JP6577569B2 - Ｃ−アリールグリコシド誘導体、その薬物組成物、及び調製方法 - Google Patents

Info

Publication number

JP6577569B2

JP6577569B2 JP2017505695A JP2017505695A JP6577569B2 JP 6577569 B2 JP6577569 B2 JP 6577569B2 JP 2017505695 A JP2017505695 A JP 2017505695A JP 2017505695 A JP2017505695 A JP 2017505695A JP 6577569 B2 JP6577569 B2 JP 6577569B2

Authority

JP

Japan

Prior art keywords

compound

solvent

mmol

reaction

formula

Prior art date

2014-04-14

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• 238000002360 preparation method Methods 0.000 title claims description 52
• 239000000203 mixture Substances 0.000 title claims description 39
• 229930182470 glycoside Natural products 0.000 title claims description 31
• 239000003814 drug Substances 0.000 title claims description 29
• 229940079593 drug Drugs 0.000 title claims description 16
• 150000001875 compounds Chemical class 0.000 claims description 207
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 176
• 238000006243 chemical reaction Methods 0.000 claims description 169
• 239000002904 solvent Substances 0.000 claims description 113
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 98
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 72
• 238000000034 method Methods 0.000 claims description 65
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 64
• -1 aryl glycoside Chemical class 0.000 claims description 64
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 36
• 229910052799 carbon Inorganic materials 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 26
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims description 24
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 22
• 229910052760 oxygen Inorganic materials 0.000 claims description 21
• 125000006239 protecting group Chemical group 0.000 claims description 19
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 18
• 239000003513 alkali Substances 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 18
• 239000008103 glucose Substances 0.000 claims description 18
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 150000002367 halogens Chemical class 0.000 claims description 17
• 150000003839 salts Chemical class 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 16
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 14
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 229910015900 BF3 Inorganic materials 0.000 claims description 13
• 229910052731 fluorine Inorganic materials 0.000 claims description 13
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
• 229940124597 therapeutic agent Drugs 0.000 claims description 11
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
• 230000009471 action Effects 0.000 claims description 10
• 239000000460 chlorine Substances 0.000 claims description 10
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 239000012046 mixed solvent Substances 0.000 claims description 10
• 238000011282 treatment Methods 0.000 claims description 10
• 239000003153 chemical reaction reagent Substances 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 238000001953 recrystallisation Methods 0.000 claims description 9
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 238000002156 mixing Methods 0.000 claims description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 238000006722 reduction reaction Methods 0.000 claims description 7
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• 229940127003 anti-diabetic drug Drugs 0.000 claims description 5
• 239000003472 antidiabetic agent Substances 0.000 claims description 5
• 125000001246 bromo group Chemical group Br* 0.000 claims description 5
• 229940098779 methanesulfonic acid Drugs 0.000 claims description 5
• PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 claims description 5
• 208000002249 Diabetes Complications Diseases 0.000 claims description 4
• 206010012655 Diabetic complications Diseases 0.000 claims description 4
• 206010020772 Hypertension Diseases 0.000 claims description 4
• 208000008589 Obesity Diseases 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
• 125000002346 iodo group Chemical group I* 0.000 claims description 4
• 230000001404 mediated effect Effects 0.000 claims description 4
• 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 4
• 235000020824 obesity Nutrition 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• 238000006751 Mitsunobu reaction Methods 0.000 claims description 3
• 229910052740 iodine Chemical group 0.000 claims description 3
• 239000011630 iodine Chemical group 0.000 claims description 3
• 208000030159 metabolic disease Diseases 0.000 claims description 3
• 125000001979 organolithium group Chemical group 0.000 claims description 3
• 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 claims description 2
• 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 229940121377 sodium-glucose co-transporter inhibitor Drugs 0.000 claims description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 230000000155 isotopic effect Effects 0.000 claims 5
• 238000006467 substitution reaction Methods 0.000 claims 5
• 208000035473 Communicable disease Diseases 0.000 claims 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
• 125000001931 aliphatic group Chemical group 0.000 claims 1
• 230000003750 conditioning effect Effects 0.000 claims 1
• 125000006165 cyclic alkyl group Chemical group 0.000 claims 1
• 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
• 239000000243 solution Substances 0.000 description 74
• 238000005481 NMR spectroscopy Methods 0.000 description 73
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
• 239000012074 organic phase Substances 0.000 description 43
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
• 239000003208 petroleum Substances 0.000 description 33
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 238000010898 silica gel chromatography Methods 0.000 description 29
• 239000007787 solid Substances 0.000 description 29
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
• 230000015572 biosynthetic process Effects 0.000 description 26
• 238000003786 synthesis reaction Methods 0.000 description 26
• 238000004458 analytical method Methods 0.000 description 23
• 125000000753 cycloalkyl group Chemical group 0.000 description 23
• 239000012043 crude product Substances 0.000 description 22
• 239000010410 layer Substances 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
• 239000011734 sodium Substances 0.000 description 20
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 17
