JP7461104B2 - Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 - Google Patents
Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 Download PDFInfo
- Publication number
- JP7461104B2 JP7461104B2 JP2018223465A JP2018223465A JP7461104B2 JP 7461104 B2 JP7461104 B2 JP 7461104B2 JP 2018223465 A JP2018223465 A JP 2018223465A JP 2018223465 A JP2018223465 A JP 2018223465A JP 7461104 B2 JP7461104 B2 JP 7461104B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- alkyl
- minutes
- independently selected
- mmol
- 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.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 28
- 230000000694 effects Effects 0.000 title description 11
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 title description 8
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 title description 7
- 150000005229 pyrazolopyridines Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 566
- 125000000217 alkyl group Chemical group 0.000 claims description 208
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 81
- 125000005843 halogen group Chemical group 0.000 claims description 69
- 125000001424 substituent group Chemical group 0.000 claims description 67
- 125000000623 heterocyclic group Chemical group 0.000 claims description 55
- 125000003545 alkoxy group Chemical group 0.000 claims description 46
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 35
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000006647 (C3-C15) cycloalkyl group Chemical group 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 208000008589 Obesity Diseases 0.000 claims description 10
- 235000020824 obesity Nutrition 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical group C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 claims 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 303
- 230000014759 maintenance of location Effects 0.000 description 162
- 238000004458 analytical method Methods 0.000 description 158
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
- 238000004949 mass spectrometry Methods 0.000 description 148
- 239000003153 chemical reaction reagent Substances 0.000 description 132
- 239000000243 solution Substances 0.000 description 121
- -1 3,3,3-trifluoropropyl Chemical group 0.000 description 120
- 239000000203 mixture Substances 0.000 description 111
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
- 239000002904 solvent Substances 0.000 description 96
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 88
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 87
- 238000000034 method Methods 0.000 description 85
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 76
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
- 238000006243 chemical reaction Methods 0.000 description 62
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
- 230000002829 reductive effect Effects 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 238000003786 synthesis reaction Methods 0.000 description 54
- 230000015572 biosynthetic process Effects 0.000 description 52
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 48
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
- 239000013078 crystal Substances 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000002585 base Substances 0.000 description 42
- 150000003839 salts Chemical class 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 38
- 235000019253 formic acid Nutrition 0.000 description 38
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- 229940079593 drug Drugs 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 30
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 27
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 26
- 239000007787 solid Substances 0.000 description 26
- 230000035484 reaction time Effects 0.000 description 25
- 238000010898 silica gel chromatography Methods 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000002253 acid Substances 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-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
- 239000004210 ether based solvent Substances 0.000 description 19
- 238000001914 filtration Methods 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- 239000012453 solvate Substances 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 229960004132 diethyl ether Drugs 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 150000001408 amides Chemical class 0.000 description 16
- 229940125904 compound 1 Drugs 0.000 description 16
- 150000002366 halogen compounds Chemical class 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 230000008569 process Effects 0.000 description 15
- 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 14
- 108010011459 Exenatide Proteins 0.000 description 14
- 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 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 239000008103 glucose Substances 0.000 description 14
- 238000005259 measurement Methods 0.000 description 14
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 13
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 12
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 12
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical compound O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 12
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- ZQNPDAVSHFGLIQ-UHFFFAOYSA-N calcium;hydrate Chemical compound O.[Ca] ZQNPDAVSHFGLIQ-UHFFFAOYSA-N 0.000 description 12
- 229960001519 exenatide Drugs 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- JYEVUDXCQHLXNG-UHFFFAOYSA-N tert-butyl pyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=CN=C1 JYEVUDXCQHLXNG-UHFFFAOYSA-N 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 11
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 11
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 10
- YJOQUFUSNSCGHN-UHFFFAOYSA-N 5-bromo-4-fluoro-1h-indazole Chemical compound FC1=C(Br)C=CC2=C1C=NN2 YJOQUFUSNSCGHN-UHFFFAOYSA-N 0.000 description 10
- UFKQUKNNNCABIH-ZIDLFYJRSA-N C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(Br)ccc12)C(O)=O Chemical compound C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(Br)ccc12)C(O)=O UFKQUKNNNCABIH-ZIDLFYJRSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 235000011054 acetic acid Nutrition 0.000 description 10
- 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 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 235000011181 potassium carbonates Nutrition 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 10
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 10
- FUZIXXDNICKCSP-KGLIPLIRSA-N (4S,6R)-2-(4-fluoro-3,5-dimethylphenyl)-4,6-dimethyl-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbaldehyde Chemical compound FC1=C(C=C(C=C1C)N1N=C2C([C@@H](N([C@@H](C2)C)C=O)C)=C1N1C(NC=C1)=O)C FUZIXXDNICKCSP-KGLIPLIRSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 9
- 150000004703 alkoxides Chemical class 0.000 description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 9
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 9
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 9
- 150000003512 tertiary amines Chemical class 0.000 description 9
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 8
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
- 229910000024 caesium carbonate Inorganic materials 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 230000037406 food intake Effects 0.000 description 8
- 235000012631 food intake Nutrition 0.000 description 8
- 229910052987 metal hydride Inorganic materials 0.000 description 8
- 150000004681 metal hydrides Chemical class 0.000 description 8
- 229940098779 methanesulfonic acid Drugs 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 8
- 229910000105 potassium hydride Inorganic materials 0.000 description 8
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000000634 powder X-ray diffraction Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- 206010012289 Dementia Diseases 0.000 description 7
- 241000282567 Macaca fascicularis Species 0.000 description 7
- 239000005456 alcohol based solvent Substances 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 6
- PPZIXNHXYHACGY-UHFFFAOYSA-N 5-bromo-1-(2-methoxyethyl)indazole Chemical compound BrC1=CC=C2N(CCOC)N=CC2=C1 PPZIXNHXYHACGY-UHFFFAOYSA-N 0.000 description 6
- RMCHMXPTUMFFBZ-UHFFFAOYSA-N 5-bromo-1-methylindazole Chemical compound BrC1=CC=C2N(C)N=CC2=C1 RMCHMXPTUMFFBZ-UHFFFAOYSA-N 0.000 description 6
- ANLXRMBQONDZBQ-UHFFFAOYSA-N 5-bromo-4-fluoro-1-methylindazole Chemical compound BrC1=CC=C2N(C)N=CC2=C1F ANLXRMBQONDZBQ-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 239000012973 diazabicyclooctane Substances 0.000 description 6
- 238000004455 differential thermal analysis Methods 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 150000002430 hydrocarbons Chemical class 0.000 description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
- 230000003914 insulin secretion Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- QPDJILZPDAMLFH-UHFFFAOYSA-N lithium;2-methylbutan-2-olate Chemical compound [Li]OC(C)(C)CC QPDJILZPDAMLFH-UHFFFAOYSA-N 0.000 description 6
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 235000017550 sodium carbonate Nutrition 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000004808 supercritical fluid chromatography Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 238000002411 thermogravimetry Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 5
- PVROXABUTLQXRX-UHFFFAOYSA-N 1-[2-(4-fluoro-3,5-dimethylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(1-methylindazol-5-yl)imidazol-2-one hydrochloride Chemical compound Cl.Cc1cc(cc(C)c1F)-n1nc2CCNCc2c1-n1ccn(-c2ccc3n(C)ncc3c2)c1=O PVROXABUTLQXRX-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- QMIGRBUPMKCTCV-UHFFFAOYSA-N 2-(4-bromo-2-methoxyphenoxy)-2-methylpropan-1-ol Chemical compound BrC1=CC(=C(OC(CO)(C)C)C=C1)OC QMIGRBUPMKCTCV-UHFFFAOYSA-N 0.000 description 5
- VTKOAUFJGFMTQK-VWXFXROWSA-N 3-[(1S,2S)-1-[2-[(4S,6R)-2-(4-fluoro-3,5-dimethylphenyl)-4,6-dimethyl-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)C1CCOCC1)C(=O)N1[C@H](C)CC2=NN(C(N3C=CN(C3=O)C3=CC4=C(C=C3)N(C)N=C4)=C2[C@@H]1C)C1=CC(C)=C(F)C(C)=C1)C1=NOC(=O)N1 VTKOAUFJGFMTQK-VWXFXROWSA-N 0.000 description 5
- MWVKLRSIDOXBSE-UHFFFAOYSA-N 5-(1-piperidin-4-ylpyrazol-4-yl)-3-(6-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound NC1=NC=C(C2=CN(N=C2)C2CCNCC2)C=C1C(OC1=C2)=NC1=CC=C2N1CCCC1 MWVKLRSIDOXBSE-UHFFFAOYSA-N 0.000 description 5
