JP5647356B2 - Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 - Google Patents
Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 Download PDFInfo
- Publication number
- JP5647356B2 JP5647356B2 JP2013535549A JP2013535549A JP5647356B2 JP 5647356 B2 JP5647356 B2 JP 5647356B2 JP 2013535549 A JP2013535549 A JP 2013535549A JP 2013535549 A JP2013535549 A JP 2013535549A JP 5647356 B2 JP5647356 B2 JP 5647356B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- reaction
- tert
- added
- carboxylic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims description 288
- 150000003839 salts Chemical class 0.000 claims description 54
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 239000000654 additive Substances 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 10
- 230000000996 additive effect Effects 0.000 claims description 9
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 423
- 238000006243 chemical reaction Methods 0.000 description 200
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 159
- 239000000203 mixture Substances 0.000 description 145
- 238000005481 NMR spectroscopy Methods 0.000 description 140
- 239000000243 solution Substances 0.000 description 123
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 122
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 116
- 239000007787 solid Substances 0.000 description 115
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 106
- 239000000543 intermediate Substances 0.000 description 105
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
- -1 pyrrolopyridinyl Chemical group 0.000 description 94
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 92
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
- 238000000034 method Methods 0.000 description 80
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 75
- 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 63
- 239000002904 solvent Substances 0.000 description 57
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 56
- 229910052938 sodium sulfate Inorganic materials 0.000 description 56
- 235000011152 sodium sulphate Nutrition 0.000 description 56
- 238000003818 flash chromatography Methods 0.000 description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 51
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
- 239000012267 brine Substances 0.000 description 43
- 239000003112 inhibitor Substances 0.000 description 43
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 43
- 238000003756 stirring Methods 0.000 description 43
- 239000003921 oil Substances 0.000 description 40
- 235000019198 oils Nutrition 0.000 description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 39
- 229920006395 saturated elastomer Polymers 0.000 description 38
- 239000010410 layer Substances 0.000 description 37
- 238000000746 purification Methods 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
- 235000019341 magnesium sulphate Nutrition 0.000 description 25
- 230000002829 reductive effect Effects 0.000 description 25
- 238000011282 treatment Methods 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 239000002585 base Substances 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 23
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 22
- 238000001914 filtration Methods 0.000 description 22
- 239000002244 precipitate Substances 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- 235000017557 sodium bicarbonate Nutrition 0.000 description 22
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 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
- 102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 20
- 108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 20
- 108010018763 Biotin carboxylase Proteins 0.000 description 20
- 101000677540 Homo sapiens Acetyl-CoA carboxylase 2 Proteins 0.000 description 20
- 239000000556 agonist Substances 0.000 description 20
- 201000010099 disease Diseases 0.000 description 20
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
- 208000035475 disorder Diseases 0.000 description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
- 208000008589 Obesity Diseases 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 16
- 230000005764 inhibitory process Effects 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
- 230000015572 biosynthetic process Effects 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 102100021334 Bcl-2-related protein A1 Human genes 0.000 description 14
- 101000894929 Homo sapiens Bcl-2-related protein A1 Proteins 0.000 description 14
- LTYOQGRJFJAKNA-KKIMTKSISA-N Malonyl CoA Natural products S(C(=O)CC(=O)O)CCNC(=O)CCNC(=O)[C@@H](O)C(CO[P@](=O)(O[P@](=O)(OC[C@H]1[C@@H](OP(=O)(O)O)[C@@H](O)[C@@H](n2c3ncnc(N)c3nc2)O1)O)O)(C)C LTYOQGRJFJAKNA-KKIMTKSISA-N 0.000 description 14
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-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)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 14
- LTYOQGRJFJAKNA-DVVLENMVSA-N malonyl-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)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-DVVLENMVSA-N 0.000 description 14
- 239000007858 starting material Substances 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 102100039164 Acetyl-CoA carboxylase 1 Human genes 0.000 description 11
- 239000005557 antagonist Substances 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 11
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000003472 antidiabetic agent Substances 0.000 description 10
- 150000001733 carboxylic acid esters Chemical class 0.000 description 10
- 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 10
- 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 10
- 238000010561 standard procedure Methods 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 101710190443 Acetyl-CoA carboxylase 1 Proteins 0.000 description 9
- 206010022489 Insulin Resistance Diseases 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 9
- 229940125708 antidiabetic agent Drugs 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- 206010012601 diabetes mellitus Diseases 0.000 description 9
- 230000002440 hepatic effect Effects 0.000 description 9
- 210000004185 liver Anatomy 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 239000003039 volatile agent Substances 0.000 description 8
- QDXQAOGNBCOEQX-UHFFFAOYSA-N 1-methylcyclohexa-1,4-diene Chemical compound CC1=CCC=CC1 QDXQAOGNBCOEQX-UHFFFAOYSA-N 0.000 description 7
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- 239000000010 aprotic solvent Substances 0.000 description 7
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 7
- 239000012948 isocyanate Substances 0.000 description 7
- 150000003951 lactams Chemical class 0.000 description 7
- 239000008177 pharmaceutical agent Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000004007 reversed phase HPLC Methods 0.000 description 7
- 239000012453 solvate Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000003643 water by type Substances 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-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
- 208000001145 Metabolic Syndrome Diseases 0.000 description 6
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 239000012491 analyte Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 102000047784 human ACACB Human genes 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000005897 peptide coupling reaction Methods 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
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 5
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 102000016267 Leptin Human genes 0.000 description 5
- 108010092277 Leptin Proteins 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 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
- 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
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 150000002513 isocyanates Chemical class 0.000 description 5
- 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 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000011780 sodium chloride Substances 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
- 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 4
- DWDQVPVFBKEWSW-UHFFFAOYSA-N 1-tert-butyl-4-[[4-carbamoyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]methyl]pyrazole-3-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C(N)=O)CC1=CN(C(C)(C)C)N=C1C(O)=O DWDQVPVFBKEWSW-UHFFFAOYSA-N 0.000 description 4