• 238000010791 quenching Methods 0.000 description 17
• 238000002390 rotary evaporation Methods 0.000 description 17
• 238000004821 distillation Methods 0.000 description 16
• 239000007788 liquid Substances 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 15
• 238000001308 synthesis method Methods 0.000 description 15
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical compound CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 description 12
• 125000002619 bicyclic group Chemical group 0.000 description 12
• MYRTYDVEIRVNKP-UHFFFAOYSA-N divinylbenzene Substances C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 230000000171 quenching effect Effects 0.000 description 12
• 239000000741 silica gel Substances 0.000 description 12
• 229910002027 silica gel Inorganic materials 0.000 description 12
• 238000000746 purification Methods 0.000 description 11
• 125000001072 heteroaryl group Chemical group 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical group CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 230000014759 maintenance of location Effects 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 230000002194 synthesizing effect Effects 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 125000003118 aryl group Chemical group 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 125000005842 heteroatom Chemical group 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 238000010521 absorption reaction Methods 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 7
• 238000004128 high performance liquid chromatography Methods 0.000 description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 239000012279 sodium borohydride Substances 0.000 description 7
• 229910000033 sodium borohydride Inorganic materials 0.000 description 7
• 229910052717 sulfur Inorganic materials 0.000 description 7
• 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 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 6
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 6
• 235000019270 ammonium chloride Nutrition 0.000 description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
• 229940007550 benzyl acetate Drugs 0.000 description 6
• 239000001569 carbon dioxide Substances 0.000 description 6
• 229910002092 carbon dioxide Inorganic materials 0.000 description 6
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
• 238000007796 conventional method Methods 0.000 description 6
• 125000004438 haloalkoxy group Chemical group 0.000 description 6
• 229940089468 hydroxyethylpiperazine ethane sulfonic acid Drugs 0.000 description 6
• 125000002950 monocyclic group Chemical group 0.000 description 6
• 239000003960 organic solvent Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
• DPIALHFJIMHDAS-RUPQSZEGSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@@H]1OC2=C(C1)C=CC=C2 Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@@H]1OC2=C(C1)C=CC=C2 DPIALHFJIMHDAS-RUPQSZEGSA-N 0.000 description 5
• DPIALHFJIMHDAS-RIVXRUHVSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OC2=C(C1)C=CC=C2 Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OC2=C(C1)C=CC=C2 DPIALHFJIMHDAS-RIVXRUHVSA-N 0.000 description 5
• 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 5
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 5
• 125000003282 alkyl amino group Chemical group 0.000 description 5
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• 150000001721 carbon Chemical group 0.000 description 5
• 239000012230 colorless oil Substances 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 210000002700 urine Anatomy 0.000 description 5
• DPIALHFJIMHDAS-QYENANPWSA-N (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-(2,3-dihydro-1-benzofuran-2-ylmethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2 DPIALHFJIMHDAS-QYENANPWSA-N 0.000 description 4
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 4
• NNQDMQVWOWCVEM-UHFFFAOYSA-N 1-bromoprop-1-ene Chemical compound CC=CBr NNQDMQVWOWCVEM-UHFFFAOYSA-N 0.000 description 4
• RRUIKDIGARKZIA-UHFFFAOYSA-N 3-fluoro-2-prop-2-enylphenol Chemical compound OC1=CC=CC(F)=C1CC=C RRUIKDIGARKZIA-UHFFFAOYSA-N 0.000 description 4
• BLKGHTVOWGHABE-KGFFULNXSA-N C1(OCC2=CC=CC=C12)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound C1(OCC2=CC=CC=C12)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 BLKGHTVOWGHABE-KGFFULNXSA-N 0.000 description 4
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 4
• ICPXVOYHMMUINK-AARQZCDPSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1(OC2=C(C1)C=CC=C2)C Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1(OC2=C(C1)C=CC=C2)C ICPXVOYHMMUINK-AARQZCDPSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• 229910052783 alkali metal Inorganic materials 0.000 description 4
• 125000003342 alkenyl group Chemical group 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
• 229910000024 caesium carbonate Inorganic materials 0.000 description 4
• DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 4
• 239000012141 concentrate Substances 0.000 description 4
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 4
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
• 229960003345 empagliflozin Drugs 0.000 description 4
• OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 description 4
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 4
• 238000000605 extraction Methods 0.000 description 4
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
• 230000002485 urinary effect Effects 0.000 description 4
• QYFBYHXEEODTMX-QMMMGPOBSA-N (2S)-2-(bromomethyl)-2,3-dihydro-1-benzofuran Chemical compound BrC[C@H]1OC2=C(C1)C=CC=C2 QYFBYHXEEODTMX-QMMMGPOBSA-N 0.000 description 3
• CJBNUOVCABHNLY-NSDXNHJYSA-N (2S,3R,4R,5S,6S)-2-[4-chloro-3-[[4-[(7-fluoro-2,3-dihydro-1-benzofuran-2-yl)methoxy]phenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2F CJBNUOVCABHNLY-NSDXNHJYSA-N 0.000 description 3
• KIMJBSWICNBTOJ-UHFFFAOYSA-N (3,3-dimethyl-1h-2-benzofuran-1-yl)methanol Chemical compound C1=CC=C2C(C)(C)OC(CO)C2=C1 KIMJBSWICNBTOJ-UHFFFAOYSA-N 0.000 description 3
• VFXRFXAEZVQAHB-UHFFFAOYSA-N (5-fluoro-1-benzofuran-2-yl)methanol Chemical compound FC1=CC=C2OC(CO)=CC2=C1 VFXRFXAEZVQAHB-UHFFFAOYSA-N 0.000 description 3
• UWOCHNNRMCCPTF-UHFFFAOYSA-N (7-fluoro-2,3-dihydro-1-benzofuran-2-yl)methanol Chemical compound C1=CC(F)=C2OC(CO)CC2=C1 UWOCHNNRMCCPTF-UHFFFAOYSA-N 0.000 description 3
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
