EA022406B1 - Кристаллические формы гидрохлорида (4a-r,9a-s)-1-(1h-бензоимидазол-5-карбонил)-2,3,4,4a,9,9a-гексагидро-1h-индено[2,1-b]пиридин-6-карбонитрила и их применение в качестве ингибиторов hsd 1 - Google Patents

Info

Publication number

EA022406B1

EA022406B1 EA201390643A EA201390643A EA022406B1 EA 022406 B1 EA022406 B1 EA 022406B1 EA 201390643 A EA201390643 A EA 201390643A EA 201390643 A EA201390643 A EA 201390643A EA 022406 B1 EA022406 B1 EA 022406B1

Authority

EA

Eurasian Patent Office

Prior art keywords

group

compound

alkyl

acid

crystalline form

Prior art date

2010-11-05

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003112 inhibitor Substances 0.000 title abstract description 16
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 title description 4
• 101100451537 Caenorhabditis elegans hsd-1 gene Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 376
• 238000011282 treatment Methods 0.000 claims abstract description 31
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 14
• 102000004190 Enzymes Human genes 0.000 claims abstract description 10
• 108090000790 Enzymes Proteins 0.000 claims abstract description 10
• 230000006806 disease prevention Effects 0.000 claims abstract description 4
• 102000008645 11-beta-Hydroxysteroid Dehydrogenase Type 1 Human genes 0.000 claims abstract description 3
• 108010088011 11-beta-Hydroxysteroid Dehydrogenase Type 1 Proteins 0.000 claims abstract description 3
• 238000000034 method Methods 0.000 claims description 309
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 171
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 101
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 80
• 238000001816 cooling Methods 0.000 claims description 46
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 31
• 239000012458 free base Substances 0.000 claims description 29
• 230000015572 biosynthetic process Effects 0.000 claims description 23
• 239000002585 base Substances 0.000 claims description 20
• 239000000126 substance Substances 0.000 claims description 20
• 101710088194 Dehydrogenase Proteins 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
• 201000010099 disease Diseases 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 239000000725 suspension Substances 0.000 claims description 10
• 239000003085 diluting agent Substances 0.000 claims description 7
• 230000005588 protonation Effects 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 3
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 3
• 238000002156 mixing Methods 0.000 claims description 2
• 208000030159 metabolic disease Diseases 0.000 abstract description 7
• 208000008589 Obesity Diseases 0.000 abstract description 5
• 235000020824 obesity Nutrition 0.000 abstract description 5
• 208000032928 Dyslipidaemia Diseases 0.000 abstract description 4
• 208000017170 Lipid metabolism disease Diseases 0.000 abstract description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 4
• 230000000144 pharmacologic effect Effects 0.000 abstract description 3
• 230000001747 exhibiting effect Effects 0.000 abstract 1
• -1 heterocyclic amines Chemical class 0.000 description 510
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 268
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 201
• 239000000203 mixture Substances 0.000 description 192
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 164
• 238000001819 mass spectrum Methods 0.000 description 150
• 239000000543 intermediate Substances 0.000 description 106
• 239000000243 solution Substances 0.000 description 103
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 100
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
• 229910001868 water Inorganic materials 0.000 description 85
• 239000001257 hydrogen Substances 0.000 description 81
• 229910052739 hydrogen Inorganic materials 0.000 description 81
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 78
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 66
• 238000006243 chemical reaction Methods 0.000 description 66
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 65
• 239000002243 precursor Substances 0.000 description 64
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 63
• 239000002904 solvent Substances 0.000 description 60
• 239000007864 aqueous solution Substances 0.000 description 59
• 125000003118 aryl group Chemical group 0.000 description 55
• 150000003839 salts Chemical class 0.000 description 55
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 53
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 53
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
• 125000000217 alkyl group Chemical group 0.000 description 50
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 48
• 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 46
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
• 239000002253 acid Substances 0.000 description 45
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 43
• 239000000460 chlorine Substances 0.000 description 41
• 239000000741 silica gel Substances 0.000 description 40
• 229910002027 silica gel Inorganic materials 0.000 description 40
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 36
• 229910052731 fluorine Inorganic materials 0.000 description 34
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 33
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 32
• 239000011737 fluorine Substances 0.000 description 32
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 31
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 31
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
• 125000004093 cyano group Chemical group *C#N 0.000 description 29
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 28
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
• 229910052801 chlorine Inorganic materials 0.000 description 28
• 239000007787 solid Substances 0.000 description 27
• 229910052794 bromium Inorganic materials 0.000 description 26
• 239000003054 catalyst Substances 0.000 description 26
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 25
• 239000012071 phase Substances 0.000 description 25
• 125000004432 carbon atom Chemical group C* 0.000 description 24
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 23
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 22
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
• COYPLDIXZODDDL-UHFFFAOYSA-N 3h-benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N=CNC2=C1 COYPLDIXZODDDL-UHFFFAOYSA-N 0.000 description 21
• 239000000284 extract Substances 0.000 description 21
• 239000012074 organic phase Substances 0.000 description 21
• 229910052723 transition metal Inorganic materials 0.000 description 21
• 150000003624 transition metals Chemical class 0.000 description 20
• 230000009467 reduction Effects 0.000 description 19
• 238000006722 reduction reaction Methods 0.000 description 19
• 238000004809 thin layer chromatography Methods 0.000 description 19
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 18
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 17
• 229910052799 carbon Inorganic materials 0.000 description 17
• 150000002431 hydrogen Chemical class 0.000 description 17
• 229910052740 iodine Inorganic materials 0.000 description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 17
• 125000001424 substituent group Chemical group 0.000 description 17
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 16
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 16
• 125000003545 alkoxy group Chemical group 0.000 description 16
• 239000012267 brine Substances 0.000 description 16
• 125000001072 heteroaryl group Chemical group 0.000 description 16
• 230000008569 process Effects 0.000 description 16
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
• 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 16
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 239000012298 atmosphere Substances 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 125000005842 heteroatom Chemical group 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 15
• QRDZFPUVLYEQTA-UHFFFAOYSA-N quinoline-8-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=CC=CC2=C1 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 description 15
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 15
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 14
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 14
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 14
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 14
• XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 14
• 229910052763 palladium Inorganic materials 0.000 description 14
• 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 14
• 239000002244 precipitate Substances 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 12
• 125000003277 amino group Chemical group 0.000 description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
• 239000012039 electrophile Substances 0.000 description 12
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 12
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 11
• 239000000654 additive Substances 0.000 description 11
• 125000003342 alkenyl group Chemical group 0.000 description 11
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
• 238000001914 filtration Methods 0.000 description 11
• 229960000890 hydrocortisone Drugs 0.000 description 11