- VWANSYGDVGYGTG-RGDDPNHNSA-N 5-[(4S)-2,2-dimethyloxan-4-yl]-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid Chemical compound CC1(OCC[C@@H](C1)C=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)O)C VWANSYGDVGYGTG-RGDDPNHNSA-N 0.000 description 5
- STVHMYNPQCLUNJ-UHFFFAOYSA-N 5-bromo-1h-indazole Chemical compound BrC1=CC=C2NN=CC2=C1 STVHMYNPQCLUNJ-UHFFFAOYSA-N 0.000 description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 5
- 208000002249 Diabetes Complications Diseases 0.000 description 5
- 206010012655 Diabetic complications Diseases 0.000 description 5
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 5
- 208000002705 Glucose Intolerance Diseases 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 5
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- YBFBENHWPRGUMU-UHFFFAOYSA-N chembl398496 Chemical compound OC(=O)C1=CC=CC=C1NC(=O)N1CCN(C=2N=C3C=CC(O)=CC3=NC=2)CC1 YBFBENHWPRGUMU-UHFFFAOYSA-N 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 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 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 201000001421 hyperglycemia Diseases 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 5
- 239000012046 mixed solvent Substances 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- 150000003460 sulfonic acids Chemical class 0.000 description 5
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 4
- LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 4
- COXVPYKZDDKVRF-ULQDDVLXSA-N (4,4-difluorocyclohexyl)methyl N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C[C@@H]1CCNC1=O)C=O)NC(=O)OCC2CCC(CC2)(F)F COXVPYKZDDKVRF-ULQDDVLXSA-N 0.000 description 4
- RXVUTTVDLRZXPI-KIYNQFGBSA-N (4S)-3-amino-2-(4-fluoro-3,5-dimethylphenyl)-4,6-dimethyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbaldehyde Chemical compound NC=1N(N=C2C=1[C@@H](N(C(C2)C)C=O)C)C1=CC(=C(C(=C1)C)F)C RXVUTTVDLRZXPI-KIYNQFGBSA-N 0.000 description 4
- GXQPCEBJSKTLMS-MLWJPKLSSA-N (6S)-1-formyl-4-hydroxy-2,6-dimethyl-3,6-dihydro-2H-pyridine-5-carbonitrile Chemical compound C(=O)N1C(CC(=C([C@@H]1C)C#N)O)C GXQPCEBJSKTLMS-MLWJPKLSSA-N 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 4
- QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 4
- NNBUKAPOVBEMNI-UHFFFAOYSA-N 1,2-dichloro-1-ethoxyethane Chemical compound CCOC(Cl)CCl NNBUKAPOVBEMNI-UHFFFAOYSA-N 0.000 description 4
- FBRKXKRNZGUFMU-UHFFFAOYSA-N 1-(5-bromo-4-fluoroindazol-1-yl)-2-methylpropan-2-ol Chemical compound CC(C)(O)Cn1ncc2c(F)c(Br)ccc12 FBRKXKRNZGUFMU-UHFFFAOYSA-N 0.000 description 4
- XWHYJFBCSSJIQV-IBGZPJMESA-N 1-(cyanomethyl)-5-[(4S)-2,2-dimethyloxan-4-yl]-N-methyl-N-phenylindole-2-carboxamide Chemical compound CN(C(=O)c1cc2cc(ccc2n1CC#N)[C@H]1CCOC(C)(C)C1)c1ccccc1 XWHYJFBCSSJIQV-IBGZPJMESA-N 0.000 description 4
- SIHRUEQWCINRBY-YHNPMGDBSA-N 1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-N-methyl-5-[(2S,4S)-2-methyloxan-4-yl]-N-phenylindole-2-carboxamide Chemical compound C(#N)[C@]1([C@H](C1)C)N1C(=CC2=CC(=CC=C12)[C@@H]1C[C@@H](OCC1)C)C(=O)N(C1=CC=CC=C1)C SIHRUEQWCINRBY-YHNPMGDBSA-N 0.000 description 4
- FUSLOTQXBYHKLX-LMOVPXPDSA-N 1-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(1-methylindazol-5-yl)imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1ccn(-c2ccc3n(C)ncc3c2)c1=O)-c1cc(C)c(F)c(C)c1 FUSLOTQXBYHKLX-LMOVPXPDSA-N 0.000 description 4
- LYGOKCKPKHGGBQ-MSOLQXFVSA-N 1-[(4S,6R)-2-(4-fluoro-3,5-dimethylphenyl)-4,6-dimethyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(1-methylindazol-5-yl)imidazol-2-one Chemical compound FC1=C(C=C(C=C1C)N1N=C2C([C@@H](N[C@@H](C2)C)C)=C1N1C(N(C=C1)C=1C=C2C=NN(C2=CC=1)C)=O)C LYGOKCKPKHGGBQ-MSOLQXFVSA-N 0.000 description 4
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 4
- GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 4
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 4
- VBUXOCUATMPPBW-UHFFFAOYSA-N 2-ethyl-4-iodooxane Chemical compound CCC1CC(I)CCO1 VBUXOCUATMPPBW-UHFFFAOYSA-N 0.000 description 4
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 4
- OUUPXDOFQQOKSS-WQCZWTJXSA-N 3-[(1S,2S)-1-[5-[(4S)-2,2-dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3-methylphenyl)-4-methyl-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)[C@H]1CCOC(C)(C)C1)C(=O)N1CCC2=NN(C(N3C=CNC3=O)=C2[C@@H]1C)C1=CC(C)=C(F)C=C1)C1=NOC(=O)N1 OUUPXDOFQQOKSS-WQCZWTJXSA-N 0.000 description 4
- KNSVGVNCRWCSPL-YDALLXLXSA-N 3-[(4S)-2-(4-chloro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-1H-imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1cc[nH]c1=O)-c1cc(C)c(Cl)c(C)c1 KNSVGVNCRWCSPL-YDALLXLXSA-N 0.000 description 4
- MJGYKJQUYGQZEB-MERQFXBCSA-N 3-[(4S)-2-(4-fluoro-3-methylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-1H-imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1cc[nH]c1=O)-c1ccc(F)c(C)c1 MJGYKJQUYGQZEB-MERQFXBCSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- ZAJBYTSUTBCMRM-UHFFFAOYSA-N 5-(2-methylpyrazol-3-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxylic acid Chemical compound CN1N=CC=C1C1CC(C(C(O)=O)=NN2)=C2C1 ZAJBYTSUTBCMRM-UHFFFAOYSA-N 0.000 description 4
- NVBMOQKLLRKTRD-NSHDSACASA-N 5-[(4S)-2,2-dimethyloxan-4-yl]-1H-indole-2-carboxylic acid Chemical compound CC1(C)C[C@H](CCO1)c1ccc2[nH]c(cc2c1)C(O)=O NVBMOQKLLRKTRD-NSHDSACASA-N 0.000 description 4
- SIYHUHPATYQMMF-YSDGCRRSSA-N 5-[(4S)-2,2-dimethyloxan-4-yl]-N-methyl-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]-N-phenylindole-2-carboxamide Chemical compound CC1(OCC[C@@H](C1)C=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)N(C1=CC=CC=C1)C)C SIYHUHPATYQMMF-YSDGCRRSSA-N 0.000 description 4
- QVAFKQGZWRFOAC-KRWDZBQOSA-N 5-[(4S)-2,2-dimethyloxan-4-yl]-N-methyl-N-phenyl-1H-indole-2-carboxamide Chemical compound CC1(OCC[C@@H](C1)C=1C=C2C=C(NC2=CC=1)C(=O)N(C1=CC=CC=C1)C)C QVAFKQGZWRFOAC-KRWDZBQOSA-N 0.000 description 4
- WIGMOFXYYNJVQN-UHFFFAOYSA-N 5-bromo-6-fluoro-1-(2-methoxyethyl)indazole Chemical compound COCCn1ncc2cc(Br)c(F)cc12 WIGMOFXYYNJVQN-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- VBGRFQHKVHPDGR-SAHAZLINSA-N COc1nccc(c1C)-c1ccc2n(c(cc2c1)C(O)=O)[C@]1(C[C@@H]1C)c1nc(=O)o[nH]1 Chemical compound COc1nccc(c1C)-c1ccc2n(c(cc2c1)C(O)=O)[C@]1(C[C@@H]1C)c1nc(=O)o[nH]1 VBGRFQHKVHPDGR-SAHAZLINSA-N 0.000 description 4
- QBXVXKRWOVBUDB-GRKNLSHJSA-N ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C Chemical compound ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C QBXVXKRWOVBUDB-GRKNLSHJSA-N 0.000 description 4
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 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 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 4
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 4
- 229940092714 benzenesulfonic acid Drugs 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 229960004365 benzoic acid Drugs 0.000 description 4
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 4
- 150000001639 boron compounds Chemical class 0.000 description 4
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 4
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 4
- 159000000007 calcium salts Chemical class 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 229960001701 chloroform Drugs 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 4
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 4
- WCBCWHOAEMVMNJ-INTFFVIUSA-N ethyl (E)-3-[[(2S)-1-cyanopropan-2-yl]amino]but-2-enoate Chemical compound CCOC(=O)\C=C(/C)N[C@@H](C)CC#N WCBCWHOAEMVMNJ-INTFFVIUSA-N 0.000 description 4
- VGDGLTWAPMWKOD-IENPIDJESA-N ethyl 3-[[(2S)-1-cyanopropan-2-yl]amino]butanoate Chemical compound C(#N)C[C@H](C)NC(CC(=O)OCC)C VGDGLTWAPMWKOD-IENPIDJESA-N 0.000 description 4
- ZXYNOALDDLZUJI-UHFFFAOYSA-N ethyl 5-(2,2-dimethyloxan-4-yl)-1H-indole-2-carboxylate Chemical compound CCOC(=O)c1cc2cc(ccc2[nH]1)C1CCOC(C)(C)C1 ZXYNOALDDLZUJI-UHFFFAOYSA-N 0.000 description 4
- ZXYNOALDDLZUJI-ZDUSSCGKSA-N ethyl 5-[(4S)-2,2-dimethyloxan-4-yl]-1H-indole-2-carboxylate Chemical compound CC1(OCC[C@@H](C1)C=1C=C2C=C(NC2=CC=1)C(=O)OCC)C ZXYNOALDDLZUJI-ZDUSSCGKSA-N 0.000 description 4
- 239000001530 fumaric acid Substances 0.000 description 4
- 239000000174 gluconic acid Substances 0.000 description 4
- 235000012208 gluconic acid Nutrition 0.000 description 4
- 229950006191 gluconic acid Drugs 0.000 description 4
- 230000010030 glucose lowering effect Effects 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 4
- 229940071870 hydroiodic acid Drugs 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- QCAIHJCIFPDZIX-UHFFFAOYSA-M iodozinc(1+) 3,4,5,6-tetrahydro-2H-pyran-4-ide Chemical compound I[Zn+].C1COCC[CH-]1 QCAIHJCIFPDZIX-UHFFFAOYSA-M 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910000103 lithium hydride Inorganic materials 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- 239000001630 malic acid Substances 0.000 description 4
- 235000011090 malic acid Nutrition 0.000 description 4
- 229960002510 mandelic acid Drugs 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 235000006408 oxalic acid Nutrition 0.000 description 4
- 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 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 description 4
- 235000011009 potassium phosphates Nutrition 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 4
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical class O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
- 229960004889 salicylic acid Drugs 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 4
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- QWKYXWNTBHRWEI-OXCVABKISA-N (1S,2S)-2-ethyl-1-[2-[2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]cyclopropane-1-carbonitrile Chemical compound CC[C@H]1C[C@]1(C#N)N1C(=CC2=C1C=CC(=C2)C1CCOCC1)C(=O)N1CCC2=NN(C(N3C=CN(C3=O)C3=CC4=C(C=C3)N(C)N=C4)=C2C1)C1=CC(C)=C(F)C(C)=C1 QWKYXWNTBHRWEI-OXCVABKISA-N 0.000 description 3
- LAJAFFLJAJMYLK-CVOKMOJFSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[[(7s)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5h-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound N1([C@H]2CCC3=CC=C(C(=C3CC2)OC)NC=2N=C(C(=CN=2)Cl)N[C@H]2[C@H]([C@@]3([H])C[C@@]2(C=C3)[H])C(N)=O)CCOCC1 LAJAFFLJAJMYLK-CVOKMOJFSA-N 0.000 description 3
- DIXMBHMNEHPFCX-MCMMXHMISA-N (2r)-2-[5-[6-amino-5-[(1r)-1-[5-fluoro-2-(triazol-2-yl)phenyl]ethoxy]pyridin-3-yl]-4-methyl-1,3-thiazol-2-yl]propane-1,2-diol Chemical compound O([C@H](C)C=1C(=CC=C(F)C=1)N1N=CC=N1)C(C(=NC=1)N)=CC=1C=1SC([C@](C)(O)CO)=NC=1C DIXMBHMNEHPFCX-MCMMXHMISA-N 0.000 description 3