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 102000004276 BCL2-related protein A1 Human genes 0.000 description 4
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 4
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- 206010033307 Overweight Diseases 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 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 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
- 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 4
- RSUGKABMEVWWKL-UHFFFAOYSA-N ethyl 5-bromo-1-tert-butylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C(C)(C)C)C=1Br RSUGKABMEVWWKL-UHFFFAOYSA-N 0.000 description 4
- 230000004136 fatty acid synthesis Effects 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
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 4
- 229940039781 leptin Drugs 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 239000012026 peptide coupling reagents Substances 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
- VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical compound O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 4
- 239000012266 salt solution Substances 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- FXGCJQBVRDVSDW-UHFFFAOYSA-N tert-butyl 4-[(1-tert-butyl-3-ethoxycarbonylpyrazol-4-yl)methyl]-4-cyanopiperidine-1-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)(C)C)C=C1CC1(C#N)CCN(C(=O)OC(C)(C)C)CC1 FXGCJQBVRDVSDW-UHFFFAOYSA-N 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 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
- 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 3
- 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 3
- 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 3
- XMFAZNDFEXEANH-UHFFFAOYSA-N 1-(4-bromo-2-fluorophenyl)-2,2,2-trifluoroethanone Chemical compound FC1=CC(Br)=CC=C1C(=O)C(F)(F)F XMFAZNDFEXEANH-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
- AVGUDUBPDBIJTB-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 4-[(5-bromo-1-tert-butylpyrazol-4-yl)methyl]piperidine-1,4-dicarboxylate Chemical compound C1=NN(C(C)(C)C)C(Br)=C1CC1(C(=O)OCC)CCN(C(=O)OC(C)(C)C)CC1 AVGUDUBPDBIJTB-UHFFFAOYSA-N 0.000 description 3
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-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
- 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 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
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- JEDALECUOKHQDK-UHFFFAOYSA-M 4-ethyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylate Chemical compound CCC1(C([O-])=O)CCN(C(=O)OC(C)(C)C)CC1 JEDALECUOKHQDK-UHFFFAOYSA-M 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
- CBAXYISWNGGXOZ-UHFFFAOYSA-N 5-bromo-2-methylpyridin-3-amine Chemical compound CC1=NC=C(Br)C=C1N CBAXYISWNGGXOZ-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
- 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 3
- FONNZZMIJPHSJP-UHFFFAOYSA-N 6-bromo-1h-pyrazolo[4,3-b]pyridine Chemical compound BrC1=CN=C2C=NNC2=C1 FONNZZMIJPHSJP-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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 3
- 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 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108010011459 Exenatide Proteins 0.000 description 3
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 3
- 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 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 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 group [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
- IRAKEASBHQRODM-UHFFFAOYSA-N [3-bromo-1-(2-methylbutan-2-yl)pyrazol-4-yl]methanol Chemical compound CCC(C)(C)N1C=C(CO)C(Br)=N1 IRAKEASBHQRODM-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000012190 activator Substances 0.000 description 3
- 210000000577 adipose tissue Anatomy 0.000 description 3
- 125000006242 amine protecting group Chemical group 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 239000003524 antilipemic agent Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 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
- 239000013058 crude material Substances 0.000 description 3
- 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 3
- JMQGGPRJQOQKRT-UHFFFAOYSA-N diphenyl hydrogen phosphate;azide Chemical compound [N-]=[N+]=[N-].C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 JMQGGPRJQOQKRT-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 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
- 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 3
- 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 3
- FUBGSHXHSIWUKA-UHFFFAOYSA-N ethyl 1-tert-butyl-4-formylpyrazole-3-carboxylate Chemical compound CCOC(=O)C1=NN(C(C)(C)C)C=C1C=O FUBGSHXHSIWUKA-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
- 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 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
- 238000011156 evaluation Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 3
- TUSICEWIXLMXEY-UHFFFAOYSA-N methyl 1h-indazole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=NNC2=C1 TUSICEWIXLMXEY-UHFFFAOYSA-N 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
- 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 3
- 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 3
- 238000002552 multiple reaction monitoring Methods 0.000 description 3
- 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 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000010502 orange oil Substances 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 Chemical group 0.000 description 3
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 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
- 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
- 238000011160 research Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 229910052717 sulfur Chemical group 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- 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 3
- 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 3
- HKXICUDOIXLKLJ-PBINXNQUSA-N (1r,5s)-8-[(2-methylpropan-2-yl)oxycarbonyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound C1C(C(O)=O)C[C@H]2CC[C@@H]1N2C(=O)OC(C)(C)C HKXICUDOIXLKLJ-PBINXNQUSA-N 0.000 description 2
- 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
- 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 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
- 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
- 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
- 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
- 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 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
- 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 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
- 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 2
- 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 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
- 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 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
- 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 2
- SBARGJCSIIHYGR-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 4-[(3-iodo-1-propan-2-ylpyrazol-4-yl)methyl]piperidine-1,4-dicarboxylate Chemical compound C=1N(C(C)C)N=C(I)C=1CC1(C(=O)OCC)CCN(C(=O)OC(C)(C)C)CC1 SBARGJCSIIHYGR-UHFFFAOYSA-N 0.000 description 2
- PTNXCNSQCRVQBB-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 4-[(5-bromo-1-propan-2-ylpyrazol-4-yl)methyl]piperidine-1,4-dicarboxylate Chemical compound C1=NN(C(C)C)C(Br)=C1CC1(C(=O)OCC)CCN(C(=O)OC(C)(C)C)CC1 PTNXCNSQCRVQBB-UHFFFAOYSA-N 0.000 description 2
- BMHOAEQKRSPMLK-UHFFFAOYSA-N 1-oxo-2h-isoquinoline-6-carboxylic acid Chemical compound C1=CNC(=O)C=2C1=CC(C(=O)O)=CC=2 BMHOAEQKRSPMLK-UHFFFAOYSA-N 0.000 description 2
- POVYCMYIJRLRGP-UHFFFAOYSA-N 1-oxo-2h-isoquinoline-7-carboxylic acid Chemical compound C1=CNC(=O)C2=CC(C(=O)O)=CC=C21 POVYCMYIJRLRGP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- IYKMDFWCKOYTHV-UHFFFAOYSA-N 1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one;hydrochloride Chemical compound Cl.N1C(=O)C=2N(C(C)C)N=CC=2CC21CCNCC2 IYKMDFWCKOYTHV-UHFFFAOYSA-N 0.000 description 2
- NMQRSNGVNQRDDW-UHFFFAOYSA-N 1-tert-butyl-1'-(3,7-dimethyl-2h-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2C(C)=NNC2=C(C)C=C1C(=O)N(CC1)CCC1(NC1=O)CC2=C1N(C(C)(C)C)N=C2 NMQRSNGVNQRDDW-UHFFFAOYSA-N 0.000 description 2
- BSCBUAAVCSXPAW-UHFFFAOYSA-N 1-tert-butyl-4-[[4-isocyanato-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]methyl]pyrazole-3-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(N=C=O)CC1=CN(C(C)(C)C)N=C1C(O)=O BSCBUAAVCSXPAW-UHFFFAOYSA-N 0.000 description 2
- DNCVTVVLMRHJCJ-UHFFFAOYSA-N 1h-indazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=NNC2=C1 DNCVTVVLMRHJCJ-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
- 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 2
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 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
- AHNWNVNIBYKVEQ-UHFFFAOYSA-N 2-(2-methylbutan-2-yl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound N1C(=O)C2=NN(C(C)(C)CC)C=C2CC21CCNCC2 AHNWNVNIBYKVEQ-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
- 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 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
- 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 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
- 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
- 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
- UYVATUDIEIGCHF-UHFFFAOYSA-N 2-tert-butyl-1'-[1-(dimethylamino)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(N(C)C)C2=C1 UYVATUDIEIGCHF-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
- 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 2
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-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
- 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
- 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 2
- 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 2
- ABWAIXZOQFFYQJ-UHFFFAOYSA-N 3-bromo-4-(chloromethyl)-1-(2-methylbutan-2-yl)pyrazole Chemical compound CCC(C)(C)N1C=C(CCl)C(Br)=N1 ABWAIXZOQFFYQJ-UHFFFAOYSA-N 0.000 description 2
- KDXOQQFQPTUCSI-UHFFFAOYSA-N 3-bromo-4-(iodomethyl)-1-(2-methylbutan-2-yl)pyrazole Chemical compound CCC(C)(C)N1C=C(CI)C(Br)=N1 KDXOQQFQPTUCSI-UHFFFAOYSA-N 0.000 description 2
- NWMDDFOCGJAESH-UHFFFAOYSA-N 3-carbamoyl-1h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(C(=O)N)=NNC2=C1 NWMDDFOCGJAESH-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
- 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 2
- 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 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
- QASUNHBHNOVFQK-UHFFFAOYSA-N 3-oxo-1,2-dihydroindazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(O)=NNC2=C1 QASUNHBHNOVFQK-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
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-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
- 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
- DSAREEUXBAIGHA-UHFFFAOYSA-N 5-bromo-3-(trifluoromethyl)-2h-indazole Chemical compound C1=C(Br)C=C2C(C(F)(F)F)=NNC2=C1 DSAREEUXBAIGHA-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 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
- GMYSAWPFYXURBS-UHFFFAOYSA-N 6-bromo-3-(trifluoromethyl)-2h-indazole Chemical compound BrC1=CC=C2C(C(F)(F)F)=NNC2=C1 GMYSAWPFYXURBS-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
- 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
- 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 2
- AMBCTFGOVMCGIL-FGWVZKOKSA-N 8-o-tert-butyl 3-o-methyl (1r,5s)-8-azabicyclo[3.2.1]octane-3,8-dicarboxylate Chemical compound C1C(C(=O)OC)C[C@@]2([H])CC[C@]1([H])N2C(=O)OC(C)(C)C AMBCTFGOVMCGIL-FGWVZKOKSA-N 0.000 description 2
- 101710159293 Acyl-CoA desaturase 1 Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 108010074051 C-Reactive Protein Proteins 0.000 description 2
- 102100032752 C-reactive protein Human genes 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 description 2
- 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 101710150887 Cholecystokinin A Proteins 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- 102100035762 Diacylglycerol O-acyltransferase 2 Human genes 0.000 description 2
- 101710167503 Diacylglycerol O-acyltransferase 2 Proteins 0.000 description 2
- DVJAMEIQRSHVKC-BDAKNGLRSA-N Dutogliptin Chemical compound OB(O)[C@@H]1CCCN1C(=O)CN[C@H]1CNCC1 DVJAMEIQRSHVKC-BDAKNGLRSA-N 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 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
- 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
- 108010063919 Glucagon Receptors Proteins 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 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
- 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 101710151321 Melanostatin Proteins 0.000 description 2
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 2
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 2
- 102100021316 Mineralocorticoid receptor Human genes 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 102400000064 Neuropeptide Y Human genes 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 102000002512 Orexin Human genes 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 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
- 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
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 238000004458 analytical method Methods 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
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 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 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
- 230000037396 body weight Effects 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
- 150000001721 carbon Chemical group 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical group [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
- 239000012230 colorless oil Substances 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 239000011928 denatured alcohol Substances 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 229950003693 dutogliptin Drugs 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 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
- 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
- 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
- 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 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
- 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 2
- 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 2
- SVHHAAQTOHCWJX-UHFFFAOYSA-N ethyl quinoline-6-carboxylate Chemical compound N1=CC=CC2=CC(C(=O)OCC)=CC=C21 SVHHAAQTOHCWJX-UHFFFAOYSA-N 0.000 description 2
- PPZOEUCJAYRMHY-UHFFFAOYSA-N ethyl quinoline-7-carboxylate Chemical compound C1=CC=NC2=CC(C(=O)OCC)=CC=C21 PPZOEUCJAYRMHY-UHFFFAOYSA-N 0.000 description 2
- 229960001519 exenatide Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 238000001030 gas--liquid chromatography Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 229960004580 glibenclamide Drugs 0.000 description 2
- 229940124828 glucokinase activator Drugs 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
- 238000000099 in vitro assay Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 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 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
- ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 238000001819 mass spectrum Methods 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
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 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
- 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 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
- 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 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
- 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
- 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
- 239000003887 narcotic antagonist Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 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
- 108060005714 orexin Proteins 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 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
- 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
- IIKFXOLJMNWWCH-UHFFFAOYSA-N piperidine-1,4-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)CC1 IIKFXOLJMNWWCH-UHFFFAOYSA-N 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 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
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000011002 quantification 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
- 229940075993 receptor modulator Drugs 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000002461 renin inhibitor Substances 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000005070 sampling Methods 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
- 229960004937 saxagliptin Drugs 0.000 description 2
- 108010033693 saxagliptin Proteins 0.000 description 2
- 229960004425 sibutramine Drugs 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
- 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
- 239000011734 sodium Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride 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
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 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
- 239000007921 spray Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 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 2
- SOTIYYYDKMHAIB-UHFFFAOYSA-N tert-butyl 7-oxo-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-1'-carboxylate Chemical compound N1C(=O)C=2N(C(C)C)N=CC=2CC21CCN(C(=O)OC(C)(C)C)CC2 SOTIYYYDKMHAIB-UHFFFAOYSA-N 0.000 description 2
- DDPWVABNMBRBFI-UHFFFAOYSA-N tert-butylhydrazine;hydron;chloride Chemical compound Cl.CC(C)(C)NN DDPWVABNMBRBFI-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- 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
- 235000015870 tripotassium citrate Nutrition 0.000 description 2
- 238000001323 two-dimensional chromatography Methods 0.000 description 2
- 238000003828 vacuum filtration 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
- 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
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- IFGMSDPTDLRLEZ-UHFFFAOYSA-N (1-propan-2-ylspiro[4,6-dihydro-2H-pyrazolo[3,4-c]pyridine-5,4'-piperidine]-1'-yl)-quinolin-7-ylmethanone Chemical compound C(C)(C)N1NC=C2C1=CNC1(C2)CCN(CC1)C(=O)C1=CC=C2C=CC=NC2=C1 IFGMSDPTDLRLEZ-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- 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
- 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
- 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
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 229940095131 (r)- propylene glycol Drugs 0.000 description 1
- 229960004463 (s)- propylene glycol Drugs 0.000 description 1
- HKXDPIHMBBAVDY-UHFFFAOYSA-N 1'-(1-aminoisoquinoline-6-carbonyl)-2-tert-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound NC1=NC=CC2=CC(C(=O)N3CCC4(CC5=CN(N=C5C(=O)N4)C(C)(C)C)CC3)=CC=C21 HKXDPIHMBBAVDY-UHFFFAOYSA-N 0.000 description 1
- RMVMTPGYQHGXEO-UHFFFAOYSA-N 1'-(1-methylindazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2N(C)N=CC2=CC(C(=O)N2CCC3(CC=4C=NN(C=4C(=O)N3)C(C)C)CC2)=C1 RMVMTPGYQHGXEO-UHFFFAOYSA-N 0.000 description 1
- QWJDVEWFAZZMBP-UHFFFAOYSA-N 1'-(1h-indazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2NN=CC2=CC(C(=O)N2CCC3(CC=4C=NN(C=4C(=O)N3)C(C)C)CC2)=C1 QWJDVEWFAZZMBP-UHFFFAOYSA-N 0.000 description 1
- BUZWYKGFKYZACV-UHFFFAOYSA-N 1'-(2-amino-3h-benzimidazole-5-carbonyl)-2-tert-butylspiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2NC(N)=NC2=CC(C(=O)N2CCC3(NC(=O)C4=C(C3)CN(N4)C(C)(C)C)CC2)=C1 BUZWYKGFKYZACV-UHFFFAOYSA-N 0.000 description 1
- QVRZPQISGOAIJN-UHFFFAOYSA-N 1'-(2-methyl-3h-benzimidazole-5-carbonyl)-2-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(CC4=CN(N=C4C(=O)N3)C(C)C)CC2)=C1 QVRZPQISGOAIJN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- APCXAHGLEYYAET-UHFFFAOYSA-N 1'-(3,7-dimethyl-2h-indazole-5-carbonyl)-2-propan-2-ylspiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound CC1=C2NN=C(C)C2=CC(C(=O)N2CCC3(NC(=O)C4=C(C3)CN(N4)C(C)C)CC2)=C1 APCXAHGLEYYAET-UHFFFAOYSA-N 0.000 description 1
- QZHABRLDXRYFDG-UHFFFAOYSA-N 1'-(3-ethyl-2h-indazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2C(CC)=NNC2=CC=C1C(=O)N(CC1)CCC1(NC1=O)CC2=C1N(C(C)C)N=C2 QZHABRLDXRYFDG-UHFFFAOYSA-N 0.000 description 1
- QWGACACZONOJFB-UHFFFAOYSA-N 1'-(4,8-dimethoxyquinoline-2-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound N1=C2C(OC)=CC=CC2=C(OC)C=C1C(=O)N(CC1)CCC1(NC1=O)CC2=C1N(C(C)C)N=C2 QWGACACZONOJFB-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
- BVCACBTXXMTIIR-UHFFFAOYSA-N 1'-(7-methyl-1h-indazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound CC1=C2NN=CC2=CC(C(=O)N2CCC3(CC=4C=NN(C=4C(=O)N3)C(C)C)CC2)=C1 BVCACBTXXMTIIR-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
- 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
- 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
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- LBAIDXPGPXOFGU-UHFFFAOYSA-N 1-O-ethyl 5-O-methyl 2-methyl-3-oxoindazole-1,5-dicarboxylate 2-methyl-3-oxo-1H-indazole-5-carboxylic acid Chemical compound CN1N(C2=CC=C(C=C2C1=O)C(=O)OC)C(=O)OCC.CN1NC2=CC=C(C=C2C1=O)C(=O)O LBAIDXPGPXOFGU-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
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-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
- HGGJDPGZCATJNC-UHFFFAOYSA-N 1-oxo-2h-isoquinoline-7-carbonitrile Chemical compound C1=C(C#N)C=C2C(=O)NC=CC2=C1 HGGJDPGZCATJNC-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
- 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
- WVVBBPZSQOJXJR-UHFFFAOYSA-N 1-tert-butyl-3-iodo-4-(iodomethyl)pyrazole Chemical compound CC(C)(C)N1C=C(CI)C(I)=N1 WVVBBPZSQOJXJR-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
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 125000000980 1H-indol-3-ylmethyl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[*])C2=C1[H] 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
- 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
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- OVRWUZYZECPJOB-UHFFFAOYSA-N 2,2-difluoroethanamine Chemical compound NCC(F)F OVRWUZYZECPJOB-UHFFFAOYSA-N 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-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
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-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
- 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
- IQRUSQUYPCHEKN-UHFFFAOYSA-N 2-iodobutane Chemical compound CCC(C)I IQRUSQUYPCHEKN-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 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 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
- NMSNAHXMMZJPTG-UHFFFAOYSA-N 2-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound N1C(=O)C2=NN(C(C)C)C=C2CC21CCNCC2 NMSNAHXMMZJPTG-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
- 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 1
- 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 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
- RLBGBGWZALKBFW-UHFFFAOYSA-N 2-tert-butyl-1'-(2-methoxyquinoline-7-carbonyl)spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C=1C2=NC(OC)=CC=C2C=CC=1C(=O)N(CC1)CCC1(NC1=O)CC2=C1NN(C(C)(C)C)C2 RLBGBGWZALKBFW-UHFFFAOYSA-N 0.000 description 1
- NUAUHEMJQPCVTN-UHFFFAOYSA-N 2-tert-butyl-1'-(3-chloro-1h-indole-6-carbonyl)spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2C(Cl)=CNC2=CC(C(=O)N2CCC3(NC(=O)C4=C(C3)CN(N4)C(C)(C)C)CC2)=C1 NUAUHEMJQPCVTN-UHFFFAOYSA-N 0.000 description 1
- DNHHKRPTHPXZGQ-UHFFFAOYSA-N 2-tert-butyl-1'-(3-chloro-1h-pyrrolo[3,2-b]pyridine-6-carbonyl)spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound N1=C2C(Cl)=CNC2=CC(C(=O)N2CCC3(NC(=O)C4=C(C3)CN(N4)C(C)(C)C)CC2)=C1 DNHHKRPTHPXZGQ-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
- MFLKGEABCKJOJW-UHFFFAOYSA-N 2-tert-butyl-1'-(7-methoxy-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=C1OC)=CC2=C1NN=C2 MFLKGEABCKJOJW-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
- ACWUVYZHKCIABS-UHFFFAOYSA-N 2-tert-butyl-1'-[1-(methylamino)isoquinoline-7-carbonyl]spiro[1,3,4,6-tetrahydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1=C2C(NC)=NC=CC2=CC=C1C(=O)N(CC1)CCC1(NC1=O)CC2=C1NN(C(C)(C)C)C2 ACWUVYZHKCIABS-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
- UJIFQMYFKSXDML-UHFFFAOYSA-N 2-tert-butyl-1'-[2-(dimethylamino)quinoline-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=CC2=NC(N(C)C)=CC=C2C=C1 UJIFQMYFKSXDML-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
- BTCOXLFVOPZBPN-UHFFFAOYSA-N 2-tert-butylspiro[4,6-dihydro-1H-pyrazolo[3,4-c]pyridine-5,4'-piperidine] Chemical compound C(C)(C)(C)N1NC2=CNC3(CC2=C1)CCNCC3 BTCOXLFVOPZBPN-UHFFFAOYSA-N 0.000 description 1
- IHSXILCXOPSQIM-UHFFFAOYSA-N 2-tert-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,3'-8-azabicyclo[3.2.1]octane]-7-one;hydrochloride Chemical compound Cl.C1C(N2)CCC2CC21CC1=CN(C(C)(C)C)N=C1C(=O)N2 IHSXILCXOPSQIM-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 compound N1C(=O)C2=NN(C(C)(C)C)C=C2CC21CCNCC2 IMAQITWQJIXTFR-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
- VQNDBXJTIJKJPV-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridine Chemical compound C1=CC=NC2=NNN=C21 VQNDBXJTIJKJPV-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
- IJCAHURHZANYQX-UHFFFAOYSA-N 3-(methylamino)-1H-indazole-5-carboxylic acid methyl 3-(methylamino)-1H-indazole-5-carboxylate Chemical compound CNC1=NNC2=CC=C(C=C12)C(=O)OC.CNC1=NNC2=CC=C(C=C12)C(=O)O IJCAHURHZANYQX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- WQNLFKBQZSFFSP-UHFFFAOYSA-N 3-(methylamino)isoquinoline-6-carboxylic acid methyl 3-(methylamino)isoquinoline-6-carboxylate Chemical compound CNC=1N=CC2=CC=C(C=C2C1)C(=O)OC.CNC=1N=CC2=CC=C(C=C2C1)C(=O)O WQNLFKBQZSFFSP-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
- MISVITGIPFDQOH-UHFFFAOYSA-N 3-chloro-1H-pyrrolo[3,2-b]pyridine-6-carboxylic acid methyl 3-chloro-1H-pyrrolo[3,2-b]pyridine-6-carboxylate Chemical compound ClC1=CNC=2C1=NC=C(C2)C(=O)OC.ClC2=CNC=1C2=NC=C(C1)C(=O)O MISVITGIPFDQOH-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
- 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 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
- HFJDUDWMJXQGDJ-UHFFFAOYSA-N 3-ethyl-2h-indazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(CC)=NNC2=C1 HFJDUDWMJXQGDJ-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 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
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 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
- 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
- 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
- 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
- QSFFBQNKTUMKNW-UHFFFAOYSA-N 6-methoxyquinoline-3-carboxylic acid Chemical compound N1=CC(C(O)=O)=CC2=CC(OC)=CC=C21 QSFFBQNKTUMKNW-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 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
- 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
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- 229940123324 Acyltransferase inhibitor Drugs 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
- 102100034608 Angiopoietin-2 Human genes 0.000 description 1
- 108010048036 Angiopoietin-2 Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 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
- 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
- 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
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- RJPLKWWYTMYRSJ-UHFFFAOYSA-N CC(C)(C)N1C=C2CC3(CCN(CC3)C(=O)C4=CC5=C(C=C4)C=CC(=N5)N)NC=C2N1 Chemical compound CC(C)(C)N1C=C2CC3(CCN(CC3)C(=O)C4=CC5=C(C=C4)C=CC(=N5)N)NC=C2N1 RJPLKWWYTMYRSJ-UHFFFAOYSA-N 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
- SOLGWTKBCSIBPH-UHFFFAOYSA-N CC(C)N1C2=CNC3(CCN(CC3)C(=O)C4=CC5=C(C=C4)C=CN=C5)CC2=CN1 Chemical compound CC(C)N1C2=CNC3(CCN(CC3)C(=O)C4=CC5=C(C=C4)C=CN=C5)CC2=CN1 SOLGWTKBCSIBPH-UHFFFAOYSA-N 0.000 description 1
- CELVEQPWXLWTIS-UHFFFAOYSA-N CC(C)N1C=C(C(=N1)I)CC2(CCN(CC2)C(=O)O)N=C=O Chemical compound CC(C)N1C=C(C(=N1)I)CC2(CCN(CC2)C(=O)O)N=C=O CELVEQPWXLWTIS-UHFFFAOYSA-N 0.000 description 1
- ZZYGOUXUZPDEDS-UHFFFAOYSA-N COC(c(ccc1ccc2)cc1[n+]2O)=O Chemical compound COC(c(ccc1ccc2)cc1[n+]2O)=O ZZYGOUXUZPDEDS-UHFFFAOYSA-N 0.000 description 1
- TUSFOGXWSSKMJA-UHFFFAOYSA-N COC1=NN(C2=CC(=CC=C12)C(=O)OC)C(=O)OCC.COC1=NNC2=CC(=CC=C12)C(=O)O Chemical compound COC1=NN(C2=CC(=CC=C12)C(=O)OC)C(=O)OCC.COC1=NNC2=CC(=CC=C12)C(=O)O TUSFOGXWSSKMJA-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
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 239000005973 Carvone Substances 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 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
- 102100025892 Complement C1q tumor necrosis factor-related protein 1 Human genes 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 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
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-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
- 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 description 1
- 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 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
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 229940123469 Fatty acid synthase inhibitor Drugs 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
- 210000000712 G cell Anatomy 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
- 102400001370 Galanin Human genes 0.000 description 1
- 101800002068 Galanin Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101800001586 Ghrelin Proteins 0.000 description 1
- 102400000442 Ghrelin-28 Human genes 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 102100040890 Glucagon receptor Human genes 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor 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
- 101800000224 Glucagon-like peptide 1 Proteins 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
- 102100033839 Glucose-dependent insulinotropic receptor Human genes 0.000 description 1
- 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
- 108010046163 Glycogen Phosphorylase Proteins 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
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 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
- 101000994669 Homo sapiens Potassium voltage-gated channel subfamily A member 3 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
- 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
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 1
- 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 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 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-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
- 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
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 description 1
- 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
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 1
- 101800002739 Melanin-concentrating hormone 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
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 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
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-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
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102100038813 Neuromedin-U Human genes 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 229940124754 PPAR-alpha/gamma agonist Drugs 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 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
- 102100034355 Potassium voltage-gated channel subfamily A member 3 Human genes 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
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 1
- 102100024923 Protein kinase C beta 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
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 108091006277 SLC5A1 Proteins 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
- 229940121834 Serine palmitoyltransferase inhibitor Drugs 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
- 229940123185 Squalene epoxidase inhibitor Drugs 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 239000000150 Sympathomimetic Substances 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
- 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
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 1
- 101710128896 Tyrosine-protein phosphatase non-receptor type 1 Proteins 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
- 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
- PIJVDGMJGIAFIN-UHFFFAOYSA-N [3-iodosyl-2-(2,2,2-trifluoroacetyl)oxyphenyl] 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OC1=CC=CC(I=O)=C1OC(=O)C(F)(F)F PIJVDGMJGIAFIN-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
- 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
- 229960001466 acetohexamide Drugs 0.000 description 1
- VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000002404 acyltransferase inhibitor Substances 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000003392 amylase inhibitor Substances 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N anhydrous trimethylamine Natural products CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 229940127088 antihypertensive drug Drugs 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
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 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
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000004124 azulen-6-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C(*)C([H])=C([H])C2=C1[H] 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
- 229940077388 benzenesulfonate Drugs 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
- 239000002876 beta blocker Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 229930189065 blasticidin Natural products 0.000 description 1
- 238000007664 blowing Methods 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
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 229960001058 bupropion Drugs 0.000 description 1
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
- 229940047123 bupropion and naltrexone Drugs 0.000 description 1
- DLDJFQGPPSQZKI-UHFFFAOYSA-N but-2-yne-1,4-diol Chemical compound OCC#CCO DLDJFQGPPSQZKI-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
- 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
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000001721 carboxyacetyl group Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 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
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 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(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=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 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960001761 chlorpropamide Drugs 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
- 230000001684 chronic effect Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream 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
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229960003834 dapagliflozin Drugs 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
- 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
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 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
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 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
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 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
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 229950000269 emiglitate Drugs 0.000 description 1
- 239000003995 emulsifying agent 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
- KTMGNAIGXYODKQ-VOTSOKGWSA-N ethyl (e)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(/C#N)C(=O)OCC KTMGNAIGXYODKQ-VOTSOKGWSA-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
- YTGVJFSEVWPDRH-UHFFFAOYSA-N ethyl 3-bromo-1-(2-methylbutan-2-yl)pyrazole-4-carboxylate Chemical compound CCOC(=O)C1=CN(C(C)(C)CC)N=C1Br YTGVJFSEVWPDRH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- DJFSJKPXNYYPFK-UHFFFAOYSA-N ethyl 5-amino-1-tert-butylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C(C)(C)C)C=1N DJFSJKPXNYYPFK-UHFFFAOYSA-N 0.000 description 1
- ZQKGADOVRQWWOH-UHFFFAOYSA-N ethyl 5-bromo-1-cyclobutylpyrazole-4-carboxylate Chemical compound BrC1=C(C(=O)OCC)C=NN1C1CCC1 ZQKGADOVRQWWOH-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
- 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 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 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
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 108010036598 gastric inhibitory polypeptide receptor Proteins 0.000 description 1
- 239000008273 gelatin Substances 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
- GNKDKYIHGQKHHM-RJKLHVOGSA-N ghrelin Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CN)COC(=O)CCCCCCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 GNKDKYIHGQKHHM-RJKLHVOGSA-N 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
- 229960001381 glipizide Drugs 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- 229950008402 glisentide 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
- 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
- 230000036541 health Effects 0.000 description 1
- 235000020981 healthy eating habits Nutrition 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 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
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000003668 hormone analog Substances 0.000 description 1
- 239000003667 hormone antagonist Substances 0.000 description 1
- 102000055839 human AGRP Human genes 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
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 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
- 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
- 239000005457 ice water Substances 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000000338 in vitro Methods 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
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 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
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 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
- QUFUUBBLCOBJPH-UHFFFAOYSA-N isoquinoline-7-carboxylic acid Chemical compound C1=CN=CC2=CC(C(=O)O)=CC=C21 QUFUUBBLCOBJPH-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- 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 1
- 229940070765 laurate Drugs 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
- 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
- 210000005228 liver tissue Anatomy 0.000 description 1
- 108010004367 lixisenatide Proteins 0.000 description 1
- 229960001093 lixisenatide Drugs 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 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
- 239000012139 lysis buffer Substances 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
- 239000011159 matrix material Substances 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 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
- BQCAZZUXJIYHHO-UHFFFAOYSA-N methyl 1-oxo-2h-isoquinoline-6-carboxylate Chemical compound C1=CNC(=O)C=2C1=CC(C(=O)OC)=CC=2 BQCAZZUXJIYHHO-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 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 1
- 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 1
- 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 1
- WVPQEPAXNSRHPL-UHFFFAOYSA-N methyl 4-amino-3-(methylcarbamothioylamino)benzoate Chemical compound CNC(=S)NC1=CC(C(=O)OC)=CC=C1N WVPQEPAXNSRHPL-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
- 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 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960000668 metreleptin Drugs 0.000 description 1
- 108700008455 metreleptin Proteins 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
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-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
- 150000002759 monoacylglycerols Chemical class 0.000 description 1
- 230000000407 monoamine reuptake Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 102000051367 mu Opioid Receptors Human genes 0.000 description 1
- 210000004165 myocardium Anatomy 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
- 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
- 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 1
- 229960003086 naltrexone Drugs 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
- 108010021512 neuromedin U Proteins 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 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
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-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
- 239000005416 organic matter Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- FIYYMXYOBLWYQO-UHFFFAOYSA-N ortho-iodylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I(=O)=O FIYYMXYOBLWYQO-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 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
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor 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
- 239000003208 petroleum 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 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
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-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
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 239000002469 receptor inverse agonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 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
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class 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
- 150000005376 secondary alkyl halides Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000002485 serotonin 2C agonist Substances 0.000 description 1
- 210000002966 serum Anatomy 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
- 238000010583 slow cooling Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 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
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 108010082379 somatostatin receptor type 1 Proteins 0.000 description 1
- 241000894007 species Species 0.000 description 1
- MNXXSWTUBHXLNE-UHFFFAOYSA-N spiro[4,6-dihydro-1H-pyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one Chemical compound C1C2=CNN=C2C(=O)NC21CCNCC2 MNXXSWTUBHXLNE-UHFFFAOYSA-N 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000001694 spray drying 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
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 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
- 230000001629 suppression Effects 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
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 108010048573 taspoglutide Proteins 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
- 229950007151 taspoglutide Drugs 0.000 description 1
- 229950001790 tendamistat Drugs 0.000 description 1
- 108010037401 tendamistate Proteins 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DULVZDJHQKYNEW-UHFFFAOYSA-N tert-butyl 1-tert-butyl-7-oxospiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-1'-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC21NC(=O)C(N(N=C1)C(C)(C)C)=C1C2 DULVZDJHQKYNEW-UHFFFAOYSA-N 0.000 description 1
- GNFHKLLEXDIZBL-UHFFFAOYSA-N tert-butyl 2-tert-butyl-7-oxospiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-1'-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC21NC(=O)C1=NN(C(C)(C)C)C=C1C2 GNFHKLLEXDIZBL-UHFFFAOYSA-N 0.000 description 1
- RGVMDDSLHHWGAP-UHFFFAOYSA-N tert-butyl 7-oxo-2-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-1'-carboxylate Chemical compound N1C(=O)C2=NN(C(C)C)C=C2CC21CCN(C(=O)OC(C)(C)C)CC2 RGVMDDSLHHWGAP-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
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 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
- DQLXXYMNINXQSV-QTRRCMKVSA-J tetralithium;[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-2-[[[[(3r)-4-[[3-[2-(2-carboxyacetyl)sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl] phosphate Chemical compound [Li+].[Li+].[Li+].[Li+].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)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 DQLXXYMNINXQSV-QTRRCMKVSA-J 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-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
- 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 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
- 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
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 238000005406 washing Methods 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
- 239000002023 wood 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40812710P | 2010-10-29 | 2010-10-29 | |
| US61/408,127 | 2010-10-29 | ||
| US201161531744P | 2011-09-07 | 2011-09-07 | |
| US61/531,744 | 2011-09-07 | ||
| PCT/IB2011/054643 WO2012056372A1 (en) | 2010-10-29 | 2011-10-18 | N1/N2-LACTAM ACETYL-CoA CARBOXYLASE INHIBITORS |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014225021A Division JP2015057416A (ja) | 2010-10-29 | 2014-11-05 | Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013542218A JP2013542218A (ja) | 2013-11-21 |
| JP2013542218A5 JP2013542218A5 (https=) | 2014-01-30 |
| JP5647356B2 true JP5647356B2 (ja) | 2014-12-24 |
Family
ID=44993633
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013535549A Expired - Fee Related JP5647356B2 (ja) | 2010-10-29 | 2011-10-18 | Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 |
| JP2014225021A Withdrawn JP2015057416A (ja) | 2010-10-29 | 2014-11-05 | Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014225021A Withdrawn JP2015057416A (ja) | 2010-10-29 | 2014-11-05 | Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 |
Country Status (26)
| Country | Link |
|---|---|
| US (3) | US8859773B2 (https=) |
| EP (2) | EP2952514A1 (https=) |
| JP (2) | JP5647356B2 (https=) |
| KR (2) | KR101529404B1 (https=) |
| CN (2) | CN104774205A (https=) |
| AR (1) | AR083578A1 (https=) |
| AU (1) | AU2011322117B2 (https=) |
| BR (1) | BR112013010310A2 (https=) |
| CA (1) | CA2815169C (https=) |
| CY (1) | CY1116405T1 (https=) |
| DK (1) | DK2632925T3 (https=) |
| ES (1) | ES2546465T3 (https=) |
| HK (1) | HK1209733A1 (https=) |
| HU (1) | HUE025078T2 (https=) |
| IL (1) | IL225779A0 (https=) |
| MX (1) | MX2013004733A (https=) |
| NZ (1) | NZ609527A (https=) |
| PL (1) | PL2632925T3 (https=) |
| PT (1) | PT2632925E (https=) |
| RU (1) | RU2540337C2 (https=) |
| SG (1) | SG189883A1 (https=) |
| SI (1) | SI2632925T1 (https=) |
| TW (3) | TWI441823B (https=) |
| UY (1) | UY33694A (https=) |
| WO (1) | WO2012056372A1 (https=) |
| ZA (1) | ZA201303882B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015057416A (ja) * | 2010-10-29 | 2015-03-26 | ファイザー・インク | Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2953942T3 (pl) | 2013-02-06 | 2018-03-30 | Bayer Cropscience Aktiengesellschaft | Podstawione halogenem pochodne pirazolu jako środki do zwalczania szkodników |
| US8652527B1 (en) | 2013-03-13 | 2014-02-18 | Upsher-Smith Laboratories, Inc | Extended-release topiramate capsules |
| US9101545B2 (en) | 2013-03-15 | 2015-08-11 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
| CN103214327A (zh) * | 2013-03-22 | 2013-07-24 | 郑州泰基鸿诺药物科技有限公司 | 一种芳香环或芳杂环三氟甲基酮化合物及其制备方法 |
| CN104230922B (zh) | 2013-06-19 | 2016-12-28 | 中国科学院上海药物研究所 | 一类五元杂环并吡啶类化合物及其制备方法和用途 |
| US20160220557A1 (en) | 2013-09-12 | 2016-08-04 | Pfizer Inc. | Use of acetyl-coa carboxylase inhibitors for treating acne vulgaris |
| MX2016008653A (es) | 2014-01-03 | 2016-09-26 | Bayer Animal Health Gmbh | Nuevas pirazolil-heteroarilamidas como agentes plaguicidas. |
| CN104844509A (zh) * | 2014-02-14 | 2015-08-19 | 河南工业大学 | 一种条件温和无金属参与的胺基喹啉衍生物的制备方法 |
| KR101731624B1 (ko) * | 2014-07-01 | 2017-05-04 | 광주과학기술원 | 세포 리프로그래밍 유도용 조성물 |
| CN106749002A (zh) * | 2015-02-12 | 2017-05-31 | 佛山市赛维斯医药科技有限公司 | 一种含硝基喹啉结构的葡萄糖激酶活化剂及其用途 |
| BR112017019266B1 (pt) | 2015-03-10 | 2022-05-10 | Bayer Animal Health Gmbh | Compostos derivados de pirazolila e composição farmacêutica compreendendo o referido composto |
| IL243707A0 (en) | 2016-01-20 | 2016-05-01 | Galmed Res And Dev Ltd | Treatment to regulate the microbiota in the intestine |
| US11197870B2 (en) | 2016-11-10 | 2021-12-14 | Galmed Research And Development Ltd | Treatment for hepatic fibrosis |
| WO2018170203A1 (en) | 2017-03-16 | 2018-09-20 | Celgene Car Llc | Mk2 inhibitors, synthesis thereof, and intermediates thereto |
| WO2018170200A1 (en) | 2017-03-16 | 2018-09-20 | Celgene Car Llc | Heteroaryl compounds useful as mk2 inhibitors |
| AU2018233367B2 (en) | 2017-03-16 | 2021-08-12 | Jiangsu Hengrui Medicine Co., Ltd. | Heteroaryl[4,3-c]pyrimidine-5-amine derivative, preparation method therefor, and medical uses thereof |
| EP3601259B1 (en) | 2017-03-30 | 2022-02-23 | F. Hoffmann-La Roche AG | Isoquinolines as inhibitors of hpk1 |
| CN111406056B (zh) | 2017-11-21 | 2023-02-28 | 辉瑞公司 | 选择性acc抑制剂的结晶2-氨基-2-(羟甲基)丙烷-1,3-二醇盐 |
| TW202019905A (zh) | 2018-07-24 | 2020-06-01 | 瑞士商赫孚孟拉羅股份公司 | 異喹啉化合物及其用途 |
| TW202024053A (zh) | 2018-10-02 | 2020-07-01 | 美商建南德克公司 | 異喹啉化合物及其用途 |
| US11612606B2 (en) | 2018-10-03 | 2023-03-28 | Genentech, Inc. | 8-aminoisoquinoline compounds and uses thereof |
| CN109824669A (zh) * | 2018-12-21 | 2019-05-31 | 西南大学 | 哌啶螺环酒石酸类化合物制备及应用 |
| EP4149917B1 (en) * | 2020-05-12 | 2025-07-30 | Merck Sharp & Dohme LLC | Factor xi activation inhibitors |
| EP4154880A4 (en) * | 2020-05-21 | 2024-06-05 | Shionogi & Co., Ltd | Pharmaceutical for treating fatty liver diseases |
| CN116670142A (zh) | 2021-02-01 | 2023-08-29 | 细胞基因公司 | Mk2抑制剂、其合成和其中间体 |
| TW202317104A (zh) * | 2021-06-25 | 2023-05-01 | 美商賽迪拉治療股份有限公司 | Ｔｅａｄ抑制劑及其用途 |
| MA71611A (fr) * | 2022-07-29 | 2025-05-30 | Pfizer Inc. | Nouveaux inhibiteurs de l'acc |
| CN121241054A (zh) * | 2023-04-14 | 2025-12-30 | 北京双鹤润创科技有限公司 | 氮杂环羰基稠环衍生物及其用途 |
| CN121909191A (zh) * | 2023-08-16 | 2026-04-21 | 智擎生技制药股份有限公司 | Mta协同性的prmt5抑制剂 |
| TW202602453A (zh) * | 2024-03-14 | 2026-01-16 | 智擎生技製藥股份有限公司 | Mta協同性的prmt5抑制劑 |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2002100A (en) | 1932-06-27 | 1935-05-21 | Smith Sheffield | Shock absorber |
| JPS4925673B1 (https=) * | 1970-05-22 | 1974-07-02 | ||
| ES2287971T3 (es) | 1997-08-11 | 2007-12-16 | Pfizer Products Inc. | Dispersiones farmaceuticas solidas con biodisponibilidad incrementada. |
| CA2439152C (en) | 2001-02-28 | 2008-06-17 | Merck & Co., Inc. | Acylated piperidine derivatives as melanocortin-4 receptor agonists |
| JP2005504059A (ja) | 2001-08-24 | 2005-02-10 | ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー | 疾患を処置するための置換アリール７−アザ［２．２．１］ビシクロヘプタン |
| WO2003072578A1 (en) | 2002-02-20 | 2003-09-04 | Pharmacia & Upjohn Company | Azabicyclic compounds with alfa7 nicotinic acetylcholine receptor activity |
| CN1642599A (zh) | 2002-02-27 | 2005-07-20 | 辉瑞产品公司 | Acc抑制剂 |
| US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| WO2004092179A1 (ja) | 2003-04-14 | 2004-10-28 | Nippon Soda Co. Ltd. | スピロ誘導体、製造法および抗酸化薬 |
| JP2005119987A (ja) | 2003-10-15 | 2005-05-12 | Ajinomoto Co Inc | アシルスルホンアミド誘導体 |
| PL1753748T3 (pl) | 2004-05-12 | 2010-01-29 | Pfizer Prod Inc | Pochodne proliny i ich zastosowanie jako inhibitorów peptydazy dipeptylowej IV |
| WO2005113069A2 (en) | 2004-05-14 | 2005-12-01 | Research Development Foundation | Use of circumin and analogues as inhibitors of acc2 |
| AP2006003768A0 (en) | 2004-05-25 | 2006-10-31 | Pfizer Prod Inc | TetraazabenzoÄeÜazulene derivatives and analogs tehereof |
| PA8660701A1 (es) | 2005-02-04 | 2006-09-22 | Pfizer Prod Inc | Agonistas de pyy y sus usos |
| WO2007011809A1 (en) | 2005-07-19 | 2007-01-25 | Merck & Co., Inc. | Spirochromanone derivatives as acetyl coenzyme a carboxylase (acc) inhibitors |
| CA2617042A1 (en) | 2005-07-29 | 2007-02-01 | Takeda Pharmaceutical Company Limited | Spiro-cyclic compound |
| JP2009515971A (ja) | 2005-11-18 | 2009-04-16 | メルク エンド カムパニー インコーポレーテッド | スピロヒダントインアリールｃｇｒｐ受容体アンタゴニスト |
| JP2009526868A (ja) | 2006-02-15 | 2009-07-23 | アボット・ラボラトリーズ | 新規なアセチル−ＣｏＡカルボキシラーゼ（ＡＣＣ）阻害薬およびこれらの糖尿病、肥満および代謝症候群における使用 |
| EP2010520B1 (en) | 2006-04-20 | 2012-09-12 | Pfizer Products Inc. | Heterobicyclic amides for the prevention and treatment of glucokinase-mediated diseases |
| BRPI0721053A2 (pt) | 2006-11-29 | 2014-07-29 | Pfizer Prod Inc | INIBIDORES DE ESPIROCETONA ACETIL-CoA CARBOXILASE |
| PE20081559A1 (es) | 2007-01-12 | 2008-11-20 | Merck & Co Inc | DERIVADOS DE ESPIROCROMANONA SUSTITUIDOS COMO INHIBIDORES DE ACETIL CoA CARBOXILASA |
| JPWO2008102749A1 (ja) * | 2007-02-20 | 2010-05-27 | 武田薬品工業株式会社 | 複素環化合物 |
| AU2008237660B2 (en) | 2007-04-12 | 2011-12-22 | Pfizer Inc. | 3-amido-pyrrolo [3, 4-C] pyrazole-5 (1H, 4H, 6H) carbaldehyde derivatives as inhibitors of protein kinase C |
| US20090036425A1 (en) | 2007-08-02 | 2009-02-05 | Pfizer Inc | Substituted bicyclolactam compounds |
| US7981904B2 (en) | 2008-03-20 | 2011-07-19 | Takeda Pharmaceutical Company Limited | Acetyl CoA carboxylase inhibitors |
| JP5435592B2 (ja) | 2008-05-28 | 2014-03-05 | ファイザー・インク | ピラゾロスピロケトンアセチルＣｏＡカルボキシラーゼ阻害剤 |
| WO2009144555A1 (en) | 2008-05-28 | 2009-12-03 | Pfizer Inc. | Pyrazolospiroketone acetyl-coa carboxylase inhibitors |
| WO2010002010A1 (en) | 2008-07-04 | 2010-01-07 | Banyu Pharmaceutical Co.,Ltd. | Novel spirochromanone carboxylic acids |
| AU2009271634A1 (en) * | 2008-07-14 | 2010-01-21 | Cropsolution, Inc. | Modulators of acetyl-coenzyme a carboxylase and methods of use thereof |
| JP2011529483A (ja) | 2008-07-29 | 2011-12-08 | ファイザー・インク | フッ素化ヘテロアリール |
| AU2009286380B2 (en) | 2008-08-28 | 2011-09-15 | Pfizer Inc. | Dioxa-bicyclo[3.2.1.]octane-2,3,4-triol derivatives |
| TW201038580A (en) | 2009-02-02 | 2010-11-01 | Pfizer | 4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl derivatives |
| CA2754685A1 (en) | 2009-03-11 | 2010-09-16 | Pfizer Inc. | Substituted indazole amides |
| EP2604604A1 (en) | 2009-03-11 | 2013-06-19 | Pfizer Inc | Benzofuranyl derivatives used as glucokinase inhibitors |
| WO2010106457A2 (en) | 2009-03-20 | 2010-09-23 | Pfizer Inc. | 3-oxa-7-azabicyclo[3.3.1]nonanes |
| CA2759843A1 (en) | 2009-05-08 | 2010-11-10 | Pfizer Inc. | Gpr 119 modulators |
| US20120052130A1 (en) | 2009-05-08 | 2012-03-01 | Pfizer Inc. | Gpr 119 modulators |
| NZ596467A (en) | 2009-06-05 | 2014-01-31 | Pfizer | L- ( piperidin-4-yl) -pyrazole derivatives as gpr 119 modulators |
| WO2011005611A1 (en) | 2009-07-09 | 2011-01-13 | Merck Sharp & Dohme Corp. | Neuromedin u receptor agonists and uses thereof |
| EP2499140A1 (en) * | 2009-11-10 | 2012-09-19 | Pfizer Inc. | N2-pyrazolospiroketone acetyl-coa carboxylase inhibitors |
| EP2947082A1 (en) * | 2009-11-10 | 2015-11-25 | Pfizer Inc | N1-PYRAZOLOSPIROKETONE ACETYL-CoA CARBOXYLASE INHIBITORS |
| HRP20161178T1 (hr) | 2010-09-30 | 2016-11-04 | Pfizer Inc. | N1-PIRAZOLOSPIROKETONSKI INHIBITORI ACETIL-CoA-KARBOKSILAZE |
| ES2546465T3 (es) * | 2010-10-29 | 2015-09-23 | Pfizer Inc | Inhibidores de N1/N2-lactama acetil-CoA carboxilasa |
-
2011
- 2011-10-18 ES ES11784783.0T patent/ES2546465T3/es active Active
- 2011-10-18 AU AU2011322117A patent/AU2011322117B2/en not_active Ceased
- 2011-10-18 EP EP15164071.1A patent/EP2952514A1/en not_active Withdrawn
- 2011-10-18 CN CN201510087893.2A patent/CN104774205A/zh active Pending
- 2011-10-18 CN CN201180052416.2A patent/CN103189377B/zh not_active Expired - Fee Related
- 2011-10-18 SG SG2013027446A patent/SG189883A1/en unknown
- 2011-10-18 EP EP11784783.0A patent/EP2632925B1/en not_active Not-in-force
- 2011-10-18 PL PL11784783T patent/PL2632925T3/pl unknown
- 2011-10-18 KR KR1020137013652A patent/KR101529404B1/ko not_active Expired - Fee Related
- 2011-10-18 BR BR112013010310A patent/BR112013010310A2/pt not_active IP Right Cessation
- 2011-10-18 KR KR20147036653A patent/KR20150006899A/ko not_active Withdrawn
- 2011-10-18 RU RU2013116924/04A patent/RU2540337C2/ru not_active IP Right Cessation
- 2011-10-18 CA CA2815169A patent/CA2815169C/en not_active Expired - Fee Related
- 2011-10-18 HU HUE11784783A patent/HUE025078T2/en unknown
- 2011-10-18 PT PT117847830T patent/PT2632925E/pt unknown
- 2011-10-18 WO PCT/IB2011/054643 patent/WO2012056372A1/en not_active Ceased
- 2011-10-18 NZ NZ609527A patent/NZ609527A/en not_active IP Right Cessation
- 2011-10-18 SI SI201130519T patent/SI2632925T1/sl unknown
- 2011-10-18 MX MX2013004733A patent/MX2013004733A/es unknown
- 2011-10-18 DK DK11784783.0T patent/DK2632925T3/en active
- 2011-10-18 JP JP2013535549A patent/JP5647356B2/ja not_active Expired - Fee Related
- 2011-10-26 TW TW100138909A patent/TWI441823B/zh not_active IP Right Cessation
- 2011-10-26 TW TW103102453A patent/TWI507406B/zh not_active IP Right Cessation
- 2011-10-26 TW TW104115757A patent/TW201531472A/zh unknown
- 2011-10-27 US US13/282,964 patent/US8859773B2/en active Active
- 2011-10-27 AR ARP110103976A patent/AR083578A1/es unknown
- 2011-10-28 UY UY0001033694A patent/UY33694A/es not_active Application Discontinuation
-
2013
- 2013-04-15 IL IL225779A patent/IL225779A0/en unknown
- 2013-05-28 ZA ZA2013/03882A patent/ZA201303882B/en unknown
-
2014
- 2014-09-26 US US14/497,396 patent/US8993586B2/en active Active
- 2014-11-05 JP JP2014225021A patent/JP2015057416A/ja not_active Withdrawn
-
2015
- 2015-02-13 US US14/621,723 patent/US9181252B2/en active Active
- 2015-06-12 CY CY20151100518T patent/CY1116405T1/el unknown
- 2015-10-22 HK HK15110405.1A patent/HK1209733A1/xx unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015057416A (ja) * | 2010-10-29 | 2015-03-26 | ファイザー・インク | Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5647356B2 (ja) | Ｎ１／Ｎ２−ラクタムアセチル−ＣｏＡカルボキシラーゼ阻害剤 | |
| JP5657174B2 (ja) | アセチルＣｏＡカルボキシラーゼ阻害剤として使用するためのピラゾロスピロケトン誘導体 | |
| OA16631A (en) | Pyrazolospiroketone derivatives for use as ACETYL-COA Carboxylase inhibitors | |
| HK1186724B (en) | N1/n2-lactam acetyl-coa carboxylase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131205 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131205 |
|
| TRDD | Decision of grant or rejection written | ||
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20141016 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20141020 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20141106 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5647356 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |