan-2-ylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C(C)C)C=1Br XBFFWXCMGUSKSU-UHFFFAOYSA-N 0.000 description 1
• IVQVZFBFLOSVCT-UHFFFAOYSA-N ethyl 5-iodo-1-propan-2-ylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C(C)C)C=1I IVQVZFBFLOSVCT-UHFFFAOYSA-N 0.000 description 1
• VORDQTLCWUKJBM-UHFFFAOYSA-N ethyl 7-hydroxy-1-(oxan-2-yl)indazole-5-carboxylate Chemical compound N1=CC2=CC(C(=O)OCC)=CC(O)=C2N1C1CCCCO1 VORDQTLCWUKJBM-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• 229940117360 ethyl pyruvate Drugs 0.000 description 1
• SVHHAAQTOHCWJX-UHFFFAOYSA-N ethyl quinoline-6-carboxylate Chemical compound N1=CC=CC2=CC(C(=O)OCC)=CC=C21 SVHHAAQTOHCWJX-UHFFFAOYSA-N 0.000 description 1
• PPZOEUCJAYRMHY-UHFFFAOYSA-N ethyl quinoline-7-carboxylate Chemical compound C1=CC=NC2=CC(C(=O)OCC)=CC=C21 PPZOEUCJAYRMHY-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 201000005884 exanthem Diseases 0.000 description 1
• 229960001519 exenatide Drugs 0.000 description 1
• 108010015174 exendin 3 Proteins 0.000 description 1
• LMHMJYMCGJNXRS-IOPUOMRJSA-N exendin-3 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](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@H](C)O)[C@H](C)O)C(C)C)C1=CC=CC=C1 LMHMJYMCGJNXRS-IOPUOMRJSA-N 0.000 description 1
• 239000012847 fine chemical Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 238000005187 foaming Methods 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 108010036598 gastric inhibitory polypeptide receptor Proteins 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 235000021474 generally recognized As safe (food) Nutrition 0.000 description 1
• 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229960000346 gliclazide Drugs 0.000 description 1
• 229960004346 glimepiride 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
• 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
• 229960001381 glipizide Drugs 0.000 description 1
• 229960003468 gliquidone Drugs 0.000 description 1
• NSJYMFYVNWVGON-UHFFFAOYSA-N glisentide Chemical compound COC1=CC=CC=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCC2)C=C1 NSJYMFYVNWVGON-UHFFFAOYSA-N 0.000 description 1
• 229950008402 glisentide Drugs 0.000 description 1
• 229950005319 glisolamide Drugs 0.000 description 1
• GZKDXUIWCNCNBJ-UHFFFAOYSA-N glisolamide Chemical compound O1C(C)=CC(C(=O)NCCC=2C=CC(=CC=2)S(=O)(=O)NC(=O)NC2CCCCC2)=N1 GZKDXUIWCNCNBJ-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
• 239000003862 glucocorticoid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 235000009200 high fat diet Nutrition 0.000 description 1
• 229960001340 histamine Drugs 0.000 description 1
• 239000003667 hormone antagonist Substances 0.000 description 1
• 102000055839 human AGRP Human genes 0.000 description 1
• 108010046780 hydrocortisone receptor Proteins 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• ILULYDJFTJKQAP-UHFFFAOYSA-N hydron;propan-2-ylhydrazine;chloride Chemical compound [Cl-].CC(C)N[NH3+] ILULYDJFTJKQAP-UHFFFAOYSA-N 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• GFAZHVHNLUBROE-UHFFFAOYSA-N hydroxymethyl propionaldehyde Natural products CCC(=O)CO GFAZHVHNLUBROE-UHFFFAOYSA-N 0.000 description 1
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
• 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
• 201000008980 hyperinsulinism Diseases 0.000 description 1
• PUTJFIQGLGDLIT-UHFFFAOYSA-N hyrtiosal Natural products O=CC1(C)CC(C2(CCCC(C)(C)C2CC2)C)C2(C)C1CC(O)C=1C=COC=1 PUTJFIQGLGDLIT-UHFFFAOYSA-N 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
• 229950005809 implitapide Drugs 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• ADFCQWZHKCXPAJ-UHFFFAOYSA-N indofine Natural products C1=CC(O)=CC=C1C1CC2=CC=C(O)C=C2OC1 ADFCQWZHKCXPAJ-UHFFFAOYSA-N 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000012739 integrated shape imaging system Methods 0.000 description 1