- NGMUFGQLFKCUCT-UHFFFAOYSA-N (4-fluoro-3-methylphenyl)hydrazine;hydrochloride Chemical compound Cl.CC1=CC(NN)=CC=C1F NGMUFGQLFKCUCT-UHFFFAOYSA-N 0.000 description 3
- RXNPEQZHMGFNAY-GEALJGNFSA-N (5R)-4-[(1S,6R)-5-[(2S)-2-(4-chlorophenyl)-3-(propan-2-ylamino)propanoyl]-2,5-diazabicyclo[4.1.0]heptan-2-yl]-5-methyl-6,8-dihydro-5H-pyrido[2,3-d]pyrimidin-7-one Chemical compound C[C@@H]1CC(=O)NC2=C1C(=NC=N2)N3CCN([C@H]4[C@@H]3C4)C(=O)[C@H](CNC(C)C)C5=CC=C(C=C5)Cl RXNPEQZHMGFNAY-GEALJGNFSA-N 0.000 description 3
- VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 3
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 3
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 3
- SLWFBRYPJMNQBQ-NTISSMGPSA-N 1-(4-chloro-1-methylindazol-5-yl)-3-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1ccn(-c2ccc3n(C)ncc3c2Cl)c1=O)-c1cc(C)c(F)c(C)c1 SLWFBRYPJMNQBQ-NTISSMGPSA-N 0.000 description 3
- OGYKZGYLOZJXTL-RSAXXLAASA-N 1-(4-fluoro-1-methylindazol-5-yl)-3-[(4S)-2-(4-fluoro-3-methylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1ccn(-c2ccc3n(C)ncc3c2F)c1=O)-c1ccc(F)c(C)c1 OGYKZGYLOZJXTL-RSAXXLAASA-N 0.000 description 3
- HKDZDEGPQNCOPX-UHFFFAOYSA-N 1-(5-bromoindazol-1-yl)-2-methylpropan-2-ol Chemical compound BrC=1C=C2C=NN(C2=CC=1)CC(C)(O)C HKDZDEGPQNCOPX-UHFFFAOYSA-N 0.000 description 3
- WUARECJMJFLEJP-LHXZUMEBSA-N 1-[(1S,2S)-1-cyano-2-(phenylmethoxymethyl)cyclopropyl]-N-methyl-5-(oxan-4-yl)-N-phenylindole-2-carboxamide Chemical compound C(#N)[C@]1([C@H](C1)COCC1=CC=CC=C1)N1C(=CC2=CC(=CC=C12)C1CCOCC1)C(=O)N(C1=CC=CC=C1)C WUARECJMJFLEJP-LHXZUMEBSA-N 0.000 description 3
- QFJNSYYYXGTYFK-MRDQGFSESA-N 1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-7-fluoro-N-methyl-5-(oxan-4-yl)-N-phenylindole-2-carboxamide Chemical compound C(#N)[C@]1([C@H](C1)C)N1C(=CC2=CC(=CC(=C12)F)C1CCOCC1)C(=O)N(C1=CC=CC=C1)C QFJNSYYYXGTYFK-MRDQGFSESA-N 0.000 description 3
- BENHZNGOJPXMRZ-NTISSMGPSA-N 1-[(4S)-2-(4-chloro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(4-fluoro-1-methylindazol-5-yl)imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1ccn(-c2ccc3n(C)ncc3c2F)c1=O)-c1cc(C)c(Cl)c(C)c1 BENHZNGOJPXMRZ-NTISSMGPSA-N 0.000 description 3
- CYNJUSZQVYYUMX-NTISSMGPSA-N 1-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(4-fluoro-1-methylindazol-5-yl)imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1ccn(-c2ccc3n(C)ncc3c2F)c1=O)-c1cc(C)c(F)c(C)c1 CYNJUSZQVYYUMX-NTISSMGPSA-N 0.000 description 3
- LLCSAMJBFZDJNS-NTISSMGPSA-N 1-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(6-fluoro-1-methylindazol-5-yl)imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1ccn(-c2cc3cnn(C)c3cc2F)c1=O)-c1cc(C)c(F)c(C)c1 LLCSAMJBFZDJNS-NTISSMGPSA-N 0.000 description 3
- UNJIVCIRJZRCBC-FYZYNONXSA-N 1-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-[1-(2-methoxyethyl)indazol-5-yl]imidazol-2-one hydrochloride Chemical compound Cl.COCCn1ncc2cc(ccc12)-n1ccn(-c2c3[C@H](C)NCCc3nn2-c2cc(C)c(F)c(C)c2)c1=O UNJIVCIRJZRCBC-FYZYNONXSA-N 0.000 description 3
- DZXWRVJYINAWPT-MGBOEYOKSA-N 1-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-[1-[(3R)-oxolan-3-yl]indazol-5-yl]imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1ccn(-c2ccc3n(ncc3c2)[C@@H]2CCOC2)c1=O)-c1cc(C)c(F)c(C)c1 DZXWRVJYINAWPT-MGBOEYOKSA-N 0.000 description 3
- IPVWNKNPFRWZFK-UHFFFAOYSA-N 1-[2-(3,5-dimethylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(1-methylindazol-5-yl)imidazol-2-one hydrochloride Chemical compound Cl.Cc1cc(C)cc(c1)-n1nc2CCNCc2c1-n1ccn(-c2ccc3n(C)ncc3c2)c1=O IPVWNKNPFRWZFK-UHFFFAOYSA-N 0.000 description 3
- VSHZLTTZMQMWOQ-UHFFFAOYSA-N 1-[2-(4-fluoro-3,5-dimethylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-[1-(2-methoxyethyl)indazol-5-yl]imidazol-2-one hydrochloride Chemical compound Cl.COCCn1ncc2cc(ccc12)-n1ccn(-c2c3CNCCc3nn2-c2cc(C)c(F)c(C)c2)c1=O VSHZLTTZMQMWOQ-UHFFFAOYSA-N 0.000 description 3
- GGMYBXITOPBWPM-UHFFFAOYSA-N 1-[2-(4-fluoro-3-methylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-[1-(2-methoxyethyl)indazol-5-yl]imidazol-2-one hydrochloride Chemical compound Cl.COCCn1ncc2cc(ccc12)-n1ccn(-c2c3CNCCc3nn2-c2ccc(F)c(C)c2)c1=O GGMYBXITOPBWPM-UHFFFAOYSA-N 0.000 description 3
- RZFJBSIAXYEPBX-UHFFFAOYSA-N 1-[4-[4-[2-[4-chloro-3-(diethylsulfamoyl)anilino]pyrimidin-4-yl]pyridin-2-yl]phenyl]-3-methylurea Chemical compound C1=C(Cl)C(S(=O)(=O)N(CC)CC)=CC(NC=2N=C(C=CN=2)C=2C=C(N=CC=2)C=2C=CC(NC(=O)NC)=CC=2)=C1 RZFJBSIAXYEPBX-UHFFFAOYSA-N 0.000 description 3
- YKYWUHHZZRBGMG-JWTNVVGKSA-N 1-methyl-2-[[(1r,5s)-6-[[5-(trifluoromethyl)pyridin-2-yl]methoxymethyl]-3-azabicyclo[3.1.0]hexan-3-yl]methyl]benzimidazole Chemical compound C1([C@@H]2CN(C[C@@H]21)CC=1N(C2=CC=CC=C2N=1)C)COCC1=CC=C(C(F)(F)F)C=N1 YKYWUHHZZRBGMG-JWTNVVGKSA-N 0.000 description 3
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 3
- IGUHGPFIPCWMOW-UHFFFAOYSA-N 2-[2-[2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]acetonitrile Chemical compound FC1=C(C=C(C=C1C)N1N=C2C(CN(CC2)C(=O)C=2N(C3=CC=C(C=C3C=2)C2CCOCC2)CC#N)=C1N1C(N(C=C1)C=1C=C2C=NN(C2=CC=1)C)=O)C IGUHGPFIPCWMOW-UHFFFAOYSA-N 0.000 description 3
- PUCXFBWCMHPSOK-UHFFFAOYSA-N 2-[5-bromo-2-[2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]acetonitrile Chemical compound BrC=1C=C2C=C(N(C2=CC=1)CC#N)C(=O)N1CC=2C(CC1)=NN(C=2N1C(N(C=C1)C=1C=C2C=NN(C2=CC=1)C)=O)C1=CC(=C(C(=C1)C)F)C PUCXFBWCMHPSOK-UHFFFAOYSA-N 0.000 description 3
- AOZIFBBEWMJJLA-ZVQVHKEOSA-N 3-[(1S,2S)-1-[2-[(4S)-2-(4-chloro-3,5-dimethylphenyl)-4-methyl-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)C1CCOCC1)C(=O)N1CCC2=NN(C(N3C=CNC3=O)=C2[C@@H]1C)C1=CC(C)=C(Cl)C(C)=C1)C1=NOC(=O)N1 AOZIFBBEWMJJLA-ZVQVHKEOSA-N 0.000 description 3
- WKUDYTXNUOIHFH-RLCYQMSFSA-N 3-[(1S,2S)-1-[2-[(4S)-2-(4-fluoro-3-methylphenyl)-4-methyl-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)C1CCOCC1)C(=O)N1CCC2=NN(C(N3C=CNC3=O)=C2[C@@H]1C)C1=CC(C)=C(F)C=C1)C1=NOC(=O)N1 WKUDYTXNUOIHFH-RLCYQMSFSA-N 0.000 description 3
- IYVJYLLEPOHZIO-QGNNRMROSA-N 3-[(1S,2S)-2-ethyl-1-[2-[2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]cyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound CC[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)C1CCOCC1)C(=O)N1CCC2=NN(C(N3C=CN(C3=O)C3=CC4=C(C=C3)N(C)N=C4)=C2C1)C1=CC(C)=C(F)C(C)=C1)C1=NOC(=O)N1 IYVJYLLEPOHZIO-QGNNRMROSA-N 0.000 description 3
- JOFDSYLCZIHGGO-UHFFFAOYSA-N 4-[(4-cyclohexylphenyl)methyl-[2-[[5-(dimethylamino)naphthalen-1-yl]sulfonyl-methylamino]acetyl]amino]-2-hydroxybenzoic acid Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)N(C)CC(=O)N(C=1C=C(O)C(C(O)=O)=CC=1)CC(C=C1)=CC=C1C1CCCCC1 JOFDSYLCZIHGGO-UHFFFAOYSA-N 0.000 description 3
- OPTBGIHMIPQQPP-JEILFUBRSA-N 5-[(2S,4S)-2-methyloxan-4-yl]-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid Chemical compound C[C@@H]1OCC[C@@H](C1)C=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)O OPTBGIHMIPQQPP-JEILFUBRSA-N 0.000 description 3
- SUCHZMRFZHLFFM-UHFFFAOYSA-N 5-bromo-1-(cyanomethyl)-6-fluoro-N-methyl-N-phenylindole-2-carboxamide Chemical compound BrC=1C=C2C=C(N(C2=CC=1F)CC#N)C(=O)N(C1=CC=CC=C1)C SUCHZMRFZHLFFM-UHFFFAOYSA-N 0.000 description 3
- WBJPKIRTYZWARV-UHFFFAOYSA-N 5-bromo-1-(cyanomethyl)-7-fluoro-N-methyl-N-phenylindole-2-carboxamide Chemical compound CN(C(=O)c1cc2cc(Br)cc(F)c2n1CC#N)c1ccccc1 WBJPKIRTYZWARV-UHFFFAOYSA-N 0.000 description 3
- LQQCCBUQQFXNLG-SKCUWOTOSA-N 5-bromo-1-[(1S,2S)-1-cyano-2-(phenylmethoxymethyl)cyclopropyl]-N-methyl-N-phenylindole-2-carboxamide Chemical compound CN(C(=O)c1cc2cc(Br)ccc2n1[C@]1(C[C@@H]1COCc1ccccc1)C#N)c1ccccc1 LQQCCBUQQFXNLG-SKCUWOTOSA-N 0.000 description 3
- MLCMYSGPQLGFPA-YEJXKQKISA-N 5-bromo-1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-6-fluoro-N-methyl-N-phenylindole-2-carboxamide Chemical compound C[C@H]1C[C@]1(C#N)n1c(cc2cc(Br)c(F)cc12)C(=O)N(C)c1ccccc1 MLCMYSGPQLGFPA-YEJXKQKISA-N 0.000 description 3
- ROCFKCXNLNNABH-YEJXKQKISA-N 5-bromo-1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-7-fluoro-N-methyl-N-phenylindole-2-carboxamide Chemical compound C[C@H]1C[C@]1(C#N)n1c(cc2cc(Br)cc(F)c12)C(=O)N(C)c1ccccc1 ROCFKCXNLNNABH-YEJXKQKISA-N 0.000 description 3
- PEQIDIVDXMAUIF-XHLQUELWSA-N 5-bromo-6-fluoro-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid Chemical compound BrC=1C=C2C=C(N(C2=CC=1F)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)O PEQIDIVDXMAUIF-XHLQUELWSA-N 0.000 description 3
- QTOJJJWIZPCJFR-YTEVENLXSA-N 5-bromo-6-fluoro-N-methyl-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]-N-phenylindole-2-carboxamide Chemical compound BrC=1C=C2C=C(N(C2=CC=1F)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)N(C1=CC=CC=C1)C QTOJJJWIZPCJFR-YTEVENLXSA-N 0.000 description 3
- XGVQVCQEZLBLHW-UHFFFAOYSA-N 5-bromo-6-fluoro-N-methyl-N-phenyl-1H-indole-2-carboxamide Chemical compound BrC=1C=C2C=C(NC2=CC=1F)C(=O)N(C1=CC=CC=C1)C XGVQVCQEZLBLHW-UHFFFAOYSA-N 0.000 description 3
- XQSTXDXZVUABFH-UHFFFAOYSA-N 5-bromo-7-fluoro-N-methyl-N-phenyl-1H-indole-2-carboxamide Chemical compound CN(C(=O)c1cc2cc(Br)cc(F)c2[nH]1)c1ccccc1 XQSTXDXZVUABFH-UHFFFAOYSA-N 0.000 description 3
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 3
- NRYHNJVSZSFUQZ-OQRWROFFSA-N 7-fluoro-N-methyl-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]-5-(oxan-4-yl)-N-phenylindole-2-carboxamide Chemical compound FC=1C=C(C=C2C=C(N(C=12)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)N(C1=CC=CC=C1)C)C1CCOCC1 NRYHNJVSZSFUQZ-OQRWROFFSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- MCMSJVMUSBZUCN-UHFFFAOYSA-N 9,10-dimethoxy-3-methyl-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(N2C)=O)C1=CC2=NC1=C(C)C=C(C)C=C1C MCMSJVMUSBZUCN-UHFFFAOYSA-N 0.000 description 3
- VCUKKMIXURRDKL-UHFFFAOYSA-N 9-(dimethylamino)-3-(4-ethylphenyl)pyrido[1,2]thieno[3,4-d]pyrimidin-4-one Chemical compound C1=CC(CC)=CC=C1N1C(=O)C(SC=2C3=C(N(C)C)C=CN=2)=C3N=C1 VCUKKMIXURRDKL-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- SQYGBCHYORUWJG-UHFFFAOYSA-M C(C)C1OCCC(C1)[Zn]I Chemical compound C(C)C1OCCC(C1)[Zn]I SQYGBCHYORUWJG-UHFFFAOYSA-M 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 208000032928 Dyslipidaemia Diseases 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- UGAHVQJBQCTWTP-UHFFFAOYSA-M I[Zn]C1CCOC2(CCCC2)C1 Chemical compound I[Zn]C1CCOC2(CCCC2)C1 UGAHVQJBQCTWTP-UHFFFAOYSA-M 0.000 description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- COCIWCSHMFAFOL-YJNPBZNESA-N N-methyl-5-(oxan-4-yl)-1-[(1S,2S)-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)-2-(phenylmethoxymethyl)cyclopropyl]-N-phenylindole-2-carboxamide Chemical compound CN(C(=O)C=1N(C2=CC=C(C=C2C=1)C1CCOCC1)[C@@]1([C@H](C1)COCC1=CC=CC=C1)C1=NOC(N1)=O)C1=CC=CC=C1 COCIWCSHMFAFOL-YJNPBZNESA-N 0.000 description 3