• 229910052757 nitrogen Inorganic materials 0.000 description 11
• 125000006239 protecting group Chemical group 0.000 description 11
• 125000004076 pyridyl group Chemical group 0.000 description 11
• 125000001544 thienyl group Chemical group 0.000 description 11
• 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 description 10
• 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 10
• 239000002841 Lewis acid Substances 0.000 description 10
• 125000002252 acyl group Chemical group 0.000 description 10
• 125000000304 alkynyl group Chemical group 0.000 description 10
• 150000001408 amides Chemical class 0.000 description 10
• 238000010438 heat treatment Methods 0.000 description 10
• 150000007517 lewis acids Chemical class 0.000 description 10
• 150000004702 methyl esters Chemical class 0.000 description 10
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 description 9
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 description 9
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• 239000013543 active substance Substances 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• 125000004104 aryloxy group Chemical group 0.000 description 9
• 239000001569 carbon dioxide Substances 0.000 description 9
• 229910002092 carbon dioxide Inorganic materials 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 9
• 125000001153 fluoro group Chemical group F* 0.000 description 9
• 125000002541 furyl group Chemical group 0.000 description 9
• 150000004678 hydrides Chemical class 0.000 description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
• 239000012279 sodium borohydride Substances 0.000 description 9
• 229910000033 sodium borohydride Inorganic materials 0.000 description 9
• 235000011121 sodium hydroxide Nutrition 0.000 description 9
• 238000002411 thermogravimetry Methods 0.000 description 9
• 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 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 8
• 238000005481 NMR spectroscopy Methods 0.000 description 8
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
• 150000007513 acids Chemical class 0.000 description 8
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 229910002091 carbon monoxide Inorganic materials 0.000 description 8
• 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 description 8
• 229910052736 halogen Inorganic materials 0.000 description 8
• 150000002367 halogens Chemical class 0.000 description 8
• 125000001041 indolyl group Chemical group 0.000 description 8
• 125000000468 ketone group Chemical group 0.000 description 8
• 230000001404 mediated effect Effects 0.000 description 8
• 150000002825 nitriles Chemical class 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 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 8
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 8
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
• 150000001298 alcohols Chemical class 0.000 description 7
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
• 229910052786 argon Inorganic materials 0.000 description 7
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 7
• 238000009835 boiling Methods 0.000 description 7
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 238000003776 cleavage reaction Methods 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 150000002430 hydrocarbons Chemical group 0.000 description 7
• 125000004537 indazol-5-yl group Chemical group N1N=CC2=CC(=CC=C12)* 0.000 description 7
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 7
• 229910052742 iron Inorganic materials 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• 239000012280 lithium aluminium hydride Substances 0.000 description 7
• 229910052751 metal Inorganic materials 0.000 description 7
• 239000002184 metal Substances 0.000 description 7
• 230000003647 oxidation Effects 0.000 description 7
• 238000007254 oxidation reaction Methods 0.000 description 7
• 229910052698 phosphorus Inorganic materials 0.000 description 7
• 125000000168 pyrrolyl group Chemical group 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 230000007017 scission Effects 0.000 description 7
• 229910052725 zinc Inorganic materials 0.000 description 7
• 239000011701 zinc Substances 0.000 description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 6
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• 208000002249 Diabetes Complications Diseases 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• 238000005917 acylation reaction Methods 0.000 description 6
• 125000003282 alkyl amino group Chemical group 0.000 description 6
• 150000001491 aromatic compounds Chemical class 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• 150000001728 carbonyl compounds Chemical class 0.000 description 6
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
• 239000010949 copper Substances 0.000 description 6
• 150000004820 halides Chemical class 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• 239000011630 iodine Substances 0.000 description 6
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 6
• 230000002503 metabolic effect Effects 0.000 description 6
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 6
• 229940098779 methanesulfonic acid Drugs 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
• 229910052759 nickel Inorganic materials 0.000 description 6
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 6
• 239000000018 receptor agonist Substances 0.000 description 6
• 229940044601 receptor agonist Drugs 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 238000007363 ring formation reaction Methods 0.000 description 6
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 6
• 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 6
• BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 6
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 5
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 5
• 206010012655 Diabetic complications Diseases 0.000 description 5
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
• 230000010933 acylation Effects 0.000 description 5
• 125000003172 aldehyde group Chemical group 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 239000003125 aqueous solvent Substances 0.000 description 5
• 150000001733 carboxylic acid esters Chemical class 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 229910052802 copper Inorganic materials 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 5
• 238000006193 diazotization reaction Methods 0.000 description 5
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 229930195733 hydrocarbon Natural products 0.000 description 5
• 125000001841 imino group Chemical group [H]N=* 0.000 description 5
• 238000011534 incubation Methods 0.000 description 5
• 239000012442 inert solvent Substances 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 239000003446 ligand Substances 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 125000001624 naphthyl group Chemical group 0.000 description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
• 239000012038 nucleophile Substances 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 5
• 230000002265 prevention Effects 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 230000005855 radiation Effects 0.000 description 5
• 239000011975 tartaric acid Substances 0.000 description 5
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 5
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 5
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 5
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• ORFGTFOSNBQTJV-NEPJUHHUSA-N (4ar,9as)-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridin-7-amine Chemical compound C1CCN[C@H]2CC3=CC(N)=CC=C3[C@H]21 ORFGTFOSNBQTJV-NEPJUHHUSA-N 0.000 description 4
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
• QCNGRUOQNGJXJU-UHFFFAOYSA-N 3-(3-methoxyphenyl)pyridine-2-carboxylic acid Chemical compound COC1=CC=CC(C=2C(=NC=CC=2)C(O)=O)=C1 QCNGRUOQNGJXJU-UHFFFAOYSA-N 0.000 description 4
• KBDIRPOTVAODSA-UHFFFAOYSA-N 3-bromopyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=C1Br KBDIRPOTVAODSA-UHFFFAOYSA-N 0.000 description 4
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 4
• RCUKIURSBATLLJ-UHFFFAOYSA-N 6-methoxyindeno[2,3-b]pyridin-9-one Chemical compound C1=CC=C2C3=CC(OC)=CC=C3C(=O)C2=N1 RCUKIURSBATLLJ-UHFFFAOYSA-N 0.000 description 4
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 4
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 4
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
• 206010020772 Hypertension Diseases 0.000 description 4
• 229930194542 Keto Natural products 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 239000007868 Raney catalyst Substances 0.000 description 4
• 229910000564 Raney nickel Inorganic materials 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 229910052783 alkali metal Inorganic materials 0.000 description 4
• 230000029936 alkylation Effects 0.000 description 4
• 238000005804 alkylation reaction Methods 0.000 description 4
• 125000002947 alkylene group Chemical group 0.000 description 4
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
• 150000008064 anhydrides Chemical class 0.000 description 4
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
• 125000005100 aryl amino carbonyl group Chemical group 0.000 description 4
• 125000004658 aryl carbonyl amino group Chemical group 0.000 description 4
• 239000004305 biphenyl Substances 0.000 description 4
• 235000010290 biphenyl Nutrition 0.000 description 4
• 229910000085 borane Inorganic materials 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 150000001805 chlorine compounds Chemical class 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 4
• 239000003814 drug Substances 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 125000002883 imidazolyl group Chemical group 0.000 description 4
• UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical class C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 description 4
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 4
• 229910052744 lithium Inorganic materials 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• 239000011777 magnesium Substances 0.000 description 4
• 229910052749 magnesium Inorganic materials 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• GYZSJCOPXQZGER-UHFFFAOYSA-N methyl quinoline-8-carboxylate Chemical compound C1=CN=C2C(C(=O)OC)=CC=CC2=C1 GYZSJCOPXQZGER-UHFFFAOYSA-N 0.000 description 4
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 4
• 239000002105 nanoparticle Substances 0.000 description 4
• 229910017604 nitric acid Inorganic materials 0.000 description 4
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 4
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
• 238000002360 preparation method Methods 0.000 description 4
• 125000003226 pyrazolyl group Chemical group 0.000 description 4
• 150000003254 radicals Chemical class 0.000 description 4
• 229910052703 rhodium Inorganic materials 0.000 description 4
• 239000010948 rhodium Substances 0.000 description 4
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 4
• 238000001228 spectrum Methods 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 238000005694 sulfonylation reaction Methods 0.000 description 4
• 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 4
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
• 238000002076 thermal analysis method Methods 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• 150000003623 transition metal compounds Chemical class 0.000 description 4
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
• HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 4
• 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 3
• QDQSCYPTBGSQBP-YPMHNXCESA-N (4ar,9as)-6-methoxy-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridine Chemical compound N1CCC[C@@H]2C3=CC(OC)=CC=C3C[C@@H]21 QDQSCYPTBGSQBP-YPMHNXCESA-N 0.000 description 3
• 125000006597 (C1-C3) alkylcarbonylamino group Chemical group 0.000 description 3
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 description 3
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 3
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
• GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 3
• KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical class C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 3
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
• 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 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 3
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 3
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
• 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 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
• 239000007983 Tris buffer Substances 0.000 description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
• 239000003377 acid catalyst Substances 0.000 description 3
• 230000000996 additive effect Effects 0.000 description 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
• 229910052782 aluminium Inorganic materials 0.000 description 3
• 239000002333 angiotensin II receptor antagonist Substances 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 239000012300 argon atmosphere Substances 0.000 description 3
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
• 239000004327 boric acid Substances 0.000 description 3
• XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 3
• 235000015165 citric acid Nutrition 0.000 description 3
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
• 239000012024 dehydrating agents‎ Substances 0.000 description 3
• 150000008049 diazo compounds Chemical class 0.000 description 3
• VPLLTGLLUHLIHA-UHFFFAOYSA-N dicyclohexyl(phenyl)phosphane Chemical group C1CCCCC1P(C=1C=CC=CC=1)C1CCCCC1 VPLLTGLLUHLIHA-UHFFFAOYSA-N 0.000 description 3
• 239000002934 diuretic Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 239000003862 glucocorticoid Substances 0.000 description 3
• 238000006197 hydroboration reaction Methods 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
• 150000002440 hydroxy compounds Chemical group 0.000 description 3
• RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 3
• 239000012948 isocyanate Substances 0.000 description 3
• 150000002513 isocyanates Chemical class 0.000 description 3
• 125000000842 isoxazolyl group Chemical group 0.000 description 3
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
• 230000000269 nucleophilic effect Effects 0.000 description 3
• 150000007530 organic bases Chemical group 0.000 description 3
• 125000002971 oxazolyl group Chemical group 0.000 description 3
• 125000000466 oxiranyl group Chemical group 0.000 description 3
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
• 125000003386 piperidinyl group Chemical group 0.000 description 3
• 229910052697 platinum Inorganic materials 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 235000011181 potassium carbonates Nutrition 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 235000018102 proteins Nutrition 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 125000002577 pseudohalo group Chemical group 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 150000003378 silver Chemical class 0.000 description 3
• 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 235000010288 sodium nitrite Nutrition 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 230000006103 sulfonylation Effects 0.000 description 3
• 229940037128 systemic glucocorticoids Drugs 0.000 description 3
• 235000002906 tartaric acid Nutrition 0.000 description 3
• VTOZKVFZUWQQMU-UHFFFAOYSA-N tert-butyl quinoline-4-carboxylate Chemical compound C1=CC=C2C(C(=O)OC(C)(C)C)=CC=NC2=C1 VTOZKVFZUWQQMU-UHFFFAOYSA-N 0.000 description 3
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 125000003831 tetrazolyl group Chemical group 0.000 description 3
• 125000000335 thiazolyl group Chemical group 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• 125000001425 triazolyl group Chemical group 0.000 description 3
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 3
• 239000005051 trimethylchlorosilane Substances 0.000 description 3
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 3
• DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 3
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 3
• NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
• NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 2
• YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 2
• KKQSSLZNDOPVQO-WBVHZDCISA-N (4ar,9as)-6-(3,6-dihydro-2h-pyran-4-yl)-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridine Chemical compound C1([C@H]2CCCN[C@H]2CC1=CC=1)=CC=1C1=CCOCC1 KKQSSLZNDOPVQO-WBVHZDCISA-N 0.000 description 2
• KCJYGNALSCTFOW-WBVHZDCISA-N (4ar,9as)-6-(cyclopenten-1-yl)-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridine Chemical compound C1CCC=C1C1=CC=C(C[C@H]2[C@@H]3CCCN2)C3=C1 KCJYGNALSCTFOW-WBVHZDCISA-N 0.000 description 2
• IYRAEFWPMQIDNQ-ZBFHGGJFSA-N (4ar,9as)-6-(furan-3-yl)-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridine Chemical compound C1([C@H]2CCCN[C@H]2CC1=CC=1)=CC=1C=1C=COC=1 IYRAEFWPMQIDNQ-ZBFHGGJFSA-N 0.000 description 2
• QKBMUXPBMMDVOG-YPMHNXCESA-N (4ar,9as)-6-methyl-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridine Chemical compound N1CCC[C@@H]2C3=CC(C)=CC=C3C[C@@H]21 QKBMUXPBMMDVOG-YPMHNXCESA-N 0.000 description 2
• DYSCMGLZADELMK-AEFFLSMTSA-N (4ar,9as)-6-phenyl-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridine Chemical compound C1([C@H]2CCCN[C@H]2CC1=CC=1)=CC=1C1=CC=CC=C1 DYSCMGLZADELMK-AEFFLSMTSA-N 0.000 description 2
• 125000006599 (C1-C3) alkylaminocarbonylamino group Chemical group 0.000 description 2
• 125000006595 (C1-C3) alkylsulfinyl group Chemical group 0.000 description 2
• 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 description 2
• QJMIKHWBGQHYPT-UHFFFAOYSA-N 1,2,3,4,4a,5,5a,6-octahydrobenzo[g]quinoline Chemical compound C1=CCC2CC(CCCN3)C3=CC2=C1 QJMIKHWBGQHYPT-UHFFFAOYSA-N 0.000 description 2
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
• RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
• HONDCIFZVSMIJQ-UHFFFAOYSA-N 1,3,4,9-tetrahydroindeno[2,1-b]pyridin-2-one Chemical compound C1=CC=C2C(CCC(N3)=O)=C3CC2=C1 HONDCIFZVSMIJQ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 2
• UIQYXKUFEDBRJE-WBVHZDCISA-N 1-[(4ar,9as)-6-(3,6-dihydro-2h-pyran-4-yl)-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C([C@H]1[C@@H](C2=C3)CCCN1C(=O)C(F)(F)F)C2=CC=C3C1=CCOCC1 UIQYXKUFEDBRJE-WBVHZDCISA-N 0.000 description 2
• BXXQEVPRKMLFQV-ZBFHGGJFSA-N 1-[(4ar,9as)-6-(furan-3-yl)-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C([C@H]1[C@@H](C2=C3)CCCN1C(=O)C(F)(F)F)C2=CC=C3C=1C=COC=1 BXXQEVPRKMLFQV-ZBFHGGJFSA-N 0.000 description 2
• ACTRYKFUXSVZBI-PWSUYJOCSA-N 1-[(4ar,9as)-6-hydroxy-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C12=CC(O)=CC=C2C[C@H]2[C@@H]1CCCN2C(=O)C(F)(F)F ACTRYKFUXSVZBI-PWSUYJOCSA-N 0.000 description 2
• KGZAENOMVASVGO-YPMHNXCESA-N 1-[(4ar,9as)-6-methoxy-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C12=CC(OC)=CC=C2C[C@H]2[C@@H]1CCCN2C(=O)C(F)(F)F KGZAENOMVASVGO-YPMHNXCESA-N 0.000 description 2
• XBVMHUHRRFTALW-YPMHNXCESA-N 1-[(4ar,9as)-6-methyl-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C12=CC(C)=CC=C2C[C@H]2[C@@H]1CCCN2C(=O)C(F)(F)F XBVMHUHRRFTALW-YPMHNXCESA-N 0.000 description 2
• OWAZRPFEFVUSLG-AEFFLSMTSA-N 1-[(4ar,9as)-6-phenyl-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C([C@H]1[C@@H](C2=C3)CCCN1C(=O)C(F)(F)F)C2=CC=C3C1=CC=CC=C1 OWAZRPFEFVUSLG-AEFFLSMTSA-N 0.000 description 2
• AXKODQWYERYHPM-UHFFFAOYSA-M 1-benzyl-4-methyl-9h-indeno[2,1-b]pyridin-1-ium;bromide Chemical compound [Br-].C1=2CC3=CC=CC=C3C=2C(C)=CC=[N+]1CC1=CC=CC=C1 AXKODQWYERYHPM-UHFFFAOYSA-M 0.000 description 2
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 2
• RHHATTYTIYFAKF-UHFFFAOYSA-N 1-ethyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=CC=C2C(CC)C(=O)CCC2=C1 RHHATTYTIYFAKF-UHFFFAOYSA-N 0.000 description 2
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 2
• FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
• CINJODFGIBPBSD-UHFFFAOYSA-N 2,3,4,4a,4b,5-hexahydro-1h-indeno[2,1-b]pyridine Chemical class C1=CCC2C(CCCN3)C3=CC2=C1 CINJODFGIBPBSD-UHFFFAOYSA-N 0.000 description 2
• 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 2
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
• SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 description 2
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
• JMTMWFZXOIWTLX-UHFFFAOYSA-N 2-pyridin-2-yloxypyridine Chemical compound C=1C=CC=NC=1OC1=CC=CC=N1 JMTMWFZXOIWTLX-UHFFFAOYSA-N 0.000 description 2
• ICHGAAALDGDCHR-UHFFFAOYSA-N 3-(3-methoxyphenyl)pyridine-2-carbonitrile Chemical compound COC1=CC=CC(C=2C(=NC=CC=2)C#N)=C1 ICHGAAALDGDCHR-UHFFFAOYSA-N 0.000 description 2
• DGDUWZZICMKBNM-UHFFFAOYSA-N 3-(3-methoxyphenyl)pyridine-2-carbonyl chloride Chemical compound COC1=CC=CC(C=2C(=NC=CC=2)C(Cl)=O)=C1 DGDUWZZICMKBNM-UHFFFAOYSA-N 0.000 description 2
• HCOPIUVJCIZALB-UHFFFAOYSA-N 3-bromopyridine-2-carbonitrile Chemical compound BrC1=CC=CN=C1C#N HCOPIUVJCIZALB-UHFFFAOYSA-N 0.000 description 2
• CPNMCWQGESOVJT-UHFFFAOYSA-N 4-methyl-9h-indeno[2,1-b]pyridine Chemical compound C1C2=CC=CC=C2C2=C1N=CC=C2C CPNMCWQGESOVJT-UHFFFAOYSA-N 0.000 description 2
• BYMLCFMGXFVMTK-UHFFFAOYSA-N 7-nitro-9h-indeno[2,1-b]pyridine Chemical compound C1=CC=C2C3=CC=C([N+](=O)[O-])C=C3CC2=N1 BYMLCFMGXFVMTK-UHFFFAOYSA-N 0.000 description 2
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 2
• PFWJFKBTIBAASX-UHFFFAOYSA-N 9h-indeno[2,1-b]pyridine Chemical group C1=CN=C2CC3=CC=CC=C3C2=C1 PFWJFKBTIBAASX-UHFFFAOYSA-N 0.000 description 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
• 206010007558 Cardiac failure chronic Diseases 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
• MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
• 229910016523 CuKa Inorganic materials 0.000 description 2
• NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 102000015779 HDL Lipoproteins Human genes 0.000 description 2
• 108010010234 HDL Lipoproteins Proteins 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
• 102000016267 Leptin Human genes 0.000 description 2
• 108010092277 Leptin Proteins 0.000 description 2
• 239000012448 Lithium borohydride Substances 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 2
• IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 238000006619 Stille reaction Methods 0.000 description 2
• 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
• LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 2
• TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 2
• 229920004482 WACKER® Polymers 0.000 description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 150000001263 acyl chlorides Chemical class 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 230000001476 alcoholic effect Effects 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 150000001345 alkine derivatives Chemical group 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 150000003863 ammonium salts Chemical class 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000001837 anti-cortisol effect Effects 0.000 description 2
• 239000002220 antihypertensive agent Substances 0.000 description 2
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 150000001540 azides Chemical class 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 239000003613 bile acid Substances 0.000 description 2
• HTJWUNNIRKDDIV-UHFFFAOYSA-N bis(1-adamantyl)-butylphosphane Chemical compound C1C(C2)CC(C3)CC2CC13P(CCCC)C1(C2)CC(C3)CC2CC3C1 HTJWUNNIRKDDIV-UHFFFAOYSA-N 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• OBZHEBDUNPOCJG-SZTGPWMUSA-N carbenoxolone Chemical compound C([C@H]1C2=CC(=O)[C@@H]34)[C@](C)(C(O)=O)CC[C@@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@H]1[C@@]3(C)CC[C@@H](OC(=O)CCC(O)=O)C1(C)C OBZHEBDUNPOCJG-SZTGPWMUSA-N 0.000 description 2
• 229960000530 carbenoxolone Drugs 0.000 description 2
• 150000001785 cerium compounds Chemical class 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 2
• 229940125844 compound 46 Drugs 0.000 description 2
• 150000001879 copper Chemical class 0.000 description 2
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
• 229960004544 cortisone Drugs 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 2
• KVBKAPANDHPRDG-UHFFFAOYSA-N dibromotetrafluoroethane Chemical compound FC(F)(Br)C(F)(F)Br KVBKAPANDHPRDG-UHFFFAOYSA-N 0.000 description 2
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 2
• 238000005906 dihydroxylation reaction Methods 0.000 description 2
• GEPAYBXVXXBSKP-SEPHDYHBSA-L disodium;5-isothiocyanato-2-[(e)-2-(4-isothiocyanato-2-sulfonatophenyl)ethenyl]benzenesulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC(N=C=S)=CC=C1\C=C\C1=CC=C(N=C=S)C=C1S([O-])(=O)=O GEPAYBXVXXBSKP-SEPHDYHBSA-L 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 150000002019 disulfides Chemical class 0.000 description 2
• CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 description 2
• 229940030606 diuretics Drugs 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 229940048820 edetates Drugs 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• 125000006575 electron-withdrawing group Chemical group 0.000 description 2
• 238000006735 epoxidation reaction Methods 0.000 description 2
• 230000032050 esterification Effects 0.000 description 2
• 238000005886 esterification reaction Methods 0.000 description 2
• CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 230000004907 flux Effects 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
• 239000008103 glucose Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 150000002390 heteroarenes Chemical class 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 230000008348 humoral response Effects 0.000 description 2
• 238000005669 hydrocyanation reaction Methods 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 239000012535 impurity Substances 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 150000007529 inorganic bases Chemical group 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
• OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
• 230000000155 isotopic effect Effects 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 2
• 229940039781 leptin Drugs 0.000 description 2
• 238000004811 liquid chromatography Methods 0.000 description 2
• 210000001853 liver microsome Anatomy 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 229910052987 metal hydride Inorganic materials 0.000 description 2
• 150000004681 metal hydrides Chemical class 0.000 description 2
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
• UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 2
• 230000003228 microsomal effect Effects 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 229910052901 montmorillonite Inorganic materials 0.000 description 2
• QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 2
• NLEUXPOVZGDKJI-UHFFFAOYSA-N nickel(2+);dicyanide Chemical compound [Ni+2].N#[C-].N#[C-] NLEUXPOVZGDKJI-UHFFFAOYSA-N 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 230000009935 nitrosation Effects 0.000 description 2
• 238000007034 nitrosation reaction Methods 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• 239000007800 oxidant agent Substances 0.000 description 2
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
• 238000005949 ozonolysis reaction Methods 0.000 description 2
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 2
• 150000003003 phosphines Chemical class 0.000 description 2
• AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 229910003446 platinum oxide Inorganic materials 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
• 239000011698 potassium fluoride Substances 0.000 description 2
• 235000003270 potassium fluoride Nutrition 0.000 description 2
• YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
• VQMSRUREDGBWKT-UHFFFAOYSA-N quinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=NC2=C1 VQMSRUREDGBWKT-UHFFFAOYSA-N 0.000 description 2
• 230000008707 rearrangement Effects 0.000 description 2
• 238000005932 reductive alkylation reaction Methods 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 229910052707 ruthenium Inorganic materials 0.000 description 2
• 150000003333 secondary alcohols Chemical class 0.000 description 2
• NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
• 239000010802 sludge Substances 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 2
• 229910000080 stannane Inorganic materials 0.000 description 2
• RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
• ZTXUNQRBUQZFKB-CABCVRRESA-N tert-butyl (4ar,9as)-7-amino-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridine-1-carboxylate Chemical compound NC1=CC=C2[C@H]3CCCN(C(=O)OC(C)(C)C)[C@H]3CC2=C1 ZTXUNQRBUQZFKB-CABCVRRESA-N 0.000 description 2
• XTDXZSGSIMLARD-UHFFFAOYSA-N tert-butyl 2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=CC=C1 XTDXZSGSIMLARD-UHFFFAOYSA-N 0.000 description 2
• 150000003509 tertiary alcohols Chemical class 0.000 description 2
• 150000003512 tertiary amines Chemical class 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 150000007970 thio esters Chemical class 0.000 description 2
• 125000003396 thiol group Chemical class [H]S* 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-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
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
• 229940116269 uric acid Drugs 0.000 description 2
• 230000004580 weight loss Effects 0.000 description 2
• 229940075966 (+)- menthol Drugs 0.000 description 1
• NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
• RYGOBSYXIIUFOR-UHFFFAOYSA-N (1-methylpyrazol-4-yl)boronic acid Chemical compound CN1C=C(B(O)O)C=N1 RYGOBSYXIIUFOR-UHFFFAOYSA-N 0.000 description 1
• 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 1
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
• IOCYQQQCJYMWDT-UHFFFAOYSA-N (3-ethyl-2-methoxyquinolin-6-yl)-(4-methoxycyclohexyl)methanone Chemical compound C=1C=C2N=C(OC)C(CC)=CC2=CC=1C(=O)C1CCC(OC)CC1 IOCYQQQCJYMWDT-UHFFFAOYSA-N 0.000 description 1
• AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
• VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
• NGDCMDXCWSJEDF-ZBFHGGJFSA-N (4ar,9as)-6-(1-methylpyrazol-4-yl)-2,3,4,4a,9,9a-hexahydro-1h-indeno[2,1-b]pyridine Chemical compound C1=NN(C)C=C1C1=CC=C(C[C@H]2[C@@H]3CCCN2)C3=C1 NGDCMDXCWSJEDF-ZBFHGGJFSA-N 0.000 description 1
• 125000006603 (C1-C3) alkylaminosulfonyl group Chemical group 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006593 (C2-C3) alkynyl group Chemical group 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• KFHHPVVJLXPHJL-UPHRSURJSA-N (z)-4-hydroperoxy-4-oxobut-2-enoic acid Chemical class OOC(=O)\C=C/C(O)=O KFHHPVVJLXPHJL-UPHRSURJSA-N 0.000 description 1
• FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 1
• IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
• OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
• ILROLYQPRYHHFG-UHFFFAOYSA-N 1-$l^{1}-oxidanylprop-2-en-1-one Chemical group [O]C(=O)C=C ILROLYQPRYHHFG-UHFFFAOYSA-N 0.000 description 1
• UZNQNWYIDSYPLV-UHFFFAOYSA-N 1-(1h-inden-2-yl)pyrrolidine Chemical compound C1CCCN1C1=CC2=CC=CC=C2C1 UZNQNWYIDSYPLV-UHFFFAOYSA-N 0.000 description 1
• UAXKBFHONACCHL-UHFFFAOYSA-N 1-(2-chloroethyl)-3-(1-$l^{1}-oxidanyl-2,2,6,6-tetramethylpiperidin-4-yl)-1-nitrosourea Chemical compound CC1(C)CC(NC(=O)N(CCCl)N=O)CC(C)(C)N1[O] UAXKBFHONACCHL-UHFFFAOYSA-N 0.000 description 1
• YWYAUYAEQBYZFN-UHFFFAOYSA-N 1-(3,4-dihydronaphthalen-2-yl)pyrrolidine Chemical compound C1CCCN1C1=CC2=CC=CC=C2CC1 YWYAUYAEQBYZFN-UHFFFAOYSA-N 0.000 description 1
• RKFHCVVZEYJHGO-NEPJUHHUSA-N 1-[(4ar,9as)-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C1=CC=C2[C@H]3CCCN(C(=O)C(F)(F)F)[C@H]3CC2=C1 RKFHCVVZEYJHGO-NEPJUHHUSA-N 0.000 description 1
• WKDUIUVKYDLOKZ-ZBFHGGJFSA-N 1-[(4ar,9as)-6-(1-methylpyrazol-4-yl)-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C1=NN(C)C=C1C1=CC=C(C[C@@H]2N(CCC[C@@H]22)C(=O)C(F)(F)F)C2=C1 WKDUIUVKYDLOKZ-ZBFHGGJFSA-N 0.000 description 1
• HRWRZDQSRIVIDN-WBVHZDCISA-N 1-[(4ar,9as)-6-(cyclopenten-1-yl)-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-2,2,2-trifluoroethanone Chemical compound C([C@H]1[C@@H](C2=C3)CCCN1C(=O)C(F)(F)F)C2=CC=C3C1=CCCC1 HRWRZDQSRIVIDN-WBVHZDCISA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000006039 1-hexenyl group Chemical group 0.000 description 1
• VGZQKUJGVYFKBP-UHFFFAOYSA-N 1-methyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=CC=C2C(C)C(=O)CCC2=C1 VGZQKUJGVYFKBP-UHFFFAOYSA-N 0.000 description 1
• 125000006023 1-pentenyl group Chemical group 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 1
• NRVIZYWYHXROKA-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyridine-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=NC2=N1 NRVIZYWYHXROKA-UHFFFAOYSA-N 0.000 description 1
• HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 description 1
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• SLMHHOVQRSSRCV-UHFFFAOYSA-N 2,3-dibromopyridine Chemical compound BrC1=CC=CN=C1Br SLMHHOVQRSSRCV-UHFFFAOYSA-N 0.000 description 1
• MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
• JGFXUYLYPITYGR-UHFFFAOYSA-N 2-(2-diphenylphosphanylphenyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 JGFXUYLYPITYGR-UHFFFAOYSA-N 0.000 description 1
• NIJWAAUHTPDGOM-UHFFFAOYSA-N 2-(2-phenylethyl)pyridine Chemical compound C=1C=CC=CC=1CCC1=CC=CC=N1 NIJWAAUHTPDGOM-UHFFFAOYSA-N 0.000 description 1
• WFZZMEOXDLWFHI-UHFFFAOYSA-N 2-(3-methoxy-2-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound COC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=C1C WFZZMEOXDLWFHI-UHFFFAOYSA-N 0.000 description 1
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• PCFUWBOSXMKGIP-UHFFFAOYSA-N 2-benzylpyridine Chemical group C=1C=CC=NC=1CC1=CC=CC=C1 PCFUWBOSXMKGIP-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
• 125000006040 2-hexenyl group Chemical group 0.000 description 1
• MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 1
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
• JSBBMMHTNIUVTC-UHFFFAOYSA-N 2-hydroxyethanone Chemical group OC[C]=O JSBBMMHTNIUVTC-UHFFFAOYSA-N 0.000 description 1
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
• USZSGINUZRHINQ-UHFFFAOYSA-N 2-oxo-3h-1,3-benzothiazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC(=O)SC2=C1 USZSGINUZRHINQ-UHFFFAOYSA-N 0.000 description 1
• 125000006024 2-pentenyl group Chemical group 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• PHBYNHYLFOEGDK-UHFFFAOYSA-N 3-bromo-2-(2-phenylethyl)pyridine Chemical compound BrC1=CC=CN=C1CCC1=CC=CC=C1 PHBYNHYLFOEGDK-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• PRORLQAJNJMGAR-UHFFFAOYSA-N 3-chloro-6-methylpyridazine Chemical compound CC1=CC=C(Cl)N=N1 PRORLQAJNJMGAR-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• YDPLFBIGFQFIDB-UHFFFAOYSA-N 3-chloropyridine-2-carbonitrile Chemical compound ClC1=CC=CN=C1C#N YDPLFBIGFQFIDB-UHFFFAOYSA-N 0.000 description 1
• 125000006041 3-hexenyl group Chemical group 0.000 description 1
• NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 description 1
• 239000003148 4 aminobutyric acid receptor blocking agent Substances 0.000 description 1
• CWXUCOIJSLPOCZ-UHFFFAOYSA-N 4,4-dimethyl-1,3-dihydronaphthalen-2-one Chemical compound C1=CC=C2C(C)(C)CC(=O)CC2=C1 CWXUCOIJSLPOCZ-UHFFFAOYSA-N 0.000 description 1
• JMHSCWJIDIKGNZ-UHFFFAOYSA-N 4-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=C(C(O)=O)C=C1 JMHSCWJIDIKGNZ-UHFFFAOYSA-N 0.000 description 1
• 125000006042 4-hexenyl group Chemical group 0.000 description 1
• HOUVATQQKYAEBB-UHFFFAOYSA-N 5,7-difluoro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(F)=CC(F)=C21 HOUVATQQKYAEBB-UHFFFAOYSA-N 0.000 description 1
• 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
• 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
• IMVDZFOSXJSXFP-UHFFFAOYSA-N 5-chloro-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carbaldehyde Chemical compound CCCC1=NC(Cl)=C(C=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 IMVDZFOSXJSXFP-UHFFFAOYSA-N 0.000 description 1
• 125000006043 5-hexenyl group Chemical group 0.000 description 1
• MDAIAXRTLTVEOU-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=C1C=CC=C2OC MDAIAXRTLTVEOU-UHFFFAOYSA-N 0.000 description 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• BYHKDUFPSJWJDI-UHFFFAOYSA-N 6-bromo-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(Br)=CC=C21 BYHKDUFPSJWJDI-UHFFFAOYSA-N 0.000 description 1
• HRUYBRGMRSNLNW-UHFFFAOYSA-N 6-methoxy-2-[(4-methylphenyl)methylsulfanyl]-1h-benzimidazole Chemical compound N1C2=CC(OC)=CC=C2N=C1SCC1=CC=C(C)C=C1 HRUYBRGMRSNLNW-UHFFFAOYSA-N 0.000 description 1
• RMRKDYNVZWKAFP-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(OC)=CC=C21 RMRKDYNVZWKAFP-UHFFFAOYSA-N 0.000 description 1
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
• XEAPZXNZOJGVCZ-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(OC)=CC=C21 XEAPZXNZOJGVCZ-UHFFFAOYSA-N 0.000 description 1
• BIZFHQDZRNKNAU-UHFFFAOYSA-N 7-nitro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC([N+](=O)[O-])=CC=C21 BIZFHQDZRNKNAU-UHFFFAOYSA-N 0.000 description 1
• RWEVGLMABSFMKW-UHFFFAOYSA-N 8-bromo-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=CC=C2Br RWEVGLMABSFMKW-UHFFFAOYSA-N 0.000 description 1
• MQCCLMXABWLNIF-UHFFFAOYSA-N 8-fluoro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=CC=C2F MQCCLMXABWLNIF-UHFFFAOYSA-N 0.000 description 1
• BTYBORAHYUCUMH-UHFFFAOYSA-N 8-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=CC=C2OC BTYBORAHYUCUMH-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
• 208000009304 Acute Kidney Injury Diseases 0.000 description 1
• 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
• 102000008873 Angiotensin II receptor Human genes 0.000 description 1
• 108050000824 Angiotensin II receptor Proteins 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 229910015900 BF3 Inorganic materials 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 206010065687 Bone loss Diseases 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• OEIYRAUTJALFIG-UHFFFAOYSA-N BrC1(NC=CC=C1)CCC1=CC=CC=C1 Chemical compound BrC1(NC=CC=C1)CCC1=CC=CC=C1 OEIYRAUTJALFIG-UHFFFAOYSA-N 0.000 description 1
• 239000007848 Bronsted acid Substances 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
• 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
• 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 description 1
• BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 1
• JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 101150065749 Churc1 gene Proteins 0.000 description 1
• FZLWTRLVFXUTLF-UHFFFAOYSA-N ClBr(=O)=O.ClBr(=O)=O.C1=CC=NC=C1 Chemical compound ClBr(=O)=O.ClBr(=O)=O.C1=CC=NC=C1 FZLWTRLVFXUTLF-UHFFFAOYSA-N 0.000 description 1
• 208000028698 Cognitive impairment Diseases 0.000 description 1
• OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
• QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
• 239000005751 Copper oxide Substances 0.000 description 1
• AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 208000008960 Diabetic foot Diseases 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
• 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 108010011459 Exenatide Proteins 0.000 description 1
• 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
• 102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
• 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 1
• 229940098788 GABA receptor antagonist Drugs 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• 229940122904 Glucagon receptor antagonist Drugs 0.000 description 1
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
• 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
• 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
• 102000030595 Glucokinase Human genes 0.000 description 1
• 108010021582 Glucokinase Proteins 0.000 description 1
• 102000003638 Glucose-6-Phosphatase Human genes 0.000 description 1
• 108010086800 Glucose-6-Phosphatase Proteins 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
• 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
• 108010001483 Glycogen Synthase Proteins 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
• MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 108700024827 HOC1 Proteins 0.000 description 1
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
• 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 201000001431 Hyperuricemia Diseases 0.000 description 1
• 208000013016 Hypoglycemia Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
• 208000007976 Ketosis Diseases 0.000 description 1
• 238000005577 Kumada cross-coupling reaction Methods 0.000 description 1
• 150000000994 L-ascorbates Chemical class 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
• 102000006835 Lamins Human genes 0.000 description 1
• 108010047294 Lamins Proteins 0.000 description 1
• 206010024229 Leprosy Diseases 0.000 description 1
• LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 1
• 101150034680 Lis-1 gene Proteins 0.000 description 1
• 238000006644 Lossen rearrangement reaction Methods 0.000 description 1
• 206010054805 Macroangiopathy Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• NMMIHXMBOZYNET-UHFFFAOYSA-N Methyl picolinate Chemical compound COC(=O)C1=CC=CC=N1 NMMIHXMBOZYNET-UHFFFAOYSA-N 0.000 description 1
• 229910017976 MgO 4 Inorganic materials 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
• XJLXINKUBYWONI-NNYOXOHSSA-N NADP zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 238000006411 Negishi coupling reaction Methods 0.000 description 1
• KEJOCWOXCDWNID-UHFFFAOYSA-N Nitrilooxonium Chemical compound [O+]#N KEJOCWOXCDWNID-UHFFFAOYSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 239000005480 Olmesartan Substances 0.000 description 1
• 238000006036 Oppenauer oxidation reaction Methods 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
• 101150084844 PAFAH1B1 gene Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 238000003527 Peterson olefination reaction Methods 0.000 description 1
• 102100033616 Phospholipid-transporting ATPase ABCA1 Human genes 0.000 description 1
• 101710205202 Phospholipid-transporting ATPase ABCA1 Proteins 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 102100038239 Protein Churchill Human genes 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
• 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 1
• 208000033626 Renal failure acute Diseases 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 101100178273 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HOC1 gene Proteins 0.000 description 1
• 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 1
• 238000000297 Sandmeyer reaction Methods 0.000 description 1
• 238000006085 Schmidt reaction Methods 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
• 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
• 229940100389 Sulfonylurea Drugs 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• 229940123464 Thiazolidinedione Drugs 0.000 description 1
• 241001161507 Titanus Species 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
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
• 241000009298 Trigla lyra Species 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 102000008316 Type 4 Melanocortin Receptor Human genes 0.000 description 1
• 108010021436 Type 4 Melanocortin Receptor Proteins 0.000 description 1
• 208000025865 Ulcer Diseases 0.000 description 1
• 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 description 1
• FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
• 238000007239 Wittig reaction Methods 0.000 description 1
• 238000002441 X-ray diffraction Methods 0.000 description 1
• AKZWRTCWNXHHFR-PDIZUQLASA-N [(3S)-oxolan-3-yl] N-[(2S,3S)-4-[(5S)-5-benzyl-3-[(2R)-2-carbamoyloxy-2,3-dihydro-1H-inden-1-yl]-4-oxo-3H-pyrrol-5-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound NC(=O)O[C@@H]1Cc2ccccc2C1C1C=N[C@](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CCOC2)(Cc2ccccc2)C1=O AKZWRTCWNXHHFR-PDIZUQLASA-N 0.000 description 1
• RVRZJXHWUXJAGO-YKSBVNFPSA-N [(4ar,9as)-6-(cyclopenten-1-yl)-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridin-1-yl]-(3h-benzimidazol-5-yl)methanone Chemical compound C([C@H]1[C@@H](C2=C3)CCCN1C(=O)C=1C=C4NC=NC4=CC=1)C2=CC=C3C1=CCCC1 RVRZJXHWUXJAGO-YKSBVNFPSA-N 0.000 description 1
• FDKIDFYIEWFERB-UHFFFAOYSA-N [2-butyl-5-chloro-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol;potassium Chemical compound [K].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 FDKIDFYIEWFERB-UHFFFAOYSA-N 0.000 description 1
• YSVZGWAJIHWNQK-UHFFFAOYSA-N [3-(hydroxymethyl)-2-bicyclo[2.2.1]heptanyl]methanol Chemical compound C1CC2C(CO)C(CO)C1C2 YSVZGWAJIHWNQK-UHFFFAOYSA-N 0.000 description 1
• UBHWUYMVJBOHKH-UHFFFAOYSA-N [Li].B Chemical compound [Li].B UBHWUYMVJBOHKH-UHFFFAOYSA-N 0.000 description 1
• 229960002632 acarbose Drugs 0.000 description 1
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
• 125000004036 acetal group Chemical group 0.000 description 1
• IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 201000011040 acute kidney failure Diseases 0.000 description 1
• 208000012998 acute renal failure Diseases 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 150000001266 acyl halides Chemical class 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
• 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
• 239000000674 adrenergic antagonist Substances 0.000 description 1
• 239000003288 aldose reductase inhibitor Substances 0.000 description 1
• 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
• 150000001337 aliphatic alkines Chemical group 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000003302 alkenyloxy group Chemical group 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 125000005133 alkynyloxy group Chemical group 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
• 229960001667 alogliptin Drugs 0.000 description 1
• 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
• 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
• 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
• 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• 229940125708 antidiabetic agent Drugs 0.000 description 1
• 239000003472 antidiabetic agent Substances 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 229940127088 antihypertensive drug Drugs 0.000 description 1
• 239000003524 antilipemic agent Substances 0.000 description 1
• 229940127218 antiplatelet drug Drugs 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 125000005002 aryl methyl group Chemical group 0.000 description 1
• 125000005163 aryl sulfanyl group Chemical group 0.000 description 1
• 125000005228 aryl sulfonate group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 108010014210 axokine Proteins 0.000 description 1
• JPNZKPRONVOMLL-UHFFFAOYSA-N azane;octadecanoic acid Chemical class [NH4+].CCCCCCCCCCCCCCCCCC([O-])=O JPNZKPRONVOMLL-UHFFFAOYSA-N 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 125000004069 aziridinyl group Chemical group 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
• 229940073608 benzyl chloride Drugs 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 229960000516 bezafibrate Drugs 0.000 description 1
• IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• UCYRAEIHXSVXPV-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)indiganyl trifluoromethanesulfonate Chemical compound [In+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F UCYRAEIHXSVXPV-UHFFFAOYSA-K 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 150000001649 bromium compounds Chemical class 0.000 description 1
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• YLBIBZCIFHPPKA-UHFFFAOYSA-N but-2-yn-1-amine Chemical compound CC#CCN YLBIBZCIFHPPKA-UHFFFAOYSA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
• 239000000292 calcium oxide Substances 0.000 description 1
• ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
• 238000011088 calibration curve Methods 0.000 description 1
• 229960004349 candesartan cilexetil Drugs 0.000 description 1
• 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 description 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
• 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 description 1
• MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
• QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
• JYHBPKNOVQWAPT-UHFFFAOYSA-N chloroform;formic acid Chemical compound OC=O.ClC(Cl)Cl JYHBPKNOVQWAPT-UHFFFAOYSA-N 0.000 description 1
• 230000001906 cholesterol absorption Effects 0.000 description 1
• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 229910017052 cobalt Inorganic materials 0.000 description 1
• 239000010941 cobalt Substances 0.000 description 1
• GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
• GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 229940125851 compound 27 Drugs 0.000 description 1
• 229910000431 copper oxide Inorganic materials 0.000 description 1
• 229910000365 copper sulfate Inorganic materials 0.000 description 1
• ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
• ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
• OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
• FDIRIOAEXPIEBL-UHFFFAOYSA-L copper;thiophene-2-carboxylate Chemical compound [Cu+2].[O-]C(=O)C1=CC=CS1.[O-]C(=O)C1=CC=CS1 FDIRIOAEXPIEBL-UHFFFAOYSA-L 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000000000 cycloalkoxy group Chemical group 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000004981 cycloalkylmethyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([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
• 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
• 229960003834 dapagliflozin Drugs 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000006356 dehydrogenation reaction Methods 0.000 description 1
• 230000003831 deregulation Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
• 229940117389 dichlorobenzene Drugs 0.000 description 1
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• JMVOCSLPMGHXPG-UHFFFAOYSA-N dipotassium;dioxido(dioxo)osmium Chemical compound [K+].[K+].[O-][Os]([O-])(=O)=O JMVOCSLPMGHXPG-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• JURBTQKVGNFPRJ-UHFFFAOYSA-N ditert-butyl(methyl)phosphane Chemical compound CC(C)(C)P(C)C(C)(C)C JURBTQKVGNFPRJ-UHFFFAOYSA-N 0.000 description 1
• XOJNEFQLMRCOMS-UHFFFAOYSA-N ditert-butyl(phenyl)phosphane Chemical class CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1 XOJNEFQLMRCOMS-UHFFFAOYSA-N 0.000 description 1
• 230000001882 diuretic effect Effects 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000008846 dynamic interplay Effects 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 238000007345 electrophilic aromatic substitution reaction Methods 0.000 description 1
• 238000007336 electrophilic substitution reaction Methods 0.000 description 1
• 125000005610 enamide group Chemical group 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002792 enkephalinase inhibitor Substances 0.000 description 1
• 229960000573 eprosartan mesylate Drugs 0.000 description 1
• DJSLTDBPKHORNY-XMMWENQYSA-N eprosartan methanesulfonate Chemical compound CS(O)(=O)=O.C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 DJSLTDBPKHORNY-XMMWENQYSA-N 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
• PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
• ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
• GWQVMPWSEVRGPY-UHFFFAOYSA-N europium cryptate Chemical compound [Eu+3].N=1C2=CC=CC=1CN(CC=1N=C(C=CC=1)C=1N=C(C3)C=CC=1)CC(N=1)=CC(C(=O)NCCN)=CC=1C(N=1)=CC(C(=O)NCCN)=CC=1CN3CC1=CC=CC2=N1 GWQVMPWSEVRGPY-UHFFFAOYSA-N 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 229960001519 exenatide Drugs 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
• 229960000815 ezetimibe Drugs 0.000 description 1
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
• 229960002297 fenofibrate Drugs 0.000 description 1
• 229940125753 fibrate Drugs 0.000 description 1
• 238000001506 fluorescence spectroscopy Methods 0.000 description 1
• 150000004673 fluoride salts Chemical class 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• KHBKYYUHCSVLIX-UHFFFAOYSA-N furan-3-yloxyboronic acid Chemical compound OB(O)OC=1C=COC=1 KHBKYYUHCSVLIX-UHFFFAOYSA-N 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 229960004580 glibenclamide Drugs 0.000 description 1
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
• 229960004346 glimepiride Drugs 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 230000009229 glucose formation Effects 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 125000005553 heteroaryloxy group Chemical group 0.000 description 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
• 239000012456 homogeneous solution Substances 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 229960002003 hydrochlorothiazide Drugs 0.000 description 1
• JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 1
• 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
• 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
• 201000008980 hyperinsulinism Diseases 0.000 description 1
• ONOJJCTXSDBVSP-UHFFFAOYSA-N imidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC2=NC=CN21 ONOJJCTXSDBVSP-UHFFFAOYSA-N 0.000 description 1
• 150000002461 imidazolidines Chemical class 0.000 description 1
• 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 238000002649 immunization Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 229910017053 inorganic salt Inorganic materials 0.000 description 1
• 238000009434 installation Methods 0.000 description 1
• 230000004410 intraocular pressure Effects 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 150000004694 iodide salts Chemical class 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 229960002198 irbesartan Drugs 0.000 description 1
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
• PVFSDGKDKFSOTB-UHFFFAOYSA-K iron(3+);triacetate Chemical compound [Fe+3].CC([O-])=O.CC([O-])=O.CC([O-])=O PVFSDGKDKFSOTB-UHFFFAOYSA-K 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 125000006328 iso-butylcarbonyl group Chemical group [H]C([H])([H])C([H])(C(*)=O)C([H])([H])[H] 0.000 description 1
• 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 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
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000005921 isopentoxy group Chemical group 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
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([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
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 230000004140 ketosis Effects 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 150000003903 lactic acid esters Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 210000005053 lamin Anatomy 0.000 description 1
• 229960004873 levomenthol Drugs 0.000 description 1
• 229960002397 linagliptin Drugs 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• ZEUXAIYYDDCIRX-UHFFFAOYSA-N losartan carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 ZEUXAIYYDDCIRX-UHFFFAOYSA-N 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 150000004701 malic acid derivatives Chemical class 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 125000005905 mesyloxy group Chemical group 0.000 description 1
• LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
• 229960003105 metformin Drugs 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
• QRLHANNSPRAJFN-UHFFFAOYSA-N methyl 3-chloropyridine-2-carboxylate Chemical compound COC(=O)C1=NC=CC=C1Cl QRLHANNSPRAJFN-UHFFFAOYSA-N 0.000 description 1
• GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
• IONAZPGKBDAGBA-UHFFFAOYSA-N methylperoxyboronic acid Chemical compound COOB(O)O IONAZPGKBDAGBA-UHFFFAOYSA-N 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 210000001589 microsome Anatomy 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 125000002912 morpholin-4-ylsulfonyl group Chemical group O1C([H])([H])C([H])([H])N(S(=O)(=O)[*])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• SXFKGLXJEKJXEW-UHFFFAOYSA-N n,n-dimethylquinoline-8-carboxamide Chemical compound C1=CN=C2C(C(=O)N(C)C)=CC=CC2=C1 SXFKGLXJEKJXEW-UHFFFAOYSA-N 0.000 description 1
• UKXDZOZWBDCBGL-UHFFFAOYSA-N n-methylquinoline-8-carboxamide Chemical compound C1=CN=C2C(C(=O)NC)=CC=CC2=C1 UKXDZOZWBDCBGL-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 101150069091 nae1 gene Proteins 0.000 description 1
• MERIVZAHHVOBCI-UHFFFAOYSA-N naphthalene-1-carboperoxoic acid Chemical class C1=CC=C2C(C(=O)OO)=CC=CC2=C1 MERIVZAHHVOBCI-UHFFFAOYSA-N 0.000 description 1
• OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
• 229960000698 nateglinide Drugs 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 125000005484 neopentoxy group Chemical group 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• UQPSGBZICXWIAG-UHFFFAOYSA-L nickel(2+);dibromide;trihydrate Chemical compound O.O.O.Br[Ni]Br UQPSGBZICXWIAG-UHFFFAOYSA-L 0.000 description 1
• ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+2].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 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• JCZMXVGQBBATMY-UHFFFAOYSA-N nitro acetate Chemical compound CC(=O)O[N+]([O-])=O JCZMXVGQBBATMY-UHFFFAOYSA-N 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• IQZPDFORWZTSKT-UHFFFAOYSA-N nitrosulphonic acid Chemical compound OS(=O)(=O)[N+]([O-])=O IQZPDFORWZTSKT-UHFFFAOYSA-N 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 1
• 229960005117 olmesartan Drugs 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000002902 organometallic compounds Chemical class 0.000 description 1
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
• 150000002905 orthoesters Chemical class 0.000 description 1
• 239000012285 osmium tetroxide Substances 0.000 description 1
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• GNWXVOQHLPBSSR-UHFFFAOYSA-N oxolane;toluene Chemical compound C1CCOC1.CC1=CC=CC=C1 GNWXVOQHLPBSSR-UHFFFAOYSA-N 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• BEZDDPMMPIDMGJ-UHFFFAOYSA-N pentamethylbenzene Chemical compound CC1=CC(C)=C(C)C(C)=C1C BEZDDPMMPIDMGJ-UHFFFAOYSA-N 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 125000003884 phenylalkyl group Chemical group 0.000 description 1
• XPPWLXNXHSNMKC-UHFFFAOYSA-N phenylboron Chemical compound [B]C1=CC=CC=C1 XPPWLXNXHSNMKC-UHFFFAOYSA-N 0.000 description 1
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
• QZRXRMPNCPCMSW-UHFFFAOYSA-N phosphanyl(phosphanylidene)phosphane Chemical compound PP=P QZRXRMPNCPCMSW-UHFFFAOYSA-N 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920001843 polymethylhydrosiloxane Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates Nutrition 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 150000003138 primary alcohols Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 239000003881 protein kinase C inhibitor Substances 0.000 description 1
• 238000010926 purge Methods 0.000 description 1
• YWVYZMVYXAVAKS-UHFFFAOYSA-N pyridin-1-ium;trifluoromethanesulfonate Chemical compound C1=CC=[NH+]C=C1.[O-]S(=O)(=O)C(F)(F)F YWVYZMVYXAVAKS-UHFFFAOYSA-N 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• CIIFKVFOVFJZDM-UHFFFAOYSA-N quinoline-8-carbonitrile Chemical compound C1=CN=C2C(C#N)=CC=CC2=C1 CIIFKVFOVFJZDM-UHFFFAOYSA-N 0.000 description 1
• HPQRQAOVNXWEEQ-UHFFFAOYSA-N quinoline-8-carboxamide Chemical compound C1=CN=C2C(C(=O)N)=CC=CC2=C1 HPQRQAOVNXWEEQ-UHFFFAOYSA-N 0.000 description 1
• FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical compound C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 description 1
• SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
• 239000002516 radical scavenger Substances 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 239000012048 reactive intermediate Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000006462 rearrangement reaction Methods 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000001603 reducing effect Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 150000003902 salicylic acid esters Chemical class 0.000 description 1
• QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
• 229960004937 saxagliptin Drugs 0.000 description 1
• 108010033693 saxagliptin Proteins 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000005920 sec-butoxy group Chemical group 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• HFLCZNNDZKKXCS-OUUBHVDSSA-N sergliflozin Chemical compound C1=CC(OC)=CC=C1CC1=CC=CC=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HFLCZNNDZKKXCS-OUUBHVDSSA-N 0.000 description 1
• 229940126842 sergliflozin Drugs 0.000 description 1
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
• 229960004425 sibutramine Drugs 0.000 description 1
• 229910000077 silane Inorganic materials 0.000 description 1
• 150000004756 silanes Chemical class 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 229910001923 silver oxide Inorganic materials 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• 229960004034 sitagliptin Drugs 0.000 description 1
• MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910001388 sodium aluminate Inorganic materials 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 239000004317 sodium nitrate Substances 0.000 description 1
• 235000010344 sodium nitrate Nutrition 0.000 description 1
• 229960001922 sodium perborate Drugs 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• UIICPZFWHBJNIG-UHFFFAOYSA-N sodium;2-methoxyethanolate Chemical compound [Na+].COCC[O-] UIICPZFWHBJNIG-UHFFFAOYSA-N 0.000 description 1
• GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
• YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
• 238000000279 solid-state nuclear magnetic resonance spectrum Methods 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 150000003900 succinic acid esters Chemical class 0.000 description 1
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
• GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical compound S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 description 1
• 150000003459 sulfonic acid esters Chemical class 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 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
• 150000003899 tartaric acid esters Chemical class 0.000 description 1
• 229960005187 telmisartan Drugs 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• KXPVHPTXRKQTEW-CVEARBPZSA-N tert-butyl (4ar,9as)-7-(methanesulfonamido)-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridine-1-carboxylate Chemical compound CS(=O)(=O)NC1=CC=C2[C@H]3CCCN(C(=O)OC(C)(C)C)[C@H]3CC2=C1 KXPVHPTXRKQTEW-CVEARBPZSA-N 0.000 description 1
• DMRVUOGOKZNPAD-SJORKVTESA-N tert-butyl (4ar,9as)-7-acetamido-2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridine-1-carboxylate Chemical compound C1CCN(C(=O)OC(C)(C)C)[C@H]2CC3=CC(NC(=O)C)=CC=C3[C@H]21 DMRVUOGOKZNPAD-SJORKVTESA-N 0.000 description 1
• HIJWYXDMMGTJKK-UHFFFAOYSA-N tert-butyl 2,3,4,4a,9,9a-hexahydroindeno[2,1-b]pyridine-1-carboxylate Chemical compound C1=CC=C2C3CCCN(C(=O)OC(C)(C)C)C3CC2=C1 HIJWYXDMMGTJKK-UHFFFAOYSA-N 0.000 description 1
• IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
• 239000012414 tert-butyl nitrite Substances 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• AWDBHOZBRXWRKS-UHFFFAOYSA-N tetrapotassium;iron(6+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+6].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] AWDBHOZBRXWRKS-UHFFFAOYSA-N 0.000 description 1
• OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 150000001467 thiazolidinediones Chemical class 0.000 description 1
• HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
• HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 229960005371 tolbutamide Drugs 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• 229960004394 topiramate Drugs 0.000 description 1
• 125000005490 tosylate group Chemical group 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
• IVIIAEVMQHEPAY-UHFFFAOYSA-N tridodecyl phosphite Chemical compound CCCCCCCCCCCCOP(OCCCCCCCCCCCC)OCCCCCCCCCCCC IVIIAEVMQHEPAY-UHFFFAOYSA-N 0.000 description 1
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
• WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
• MVJKXJPDBTXECY-UHFFFAOYSA-N trifluoroborane;hydrate Chemical compound O.FB(F)F MVJKXJPDBTXECY-UHFFFAOYSA-N 0.000 description 1
• AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 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
• GEPJPYNDFSOARB-UHFFFAOYSA-N tris(4-fluorophenyl)phosphane Chemical compound C1=CC(F)=CC=C1P(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 GEPJPYNDFSOARB-UHFFFAOYSA-N 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 201000008827 tuberculosis Diseases 0.000 description 1
• 231100000397 ulcer Toxicity 0.000 description 1
• HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
• 229960004699 valsartan Drugs 0.000 description 1
• ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
• 229960001254 vildagliptin Drugs 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229960001729 voglibose Drugs 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• AMKXMADQMVPOCK-UHFFFAOYSA-M zinc;1-methanidyl-4-methoxybenzene;chloride Chemical compound [Zn+]Cl.COC1=CC=C([CH2-])C=C1 AMKXMADQMVPOCK-UHFFFAOYSA-M 0.000 description 1
• YHVLYRZWQLDARE-UHFFFAOYSA-M zinc;ethylbenzene;bromide Chemical compound Br[Zn+].[CH2-]CC1=CC=CC=C1 YHVLYRZWQLDARE-UHFFFAOYSA-M 0.000 description 1
• PXEICVJAHKHKII-UHFFFAOYSA-N zinc;ethyne Chemical class [Zn+2].[C-]#C.[C-]#C PXEICVJAHKHKII-UHFFFAOYSA-N 0.000 description 1
• WRSWIWOVJBYZAW-UHFFFAOYSA-M zinc;methanidylbenzene;bromide Chemical compound Br[Zn+].[CH2-]C1=CC=CC=C1 WRSWIWOVJBYZAW-UHFFFAOYSA-M 0.000 description 1