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• ADAHADRJWVCICR-UHFFFAOYSA-N isoquinoline-6-carboxylic acid Chemical compound C1=NC=CC2=CC(C(=O)O)=CC=C21 ADAHADRJWVCICR-UHFFFAOYSA-N 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229960002701 liraglutide Drugs 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 1
• JCIVHYBIFRUGKO-UHFFFAOYSA-N lithium;2,2,6,6-tetramethylpiperidine Chemical compound [Li].CC1(C)CCCC(C)(C)N1 JCIVHYBIFRUGKO-UHFFFAOYSA-N 0.000 description 1
• 210000005228 liver tissue Anatomy 0.000 description 1
• 229960001093 lixisenatide Drugs 0.000 description 1
• 108010004367 lixisenatide Proteins 0.000 description 1
• 150000004668 long chain fatty acids Chemical class 0.000 description 1
• XTTZERNUQAFMOF-QMMMGPOBSA-N lorcaserin Chemical compound C[C@H]1CNCCC2=CC=C(Cl)C=C12 XTTZERNUQAFMOF-QMMMGPOBSA-N 0.000 description 1
• 229960005060 lorcaserin Drugs 0.000 description 1
• 235000015263 low fat diet Nutrition 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 229950004397 luseogliflozin Drugs 0.000 description 1
• 230000002934 lysing effect Effects 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• YUZJQBSNTHKZBZ-UHFFFAOYSA-N magnesium;2,2,6,6-tetramethylpiperidine Chemical compound [Mg].CC1(C)CCCC(C)(C)N1 YUZJQBSNTHKZBZ-UHFFFAOYSA-N 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 229950004994 meglitinide Drugs 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical class COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• WSYALRNYQFNNGP-WJOKGBTCSA-N methyl (2r)-2-phenyl-2-[4-[4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]phenyl]piperidin-1-yl]acetate Chemical compound C1CN([C@@H](C(=O)OC)C=2C=CC=CC=2)CCC1C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 WSYALRNYQFNNGP-WJOKGBTCSA-N 0.000 description 1
• DEIDCHZOPGPMQY-UHFFFAOYSA-N methyl 1-methoxyisoquinoline-7-carboxylate Chemical compound C1=CN=C(OC)C2=CC(C(=O)OC)=CC=C21 DEIDCHZOPGPMQY-UHFFFAOYSA-N 0.000 description 1
• TUSICEWIXLMXEY-UHFFFAOYSA-N methyl 1h-indazole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=NNC2=C1 TUSICEWIXLMXEY-UHFFFAOYSA-N 0.000 description 1
• CKKVTMBCMBEMMO-UHFFFAOYSA-N methyl 2-(2,2,2-trifluoroethylamino)quinoline-7-carboxylate Chemical compound C1=CC(NCC(F)(F)F)=NC2=CC(C(=O)OC)=CC=C21 CKKVTMBCMBEMMO-UHFFFAOYSA-N 0.000 description 1
• IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 description 1
• JACIMJZQARPCNA-UHFFFAOYSA-N methyl 3-(methylamino)isoquinoline-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=NC(NC)=CC2=C1 JACIMJZQARPCNA-UHFFFAOYSA-N 0.000 description 1
• GAIRQBVKPXPCST-UHFFFAOYSA-N methyl 5-methoxyquinoline-3-carboxylate Chemical compound C1=CC=C(OC)C2=CC(C(=O)OC)=CN=C21 GAIRQBVKPXPCST-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 230000003228 microsomal effect Effects 0.000 description 1
• 229960001110 miglitol Drugs 0.000 description 1
• 238000003801 milling Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000002395 mineralocorticoid Substances 0.000 description 1
• 229950000884 mitratapide Drugs 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
• PXZWGQLGAKCNKD-DPNMSELWSA-N molport-023-276-326 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(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)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 PXZWGQLGAKCNKD-DPNMSELWSA-N 0.000 description 1
• 230000000407 monoamine reuptake Effects 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 102000051367 mu Opioid Receptors Human genes 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• SXQHSZQHSFFJLL-UHFFFAOYSA-N n,n-dimethylformamide;2-methylpropanal Chemical compound CC(C)C=O.CN(C)C=O SXQHSZQHSFFJLL-UHFFFAOYSA-N 0.000 description 1
• WIEDUMBCZQRGSY-UHFFFAOYSA-N n-[[2,6-difluoro-4-[3-(1h-1,2,4-triazol-5-yl)phenyl]phenyl]methyl]-2,3-dihydro-1h-inden-2-amine Chemical compound C=1C(F)=C(CNC2CC3=CC=CC=C3C2)C(F)=CC=1C(C=1)=CC=CC=1C1=NC=NN1 WIEDUMBCZQRGSY-UHFFFAOYSA-N 0.000 description 1
• HJPHMPYPXOYPBI-UHFFFAOYSA-N n-chlorobutan-1-imine Chemical compound CCCC=NCl HJPHMPYPXOYPBI-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
• 125000005487 naphthalate group Chemical group 0.000 description 1
• 239000000712 neurohormone Substances 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 102000008434 neuropeptide hormone activity proteins Human genes 0.000 description 1
• 108040002669 neuropeptide hormone activity proteins Proteins 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 150000002826 nitrites Chemical class 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• QNDVLZJODHBUFM-WFXQOWMNSA-N okadaic acid Chemical compound C([C@H](O1)[C@H](C)/C=C/[C@H]2CC[C@@]3(CC[C@H]4O[C@@H](C([C@@H](O)[C@@H]4O3)=C)[C@@H](O)C[C@H](C)[C@@H]3[C@@H](CC[C@@]4(OCCCC4)O3)C)O2)C(C)=C[C@]21O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]2O QNDVLZJODHBUFM-WFXQOWMNSA-N 0.000 description 1
• VEFJHAYOIAAXEU-UHFFFAOYSA-N okadaic acid Natural products CC(CC(O)C1OC2CCC3(CCC(O3)C=CC(C)C4CC(=CC5(OC(CC(C)(O)C(=O)O)CCC5O)O4)C)OC2C(O)C1C)C6OC7(CCCCO7)CCC6C VEFJHAYOIAAXEU-UHFFFAOYSA-N 0.000 description 1
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
• 239000003605 opacifier Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 1
• 125000000466 oxiranyl group Chemical group 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
• 238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 1
• 238000002638 palliative care Methods 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• BUKOKLAGGXEPIR-UHFFFAOYSA-N phenyl-bis(2,2,2-trifluoroethoxy)-$l^{3}-iodane Chemical compound FC(F)(F)COI(OCC(F)(F)F)C1=CC=CC=C1 BUKOKLAGGXEPIR-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• PJPOCNJHYFUPCE-UHFFFAOYSA-N picen-1-ol Chemical compound C1=CC=CC2=C(C=CC=3C4=CC=C5C=CC=C(C=35)O)C4=CC=C21 PJPOCNJHYFUPCE-UHFFFAOYSA-N 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• IIKFXOLJMNWWCH-UHFFFAOYSA-N piperidine-1,4-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)CC1 IIKFXOLJMNWWCH-UHFFFAOYSA-N 0.000 description 1
• FSDNTQSJGHSJBG-UHFFFAOYSA-N piperidine-4-carbonitrile Chemical class N#CC1CCNCC1 FSDNTQSJGHSJBG-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 244000144977 poultry Species 0.000 description 1
• 238000000634 powder X-ray diffraction Methods 0.000 description 1
• 229960002847 prasterone Drugs 0.000 description 1
• 239000012041 precatalyst Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• WPDCHTSXOPUOII-UHFFFAOYSA-N propan-2-yl 4-[5-methoxy-6-[(2-methyl-6-methylsulfonylpyridin-3-yl)amino]pyrimidin-4-yl]oxypiperidine-1-carboxylate Chemical compound N1=CN=C(OC2CCN(CC2)C(=O)OC(C)C)C(OC)=C1NC1=CC=C(S(C)(=O)=O)N=C1C WPDCHTSXOPUOII-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• QAQREVBBADEHPA-IEXPHMLFSA-N propionyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QAQREVBBADEHPA-IEXPHMLFSA-N 0.000 description 1
• 229960004063 propylene glycol Drugs 0.000 description 1
• AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
• 235000019833 protease Nutrition 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
• WXXVQWSDMOAHHV-UHFFFAOYSA-N quinoline-7-carboxylic acid Chemical compound C1=CC=NC2=CC(C(=O)O)=CC=C21 WXXVQWSDMOAHHV-UHFFFAOYSA-N 0.000 description 1
• 206010037844 rash Diseases 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 239000002461 renin inhibitor Substances 0.000 description 1
• 230000036454 renin-angiotensin system Effects 0.000 description 1
• 229940086526 renin-inhibitors Drugs 0.000 description 1
• 235000021283 resveratrol Nutrition 0.000 description 1
• 229940016667 resveratrol Drugs 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• VIHDTGHDWPVSMM-UHFFFAOYSA-N ruthenium;triphenylphosphane Chemical compound [Ru].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VIHDTGHDWPVSMM-UHFFFAOYSA-N 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229950011186 semaglutide Drugs 0.000 description 1
• 108010060325 semaglutide Proteins 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
• 229910001958 silver carbonate Inorganic materials 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 239000012748 slip agent Substances 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000009518 sodium iodide 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
• SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical group [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
• 108010082379 somatostatin receptor type 1 Proteins 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000001694 spray drying Methods 0.000 description 1
• 238000010922 spray-dried dispersion Methods 0.000 description 1
• 239000004059 squalene synthase inhibitor Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 235000000891 standard diet Nutrition 0.000 description 1
• 229940114926 stearate Drugs 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 229940099093 symlin Drugs 0.000 description 1
• 230000001975 sympathomimetic effect Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• WRGVLTAWMNZWGT-VQSPYGJZSA-N taspoglutide 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)NC(C)(C)C(=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(C)(C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 WRGVLTAWMNZWGT-VQSPYGJZSA-N 0.000 description 1
• 108010048573 taspoglutide Proteins 0.000 description 1
• 229950007151 taspoglutide Drugs 0.000 description 1
• 229920001897 terpolymer Polymers 0.000 description 1
• JELONQLAVHGMSL-UHFFFAOYSA-N tert-butyl 4-[(3-iodo-1-propan-2-ylpyrazol-4-yl)methyl]-4-isocyanatopiperidine-1-carboxylate Chemical compound IC1=NN(C(C)C)C=C1CC1(N=C=O)CCN(C(=O)OC(C)(C)C)CC1 JELONQLAVHGMSL-UHFFFAOYSA-N 0.000 description 1
• YYUAFDJZVMRLTH-UHFFFAOYSA-N tert-butyl 4-[(5-bromo-1-propan-2-ylpyrazol-4-yl)methyl]-4-isocyanatopiperidine-1-carboxylate Chemical compound CC(C)N1N=CC(CC2(CCN(CC2)C(=O)OC(C)(C)C)N=C=O)=C1Br YYUAFDJZVMRLTH-UHFFFAOYSA-N 0.000 description 1
• DQWJEPHSBBCSBB-UHFFFAOYSA-N tert-butyl 4-[(5-bromo-1-tert-butylpyrazol-4-yl)methyl]-4-isocyanatopiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(N=C=O)CC1=C(Br)N(C(C)(C)C)N=C1 DQWJEPHSBBCSBB-UHFFFAOYSA-N 0.000 description 1
• IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• VCVWXKKWDOJNIT-ZOMKSWQUSA-N tesofensine Chemical compound C1([C@H]2C[C@@H]3CC[C@@H](N3C)[C@@H]2COCC)=CC=C(Cl)C(Cl)=C1 VCVWXKKWDOJNIT-ZOMKSWQUSA-N 0.000 description 1
• 229950009970 tesofensine Drugs 0.000 description 1
• 229960002180 tetracycline Drugs 0.000 description 1
• 229930101283 tetracycline Natural products 0.000 description 1
• 235000019364 tetracycline Nutrition 0.000 description 1
• 150000003522 tetracyclines Chemical class 0.000 description 1
• CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
• WMSCYGTVHFMKNS-UHFFFAOYSA-N tributyl(methyl)stannane Chemical compound CCCC[Sn](C)(CCCC)CCCC WMSCYGTVHFMKNS-UHFFFAOYSA-N 0.000 description 1
• YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 1
• 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
• 150000003627 tricarboxylic acid derivatives Chemical class 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• WUJVPODXELZABP-FWJXURDUSA-N trodusquemine Chemical compound C([C@@H]1C[C@H]2O)[C@@H](NCCCNCCCCNCCCN)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@H](C(C)C)OS(O)(=O)=O)[C@@]2(C)CC1 WUJVPODXELZABP-FWJXURDUSA-N 0.000 description 1
• 229950004499 trodusquemine Drugs 0.000 description 1
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
• 229960001641 troglitazone Drugs 0.000 description 1
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 229950010724 usistapide Drugs 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 229950006508 velneperit Drugs 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229960001729 voglibose Drugs 0.000 description 1
• 239000002699 waste material Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1
• 229960002911 zonisamide Drugs 0.000 description 1
• 108020001612 μ-opioid receptors Proteins 0.000 description 1