- CSXLDQALGNFPOI-MRFCHNEFSA-N N-methyl-5-[(2S,4S)-2-methyloxan-4-yl]-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]-N-phenylindole-2-carboxamide Chemical compound CN(C(=O)C=1N(C2=CC=C(C=C2C=1)[C@@H]1C[C@@H](OCC1)C)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C1=CC=CC=C1 CSXLDQALGNFPOI-MRFCHNEFSA-N 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- KZVWEOXAPZXAFB-BQFCYCMXSA-N Temocaprilat Chemical compound C([C@H](N[C@H]1CS[C@@H](CN(C1=O)CC(=O)O)C=1SC=CC=1)C(O)=O)CC1=CC=CC=C1 KZVWEOXAPZXAFB-BQFCYCMXSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- BEXZJJQVPWJPOA-VOTSOKGWSA-N [(e)-hept-2-enyl] 6-methyl-4-(4-nitrophenyl)-2-oxo-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound CCCC\C=C\COC(=O)C1=C(C)NC(=O)NC1C1=CC=C([N+]([O-])=O)C=C1 BEXZJJQVPWJPOA-VOTSOKGWSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical group CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 description 3
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000003759 ester based solvent Substances 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- NFPUARSXIMWASK-GOEBONIOSA-N n-[(5r,7s)-2-(3-chlorophenyl)-1-oxa-3-azaspiro[4.5]dec-2-en-7-yl]acetamide Chemical compound C1[C@@H](NC(=O)C)CCC[C@@]11OC(C=2C=C(Cl)C=CC=2)=NC1 NFPUARSXIMWASK-GOEBONIOSA-N 0.000 description 3
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 3
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 150000002941 palladium compounds Chemical class 0.000 description 3
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 201000009104 prediabetes syndrome Diseases 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
- TZSZZENYCISATO-WIOPSUGQSA-N rodatristat Chemical compound CCOC(=O)[C@@H]1CC2(CN1)CCN(CC2)c1cc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)nc(N)n1 TZSZZENYCISATO-WIOPSUGQSA-N 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- KQYZJADWZIJORB-IBGZPJMESA-N tert-butyl (4S)-3-[3-(4-chloro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound ClC1=C2C=NN(C2=CC=C1N1C(N(C=C1)C=1N(N=C2C=1[C@@H](N(CC2)C(=O)OC(C)(C)C)C)C1=CC(=C(C(=C1)C)F)C)=O)C KQYZJADWZIJORB-IBGZPJMESA-N 0.000 description 3
- BPBSIGSERKFTHM-UHFFFAOYSA-N tert-butyl 3-(2,2-dimethoxyethylcarbamoylamino)-2-(4-fluoro-3-methylphenyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound COC(CNC(=O)Nc1c2CN(CCc2nn1-c1ccc(F)c(C)c1)C(=O)OC(C)(C)C)OC BPBSIGSERKFTHM-UHFFFAOYSA-N 0.000 description 3
- FNVXCXUKBNJCOF-UHFFFAOYSA-N tert-butyl 3-amino-2-(4-chloro-3,5-dimethylphenyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound Cc1cc(cc(C)c1Cl)-n1nc2CCN(Cc2c1N)C(=O)OC(C)(C)C FNVXCXUKBNJCOF-UHFFFAOYSA-N 0.000 description 3
- JASGESBSXBVBJI-UHFFFAOYSA-N tert-butyl 3-amino-2-(4-fluoro-3-methylphenyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound Cc1cc(ccc1F)-n1nc2CCN(Cc2c1N)C(=O)OC(C)(C)C JASGESBSXBVBJI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 2
- JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 2
- KSOVGRCOLZZTPF-QMKUDKLTSA-N (1s,2s,3r,4r)-3-[[5-fluoro-2-[3-methyl-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound N([C@H]1[C@H]([C@@]2([H])C[C@@]1(C=C2)[H])C(N)=O)C(C(=CN=1)F)=NC=1NC(C=C1C)=CC=C1N1CCN(C)CC1 KSOVGRCOLZZTPF-QMKUDKLTSA-N 0.000 description 2
- TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 description 2
- FOLCUFKJHSQMEL-BIXPGCQOSA-N (4-butylcyclohexyl) N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CCCCC1CCC(CC1)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)C=O FOLCUFKJHSQMEL-BIXPGCQOSA-N 0.000 description 2
- OPXRKRXGKCMCPJ-UHFFFAOYSA-N (4-fluoro-3,5-dimethylphenyl)hydrazine hydrochloride Chemical compound Cl.Cc1cc(NN)cc(C)c1F OPXRKRXGKCMCPJ-UHFFFAOYSA-N 0.000 description 2
- OQXNUCOGMMHHNA-GSVOUGTGSA-N (4r)-4-methyl-1,3,2-dioxathiolane 2,2-dioxide Chemical compound C[C@@H]1COS(=O)(=O)O1 OQXNUCOGMMHHNA-GSVOUGTGSA-N 0.000 description 2
- VPMIAOSOTOODMY-KJAPKAAFSA-N (4r)-6-[(e)-2-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1/C=C/C=1C(C(C)C)=NC(C(C)(C)C)=CC=1C1=CC=C(F)C=C1 VPMIAOSOTOODMY-KJAPKAAFSA-N 0.000 description 2
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 2
- VJGLCJCAZHSURI-GDVGLLTNSA-N (6S)-4-hydroxy-2,6-dimethyl-1,2,3,6-tetrahydropyridine-5-carbonitrile Chemical compound OC=1CC(N[C@H](C=1C#N)C)C VJGLCJCAZHSURI-GDVGLLTNSA-N 0.000 description 2
- QBTROWHSMGZXCV-RQURQNPSSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecoxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OCCCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 QBTROWHSMGZXCV-RQURQNPSSA-N 0.000 description 2
- UXKLQDCALAWFIU-VKNDCNMPSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-tetradecoxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCCCC)C1=CC=CC=C1 UXKLQDCALAWFIU-VKNDCNMPSA-N 0.000 description 2
- QPAGOTNPJABYCP-FITNPZAZSA-N (E)-N-(oxan-4-yl)-N'-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]but-2-ene-1,4-diamine Chemical compound O1CCC(CC1)NC\C=C\CN([C@H]1CCCC=2C=CC=NC1=2)C[C@@H]1NCC2=CC=CC=C2C1 QPAGOTNPJABYCP-FITNPZAZSA-N 0.000 description 2
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 2
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 2
- BHGVXSLDRULBMP-UHFFFAOYSA-N 1,1-dimethyl-3,4-dihydroisochromen-6-ol Chemical compound OC1=CC=C2C(C)(C)OCCC2=C1 BHGVXSLDRULBMP-UHFFFAOYSA-N 0.000 description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- GUTQVMVQYHUONV-FERBBOLQSA-N 1-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-[6-fluoro-1-(2-methoxyethyl)indazol-5-yl]imidazol-2-one hydrochloride Chemical compound Cl.COCCn1ncc2cc(c(F)cc12)-n1ccn(-c2c3[C@H](C)NCCc3nn2-c2cc(C)c(F)c(C)c2)c1=O GUTQVMVQYHUONV-FERBBOLQSA-N 0.000 description 2
- CLMZRJHCUITLDE-UHFFFAOYSA-N 1-[2-(4-chloro-3,5-dimethylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-3-(1-methylindazol-5-yl)imidazol-2-one hydrochloride Chemical compound Cl.Cc1cc(cc(C)c1Cl)-n1nc2CCNCc2c1-n1ccn(-c2ccc3n(C)ncc3c2)c1=O CLMZRJHCUITLDE-UHFFFAOYSA-N 0.000 description 2
- OXTVBHDILDPYAS-UHFFFAOYSA-N 1-[4-(aminomethyl)-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OCCCO)=C1 OXTVBHDILDPYAS-UHFFFAOYSA-N 0.000 description 2
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 description 2
- RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 2
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-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
- WGABOZPQOOZAOI-UHFFFAOYSA-N 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenyl]acetic acid Chemical compound COC1=C(C)C(OC)=CC(C(=O)N(CCCC=2C=CC=CC=2)CC=2C=CC(CC(O)=O)=CC=2)=C1 WGABOZPQOOZAOI-UHFFFAOYSA-N 0.000 description 2
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 2
- AZYIQXXXHJVWPP-FMDKGDDJSA-N 3-[(1S,2R)-1-[2-[2-(3,5-dimethylphenyl)-3-[3-(1-methylindol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(2-ethyl-3-methylpyridin-4-yl)indol-1-yl]-2-methylcyclopropyl]-1,2,4-oxadiazolidin-5-one Chemical compound CCC1=NC=CC(=C1C)C2=CC3=C(C=C2)N(C(=C3)C(=O)N4CCC5=NN(C(=C5C4)N6C=CN(C6=O)C7=CC8=C(C=C7)N(C=C8)C)C9=CC(=CC(=C9)C)C)[C@]1(C[C@H]1C)C1NC(=O)ON1 AZYIQXXXHJVWPP-FMDKGDDJSA-N 0.000 description 2
- QGFLVPUBAFPBSC-OBOUGVCCSA-N 3-[(1S,2S)-1-[2-[(4S)-2-(4-chloro-3,5-dimethylphenyl)-4-methyl-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-[(4S)-2,2-dimethyloxan-4-yl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)[C@H]1CCOC(C)(C)C1)C(=O)N1CCC2=NN(C(N3C=CNC3=O)=C2[C@@H]1C)C1=CC(C)=C(Cl)C(C)=C1)C1=NOC(=O)N1 QGFLVPUBAFPBSC-OBOUGVCCSA-N 0.000 description 2
- GXZASPJFMICQEV-QSSUKDSPSA-N 3-[(1S,2S)-1-[2-[2-(4-fluoro-3,5-dimethylphenyl)-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound FC1=C(C=C(C=C1C)N1N=C2C(CN(CC2)C(=O)C=2N(C3=CC=C(C=C3C=2)C2CCOCC2)[C@@]2([C@H](C2)C)C2=NOC(N2)=O)=C1N1C(NC=C1)=O)C GXZASPJFMICQEV-QSSUKDSPSA-N 0.000 description 2
- SWHPWNTVABTLTA-VVKXFPHTSA-N 3-[(1S,2S)-1-[6-fluoro-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(2-methoxy-3-methylpyridin-4-yl)indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound COC1=NC=CC(=C1C)C1=CC2=C(C=C1F)N(C(=C2)C(=O)N1CCC2=NN(C(N3C=CN(C3=O)C3=CC4=C(C=C3)N(C)N=C4)=C2[C@@H]1C)C1=CC(C)=C(F)C(C)=C1)[C@]1(C[C@@H]1C)C1=NOC(=O)N1 SWHPWNTVABTLTA-VVKXFPHTSA-N 0.000 description 2
- MWDVCHRYCKXEBY-LBPRGKRZSA-N 3-chloro-n-[2-oxo-2-[[(1s)-1-phenylethyl]amino]ethyl]benzamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(Cl)=C1 MWDVCHRYCKXEBY-LBPRGKRZSA-N 0.000 description 2
- KLYSWDGMCLWRPE-UHFFFAOYSA-N 3-methyl-3-[(4-methylphenyl)sulfonylmethyl]oxetane Chemical compound C1=CC(C)=CC=C1S(=O)(=O)CC1(C)COC1 KLYSWDGMCLWRPE-UHFFFAOYSA-N 0.000 description 2
- BMTZEAOGFDXDAD-UHFFFAOYSA-M 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium;chloride Chemical compound [Cl-].COC1=NC(OC)=NC([N+]2(C)CCOCC2)=N1 BMTZEAOGFDXDAD-UHFFFAOYSA-M 0.000 description 2
- TXEBWPPWSVMYOA-UHFFFAOYSA-N 4-[3-[(1-amino-2-chloroethyl)amino]propyl]-1-[[3-(2-chlorophenyl)phenyl]methyl]-5-hydroxyimidazolidin-2-one Chemical compound NC(CCl)NCCCC1NC(=O)N(Cc2cccc(c2)-c2ccccc2Cl)C1O TXEBWPPWSVMYOA-UHFFFAOYSA-N 0.000 description 2
- PZLKEGBSIAXWTJ-UHFFFAOYSA-N 4-bromo-2-ethyl-3-methylpyridine Chemical compound BrC1=C(C(=NC=C1)CC)C PZLKEGBSIAXWTJ-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- WUMMUAHJMRIICX-UHFFFAOYSA-N 4-iodo-2-methoxy-3-methylpyridine Chemical compound COC1=NC=CC(I)=C1C WUMMUAHJMRIICX-UHFFFAOYSA-N 0.000 description 2
- TZKBVRDEOITLRB-UHFFFAOYSA-N 4-methyl-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1h-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2C=C3C=NNC3=NC=2)=C1 TZKBVRDEOITLRB-UHFFFAOYSA-N 0.000 description 2
- VCXMYDZODXDKLB-UHFFFAOYSA-N 5-bromo-1-(2-methoxyethyl)-3-methylbenzimidazol-2-one Chemical compound COCCn1c2ccc(Br)cc2n(C)c1=O VCXMYDZODXDKLB-UHFFFAOYSA-N 0.000 description 2
- SYYRSQYFVRJYCE-UHFFFAOYSA-N 5-bromo-1-(cyanomethyl)indole-2-carboxylic acid Chemical compound BrC1=CC=C2N(CC#N)C(C(=O)O)=CC2=C1 SYYRSQYFVRJYCE-UHFFFAOYSA-N 0.000 description 2
- RYOGAUDQNUQRBX-LHSJRXKWSA-N 5-bromo-1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-N-methyl-N-phenylindole-2-carboxamide Chemical compound C[C@H]1C[C@]1(C#N)n1c(cc2cc(Br)ccc12)C(=O)N(C)c1ccccc1 RYOGAUDQNUQRBX-LHSJRXKWSA-N 0.000 description 2
- KMEXBTKLSIXRGO-SNVBAGLBSA-N 5-bromo-1-[(3R)-oxolan-3-yl]indazole Chemical compound BrC=1C=C2C=NN(C2=CC=1)[C@H]1COCC1 KMEXBTKLSIXRGO-SNVBAGLBSA-N 0.000 description 2
- KMEXBTKLSIXRGO-JTQLQIEISA-N 5-bromo-1-[(3S)-oxolan-3-yl]indazole Chemical compound Brc1ccc2n(ncc2c1)[C@H]1CCOC1 KMEXBTKLSIXRGO-JTQLQIEISA-N 0.000 description 2
- UBQPNKNEHQDPEY-UHFFFAOYSA-N 5-bromo-4-chloro-1-methylindazole Chemical compound BrC1=CC=C2N(C)N=CC2=C1Cl UBQPNKNEHQDPEY-UHFFFAOYSA-N 0.000 description 2
- IADLRNRWOINBNM-UHFFFAOYSA-N 5-bromo-4-fluoro-1-(2,2,2-trifluoroethyl)indazole Chemical compound BrC=1C(=C2C=NN(C2=CC=1)CC(F)(F)F)F IADLRNRWOINBNM-UHFFFAOYSA-N 0.000 description 2
- PKTCYYOWCRDDRU-UHFFFAOYSA-N 5-bromo-4-fluoro-1-[(3-methyloxetan-3-yl)methyl]indazole Chemical compound CC1(Cn2ncc3c(F)c(Br)ccc23)COC1 PKTCYYOWCRDDRU-UHFFFAOYSA-N 0.000 description 2
- LILHEKOPCWVHAA-UHFFFAOYSA-N 5-bromo-6-fluoro-1-methylindazole Chemical compound BrC1=C(F)C=C2N(C)N=CC2=C1 LILHEKOPCWVHAA-UHFFFAOYSA-N 0.000 description 2
- XCPAAORUBSZRLP-UHFFFAOYSA-N 5-bromo-6-fluoro-1h-indole-2-carboxylic acid Chemical compound BrC1=C(F)C=C2NC(C(=O)O)=CC2=C1 XCPAAORUBSZRLP-UHFFFAOYSA-N 0.000 description 2
- ZGJLWCKXUNHZMP-UHFFFAOYSA-N 5-bromo-7-fluoro-1h-indole-2-carboxylic acid Chemical compound BrC1=CC(F)=C2NC(C(=O)O)=CC2=C1 ZGJLWCKXUNHZMP-UHFFFAOYSA-N 0.000 description 2
- LMZMPMZLJZOQTI-UHFFFAOYSA-N 6-(4-bromo-2-methylphenyl)-N,N-dimethylpyrimidin-4-amine Chemical compound CN(C)c1cc(ncn1)-c1ccc(Br)cc1C LMZMPMZLJZOQTI-UHFFFAOYSA-N 0.000 description 2
- RRELDGDKULRRDM-UHFFFAOYSA-N 6-[2-chloro-4-nitro-5-(oxan-4-yloxy)anilino]-3,4-dihydro-1H-quinolin-2-one Chemical compound [O-][N+](=O)c1cc(Cl)c(Nc2ccc3NC(=O)CCc3c2)cc1OC1CCOCC1 RRELDGDKULRRDM-UHFFFAOYSA-N 0.000 description 2
- RXMAYPXTBQWALE-UHFFFAOYSA-N 6-bromo-1,1-dimethyl-3,4-dihydroisochromene Chemical compound BrC=1C=C2CCOC(C2=CC=1)(C)C RXMAYPXTBQWALE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LPWKFUVWWQYLOD-UHFFFAOYSA-N 9-(dimethylamino)-3-(4-methylphenyl)pyrido[2,3]thieno[2,4-d]pyrimidin-4-one Chemical compound C1=2C(N(C)C)=CN=CC=2SC(C2=O)=C1N=CN2C1=CC=C(C)C=C1 LPWKFUVWWQYLOD-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- DGJMHKMYSDYOFP-MRXNPFEDSA-N C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O Chemical compound C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O DGJMHKMYSDYOFP-MRXNPFEDSA-N 0.000 description 2
- USUWIEBBBWHKNI-KHIFEHGGSA-N C[C@H]1C[C@]1(c1noc(=O)[nH]1)n1c(cc2cc(ccc12)[C@H]1CCOC(C)(C)C1)C(=O)N1CCc2nn(c(c2[C@@H]1C)-n1ccn(-c2ccc3n(C)ncc3c2F)c1=O)-c1cc(C)c(F)c(C)c1 Chemical compound C[C@H]1C[C@]1(c1noc(=O)[nH]1)n1c(cc2cc(ccc12)[C@H]1CCOC(C)(C)C1)C(=O)N1CCc2nn(c(c2[C@@H]1C)-n1ccn(-c2ccc3n(C)ncc3c2F)c1=O)-c1cc(C)c(F)c(C)c1 USUWIEBBBWHKNI-KHIFEHGGSA-N 0.000 description 2
- CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 2
- 229940125761 Compound 6g Drugs 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- HSWVJQBEXRKOBZ-QGZVFWFLSA-N FC1=C(OC2CCN(CC2)C=2N=C3C(=NC=2N[C@H]2COCC2)CN(CC3)C(C)=O)C=CC(=C1)F Chemical compound FC1=C(OC2CCN(CC2)C=2N=C3C(=NC=2N[C@H]2COCC2)CN(CC3)C(C)=O)C=CC(=C1)F HSWVJQBEXRKOBZ-QGZVFWFLSA-N 0.000 description 2
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 description 2
- 101500028773 Homo sapiens Glucagon-like peptide 1(7-37) Proteins 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- ALQSHHUCVQOPAS-UHFFFAOYSA-N Pentane-1,5-diol Chemical compound OCCCCCO ALQSHHUCVQOPAS-UHFFFAOYSA-N 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 102100040918 Pro-glucagon Human genes 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- XBJFCYDKBDVADW-UHFFFAOYSA-N acetonitrile;formic acid Chemical compound CC#N.OC=O XBJFCYDKBDVADW-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229940084891 byetta Drugs 0.000 description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 2
- 235000011092 calcium acetate Nutrition 0.000 description 2
- 239000001639 calcium acetate Substances 0.000 description 2
- 229960005147 calcium acetate Drugs 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 229940127206 compound 14d Drugs 0.000 description 2
- 229940126212 compound 17a Drugs 0.000 description 2
- 229940125873 compound 60b Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 2
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- YOXHCYXIAVIFCZ-UHFFFAOYSA-N cyclopropanol Chemical compound OC1CC1 YOXHCYXIAVIFCZ-UHFFFAOYSA-N 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- AVAACINZEOAHHE-VFZPANTDSA-N doripenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](CNS(N)(=O)=O)C1 AVAACINZEOAHHE-VFZPANTDSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000008570 general process Effects 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 102000056448 human GLP1R Human genes 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- JFOZKMSJYSPYLN-QHCPKHFHSA-N lifitegrast Chemical compound CS(=O)(=O)C1=CC=CC(C[C@H](NC(=O)C=2C(=C3CCN(CC3=CC=2Cl)C(=O)C=2C=C3OC=CC3=CC=2)Cl)C(O)=O)=C1 JFOZKMSJYSPYLN-QHCPKHFHSA-N 0.000 description 2
- 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 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- PFGVNLZDWRZPJW-OPAMFIHVSA-N otamixaban Chemical compound C([C@@H](C(=O)OC)[C@@H](C)NC(=O)C=1C=CC(=CC=1)C=1C=C[N+]([O-])=CC=1)C1=CC=CC(C(N)=N)=C1 PFGVNLZDWRZPJW-OPAMFIHVSA-N 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- JYRWUSXRTGACLY-UHFFFAOYSA-N tert-butyl 4-[[3-(4-methylsulfonylphenyl)-[1,2]oxazolo[4,5-d]pyrimidin-7-yl]oxy]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=NC=NC2=C1ON=C2C1=CC=C(S(C)(=O)=O)C=C1 JYRWUSXRTGACLY-UHFFFAOYSA-N 0.000 description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- RBWMYPKAPIYTJQ-VMBFOHBNSA-N (1R,2S,5S)-6,6-dimethyl-N-[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]-3-[2-[4-(trifluoromethoxy)phenoxy]acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide Chemical compound CC1([C@@H]2[C@H]1[C@H](N(C2)C(=O)COC3=CC=C(C=C3)OC(F)(F)F)C(=O)N[C@@H](C[C@@H]4CCNC4=O)C=O)C RBWMYPKAPIYTJQ-VMBFOHBNSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 1
- JRHPOFJADXHYBR-YUMQZZPRSA-N (1s,2s)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@H]1CCCC[C@@H]1NC JRHPOFJADXHYBR-YUMQZZPRSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
- HPJGEESDHAUUQR-SKGSPYGFSA-N (2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[(2s)-1-[(2s)-5-(diaminomethylideneamino)-2-[[(2s)-2-[[(2s)-3-naphthalen-2-yl-2-(3-pyridin-3-ylpropanoylamino)propanoyl]amino]-3-phenylpropanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]buta Chemical compound NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)CCC=1C=NC=CC=1)CC1=CC=CC=C1 HPJGEESDHAUUQR-SKGSPYGFSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- RSBQANBNDXZFIY-UHFFFAOYSA-N (3,5-dimethylphenyl)hydrazine;hydrochloride Chemical compound [Cl-].CC1=CC(C)=CC(N[NH3+])=C1 RSBQANBNDXZFIY-UHFFFAOYSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- YUOMYYHJZHVWDF-WCCKRBBISA-N (3S)-3-aminobutanenitrile hydrochloride Chemical compound Cl.C[C@H](N)CC#N YUOMYYHJZHVWDF-WCCKRBBISA-N 0.000 description 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
- XDPCNPCKDGQBAN-SCSAIBSYSA-N (3r)-oxolan-3-ol Chemical compound O[C@@H]1CCOC1 XDPCNPCKDGQBAN-SCSAIBSYSA-N 0.000 description 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
- PPBSMPOYVPZOFM-BYPYZUCNSA-N (3s)-3-aminobutanenitrile Chemical compound C[C@H](N)CC#N PPBSMPOYVPZOFM-BYPYZUCNSA-N 0.000 description 1
- XDPCNPCKDGQBAN-BYPYZUCNSA-N (3s)-oxolan-3-ol Chemical compound O[C@H]1CCOC1 XDPCNPCKDGQBAN-BYPYZUCNSA-N 0.000 description 1
- USPADLFCDNJOTR-UHFFFAOYSA-N (4-chloro-3,5-dimethylphenyl)hydrazine Chemical compound Cc1cc(NN)cc(C)c1Cl USPADLFCDNJOTR-UHFFFAOYSA-N 0.000 description 1
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 1
- HGNFAVXSHSUMLA-SNVBAGLBSA-N (4r)-4-(phenylmethoxymethyl)-1,3,2-dioxathiolane 2,2-dioxide Chemical compound O1S(=O)(=O)OC[C@H]1COCC1=CC=CC=C1 HGNFAVXSHSUMLA-SNVBAGLBSA-N 0.000 description 1
- VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 description 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- DPRJPRMZJGWLHY-HNGSOEQISA-N (e,3r,5s)-7-[5-(4-fluorophenyl)-3-propan-2-yl-1-pyrazin-2-ylpyrazol-4-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)/C=C/C=1C(C(C)C)=NN(C=2N=CC=NC=2)C=1C1=CC=C(F)C=C1 DPRJPRMZJGWLHY-HNGSOEQISA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- 125000004867 1,1-dimethylpropylcarbonyl group Chemical group CC(CC)(C(=O)*)C 0.000 description 1
- LXEOQHPAKLYXTH-UHFFFAOYSA-N 1,2-dichloro-1-methoxyethane Chemical compound COC(Cl)CCl LXEOQHPAKLYXTH-UHFFFAOYSA-N 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- UNRFKVIECRVZQQ-UHFFFAOYSA-N 1-(1,2-dichloroethoxy)propane Chemical compound CCCOC(Cl)CCl UNRFKVIECRVZQQ-UHFFFAOYSA-N 0.000 description 1
- MILVQHAHPQLJQF-LOACHALJSA-N 1-(2,2-dimethoxyethyl)-3-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-5-formyl-4,6-dimethyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]urea Chemical compound COC(CNC(=O)Nc1c2[C@H](C)N(C=O)C(C)Cc2nn1-c1cc(C)c(F)c(C)c1)OC MILVQHAHPQLJQF-LOACHALJSA-N 0.000 description 1
- DZSJXRCRGWPYKC-BDHWGLMFSA-N 1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-5-[(4S)-2,2-dimethyloxan-4-yl]-N-methyl-N-phenylindole-2-carboxamide Chemical compound C(#N)[C@]1([C@H](C1)C)N1C(=CC2=CC(=CC=C12)[C@@H]1CC(OCC1)(C)C)C(=O)N(C1=CC=CC=C1)C DZSJXRCRGWPYKC-BDHWGLMFSA-N 0.000 description 1
- JZBFYXKKJVOEOZ-QLXKLKPCSA-N 1-[(1S,2S)-2-methyl-1-[5-oxo-4-(2-trimethylsilylethoxymethyl)-1,2,4-oxadiazol-3-yl]cyclopropyl]-5-(oxan-4-yl)indole-2-carboxylic acid Chemical compound O1CCC(CC1)C=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C1=NOC(N1COCC[Si](C)(C)C)=O)C(=O)O JZBFYXKKJVOEOZ-QLXKLKPCSA-N 0.000 description 1
- IPJDLCFSZIPYRC-NVQXNPDNSA-N 1-[(1S,2S)-2-methyl-2-[5-oxo-4-(2-trimethylsilylethoxymethyl)-1,2,4-oxadiazol-3-yl]cyclopropyl]-5-(oxan-4-yl)indole-2-carbonyl chloride Chemical compound O1CCC(CC1)C=1C=C2C=C(N(C2=CC=1)[C@@H]1[C@@](C1)(C)C1=NOC(N1COCC[Si](C)(C)C)=O)C(=O)Cl IPJDLCFSZIPYRC-NVQXNPDNSA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
- CEVMYGZHEJSOHZ-UHFFFAOYSA-N 1-bromo-3-methoxypropane Chemical compound COCCCBr CEVMYGZHEJSOHZ-UHFFFAOYSA-N 0.000 description 1
- GQIRIWDEZSKOCN-UHFFFAOYSA-N 1-chloro-n,n,2-trimethylprop-1-en-1-amine Chemical compound CN(C)C(Cl)=C(C)C GQIRIWDEZSKOCN-UHFFFAOYSA-N 0.000 description 1
- 125000004870 1-ethylpropylcarbonyl group Chemical group C(C)C(CC)C(=O)* 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 125000004678 1-methylpropylcarbonyl group Chemical group CC(CC)C(=O)* 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- YIJBVDBRPCLLEW-UHFFFAOYSA-N 1H-indol-2-yl(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)methanone Chemical compound N=1NC=C2CN(CCC2=1)C(=O)C=1NC2=CC=CC=C2C=1 YIJBVDBRPCLLEW-UHFFFAOYSA-N 0.000 description 1
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- YRAJNWYBUCUFBD-UHFFFAOYSA-N 2,2,6,6-tetramethylheptane-3,5-dione Chemical compound CC(C)(C)C(=O)CC(=O)C(C)(C)C YRAJNWYBUCUFBD-UHFFFAOYSA-N 0.000 description 1