• OKTWLGWQEYGNBA-UHFFFAOYSA-N 1,3-dihydro-2-benzofuran-1-ylmethanol Chemical compound C1=CC=C2C(CO)OCC2=C1 OKTWLGWQEYGNBA-UHFFFAOYSA-N 0.000 description 3
• MABBMHBZKPIFFV-UHFFFAOYSA-N 1-fluoro-2-prop-2-enoxybenzene Chemical compound FC1=CC=CC=C1OCC=C MABBMHBZKPIFFV-UHFFFAOYSA-N 0.000 description 3
• WTUUABQVRKOWKA-UHFFFAOYSA-N 1-fluoro-3-prop-2-enoxybenzene Chemical compound FC1=CC=CC(OCC=C)=C1 WTUUABQVRKOWKA-UHFFFAOYSA-N 0.000 description 3
• WDZLZKSUBSXWID-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-2-ol Chemical compound C1=CC=C2OC(O)CC2=C1 WDZLZKSUBSXWID-UHFFFAOYSA-N 0.000 description 3
• ADDZHRRCUWNSCS-UHFFFAOYSA-N 2-Benzofurancarboxaldehyde Chemical compound C1=CC=C2OC(C=O)=CC2=C1 ADDZHRRCUWNSCS-UHFFFAOYSA-N 0.000 description 3
• FDUBQNUDZOGOFE-UHFFFAOYSA-N 5-fluoro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(F)C=C1C=O FDUBQNUDZOGOFE-UHFFFAOYSA-N 0.000 description 3
• WUNQTXVVERFOSK-UHFFFAOYSA-N 5-fluoro-2-prop-2-enylphenol Chemical compound OC1=CC(F)=CC=C1CC=C WUNQTXVVERFOSK-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
• VLQIGOKMXCJNAM-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4F)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4F)C=C2)C=1)Cl VLQIGOKMXCJNAM-UHFFFAOYSA-N 0.000 description 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 3
• NIEOGUOGNSNLAX-UHFFFAOYSA-N CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)OC Chemical compound CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)OC NIEOGUOGNSNLAX-UHFFFAOYSA-N 0.000 description 3
• AQRNSHVFGHMMFJ-XUZJJRAFSA-N CC1(OCC2=CC=CC=C12)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound CC1(OCC2=CC=CC=C12)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 AQRNSHVFGHMMFJ-XUZJJRAFSA-N 0.000 description 3
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
• KTGWASGADVZXKH-WGWDPUIZSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OCC2=CC=CC=C12 Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OCC2=CC=CC=C12 KTGWASGADVZXKH-WGWDPUIZSA-N 0.000 description 3
• IFZLNUZUEFXQRL-VQYGVQKLSA-N O1[C@@H](CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1[C@@H](CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 IFZLNUZUEFXQRL-VQYGVQKLSA-N 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 239000007983 Tris buffer Substances 0.000 description 3
• OKTWLGWQEYGNBA-VIFPVBQESA-N [C@H]1(OCC2=CC=CC=C12)CO Chemical compound [C@H]1(OCC2=CC=CC=C12)CO OKTWLGWQEYGNBA-VIFPVBQESA-N 0.000 description 3
• 150000001340 alkali metals Chemical class 0.000 description 3
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
• 239000001110 calcium chloride Substances 0.000 description 3
• 229910001628 calcium chloride Inorganic materials 0.000 description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• RBQUPHUYCPBKSF-UHFFFAOYSA-N ethyl 5-fluoro-1-benzofuran-2-carboxylate Chemical compound FC1=CC=C2OC(C(=O)OCC)=CC2=C1 RBQUPHUYCPBKSF-UHFFFAOYSA-N 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 230000002218 hypoglycaemic effect Effects 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical group [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
• 229910001629 magnesium chloride Inorganic materials 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• 239000011259 mixed solution Substances 0.000 description 3
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
• 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 3
• 125000006574 non-aromatic ring group Chemical group 0.000 description 3
• 239000001103 potassium chloride Substances 0.000 description 3
• 235000011164 potassium chloride Nutrition 0.000 description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• 239000002994 raw material Substances 0.000 description 3
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
• XBPDGDITBHGBNK-MRXNPFEDSA-N (2R)-1-(2-methoxyphenyl)-3-phenylmethoxypropan-2-ol Chemical compound C(C1=CC=CC=C1)OC[C@@H](CC1=C(C=CC=C1)OC)O XBPDGDITBHGBNK-MRXNPFEDSA-N 0.000 description 2
• QYFBYHXEEODTMX-MRVPVSSYSA-N (2r)-2-(bromomethyl)-2,3-dihydro-1-benzofuran Chemical compound C1=CC=C2O[C@@H](CBr)CC2=C1 QYFBYHXEEODTMX-MRVPVSSYSA-N 0.000 description 2
• LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 2
• OEURLNJEQCLGPS-UHFFFAOYSA-N (5-bromo-2-chlorophenyl)-(4-ethoxyphenyl)methanone Chemical compound C1=CC(OCC)=CC=C1C(=O)C1=CC(Br)=CC=C1Cl OEURLNJEQCLGPS-UHFFFAOYSA-N 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• YUCBLVFHJWOYDN-HVLQGHBFSA-N 1,4-bis[(s)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@H](OC=3C4=CC=CC=C4C(O[C@H]([C@@H]4N5CC[C@H]([C@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-HVLQGHBFSA-N 0.000 description 2
• HSOMHPHYGAQRTF-UHFFFAOYSA-N 1-benzofuran-2-ylmethanol Chemical compound C1=CC=C2OC(CO)=CC2=C1 HSOMHPHYGAQRTF-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• NTYPQDZCDDLKLV-UHFFFAOYSA-N 1-bromo-2-prop-2-enylbenzene Chemical compound BrC1=CC=CC=C1CC=C NTYPQDZCDDLKLV-UHFFFAOYSA-N 0.000 description 2
• HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
• ZJMQZZXXIOGDIO-UHFFFAOYSA-N 2-(2,3-dihydro-1-benzofuran-2-yl)ethanol Chemical compound C1=CC=C2OC(CCO)CC2=C1 ZJMQZZXXIOGDIO-UHFFFAOYSA-N 0.000 description 2
• LSGCBNJHZGJEEJ-UHFFFAOYSA-N 2-(chloromethyl)-1-benzofuran Chemical compound C1=CC=C2OC(CCl)=CC2=C1 LSGCBNJHZGJEEJ-UHFFFAOYSA-N 0.000 description 2
• IWFBKDZCZVDZRT-UHFFFAOYSA-N 2-(chloromethyl)-5-fluoro-1-benzofuran Chemical compound FC1=CC=C2OC(CCl)=CC2=C1 IWFBKDZCZVDZRT-UHFFFAOYSA-N 0.000 description 2
• DHXICAQGITWFAS-VIFPVBQESA-N 2-[(3R)-3-bromo-3-hydroxypropyl]phenol Chemical compound Br[C@H](CCC1=C(C=CC=C1)O)O DHXICAQGITWFAS-VIFPVBQESA-N 0.000 description 2
• DHEJIZSVHGOKMJ-UHFFFAOYSA-N 2-ethenylbenzaldehyde Chemical compound C=CC1=CC=CC=C1C=O DHEJIZSVHGOKMJ-UHFFFAOYSA-N 0.000 description 2
• FZIBGCDUHZBOLA-UHFFFAOYSA-N 2-fluoro-6-hydroxybenzaldehyde Chemical compound OC1=CC=CC(F)=C1C=O FZIBGCDUHZBOLA-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• SJTBRFHBXDZMPS-UHFFFAOYSA-N 3-fluorophenol Chemical compound OC1=CC=CC(F)=C1 SJTBRFHBXDZMPS-UHFFFAOYSA-N 0.000 description 2
• KULJEMKFHPLNBR-UHFFFAOYSA-N 4-[(7-fluoro-2,3-dihydro-1-benzofuran-2-yl)methoxy]benzaldehyde Chemical compound FC1=CC=CC=2CC(OC=21)COC1=CC=C(C=C1)C=O KULJEMKFHPLNBR-UHFFFAOYSA-N 0.000 description 2
• YUCBLVFHJWOYDN-PPIALRKJSA-N 4-[(r)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-1-[(r)-[(2r,4r,5s)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@@H](OC=3C4=CC=CC=C4C(O[C@@H]([C@@H]4N5CC[C@@H]([C@@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-PPIALRKJSA-N 0.000 description 2
• ZUNCHZBITMUSRD-UHFFFAOYSA-N 4-bromo-1-chloro-2-[(4-ethoxyphenyl)methyl]benzene Chemical compound C1=CC(OCC)=CC=C1CC1=CC(Br)=CC=C1Cl ZUNCHZBITMUSRD-UHFFFAOYSA-N 0.000 description 2
• GBJJCODOZGPTBC-UHFFFAOYSA-N 4-fluoro-2-hydroxybenzaldehyde Chemical compound OC1=CC(F)=CC=C1C=O GBJJCODOZGPTBC-UHFFFAOYSA-N 0.000 description 2
• HELBBGLIOALLAF-UHFFFAOYSA-N 5-bromo-2-cyanobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC=C1C#N HELBBGLIOALLAF-UHFFFAOYSA-N 0.000 description 2
• JFDUXZIRWBYBAQ-UHFFFAOYSA-N 5-bromo-2-methoxybenzoic acid Chemical compound COC1=CC=C(Br)C=C1C(O)=O JFDUXZIRWBYBAQ-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-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
• 229910001148 Al-Li alloy Inorganic materials 0.000 description 2
• JZUIPNJQQBHLQR-UHFFFAOYSA-N BrC1=CC(=C(C#N)C=C1)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2 Chemical compound BrC1=CC(=C(C#N)C=C1)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2 JZUIPNJQQBHLQR-UHFFFAOYSA-N 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• RKGGXOVYJOETLH-GOSISDBHSA-N CC(C)[Si](C(C)C)(C(C)C)OC[C@@H]1C2=CC=CC=C2CO1 Chemical compound CC(C)[Si](C(C)C)(C(C)C)OC[C@@H]1C2=CC=CC=C2CO1 RKGGXOVYJOETLH-GOSISDBHSA-N 0.000 description 2
• WHYIFGGVIVRJAM-UHFFFAOYSA-N CC1(OCC2=CC=CC=C12)CO Chemical compound CC1(OCC2=CC=CC=C12)CO WHYIFGGVIVRJAM-UHFFFAOYSA-N 0.000 description 2
• XVGIBYTWUNKGFC-SNVBAGLBSA-N CC=1C=C2CO[C@@H](C2=CC=1)CO Chemical compound CC=1C=C2CO[C@@H](C2=CC=1)CO XVGIBYTWUNKGFC-SNVBAGLBSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• CJBNUOVCABHNLY-FMHUMOTFSA-N ClC1=C(C=C(C=C1)C1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2F Chemical compound ClC1=C(C=C(C=C1)C1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2F CJBNUOVCABHNLY-FMHUMOTFSA-N 0.000 description 2
• DSJFUERPPUSDHY-AARQZCDPSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1(OCC2=CC=CC=C12)C Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1(OCC2=CC=CC=C12)C DSJFUERPPUSDHY-AARQZCDPSA-N 0.000 description 2
• KTGWASGADVZXKH-JABWBWSPSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@@H]1OCC2=CC=CC=C12 Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@@H]1OCC2=CC=CC=C12 KTGWASGADVZXKH-JABWBWSPSA-N 0.000 description 2
• KTGWASGADVZXKH-GTMDKHCLSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OCC2=CC=CC=C12 Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OCC2=CC=CC=C12 KTGWASGADVZXKH-GTMDKHCLSA-N 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• OBWASQILIWPZMG-UHFFFAOYSA-N Empagliflozin Chemical compound OC1C(O)C(O)C(CO)OC1C1=CC=C(Cl)C(CC=2C=CC(OC3COCC3)=CC=2)=C1 OBWASQILIWPZMG-UHFFFAOYSA-N 0.000 description 2
• YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
• VFLMFIMNNIHXQU-SECBINFHSA-N FC=1C=C2CO[C@@H](C2=CC=1)CO Chemical compound FC=1C=C2CO[C@@H](C2=CC=1)CO VFLMFIMNNIHXQU-SECBINFHSA-N 0.000 description 2
• 102000018711 Facilitative Glucose Transport Proteins Human genes 0.000 description 2
• 108010027279 Facilitative Glucose Transport Proteins Proteins 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 208000013016 Hypoglycemia Diseases 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• OKTWLGWQEYGNBA-SECBINFHSA-N OC[C@H]1OCc2ccccc12 Chemical compound OC[C@H]1OCc2ccccc12 OKTWLGWQEYGNBA-SECBINFHSA-N 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• ITMGMSZDAOAVNO-QMMMGPOBSA-N [(2s)-2,3-dihydro-1-benzofuran-2-yl]methanol Chemical compound C1=CC=C2O[C@H](CO)CC2=C1 ITMGMSZDAOAVNO-QMMMGPOBSA-N 0.000 description 2
• JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• 229960001713 canagliflozin Drugs 0.000 description 2
• VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 238000004296 chiral HPLC Methods 0.000 description 2
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 125000000000 cycloalkoxy group Chemical group 0.000 description 2
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
• 238000007865 diluting Methods 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 208000016097 disease of metabolism Diseases 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 229930182478 glucoside Natural products 0.000 description 2
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• 201000001421 hyperglycemia Diseases 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 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 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 2
• PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 239000012285 osmium tetroxide Substances 0.000 description 2
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
• 210000000512 proximal kidney tubule Anatomy 0.000 description 2
• 210000000813 small intestine Anatomy 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
• 125000001424 substituent group Chemical group 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
• FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
• RDNZYEDFRMEYQF-UHFFFAOYSA-N (2-ethenylphenyl)methyl acetate Chemical compound CC(=O)OCC1=CC=CC=C1C=C RDNZYEDFRMEYQF-UHFFFAOYSA-N 0.000 description 1
• QNYBOILAKBSWFG-JTQLQIEISA-N (2r)-2-(phenylmethoxymethyl)oxirane Chemical compound C([C@@H]1OC1)OCC1=CC=CC=C1 QNYBOILAKBSWFG-JTQLQIEISA-N 0.000 description 1
• YKXCWZVUWWQSAV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O YKXCWZVUWWQSAV-BTVCFUMJSA-N 0.000 description 1
• QNYBOILAKBSWFG-SNVBAGLBSA-N (2s)-2-(phenylmethoxymethyl)oxirane Chemical compound C([C@H]1OC1)OCC1=CC=CC=C1 QNYBOILAKBSWFG-SNVBAGLBSA-N 0.000 description 1
• LVILQFKAGQFQEK-UHFFFAOYSA-N (5-bromo-2-chlorophenyl)-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC(Br)=CC=C1Cl LVILQFKAGQFQEK-UHFFFAOYSA-N 0.000 description 1
• 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 description 1
• DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• MPCAJMNYNOGXPB-UHFFFAOYSA-N 1,5-anhydrohexitol Chemical compound OCC1OCC(O)C(O)C1O MPCAJMNYNOGXPB-UHFFFAOYSA-N 0.000 description 1
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
• PIMNFNXBTGPCIL-UHFFFAOYSA-N 1-(2-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1Br PIMNFNXBTGPCIL-UHFFFAOYSA-N 0.000 description 1
• AZOVTQNTDOPLFQ-UHFFFAOYSA-N 1-[2-(3-bromophenyl)-4-fluorophenyl]ethanone Chemical compound CC(=O)c1ccc(F)cc1-c1cccc(Br)c1 AZOVTQNTDOPLFQ-UHFFFAOYSA-N 0.000 description 1
• NZKWIAVSCANBMU-UHFFFAOYSA-N 1-bromo-3-[(4-ethoxyphenyl)methyl]benzene Chemical compound C1=CC(OCC)=CC=C1CC1=CC=CC(Br)=C1 NZKWIAVSCANBMU-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• YJUFGFXVASPYFQ-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene Chemical compound C1=CC=C2SCCC2=C1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 description 1
• 125000004564 2,3-dihydrobenzofuran-2-yl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
• GNENVASJJIUNER-UHFFFAOYSA-N 2,4,6-tricyclohexyloxy-1,3,5,2,4,6-trioxatriborinane Chemical compound C1CCCCC1OB1OB(OC2CCCCC2)OB(OC2CCCCC2)O1 GNENVASJJIUNER-UHFFFAOYSA-N 0.000 description 1
• BVCOJESIQPNOIF-UHFFFAOYSA-N 2-(2-bromophenyl)acetonitrile Chemical compound BrC1=CC=CC=C1CC#N BVCOJESIQPNOIF-UHFFFAOYSA-N 0.000 description 1
• WWPKCWFXTQSXKX-UHFFFAOYSA-N 2-[[4-[(5-bromo-2-methoxyphenyl)methyl]phenyl]methyl]-1-benzofuran Chemical compound BrC=1C=CC(=C(CC2=CC=C(C=C2)CC=2OC3=C(C=2)C=CC=C3)C=1)OC WWPKCWFXTQSXKX-UHFFFAOYSA-N 0.000 description 1
• QIRNGVVZBINFMX-UHFFFAOYSA-N 2-allylphenol Chemical compound OC1=CC=CC=C1CC=C QIRNGVVZBINFMX-UHFFFAOYSA-N 0.000 description 1
• 125000005999 2-bromoethyl group Chemical group 0.000 description 1
• YKZMHGAKPDCTCH-UHFFFAOYSA-N 2-fluoro-6-(oxan-2-yloxy)benzaldehyde Chemical compound FC1=CC=CC(OC2OCCCC2)=C1C=O YKZMHGAKPDCTCH-UHFFFAOYSA-N 0.000 description 1
• HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
• FZTDYEUXQXNEER-UHFFFAOYSA-N 2-prop-2-enylbenzaldehyde Chemical compound C=CCC1=CC=CC=C1C=O FZTDYEUXQXNEER-UHFFFAOYSA-N 0.000 description 1
• YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 1
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
• BEYBTNQFCZVLQL-UHFFFAOYSA-N 4-bromo-2-[(4-ethoxyphenyl)methyl]-1-fluorobenzene Chemical compound C1=CC(OCC)=CC=C1CC1=CC(Br)=CC=C1F BEYBTNQFCZVLQL-UHFFFAOYSA-N 0.000 description 1
• MPOCPHMKKBYZMO-UHFFFAOYSA-N 4-bromo-2-[(4-ethoxyphenyl)methyl]-1-methylbenzene Chemical compound C1=CC(OCC)=CC=C1CC1=CC(Br)=CC=C1C MPOCPHMKKBYZMO-UHFFFAOYSA-N 0.000 description 1
• WJFJJYNKLXCHHX-UHFFFAOYSA-N 4-bromo-2-[(4-ethoxyphenyl)methyl]benzonitrile Chemical compound C1=CC(OCC)=CC=C1CC1=CC(Br)=CC=C1C#N WJFJJYNKLXCHHX-UHFFFAOYSA-N 0.000 description 1
• RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
• 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
• ADKYNRATSQVVPJ-UHFFFAOYSA-N 5,6,7,8,9,10-hexahydrobenzo[8]annulene Chemical compound C1CCCCCC2=CC=CC=C21 ADKYNRATSQVVPJ-UHFFFAOYSA-N 0.000 description 1
• FGERXQWKKIVFQG-UHFFFAOYSA-N 5-bromo-2-chlorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC=C1Cl FGERXQWKKIVFQG-UHFFFAOYSA-N 0.000 description 1
• IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 1
• HEOQXHNKRXRCTO-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-benzo[7]annulene Chemical compound C1CCCCC2=CC=CC=C21 HEOQXHNKRXRCTO-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
• 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 229940123208 Biguanide Drugs 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• GDGHVZJZDZYBPO-UHFFFAOYSA-N BrC1=C(C=CC=C1)CC=C.C(C=C)C1=C(C=O)C=CC=C1 Chemical compound BrC1=C(C=CC=C1)CC=C.C(C=C)C1=C(C=O)C=CC=C1 GDGHVZJZDZYBPO-UHFFFAOYSA-N 0.000 description 1
• POJHBRBRGOROEC-PKLMIRHRSA-N BrC1=C(C=CC=C1)OC.C(C1=CC=CC=C1)OC[C@@H](CC1=C(C=CC=C1)OC)O Chemical compound BrC1=C(C=CC=C1)OC.C(C1=CC=CC=C1)OC[C@@H](CC1=C(C=CC=C1)OC)O POJHBRBRGOROEC-PKLMIRHRSA-N 0.000 description 1
• YCQOIHAKJKSBAV-UHFFFAOYSA-N BrC1=CC(=C(C#N)C=C1)C(C1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2)=O.BrC2=CC(=C(C#N)C=C2)C(O)C2=CC=C(C=C2)OCC2OC1=C(C2)C=CC=C1 Chemical compound BrC1=CC(=C(C#N)C=C1)C(C1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2)=O.BrC2=CC(=C(C#N)C=C2)C(O)C2=CC=C(C=C2)OCC2OC1=C(C2)C=CC=C1 YCQOIHAKJKSBAV-UHFFFAOYSA-N 0.000 description 1
• PDXDPRVWKFYTEK-UHFFFAOYSA-N BrC1=CC(=C(C#N)C=C1)C(O)C1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2.BrC2=CC(=C(C#N)C=C2)CC2=CC=C(C=C2)OCC2OC1=C(C2)C=CC=C1 Chemical compound BrC1=CC(=C(C#N)C=C1)C(O)C1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2.BrC2=CC(=C(C#N)C=C2)CC2=CC=C(C=C2)OCC2OC1=C(C2)C=CC=C1 PDXDPRVWKFYTEK-UHFFFAOYSA-N 0.000 description 1
• MEQVJPAXGJYBRP-UHFFFAOYSA-N BrC1=CC(=C(C=C1)Cl)CC1=CC(=C(C=C1)OC)F Chemical compound BrC1=CC(=C(C=C1)Cl)CC1=CC(=C(C=C1)OC)F MEQVJPAXGJYBRP-UHFFFAOYSA-N 0.000 description 1
• WBVUGMIGLDKZCG-UHFFFAOYSA-N BrC=1C=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=CC=1 Chemical compound BrC=1C=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=CC=1 WBVUGMIGLDKZCG-UHFFFAOYSA-N 0.000 description 1
• MKEKLDFOAOQVFQ-UHFFFAOYSA-N BrC=1C=CC(=C(C1)C(=O)C1=CC=C(C=C1)OCC)Cl.BrC1=CC(=C(C=C1)Cl)CC1=CC=C(C=C1)OCC Chemical compound BrC=1C=CC(=C(C1)C(=O)C1=CC=C(C=C1)OCC)Cl.BrC1=CC(=C(C=C1)Cl)CC1=CC=C(C=C1)OCC MKEKLDFOAOQVFQ-UHFFFAOYSA-N 0.000 description 1
• IJLICWIHSZYBFU-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)C(=O)C1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2F)Cl Chemical compound BrC=1C=CC(=C(C=1)C(=O)C1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2F)Cl IJLICWIHSZYBFU-UHFFFAOYSA-N 0.000 description 1
• URVJFGYDYKPLBK-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3(OC4=C(C3)C=CC=C4)C)C=C2)C=1)C Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3(OC4=C(C3)C=CC=C4)C)C=C2)C=1)C URVJFGYDYKPLBK-UHFFFAOYSA-N 0.000 description 1
• DXBBKUCXUCCWDO-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3(OC4=C(C3)C=CC=C4)C)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3(OC4=C(C3)C=CC=C4)C)C=C2)C=1)Cl DXBBKUCXUCCWDO-UHFFFAOYSA-N 0.000 description 1
• CWJZWCRVEWUZAG-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3(OCC4=CC=CC=C34)C)C=C2)C=1)C Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3(OCC4=CC=CC=C34)C)C=C2)C=1)C CWJZWCRVEWUZAG-UHFFFAOYSA-N 0.000 description 1
• KUFBYTQYTSEBMD-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3(OCC4=CC=CC=C34)C)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3(OCC4=CC=CC=C34)C)C=C2)C=1)Cl KUFBYTQYTSEBMD-UHFFFAOYSA-N 0.000 description 1
• FGKLXDWIRXHPDM-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC(C4=CC=CC=C34)(C)C)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC(C4=CC=CC=C34)(C)C)C=C2)C=1)Cl FGKLXDWIRXHPDM-UHFFFAOYSA-N 0.000 description 1
• KEWCSGQGTMJEHR-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C(=CC=C4)F)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C(=CC=C4)F)C=C2)C=1)Cl KEWCSGQGTMJEHR-UHFFFAOYSA-N 0.000 description 1
• OEAQJQFNHMQDCC-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=C(C=C4)C)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=C(C=C4)C)C=C2)C=1)Cl OEAQJQFNHMQDCC-UHFFFAOYSA-N 0.000 description 1
• CYTSYAUVKCCCAF-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=C(C=C4)F)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=C(C=C4)F)C=C2)C=1)Cl CYTSYAUVKCCCAF-UHFFFAOYSA-N 0.000 description 1
• BWXMIBDLGJKSAK-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC(=C4)F)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC(=C4)F)C=C2)C=1)Cl BWXMIBDLGJKSAK-UHFFFAOYSA-N 0.000 description 1
• QJTBOEMYDKQCOM-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=1)C Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=1)C QJTBOEMYDKQCOM-UHFFFAOYSA-N 0.000 description 1
• SORWURQBSCSEJP-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=1)Cl SORWURQBSCSEJP-UHFFFAOYSA-N 0.000 description 1
• CATGOURPAQRYOR-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=1)OC Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OC4=C(C3)C=CC=C4)C=C2)C=1)OC CATGOURPAQRYOR-UHFFFAOYSA-N 0.000 description 1
• OMLBEQAVQZXNBE-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OCC4=CC=CC=C34)C=C2)C=1)C Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OCC4=CC=CC=C34)C=C2)C=1)C OMLBEQAVQZXNBE-UHFFFAOYSA-N 0.000 description 1
• MXFGXEDSHGDHMO-UHFFFAOYSA-N BrC=1C=CC(=C(CC2=CC=C(OCC3OCC4=CC=CC=C34)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OCC3OCC4=CC=CC=C34)C=C2)C=1)Cl MXFGXEDSHGDHMO-UHFFFAOYSA-N 0.000 description 1
• MXFGXEDSHGDHMO-QFIPXVFZSA-N BrC=1C=CC(=C(CC2=CC=C(OC[C@@H]3OCC4=CC=CC=C34)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OC[C@@H]3OCC4=CC=CC=C34)C=C2)C=1)Cl MXFGXEDSHGDHMO-QFIPXVFZSA-N 0.000 description 1
• QJTBOEMYDKQCOM-QFIPXVFZSA-N BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OC4=C(C3)C=CC=C4)C=C2)C=1)C Chemical compound BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OC4=C(C3)C=CC=C4)C=C2)C=1)C QJTBOEMYDKQCOM-QFIPXVFZSA-N 0.000 description 1
• SORWURQBSCSEJP-FQEVSTJZSA-N BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OC4=C(C3)C=CC=C4)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OC4=C(C3)C=CC=C4)C=C2)C=1)Cl SORWURQBSCSEJP-FQEVSTJZSA-N 0.000 description 1
• SAIGKYGQBCWHRO-HSZRJFAPSA-N BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OCC4=CC(=CC=C34)C)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OCC4=CC(=CC=C34)C)C=C2)C=1)Cl SAIGKYGQBCWHRO-HSZRJFAPSA-N 0.000 description 1
• JYDORGPQLIXHFE-JOCHJYFZSA-N BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OCC4=CC(=CC=C34)F)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OCC4=CC(=CC=C34)F)C=C2)C=1)Cl JYDORGPQLIXHFE-JOCHJYFZSA-N 0.000 description 1
• MXFGXEDSHGDHMO-JOCHJYFZSA-N BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OCC4=CC=CC=C34)C=C2)C=1)Cl Chemical compound BrC=1C=CC(=C(CC2=CC=C(OC[C@H]3OCC4=CC=CC=C34)C=C2)C=1)Cl MXFGXEDSHGDHMO-JOCHJYFZSA-N 0.000 description 1
• BIGVVTGYXZQHKR-UHFFFAOYSA-N BrCCC1OC2=C(C1)C=CC=C2 Chemical compound BrCCC1OC2=C(C1)C=CC=C2 BIGVVTGYXZQHKR-UHFFFAOYSA-N 0.000 description 1
• UKOHGWFAHLJCQH-PVSSEACSSA-N Br[C@H](CCC1=C(C=CC=C1)O)O.BrC[C@H]1OC2=C(C1)C=CC=C2 Chemical compound Br[C@H](CCC1=C(C=CC=C1)O)O.BrC[C@H]1OC2=C(C1)C=CC=C2 UKOHGWFAHLJCQH-PVSSEACSSA-N 0.000 description 1
• NBDBESBXUWNJLQ-UHFFFAOYSA-N C(=C)C1=C(C=O)C=CC=C1.CO Chemical compound C(=C)C1=C(C=O)C=CC=C1.CO NBDBESBXUWNJLQ-UHFFFAOYSA-N 0.000 description 1
• KXLPMZHJZRYUPP-UHFFFAOYSA-N C(C)(=O)OCC1=C(C=CC=C1)CC1=CC=CC=C1 Chemical compound C(C)(=O)OCC1=C(C=CC=C1)CC1=CC=CC=C1 KXLPMZHJZRYUPP-UHFFFAOYSA-N 0.000 description 1
• NQLGYKPQPDKDJE-UHFFFAOYSA-N C(C=C)C1=C(C=O)C=CC=C1.CO.C(C=C)C1=CC=CC=C1 Chemical compound C(C=C)C1=C(C=O)C=CC=C1.CO.C(C=C)C1=CC=CC=C1 NQLGYKPQPDKDJE-UHFFFAOYSA-N 0.000 description 1
• QOMCKHQJAWYXSL-UHFFFAOYSA-N CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)C Chemical compound CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)C QOMCKHQJAWYXSL-UHFFFAOYSA-N 0.000 description 1
• MILBLQYNLKWNKN-UHFFFAOYSA-N CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)Cl Chemical compound CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)Cl MILBLQYNLKWNKN-UHFFFAOYSA-N 0.000 description 1
• AWPDVVOQKIBNCR-UHFFFAOYSA-N CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)O.CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)OC Chemical compound CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)O.CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)OC AWPDVVOQKIBNCR-UHFFFAOYSA-N 0.000 description 1
• LHOHSRZIIUOSAN-UHFFFAOYSA-N CO.C(C=C)C1=CC=CC=C1.ClCC1=C(C=CC=C1)CC=C Chemical compound CO.C(C=C)C1=CC=CC=C1.ClCC1=C(C=CC=C1)CC=C LHOHSRZIIUOSAN-UHFFFAOYSA-N 0.000 description 1
• LZUVRDZXGRGVHU-UHFFFAOYSA-N COC1=C(C(=O)O)C=C(C=C1)Br.CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)O Chemical compound COC1=C(C(=O)O)C=C(C=C1)Br.CC(=O)C1=C(C=C(C=C1)F)C1=C(C=CC(=C1)Br)O LZUVRDZXGRGVHU-UHFFFAOYSA-N 0.000 description 1
• XTNGUQKDFGDXSJ-ZXGKGEBGSA-N Canagliflozin Chemical compound CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 XTNGUQKDFGDXSJ-ZXGKGEBGSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• VMHWCCHWWNCLPQ-UHFFFAOYSA-N ClC1(C(COC(C1O)CO)(O)C1=C(C=C(C=C1)OCC1OC(C2=CC=CC=C12)(C)C)CC1=CC=CC=C1)O Chemical compound ClC1(C(COC(C1O)CO)(O)C1=C(C=C(C=C1)OCC1OC(C2=CC=CC=C12)(C)C)CC1=CC=CC=C1)O VMHWCCHWWNCLPQ-UHFFFAOYSA-N 0.000 description 1
• VTGAJDMLNBVTRF-SJZQLPTNSA-N ClC1=C(C=C(C=C1)C1(O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)OC)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2F Chemical compound ClC1=C(C=C(C=C1)C1(O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)OC)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC=C2F VTGAJDMLNBVTRF-SJZQLPTNSA-N 0.000 description 1
• ZYPBQGOGPKQPFM-TWQRTPDCSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC(=C(C=C1)OCC1OC2=C(C1)C=CC=C2)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC(=C(C=C1)OCC1OC2=C(C1)C=CC=C2)F ZYPBQGOGPKQPFM-TWQRTPDCSA-N 0.000 description 1
• DBRFXVYVLMFFSQ-TWQRTPDCSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C(=CC=C2)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C(=CC=C2)F DBRFXVYVLMFFSQ-TWQRTPDCSA-N 0.000 description 1
• ZKCQEPKJMTVUPT-AQCDROMSSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=C(C=C2)C Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=C(C=C2)C ZKCQEPKJMTVUPT-AQCDROMSSA-N 0.000 description 1
• YLUOFFVBNMGJSO-QYENANPWSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=C(C=C2)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=C(C=C2)F YLUOFFVBNMGJSO-QYENANPWSA-N 0.000 description 1
• PVDJPDFLWJGBIA-QYENANPWSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC(=C2)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC1OC2=C(C1)C=CC(=C2)F PVDJPDFLWJGBIA-QYENANPWSA-N 0.000 description 1
• SYOQMNCJSLHWIT-DFLSAPQXSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C(=CC=C2)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C(=CC=C2)F SYOQMNCJSLHWIT-DFLSAPQXSA-N 0.000 description 1
• DBIFKCGYYMERAL-DFLSAPQXSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C=C(C=C2)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C=C(C=C2)F DBIFKCGYYMERAL-DFLSAPQXSA-N 0.000 description 1
• JVLNUVUSJZRQKS-DFLSAPQXSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C=CC(=C2)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C=CC(=C2)F JVLNUVUSJZRQKS-DFLSAPQXSA-N 0.000 description 1
• OLOATZAXGBXLGE-CBNWRBMVSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C=CC=C2F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCC=1OC2=C(C=1)C=CC=C2F OLOATZAXGBXLGE-CBNWRBMVSA-N 0.000 description 1
• RBEJDGYWSLUYEX-AQCDROMSSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCCC1OC2=C(C1)C=CC=C2 Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OCCC1OC2=C(C1)C=CC=C2 RBEJDGYWSLUYEX-AQCDROMSSA-N 0.000 description 1
• MHDQPSWZICUHJJ-CJSXUKLZSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OCC2=CC(=CC=C12)C Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OCC2=CC(=CC=C12)C MHDQPSWZICUHJJ-CJSXUKLZSA-N 0.000 description 1
• PGBNOKIUOPBGKO-GTMDKHCLSA-N ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OCC2=CC(=CC=C12)F Chemical compound ClC1=C(C=C(C=C1)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)CC1=CC=C(C=C1)OC[C@H]1OCC2=CC(=CC=C12)F PGBNOKIUOPBGKO-GTMDKHCLSA-N 0.000 description 1
• MNTRDKUFKKJRNZ-UHFFFAOYSA-N ClCC1=C(C=CC=C1)CC=C.CC1(OCC2=CC=CC=C12)CO Chemical compound ClCC1=C(C=CC=C1)CC=C.CC1(OCC2=CC=CC=C12)CO MNTRDKUFKKJRNZ-UHFFFAOYSA-N 0.000 description 1
• JVZAZWKXHOJDCX-UHFFFAOYSA-N ClCC=1OC2=C(C=1)C(=CC=C2)F Chemical compound ClCC=1OC2=C(C=1)C(=CC=C2)F JVZAZWKXHOJDCX-UHFFFAOYSA-N 0.000 description 1
• FWMZQFQQEMRXLU-UHFFFAOYSA-N ClCC=1OC2=C(C=1)C=CC(=C2)F Chemical compound ClCC=1OC2=C(C=1)C=CC(=C2)F FWMZQFQQEMRXLU-UHFFFAOYSA-N 0.000 description 1
• IEHLSVIJVDOAKT-UHFFFAOYSA-N ClCC=1OC2=C(C=1)C=CC=C2F Chemical compound ClCC=1OC2=C(C=1)C=CC=C2F IEHLSVIJVDOAKT-UHFFFAOYSA-N 0.000 description 1
• JWTSTOACXVSHNS-FYRLPREMSA-N ClCCl.O1C(CC2=C1C=CC=C2)COC2=CC=C(CC=1C=C(C=CC1C)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)C=C2 Chemical compound ClCCl.O1C(CC2=C1C=CC=C2)COC2=CC=C(CC=1C=C(C=CC1C)[C@@H]1O[C@@H]([C@H]([C@@H]([C@H]1O)O)O)CO)C=C2 JWTSTOACXVSHNS-FYRLPREMSA-N 0.000 description 1
• FLUWFVGRFVIMTA-UHFFFAOYSA-N ClS(=O)Cl.ClCC=1OC2=C(C1)C=C(C=C2)F Chemical compound ClS(=O)Cl.ClCC=1OC2=C(C1)C=C(C=C2)F FLUWFVGRFVIMTA-UHFFFAOYSA-N 0.000 description 1
• 229940126062 Compound A Drugs 0.000 description 1
• PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
• 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
• RECLUEYIMXGQLY-UHFFFAOYSA-N FC1=C(C=O)C(=CC=C1)OC1OCCCC1.FC1=C(C=O)C(=CC=C1)O Chemical compound FC1=C(C=O)C(=CC=C1)OC1OCCCC1.FC1=C(C=O)C(=CC=C1)O RECLUEYIMXGQLY-UHFFFAOYSA-N 0.000 description 1
• YVFFTHNBDJKNOL-UHFFFAOYSA-N FC=1C=C(C=CC1)C1OCCCC1.FC1=C(C=O)C(=CC=C1)OC1OCCCC1 Chemical compound FC=1C=C(C=CC1)C1OCCCC1.FC1=C(C=O)C(=CC=C1)OC1OCCCC1 YVFFTHNBDJKNOL-UHFFFAOYSA-N 0.000 description 1
• QKNRDEKOXUDPKO-UHFFFAOYSA-N FC=1C=C(C=CC1)O.FC=1C=C(C=CC1)C1OCCCC1 Chemical compound FC=1C=C(C=CC1)O.FC=1C=C(C=CC1)C1OCCCC1 QKNRDEKOXUDPKO-UHFFFAOYSA-N 0.000 description 1
• 102000004366 Glucosidases Human genes 0.000 description 1
• 108010056771 Glucosidases Proteins 0.000 description 1
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 102000004877 Insulin Human genes 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 239000005909 Kieselgur Substances 0.000 description 1
• 239000012097 Lipofectamine 2000 Substances 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
• LWQWDNDVPLPJCY-DFLSAPQXSA-N O1C(=CC2=C1C=CC=C2)COC1=C(C=C(CC=2C=C(C=CC=2Cl)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1)F Chemical compound O1C(=CC2=C1C=CC=C2)COC1=C(C=C(CC=2C=C(C=CC=2Cl)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1)F LWQWDNDVPLPJCY-DFLSAPQXSA-N 0.000 description 1
• IPBHNTPOJRNPCZ-RQKPWJHBSA-N O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC2=C(C#N)C=CC(=C2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC2=C(C#N)C=CC(=C2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 IPBHNTPOJRNPCZ-RQKPWJHBSA-N 0.000 description 1
• NIKWHNYNSIKYHY-DFLSAPQXSA-N O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 NIKWHNYNSIKYHY-DFLSAPQXSA-N 0.000 description 1
• MEIZZXIIHFPBDY-RQKPWJHBSA-N O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2C)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 MEIZZXIIHFPBDY-RQKPWJHBSA-N 0.000 description 1
• AYQMOLAIBRTRNL-DFLSAPQXSA-N O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2Cl)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2Cl)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 AYQMOLAIBRTRNL-DFLSAPQXSA-N 0.000 description 1
• LYZBNSNBRSKCKG-DFLSAPQXSA-N O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2F)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2F)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 LYZBNSNBRSKCKG-DFLSAPQXSA-N 0.000 description 1
• VYPKMXZMMOSMLR-RQKPWJHBSA-N O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2OC)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(=CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2OC)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 VYPKMXZMMOSMLR-RQKPWJHBSA-N 0.000 description 1
• AVTUFMPWLUPALP-UHFFFAOYSA-N O1C(CC2=C1C=CC=C2)CCO.BrCCC2OC1=C(C2)C=CC=C1 Chemical compound O1C(CC2=C1C=CC=C2)CCO.BrCCC2OC1=C(C2)C=CC=C1 AVTUFMPWLUPALP-UHFFFAOYSA-N 0.000 description 1
• PUWUVKYKRLFQMR-CYDVYFGRSA-N O1C(CC2=C1C=CC=C2)COC1=CC=C(CC2=C(C#N)C=CC(=C2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(CC2=C1C=CC=C2)COC1=CC=C(CC2=C(C#N)C=CC(=C2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 PUWUVKYKRLFQMR-CYDVYFGRSA-N 0.000 description 1
• XNNQAARVCUYAKW-RMFGLVLUSA-N O1C(CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 XNNQAARVCUYAKW-RMFGLVLUSA-N 0.000 description 1
• VYLYNQGAEQUOKU-QYENANPWSA-N O1C(CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2F)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2F)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 VYLYNQGAEQUOKU-QYENANPWSA-N 0.000 description 1
• GBOINAFCKBFJMU-AQCDROMSSA-N O1C(CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2OC)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 Chemical compound O1C(CC2=C1C=CC=C2)COC1=CC=C(CC=2C=C(C=CC=2OC)[C@@H]2O[C@@H]([C@H]([C@@H]([C@H]2O)O)O)CO)C=C1 GBOINAFCKBFJMU-AQCDROMSSA-N 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 229940126902 Phlorizin Drugs 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
• 229940100389 Sulfonylurea Drugs 0.000 description 1
• 102000003673 Symporters Human genes 0.000 description 1
• 108090000088 Symporters Proteins 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• KDSYNTPPPISIJB-UHFFFAOYSA-N [3-[[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxymethyl]phenyl]-(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone Chemical compound NCc1cc(OCc2cccc(c2)C(=O)N2CC(O)C(F)C2)nc(c1)C(F)(F)F KDSYNTPPPISIJB-UHFFFAOYSA-N 0.000 description 1
• SGVGVNPLNDXZTJ-KPQVYDHLSA-N [C@@H]1(OCC2=CC=CC=C12)CO[Si](C(C)C)(C(C)C)C(C)C.[C@@H]1(OCC2=CC=CC=C12)CO Chemical compound [C@@H]1(OCC2=CC=CC=C12)CO[Si](C(C)C)(C(C)C)C(C)C.[C@@H]1(OCC2=CC=CC=C12)CO SGVGVNPLNDXZTJ-KPQVYDHLSA-N 0.000 description 1
• SMFKZJJISKKNPX-UHFFFAOYSA-N [Na].O1C(=CC2=C1C=CC=C2)CO Chemical compound [Na].O1C(=CC2=C1C=CC=C2)CO SMFKZJJISKKNPX-UHFFFAOYSA-N 0.000 description 1
• 206010000059 abdominal discomfort Diseases 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
• 239000001099 ammonium carbonate Substances 0.000 description 1
• 229940101006 anhydrous sodium sulfite Drugs 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 125000004069 aziridinyl group Chemical group 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• UMIVXZPTRXBADB-UHFFFAOYSA-N benzocyclobutene Chemical compound C1=CC=C2CCC2=C1 UMIVXZPTRXBADB-UHFFFAOYSA-N 0.000 description 1
• 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 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
• 150000004283 biguanides Chemical class 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• VAOPEQGLAIKHQE-UHFFFAOYSA-N bromobenzene formaldehyde Chemical compound C=O.BrC1=CC=CC=C1 VAOPEQGLAIKHQE-UHFFFAOYSA-N 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000006727 cell loss Effects 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
• KMPWYEUPVWOPIM-LSOMNZGLSA-N cinchonine Chemical compound C1=CC=C2C([C@@H]([C@H]3N4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-LSOMNZGLSA-N 0.000 description 1
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 238000012258 culturing Methods 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
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 125000004431 deuterium atom Chemical group 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• 238000003113 dilution method Methods 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000013613 expression plasmid Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 238000011990 functional testing Methods 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 230000002641 glycemic effect Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 230000002440 hepatic effect Effects 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
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical class C1(C=CC2=CC=CC=C12)* 0.000 description 1
• LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 125000005438 isoindazolyl group Chemical group 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 238000001638 lipofection Methods 0.000 description 1
• FUJCRWPEOMXPAD-UHFFFAOYSA-N lithium oxide Chemical compound [Li+].[Li+].[O-2] FUJCRWPEOMXPAD-UHFFFAOYSA-N 0.000 description 1
• 229910001947 lithium oxide Inorganic materials 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 229940126601 medicinal product Drugs 0.000 description 1
• 239000013028 medium composition Substances 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
• ILHLLAOKTGOVCI-UHFFFAOYSA-N methanol prop-2-enylbenzene Chemical compound CO.C(C=C)C1=CC=CC=C1 ILHLLAOKTGOVCI-UHFFFAOYSA-N 0.000 description 1
• NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
• WZZMHOBVLAEJOD-UHFFFAOYSA-N methylsulfanylmethane;hydrobromide Chemical compound [Br-].C[SH+]C WZZMHOBVLAEJOD-UHFFFAOYSA-N 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
• 235000019799 monosodium phosphate Nutrition 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• GMBXBKNMMIWUED-UHFFFAOYSA-N n-(2,2,6,6-tetramethylpiperidin-4-yl)-3-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]propanamide Chemical compound C1C(C)(C)NC(C)(C)CC1NCCC(=O)NC1CC(C)(C)NC(C)(C)C1 GMBXBKNMMIWUED-UHFFFAOYSA-N 0.000 description 1
• SVEUVITYHIHZQE-UHFFFAOYSA-N n-methylpyridin-2-amine Chemical compound CNC1=CC=CC=N1 SVEUVITYHIHZQE-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000001400 nonyl 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])[H] 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 125000002347 octyl 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])[H] 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 229940127017 oral antidiabetic Drugs 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 238000011170 pharmaceutical development Methods 0.000 description 1
• IOUVKUPGCMBWBT-UHFFFAOYSA-N phloridzosid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-UHFFFAOYSA-N 0.000 description 1
• IOUVKUPGCMBWBT-GHRYLNIYSA-N phlorizin Chemical compound O[C@@H]1[C@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-GHRYLNIYSA-N 0.000 description 1
• 235000019139 phlorizin Nutrition 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• SFLGSKRGOWRGBR-UHFFFAOYSA-N phthalane Chemical compound C1=CC=C2COCC2=C1 SFLGSKRGOWRGBR-UHFFFAOYSA-N 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• HJWLCRVIBGQPNF-UHFFFAOYSA-N prop-2-enylbenzene Chemical compound C=CCC1=CC=CC=C1 HJWLCRVIBGQPNF-UHFFFAOYSA-N 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 229910021332 silicide Inorganic materials 0.000 description 1
• FVBUAEGBCNSCDD-UHFFFAOYSA-N silicide(4-) Chemical compound [Si-4] FVBUAEGBCNSCDD-UHFFFAOYSA-N 0.000 description 1
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
• 229910001415 sodium ion Inorganic materials 0.000 description 1
• 229940001482 sodium sulfite Drugs 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 125000006168 tricyclic group Chemical group 0.000 description 1
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
• 239000005051 trimethylchlorosilane Substances 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 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
• 238000001291 vacuum drying Methods 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1