- LNGQDBJPFPIRBF-UHFFFAOYSA-N 2,2-dichloroethyl carbonochloridate Chemical compound ClC(Cl)COC(Cl)=O LNGQDBJPFPIRBF-UHFFFAOYSA-N 0.000 description 1
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
- UFLFSJVTFSZTKX-UHFFFAOYSA-N 2,2-dimethylmorpholine Chemical compound CC1(C)CNCCO1 UFLFSJVTFSZTKX-UHFFFAOYSA-N 0.000 description 1
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
- BFRFZJXORRDJHY-UHFFFAOYSA-N 2-(1,1-dimethyl-3,4-dihydroisochromen-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C2C(C)(C)OCCC2=C1 BFRFZJXORRDJHY-UHFFFAOYSA-N 0.000 description 1
- HTZWATKNQYOOIT-UHFFFAOYSA-N 2-(1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane Chemical compound O1CCOB1B1OCCO1 HTZWATKNQYOOIT-UHFFFAOYSA-N 0.000 description 1
- MDNDJMCSXOXBFZ-UHFFFAOYSA-N 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane Chemical compound O1CC(C)(C)COB1B1OCC(C)(C)CO1 MDNDJMCSXOXBFZ-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
- FUSFWUFSEJXMRQ-UHFFFAOYSA-N 2-bromo-1,1-dimethoxyethane Chemical compound COC(CBr)OC FUSFWUFSEJXMRQ-UHFFFAOYSA-N 0.000 description 1
- OVXJWSYBABKZMD-UHFFFAOYSA-N 2-chloro-1,1-diethoxyethane Chemical compound CCOC(CCl)OCC OVXJWSYBABKZMD-UHFFFAOYSA-N 0.000 description 1
- CRZJPEIBPQWDGJ-UHFFFAOYSA-N 2-chloro-1,1-dimethoxyethane Chemical compound COC(CCl)OC CRZJPEIBPQWDGJ-UHFFFAOYSA-N 0.000 description 1
- GONULLRFSHKLBS-UHFFFAOYSA-N 2-chloro-3-fluoro-4-iodopyridine Chemical compound FC1=C(I)C=CN=C1Cl GONULLRFSHKLBS-UHFFFAOYSA-N 0.000 description 1
- WHCRABJNJRAJIP-UHFFFAOYSA-N 2-chloro-4-iodo-3-methylpyridine Chemical compound CC1=C(I)C=CN=C1Cl WHCRABJNJRAJIP-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004883 2-ethylbutylcarbonyl group Chemical group C(C)C(CC(=O)*)CC 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- FCLRDVPREJSWBM-UHFFFAOYSA-N 2-isocyanato-1,1-dimethoxyethane Chemical compound COC(OC)CN=C=O FCLRDVPREJSWBM-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000004680 2-methylbutylcarbonyl group Chemical group CC(CC(=O)*)CC 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- SBAJRGRUGUQKAF-UHFFFAOYSA-N 3-(2-cyanoethylamino)propanenitrile Chemical compound N#CCCNCCC#N SBAJRGRUGUQKAF-UHFFFAOYSA-N 0.000 description 1
- VGOALPIDEXVYQI-UHFFFAOYSA-N 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-n-[3-imidazol-1-yl-5-(trifluoromethyl)phenyl]-4-methylbenzamide Chemical compound C1=C(C#CC=2N3N=CC=CC3=NC=2)C(C)=CC=C1C(=O)NC(C=C(C=1)C(F)(F)F)=CC=1N1C=CN=C1 VGOALPIDEXVYQI-UHFFFAOYSA-N 0.000 description 1
- MKKJOSSWEWPKDI-FNUWOHQOSA-N 3-[(1S,2S)-1-[2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(3-fluoro-2-methylpyridin-4-yl)indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)C1=CC=NC(C)=C1F)C(=O)N1CCC2=NN(C(N3C=CNC3=O)=C2[C@@H]1C)C1=CC(C)=C(F)C(C)=C1)C1=NOC(=O)N1 MKKJOSSWEWPKDI-FNUWOHQOSA-N 0.000 description 1
- MXWXWEAOBOFSFS-ZVQVHKEOSA-N 3-[(1S,2S)-1-[2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]-5-(oxan-4-yl)indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)C1CCOCC1)C(=O)N1CCC2=NN(C(N3C=CNC3=O)=C2[C@@H]1C)C1=CC(C)=C(F)C(C)=C1)C1=NOC(=O)N1 MXWXWEAOBOFSFS-ZVQVHKEOSA-N 0.000 description 1
- WRRRLXXWGQXTIF-FPOUCGFGSA-N 3-[(1S,2S)-1-[5-(2,2-dimethylmorpholin-4-yl)-2-[2-(4-fluoro-3,5-dimethylphenyl)-3-(2-oxo-1H-imidazol-3-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=CC(=C2)N1CCOC(C)(C)C1)C(=O)N1CCC2=NN(C(N3C=CNC3=O)=C2C1)C1=CC(C)=C(F)C(C)=C1)C1=NOC(=O)N1 WRRRLXXWGQXTIF-FPOUCGFGSA-N 0.000 description 1
- IDYOAYWAKSYTNG-HMRVBTJHSA-N 3-[(1S,2S)-1-[5-(2-ethyloxan-4-yl)-2-[2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound CCC1CC(CCO1)C1=CC2=C(C=C1)N(C(=C2)C(=O)N1CCC2=NN(C(N3C=CN(C3=O)C3=CC4=C(C=C3)N(C)N=C4)=C2C1)C1=CC(C)=C(F)C(C)=C1)[C@]1(C[C@@H]1C)C1=NOC(=O)N1 IDYOAYWAKSYTNG-HMRVBTJHSA-N 0.000 description 1
- KUAHFWOFSXHWOD-OLZAFWBVSA-N 3-[(1S,2S)-1-[5-[(4S)-2,2-dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound [H][C@@]1(CCOC(C)(C)C1)C1=CC2=C(C=C1)N(C(=C2)C(=O)N1CCC2=NN(C(N3C=CN(C3=O)C3=CC4=C(C=C3)N(C)N=C4)=C2[C@@H]1C)C1=CC(C)=C(F)C(C)=C1)[C@]1(C[C@@H]1C)C1=NOC(=O)N1 KUAHFWOFSXHWOD-OLZAFWBVSA-N 0.000 description 1
- QWQWFADSAWKVRR-GGUKSXOVSA-N 3-[(1S,2S)-1-[5-bromo-6-fluoro-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-3-[3-(1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one Chemical compound C[C@H]1C[C@@]1(N1C(=CC2=C1C=C(F)C(Br)=C2)C(=O)N1CCC2=NN(C(N3C=CN(C3=O)C3=CC4=C(C=C3)N(C)N=C4)=C2[C@@H]1C)C1=CC(C)=C(F)C(C)=C1)C1=NOC(=O)N1 QWQWFADSAWKVRR-GGUKSXOVSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- HIHACTSDNCJNBP-YDALLXLXSA-N 3-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-1H-imidazol-2-one hydrochloride Chemical compound Cl.C[C@@H]1NCCc2nn(c(c12)-n1cc[nH]c1=O)-c1cc(C)c(F)c(C)c1 HIHACTSDNCJNBP-YDALLXLXSA-N 0.000 description 1
- AJUJESVPCMQANL-OLZOCXBDSA-N 3-[(4S,6R)-2-(4-fluoro-3,5-dimethylphenyl)-4,6-dimethyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-1H-imidazol-2-one Chemical compound C[C@@H]1Cc2nn(c(c2[C@H](C)N1)-n1cc[nH]c1=O)-c1cc(C)c(F)c(C)c1 AJUJESVPCMQANL-OLZOCXBDSA-N 0.000 description 1
- IXHXKHYKFCCVRN-UHFFFAOYSA-N 3-[2-(3,5-dimethylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-1H-imidazol-2-one Chemical compound Cc1cc(C)cc(c1)-n1nc2CCNCc2c1-n1cc[nH]c1=O IXHXKHYKFCCVRN-UHFFFAOYSA-N 0.000 description 1
- RWXMIZKCMYTINL-UHFFFAOYSA-N 3-[2-(4-fluoro-3,5-dimethylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-1H-imidazol-2-one hydrochloride Chemical compound Cl.Cc1cc(cc(C)c1F)-n1nc2CCNCc2c1-n1cc[nH]c1=O RWXMIZKCMYTINL-UHFFFAOYSA-N 0.000 description 1
- UNSHMXUHOHBLIQ-UHFFFAOYSA-N 3-[4-chloro-3-(2-methylphenoxy)naphthalen-1-yl]-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione Chemical compound ClC1=C(C=C(C2=CC=CC=C12)N1C(NC(=CC1=O)C(F)(F)F)=O)OC1=C(C=CC=C1)C UNSHMXUHOHBLIQ-UHFFFAOYSA-N 0.000 description 1
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 1
- ARSUQHZDPBOKDP-UHFFFAOYSA-N 4,4,6-trimethyl-1,3,2-dioxaborinane Chemical compound CC1CC(C)(C)OBO1 ARSUQHZDPBOKDP-UHFFFAOYSA-N 0.000 description 1
- UEBSWKNVDRJVHN-UHFFFAOYSA-N 4,4,6-trimethyl-2-(4,4,6-trimethyl-1,3,2-dioxaborinan-2-yl)-1,3,2-dioxaborinane Chemical compound O1C(C)CC(C)(C)OB1B1OC(C)(C)CC(C)O1 UEBSWKNVDRJVHN-UHFFFAOYSA-N 0.000 description 1
- WBTSLHPSFLNAJK-UHFFFAOYSA-N 4-(4-bromo-2-methylphenyl)-6-chloropyrimidine Chemical compound CC1=CC(Br)=CC=C1C1=CC(Cl)=NC=N1 WBTSLHPSFLNAJK-UHFFFAOYSA-N 0.000 description 1
- RQTXWKKAUMSKQA-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]cubane-1-carboxylic acid Chemical compound C12C3C4(NC(=O)OC(C)(C)C)C1C1C4C3C12C(O)=O RQTXWKKAUMSKQA-UHFFFAOYSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- PHCLIPMSNVUELH-UHFFFAOYSA-N 4-bromo-2,3-dimethylpyridine Chemical compound CC1=NC=CC(Br)=C1C PHCLIPMSNVUELH-UHFFFAOYSA-N 0.000 description 1
- MSICOAYELJUIIN-UHFFFAOYSA-N 4-chloro-3,5-dimethylaniline Chemical compound CC1=CC(N)=CC(C)=C1Cl MSICOAYELJUIIN-UHFFFAOYSA-N 0.000 description 1
- IQTHEAQKKVAXGV-UHFFFAOYSA-N 4-ditert-butylphosphanyl-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 IQTHEAQKKVAXGV-UHFFFAOYSA-N 0.000 description 1
- DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 1
- IGNFILTZSIUWBS-UHFFFAOYSA-N 4-fluoro-3,5-dimethylaniline Chemical compound CC1=CC(N)=CC(C)=C1F IGNFILTZSIUWBS-UHFFFAOYSA-N 0.000 description 1
- YGZGPBBDOIPGMN-UHFFFAOYSA-N 4-fluoro-3,5-dimethylaniline hydrochloride Chemical compound Cl.Cc1cc(N)cc(C)c1F YGZGPBBDOIPGMN-UHFFFAOYSA-N 0.000 description 1
- CTPMPYIKWARWDI-UHFFFAOYSA-N 4-iodo-2,2-dimethyloxane Chemical compound CC1(C)CC(I)CCO1 CTPMPYIKWARWDI-UHFFFAOYSA-N 0.000 description 1
- SQCYBMMCCQLJDP-UHFFFAOYSA-N 4-iodo-N,N,3-trimethylpyridin-2-amine Chemical compound CN(C)c1nccc(I)c1C SQCYBMMCCQLJDP-UHFFFAOYSA-N 0.000 description 1
- 125000004875 4-methylpentylcarbonyl group Chemical group CC(CCCC(=O)*)C 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
- ZTUDIUYHLZGDFP-LXGOIASLSA-N 5-(2-chloro-3-fluoropyridin-4-yl)-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid Chemical compound ClC1=NC=CC(=C1F)C=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)O ZTUDIUYHLZGDFP-LXGOIASLSA-N 0.000 description 1
- ZDHQVQVNOIWLNX-UHFFFAOYSA-N 5-(7-chloro-10h-benzo[1,2]cyclohepta[2,4-c][1,3]thiazol-10-yl)-1-methyl-4-sulfanylidenepyrimidin-2-one Chemical compound S=C1NC(=O)N(C)C=C1C1C2=CC=C(Cl)C=C2C=CC2=C1N=CS2 ZDHQVQVNOIWLNX-UHFFFAOYSA-N 0.000 description 1
- PRZXEJQTLDXSHY-MYODQAERSA-N 5-[2-(dimethylamino)-3-methylpyridin-4-yl]-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid Chemical compound CN(C1=NC=CC(=C1C)C=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)O)C PRZXEJQTLDXSHY-MYODQAERSA-N 0.000 description 1
- RFLFJWDQFXRMJE-UHFFFAOYSA-N 5-bromo-1-(2,2,2-trifluoroethyl)indazole Chemical compound FC(F)(F)Cn1ncc2cc(Br)ccc12 RFLFJWDQFXRMJE-UHFFFAOYSA-N 0.000 description 1
- JOEXXSBQGVPKAD-UHFFFAOYSA-N 5-bromo-1-(cyanomethyl)-N-methyl-N-phenylindole-2-carboxamide Chemical compound CN(C(=O)c1cc2cc(Br)ccc2n1CC#N)c1ccccc1 JOEXXSBQGVPKAD-UHFFFAOYSA-N 0.000 description 1
- ZDJCLWRYCCAARE-UHFFFAOYSA-N 5-bromo-1-[(3-methyloxetan-3-yl)methyl]indazole Chemical compound BrC=1C=C2C=NN(C2=CC=1)CC1(COC1)C ZDJCLWRYCCAARE-UHFFFAOYSA-N 0.000 description 1
- ZXPHUVHMBKRRJF-UHFFFAOYSA-N 5-bromo-2-fluoro-1,3-dimethylbenzene Chemical compound CC1=CC(Br)=CC(C)=C1F ZXPHUVHMBKRRJF-UHFFFAOYSA-N 0.000 description 1
- WQXHBMNNVRGWHF-UHFFFAOYSA-N 5-bromo-3-methyl-1h-benzimidazol-2-one Chemical compound BrC1=CC=C2NC(=O)N(C)C2=C1 WQXHBMNNVRGWHF-UHFFFAOYSA-N 0.000 description 1
- ULRUVOVEEXIQNQ-UHFFFAOYSA-N 5-bromo-4-fluoro-1-(2-methoxyethyl)indazole Chemical compound COCCn1ncc2c(F)c(Br)ccc12 ULRUVOVEEXIQNQ-UHFFFAOYSA-N 0.000 description 1
- ZOAXXDKNLJVNEC-ZETCQYMHSA-N 5-bromo-4-fluoro-1-[(3S)-oxolan-3-yl]indazole Chemical compound Fc1c(Br)ccc2n(ncc12)[C@H]1CCOC1 ZOAXXDKNLJVNEC-ZETCQYMHSA-N 0.000 description 1
- ZNNFNEIFQIAWNY-UHFFFAOYSA-N 5-bromo-6-fluoro-1h-indazole Chemical compound C1=C(Br)C(F)=CC2=C1C=NN2 ZNNFNEIFQIAWNY-UHFFFAOYSA-N 0.000 description 1
- KIAXZJLEXVRFBO-XMHCIUCPSA-N 5-bromo-N-methyl-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]-N-phenylindole-2-carboxamide Chemical compound BrC=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)N(C1=CC=CC=C1)C KIAXZJLEXVRFBO-XMHCIUCPSA-N 0.000 description 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- XBLZVIJCTJAQOS-FVINQWEUSA-N 7-fluoro-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]-5-(oxan-4-yl)indole-2-carboxylic acid Chemical compound FC=1C=C(C=C2C=C(N(C=12)[C@@]1([C@H](C1)C)C1=NOC(N1)=O)C(=O)O)C1CCOCC1 XBLZVIJCTJAQOS-FVINQWEUSA-N 0.000 description 1
- WLVICJHZUYQWEL-UHFFFAOYSA-N 9-iodo-6-oxaspiro[4.5]decane Chemical compound C1C(I)CCOC11CCCC1 WLVICJHZUYQWEL-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241001209435 Actus Species 0.000 description 1
- 208000000230 African Trypanosomiasis Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000272478 Aquila Species 0.000 description 1
- 101100096578 Arabidopsis thaliana SQD2 gene Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- 241001134740 Blastocrithidia Species 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
- OZOIRVWWHXMGPN-UHFFFAOYSA-L CC1=CC=CC=C1.[O-]OOO[O-].[K+].[K+] Chemical compound CC1=CC=CC=C1.[O-]OOO[O-].[K+].[K+] OZOIRVWWHXMGPN-UHFFFAOYSA-L 0.000 description 1
- WUNXLRMUOFFXHR-MYODQAERSA-N CCc1nccc(c1C)-c1ccc2n(c(cc2c1)C(O)=O)[C@]1(C[C@@H]1C)c1nc(=O)o[nH]1 Chemical compound CCc1nccc(c1C)-c1ccc2n(c(cc2c1)C(O)=O)[C@]1(C[C@@H]1C)c1nc(=O)o[nH]1 WUNXLRMUOFFXHR-MYODQAERSA-N 0.000 description 1
- QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 description 1
- WUZBOJXXYMKMMF-UHFFFAOYSA-N COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F Chemical compound COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F WUZBOJXXYMKMMF-UHFFFAOYSA-N 0.000 description 1
- RFYXMOTWRDUHHL-ZBHICJROSA-N C[C@H]1CC(I)CCO1 Chemical compound C[C@H]1CC(I)CCO1 RFYXMOTWRDUHHL-ZBHICJROSA-N 0.000 description 1
- BRFXAKGZZQDPQK-CWKPULSASA-N C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(ccc12)-c1ccnc(C)c1F)C(O)=O Chemical compound C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(ccc12)-c1ccnc(C)c1F)C(O)=O BRFXAKGZZQDPQK-CWKPULSASA-N 0.000 description 1
- IEEAIJFODIRBMY-YBTHPKLGSA-N C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(ccc12)C1CCOCC1)C(O)=O Chemical compound C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(ccc12)C1CCOCC1)C(O)=O IEEAIJFODIRBMY-YBTHPKLGSA-N 0.000 description 1
- SXXDGLBNMOFEBJ-QKVFXAPYSA-N C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(ccc12)N1CCOC(C)(C)C1)C(O)=O Chemical compound C[C@H]1C[C@]1(c1nc(=O)o[nH]1)n1c(cc2cc(ccc12)N1CCOC(C)(C)C1)C(O)=O SXXDGLBNMOFEBJ-QKVFXAPYSA-N 0.000 description 1
- 239000005973 Carvone Substances 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 239000004287 Dehydroacetic acid Substances 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- PKUDCPRQYLIEPV-UHFFFAOYSA-M I[Zn]C1CCOCC1 Chemical class I[Zn]C1CCOCC1 PKUDCPRQYLIEPV-UHFFFAOYSA-M 0.000 description 1
- TUGBNADKWCLHGD-ILKKLZGPSA-M I[Zn]C1C[C@@H](OCC1)C Chemical compound I[Zn]C1C[C@@H](OCC1)C TUGBNADKWCLHGD-ILKKLZGPSA-M 0.000 description 1
- 206010023379 Ketoacidosis Diseases 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920002884 Laureth 4 Polymers 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- WEIFBEUPKWTBTG-UHFFFAOYSA-N N-(4-bromo-2-methoxyphenyl)-N-(3-methoxypropyl)acetamide Chemical compound COCCCN(C(C)=O)c1ccc(Br)cc1OC WEIFBEUPKWTBTG-UHFFFAOYSA-N 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 1
- CUFKBIXEJQVVKV-YHOSLMMYSA-N N-[4-[3-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl]-2-oxoimidazol-1-yl]cuban-1-yl]acetamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C[C@@H]1NCCc2nn(c(c12)-n1ccn(c1=O)C12C3C4C1C1C2C3C41NC(C)=O)-c1cc(C)c(F)c(C)c1 CUFKBIXEJQVVKV-YHOSLMMYSA-N 0.000 description 1
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
- ZNSPHKJFQDEABI-NZQKXSOJSA-N Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 Chemical compound Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 ZNSPHKJFQDEABI-NZQKXSOJSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 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
- 229920001800 Shellac Polymers 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108010021119 Trichosanthin Proteins 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
- 201000004810 Vascular dementia Diseases 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- NELWQUQCCZMRPB-UBPLGANQSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(4-amino-5-ethenyl-2-oxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](C)O[C@H]1N1C(=O)N=C(N)C(C=C)=C1 NELWQUQCCZMRPB-UBPLGANQSA-N 0.000 description 1
- KPFBUSLHFFWMAI-HYRPPVSQSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-6-formyl-3-methoxy-10,13-dimethyl-1,2,7,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1C[C@@H]2[C@](CCC(OC)=C3)(C)C3=C(C=O)C[C@H]2[C@@H]2CC[C@](OC(C)=O)(C(C)=O)[C@]21C KPFBUSLHFFWMAI-HYRPPVSQSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
- KHMFYFVXTICBEL-UHFFFAOYSA-N [4-(4-fluorophenyl)phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=C(F)C=C1 KHMFYFVXTICBEL-UHFFFAOYSA-N 0.000 description 1
- JGFFTJDJHXLDNJ-UHFFFAOYSA-L [O-]OOO[O-].[K+].[K+] Chemical compound [O-]OOO[O-].[K+].[K+] JGFFTJDJHXLDNJ-UHFFFAOYSA-L 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 230000002862 amidating effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- LASLVGACQUUOEB-UHFFFAOYSA-N bicyclo[1.1.0]butane Chemical compound C1C2CC21 LASLVGACQUUOEB-UHFFFAOYSA-N 0.000 description 1
- LPCWKMYWISGVSK-UHFFFAOYSA-N bicyclo[3.2.1]octane Chemical compound C1C2CCC1CCC2 LPCWKMYWISGVSK-UHFFFAOYSA-N 0.000 description 1
- TWONWILUDBHKQU-UHFFFAOYSA-N bicyclo[5.2.0]nonane Chemical compound C1CCCCC2CCC21 TWONWILUDBHKQU-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical compound [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- LBHVNQAMWXEMLK-UHFFFAOYSA-N but-3-en-1-ol Chemical compound OCCC=C.OCCC=C LBHVNQAMWXEMLK-UHFFFAOYSA-N 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 238000013262 cAMP assay Methods 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-M carbonochloridate Chemical compound [O-]C(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-M 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 159000000006 cesium salts Chemical class 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- LSZLYWSRWXFMOI-UHFFFAOYSA-N cobalt(2+);5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Co+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 LSZLYWSRWXFMOI-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125876 compound 15a Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 229940127113 compound 57 Drugs 0.000 description 1
- YNYHGRUPNQLZHB-UHFFFAOYSA-M copper(1+);trifluoromethanesulfonate Chemical compound [Cu+].[O-]S(=O)(=O)C(F)(F)F YNYHGRUPNQLZHB-UHFFFAOYSA-M 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000003869 coulometry Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- DRNAQRXLOSUHBQ-UHFFFAOYSA-N cphos Chemical compound CN(C)C1=CC=CC(N(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 DRNAQRXLOSUHBQ-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- TXWRERCHRDBNLG-UHFFFAOYSA-N cubane Chemical compound C12C3C4C1C1C4C3C12 TXWRERCHRDBNLG-UHFFFAOYSA-N 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000019258 dehydroacetic acid Nutrition 0.000 description 1
- 229940061632 dehydroacetic acid Drugs 0.000 description 1
- JEQRBTDTEKWZBW-UHFFFAOYSA-N dehydroacetic acid Chemical compound CC(=O)C1=C(O)OC(C)=CC1=O JEQRBTDTEKWZBW-UHFFFAOYSA-N 0.000 description 1
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 125000005131 dialkylammonium group Chemical group 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- VBXDEEVJTYBRJJ-UHFFFAOYSA-N diboronic acid Chemical compound OBOBO VBXDEEVJTYBRJJ-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- AJDPNPAGZMZOMN-UHFFFAOYSA-N diethyl (4-oxo-1,2,3-benzotriazin-3-yl) phosphate Chemical compound C1=CC=C2C(=O)N(OP(=O)(OCC)OCC)N=NC2=C1 AJDPNPAGZMZOMN-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 1
- SACNIGZYDTUHKB-UHFFFAOYSA-N ditert-butyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C SACNIGZYDTUHKB-UHFFFAOYSA-N 0.000 description 1
- REWLCYPYZCHYSS-UHFFFAOYSA-N ditert-butyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group COC1=CC=C(OC)C(C=2C(=CC(=CC=2C(C)C)C(C)C)C(C)C)=C1P(C(C)(C)C)C(C)(C)C REWLCYPYZCHYSS-UHFFFAOYSA-N 0.000 description 1
- CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- LCFXLZAXGXOXAP-DAXSKMNVSA-N ethyl (2z)-2-cyano-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(=N/O)\C#N LCFXLZAXGXOXAP-DAXSKMNVSA-N 0.000 description 1
- SEVIJDSSCPWOLU-IZHWHUGBSA-N ethyl 1-[(1S,2S)-1-cyano-2-methylcyclopropyl]-5-(2-ethyl-3-methylpyridin-4-yl)indole-2-carboxylate Chemical compound C(#N)[C@]1([C@H](C1)C)N1C(=CC2=CC(=CC=C12)C1=C(C(=NC=C1)CC)C)C(=O)OCC SEVIJDSSCPWOLU-IZHWHUGBSA-N 0.000 description 1
- QQXQAEWRSVZPJM-UHFFFAOYSA-N ethyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1 QQXQAEWRSVZPJM-UHFFFAOYSA-N 0.000 description 1
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
- XGHCUBZRFMFZSU-NSHDSACASA-N ethyl 3-[[(2S)-1-cyanopropan-2-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoate Chemical compound CCOC(=O)CCN([C@@H](C)CC#N)C(=O)OC(C)(C)C XGHCUBZRFMFZSU-NSHDSACASA-N 0.000 description 1
- MTWIOYOWFKTDAR-QMMMGPOBSA-N ethyl 3-[[(2S)-1-cyanopropan-2-yl]amino]propanoate Chemical compound CCOC(=O)CCN[C@@H](C)CC#N MTWIOYOWFKTDAR-QMMMGPOBSA-N 0.000 description 1
- KKRALFOTPOOJLZ-UHFFFAOYSA-N ethyl 5-bromo-1-(cyanomethyl)indole-2-carboxylate Chemical compound BrC1=CC=C2N(CC#N)C(C(=O)OCC)=CC2=C1 KKRALFOTPOOJLZ-UHFFFAOYSA-N 0.000 description 1
- BGPPONOBRHHDPG-MGPLVRAMSA-N ethyl 5-bromo-1-[(1S,2S)-1-cyano-2-methylcyclopropyl]indole-2-carboxylate Chemical compound BrC=1C=C2C=C(N(C2=CC=1)[C@@]1([C@H](C1)C)C#N)C(=O)OCC BGPPONOBRHHDPG-MGPLVRAMSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 239000000499 gel Substances 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
- 229940050410 gluconate Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000007986 glycine-NaOH buffer Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- UKJFVOWPUXSBOM-UHFFFAOYSA-N hexane;oxolane Chemical compound C1CCOC1.CCCCCC UKJFVOWPUXSBOM-UHFFFAOYSA-N 0.000 description 1
- 208000029080 human African trypanosomiasis Diseases 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000005945 imidazopyridyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
- 239000000859 incretin Substances 0.000 description 1
- 125000004537 indazol-5-yl group Chemical group N1N=CC2=CC(=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- QBZXOWQOWPHHRA-UHFFFAOYSA-N lithium;ethane Chemical compound [Li+].[CH2-]C QBZXOWQOWPHHRA-UHFFFAOYSA-N 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- 238000007477 logistic regression Methods 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 206010062198 microangiopathy Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- DUUZHMLQQPSTJY-UHFFFAOYSA-N n-(2,2-dimethoxyethyl)imidazole-1-carboxamide Chemical compound COC(OC)CNC(=O)N1C=CN=C1 DUUZHMLQQPSTJY-UHFFFAOYSA-N 0.000 description 1
- OXHBMBUYHWMWKM-UHFFFAOYSA-N n-(4-bromo-2-methoxyphenyl)acetamide Chemical compound COC1=CC(Br)=CC=C1NC(C)=O OXHBMBUYHWMWKM-UHFFFAOYSA-N 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- XAYGBKHKBBXDAK-UHFFFAOYSA-N n-[4-[4-(cyclopropylmethyl)piperazine-1-carbonyl]phenyl]quinoline-8-sulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=CC=1C(=O)N(CC1)CCN1CC1CC1 XAYGBKHKBBXDAK-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- GSJRUEBQWPLHSN-UHFFFAOYSA-N n-methylmethanamine;oxolane Chemical compound CNC.C1CCOC1 GSJRUEBQWPLHSN-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 230000024241 parasitism Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 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
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- XJZVFIBVUSVVCB-UHFFFAOYSA-N potassium (5-cyano-1,2,3,6-tetrahydropyridin-4-yl)azanide Chemical compound C(#N)C1=C(CCNC1)[NH-].[K+] XJZVFIBVUSVVCB-UHFFFAOYSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 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
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 159000000005 rubidium salts Chemical class 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229940100515 sorbitan Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960002385 streptomycin sulfate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- HWSFSGRTZMJYGQ-IENPIDJESA-N tert-butyl (2S)-3-cyano-2-methyl-4-oxopiperidine-1-carboxylate Chemical compound C[C@H]1C(C#N)C(=O)CCN1C(=O)OC(C)(C)C HWSFSGRTZMJYGQ-IENPIDJESA-N 0.000 description 1
- CBUWRBUSKBYBBF-INIZCTEOSA-N tert-butyl (4S)-3-(2,2-dimethoxyethylcarbamoylamino)-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound COC(CNC(=O)Nc1c2[C@H](C)N(CCc2nn1-c1cc(C)c(F)c(C)c1)C(=O)OC(C)(C)C)OC CBUWRBUSKBYBBF-INIZCTEOSA-N 0.000 description 1
- VXUOASGJUKAXOS-HNNXBMFYSA-N tert-butyl (4S)-3-(2,2-dimethoxyethylcarbamoylamino)-2-(4-fluoro-3-methylphenyl)-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound COC(CNC(=O)NC=1N(N=C2C=1[C@@H](N(CC2)C(=O)OC(C)(C)C)C)C1=CC(=C(C=C1)F)C)OC VXUOASGJUKAXOS-HNNXBMFYSA-N 0.000 description 1
- TYWMHXCEKYVYGL-HYQJAOFWSA-N tert-butyl (4S)-3-[3-[4-[acetyl(2-methoxyethyl)amino]cuban-1-yl]-2-oxoimidazol-1-yl]-2-(4-fluoro-3,5-dimethylphenyl)-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound C(C)(=O)N(C12C3C4C5(C(C14)C2C53)N1C(N(C=C1)C=1N(N=C2C=1[C@@H](N(CC2)C(=O)OC(C)(C)C)C)C1=CC(=C(C(=C1)C)F)C)=O)CCOC TYWMHXCEKYVYGL-HYQJAOFWSA-N 0.000 description 1
- CHDOJVHEBJTWFW-UHFFFAOYSA-N tert-butyl 3-(2,2-dimethoxyethylcarbamoylamino)-2-(3,5-dimethylphenyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound COC(CNC(=O)Nc1c2CN(CCc2nn1-c1cc(C)cc(C)c1)C(=O)OC(C)(C)C)OC CHDOJVHEBJTWFW-UHFFFAOYSA-N 0.000 description 1
- NUMQCACRALPSHD-UHFFFAOYSA-N tert-butyl ethyl ether Chemical compound CCOC(C)(C)C NUMQCACRALPSHD-UHFFFAOYSA-N 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005458 thianyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000005503 thioxanyl group Chemical group 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 238000002096 two-dimensional nuclear Overhauser enhancement spectroscopy Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2024045935A JP2024079762A (ja) | 2017-11-29 | 2024-03-22 | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2017228661 | 2017-11-29 | ||
| JP2017228661 | 2017-11-29 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2024045935A Division JP2024079762A (ja) | 2017-11-29 | 2024-03-22 | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019099571A JP2019099571A (ja) | 2019-06-24 |
| JP2019099571A5 JP2019099571A5 (enrdf_load_stackoverflow) | 2022-01-06 |
| JP7461104B2 true JP7461104B2 (ja) | 2024-04-03 |
Family
ID=66975925
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018223465A Active JP7461104B2 (ja) | 2017-11-29 | 2018-11-29 | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 |
| JP2024045935A Pending JP2024079762A (ja) | 2017-11-29 | 2024-03-22 | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2024045935A Pending JP2024079762A (ja) | 2017-11-29 | 2024-03-22 | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 |
Country Status (1)
| Country | Link |
|---|---|
| JP (2) | JP7461104B2 (enrdf_load_stackoverflow) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12234236B1 (en) | 2023-09-14 | 2025-02-25 | Ascletis Pharma (China) Co., Limited | GLP-1R agonist and therapeutic method thereof |
| US12291530B1 (en) | 2023-11-24 | 2025-05-06 | Ascletis Pharma (China) Co., Limited | GLP-1R agonist and therapeutic method thereof |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110618208A (zh) * | 2019-09-10 | 2019-12-27 | 威海迪素制药有限公司 | 一种（s）-（+）-3-羟基四氢呋喃对映异构体含量检测方法 |
| SI4097099T1 (sl) | 2020-02-07 | 2024-10-30 | Gasherbrum Bio, Inc. | Heterociklični agonisti GLP-1 |
| WO2022048665A1 (en) * | 2020-09-07 | 2022-03-10 | Gasherbrum Bio, Inc. | Heterocyclic glp-1 agonists |
| JP2023540609A (ja) * | 2020-09-10 | 2023-09-25 | ガシャーブラム・バイオ・インコーポレイテッド | ヘテロ環ｇｌｐ－１アゴニスト |
| WO2023016546A1 (en) * | 2021-08-12 | 2023-02-16 | Gasherbrum Bio, Inc. | Heterocyclic glp-1 agonists |
| CA3233201A1 (en) | 2021-09-27 | 2023-03-30 | Terns Pharmaceuticals, Inc. | Benzimidazole carboxylic acids as glp-1r agonists |
| IL316629A (en) * | 2022-05-11 | 2024-12-01 | Lilly Co Eli | GLP1 drug compounds |
| IL316478A (en) * | 2022-05-11 | 2024-12-01 | Lilly Co Eli | GLP1 tablet preparations |
| KR20250111397A (ko) * | 2022-12-13 | 2025-07-22 | 일라이 릴리 앤드 캄파니 | 제2형 당뇨병 (t2d), 비만, 또는 적어도 하나의 체중 관련된 동반질환이 있는 과체중을 갖는 대상체를 치료하기 위한 오르포르글리프론의 투약 요법 |
| CN120457107A (zh) * | 2022-12-15 | 2025-08-08 | 维泰瑞隆有限公司 | Sarm1调节剂、其制备和用途 |
| IL321472A (en) * | 2022-12-19 | 2025-08-01 | Lilly Co Eli | Process for the production of GLP1 RA and intermediates therefor |
| WO2024153070A1 (en) * | 2023-01-17 | 2024-07-25 | Fochon Biosciences, Ltd. | Glp-1r agonists and uses thereof |
| AU2024222719A1 (en) | 2023-02-16 | 2025-08-21 | Gasherbrum Bio, Inc. | Heterocyclic glp-1 agonists |
| WO2025002250A1 (zh) * | 2023-06-29 | 2025-01-02 | 韦恩生物科技有限公司 | 一种glp-1受体激动剂及其制备方法和用途 |
| CN120574223A (zh) * | 2023-06-30 | 2025-09-02 | 正大天晴药业集团股份有限公司 | 含多稠环结构的化合物 |
| CN119431365A (zh) * | 2023-07-28 | 2025-02-14 | 江苏豪森药业集团有限公司 | 一种含苯基杂环类衍生物调节剂及其制备方法和应用 |
| WO2025026436A1 (zh) * | 2023-08-02 | 2025-02-06 | 韦恩生物科技有限公司 | 一种含氮并环化合物及其制备方法和用途 |
| WO2025097835A1 (zh) * | 2023-11-10 | 2025-05-15 | 重庆医药工业研究院有限责任公司 | 一种glp-1r激动剂化合物及其应用 |
| WO2025119206A1 (en) * | 2023-12-05 | 2025-06-12 | Fortvita Biologics Inc. | Glp-1 receptor targeting compounds and uses thereof |
| WO2025124357A1 (zh) * | 2023-12-14 | 2025-06-19 | 广东众生睿创生物科技有限公司 | 一种杂环glp-1受体激动剂及其应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006510582A (ja) | 2002-08-26 | 2006-03-30 | 武田薬品工業株式会社 | カルシウム受容体調節化合物およびその用途 |
| JP2010510987A (ja) | 2006-11-27 | 2010-04-08 | ハー・ルンドベック・アクチエゼルスカベット | ヘテロアリールアミド誘導体 |
| JP2012522060A (ja) | 2009-03-30 | 2012-09-20 | トランス テック ファーマ，インコーポレイテッド | 置換アゾアントラセン誘導体、その医薬組成物とその使用の方法 |
| WO2016038045A1 (en) | 2014-09-08 | 2016-03-17 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Pyrazolopyridine derivatives and their use in therapy |
| JP2016508506A (ja) | 2013-02-06 | 2016-03-22 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新しいインダニルオキシジヒドロベンゾフラニル酢酸 |
| JP6567778B2 (ja) | 2016-09-26 | 2019-08-28 | 中外製薬株式会社 | Ｇｌｐ−１受容体アゴニスト作用を持つピラゾロピリジン誘導体 |
-
2018
- 2018-11-29 JP JP2018223465A patent/JP7461104B2/ja active Active
-
2024
- 2024-03-22 JP JP2024045935A patent/JP2024079762A/ja active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006510582A (ja) | 2002-08-26 | 2006-03-30 | 武田薬品工業株式会社 | カルシウム受容体調節化合物およびその用途 |
| JP2010510987A (ja) | 2006-11-27 | 2010-04-08 | ハー・ルンドベック・アクチエゼルスカベット | ヘテロアリールアミド誘導体 |
| JP2012522060A (ja) | 2009-03-30 | 2012-09-20 | トランス テック ファーマ，インコーポレイテッド | 置換アゾアントラセン誘導体、その医薬組成物とその使用の方法 |
| JP2016508506A (ja) | 2013-02-06 | 2016-03-22 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新しいインダニルオキシジヒドロベンゾフラニル酢酸 |
| WO2016038045A1 (en) | 2014-09-08 | 2016-03-17 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Pyrazolopyridine derivatives and their use in therapy |
| JP6567778B2 (ja) | 2016-09-26 | 2019-08-28 | 中外製薬株式会社 | Ｇｌｐ−１受容体アゴニスト作用を持つピラゾロピリジン誘導体 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12234236B1 (en) | 2023-09-14 | 2025-02-25 | Ascletis Pharma (China) Co., Limited | GLP-1R agonist and therapeutic method thereof |
| US12291530B1 (en) | 2023-11-24 | 2025-05-06 | Ascletis Pharma (China) Co., Limited | GLP-1R agonist and therapeutic method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2024079762A (ja) | 2024-06-11 |
| JP2019099571A (ja) | 2019-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7602573B2 (ja) | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体 | |
| JP7461104B2 (ja) | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 | |
| US12410168B2 (en) | Pyrazolopyridine derivative having GLP-1 receptor agonist effect | |
| HK40004131B (en) | Pyrazolopyridine derivative having glp-1 receptor agonist effect | |
| NZ751725B2 (en) | Pyrazolopyridine derivative having glp-1 receptor agonist effect | |
| EA044109B1 (ru) | Производные пиразолопиридина, обладающие эффектом агониста рецептора glp-1 | |
| HK40004131A (en) | Pyrazolopyridine derivative having glp-1 receptor agonist effect | |
| BR112019005322B1 (pt) | Derivado de pirazolopiridina e seu sal de cálcio hemi-hidratado, composição farmacêutica e seu uso | |
| BR122021023465B1 (pt) | Derivado de pirazolopiridina, seu uso e composição farmacêutica |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20190516 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20190516 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20190523 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211126 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211126 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220906 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20221027 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230104 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230328 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230525 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230822 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231020 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20240123 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20240220 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240322 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7461104 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |