HUE029480T2 - Chemical compounds - Google Patents

Info

Publication number

HUE029480T2

HUE029480T2 HUE11775513A HUE11775513A HUE029480T2 HU E029480 T2 HUE029480 T2 HU E029480T2 HU E11775513 A HUE11775513 A HU E11775513A HU E11775513 A HUE11775513 A HU E11775513A HU E029480 T2 HUE029480 T2 HU E029480T2

Authority

HU

Hungary

Prior art keywords

mmol

phenyl

methyloxy

ethyl

butyl

Prior art date

2010-04-27

Links

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• 150000001875 compounds Chemical class 0.000 title claims description 134
• 238000000034 method Methods 0.000 claims description 35
• 150000003839 salts Chemical class 0.000 claims description 25
• 206010012601 diabetes mellitus Diseases 0.000 claims description 21
• 239000003814 drug Substances 0.000 claims description 16
• 238000002360 preparation method Methods 0.000 claims description 15
• 241000282414 Homo sapiens Species 0.000 claims description 12
• 238000011282 treatment Methods 0.000 claims description 12
• 208000008589 Obesity Diseases 0.000 claims description 7
• 235000020824 obesity Nutrition 0.000 claims description 7
• 239000000126 substance Substances 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims 1
• 206010003658 Atrial Fibrillation Diseases 0.000 claims 1
• 235000000832 Ayote Nutrition 0.000 claims 1
• 235000009854 Cucurbita moschata Nutrition 0.000 claims 1
• 240000001980 Cucurbita pepo Species 0.000 claims 1
• 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 claims 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
• 230000036506 anxiety Effects 0.000 claims 1
• 239000002243 precursor Substances 0.000 claims 1
• 238000011321 prophylaxis Methods 0.000 claims 1
• 235000015136 pumpkin Nutrition 0.000 claims 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
• 238000012384 transportation and delivery Methods 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 340
• 229910001868 water Inorganic materials 0.000 description 210
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 180
• 239000000243 solution Substances 0.000 description 169
• 239000011541 reaction mixture Substances 0.000 description 160
• 239000000203 mixture Substances 0.000 description 142
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 141
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
• 239000007787 solid Substances 0.000 description 132
• 238000005160 1H NMR spectroscopy Methods 0.000 description 121
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 108
• 238000006243 chemical reaction Methods 0.000 description 103
• 230000002829 reductive effect Effects 0.000 description 103
• 239000000543 intermediate Substances 0.000 description 101
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 87
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 76
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 76
• 238000000746 purification Methods 0.000 description 74
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 70
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 67
• 235000019439 ethyl acetate Nutrition 0.000 description 66
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 60
• 239000012044 organic layer Substances 0.000 description 55
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
• 239000003921 oil Substances 0.000 description 54
• 235000019198 oils Nutrition 0.000 description 54
• 238000004007 reversed phase HPLC Methods 0.000 description 52
• 239000010410 layer Substances 0.000 description 51
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 50
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 48
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
• 239000000741 silica gel Substances 0.000 description 44
• 229910002027 silica gel Inorganic materials 0.000 description 44
• 229960001866 silicon dioxide Drugs 0.000 description 44
• 239000000047 product Substances 0.000 description 41
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 39
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
• 238000003756 stirring Methods 0.000 description 35
• -1 diethanolamine salts Chemical class 0.000 description 32
• 239000012267 brine Substances 0.000 description 30
• 239000012074 organic phase Substances 0.000 description 30
• PZYIRIHLNKVQKW-DHIUTWEWSA-N (3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepine-8-carbaldehyde Chemical compound C1([C@@H]2C3=CC(OC)=C(C=O)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 PZYIRIHLNKVQKW-DHIUTWEWSA-N 0.000 description 29
• 229960000583 acetic acid Drugs 0.000 description 27
• 239000002002 slurry Substances 0.000 description 27
• 238000001914 filtration Methods 0.000 description 26
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 23
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 22
• 235000011114 ammonium hydroxide Nutrition 0.000 description 22
• 239000008346 aqueous phase Substances 0.000 description 22
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 22
• 235000011054 acetic acid Nutrition 0.000 description 21
• PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 20
• 239000003613 bile acid Substances 0.000 description 20
• 239000012071 phase Substances 0.000 description 20
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 20
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• 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 18
• 239000002253 acid Substances 0.000 description 18
• 239000008103 glucose Substances 0.000 description 18
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 17
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 16
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
• 238000004587 chromatography analysis Methods 0.000 description 15
• 238000001816 cooling Methods 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 14
• 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• PXJFLUYRGQUUIN-UHFFFAOYSA-N dimethyl 3-aminopentanedioate Chemical compound COC(=O)CC(N)CC(=O)OC PXJFLUYRGQUUIN-UHFFFAOYSA-N 0.000 description 13
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• 229940079593 drug Drugs 0.000 description 12
• 239000000377 silicon dioxide Substances 0.000 description 12
• 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 12
• NLCSQMQPMRVENI-FGZHOGPDSA-N (3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepin-8-ol Chemical compound C1([C@@H]2C3=CC(OC)=C(O)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 NLCSQMQPMRVENI-FGZHOGPDSA-N 0.000 description 11
• BXZSTNOKQQGVMY-JWQCQUIFSA-N 3-[(3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepin-8-yl]propanoic acid Chemical compound C1([C@@H]2C3=CC(OC)=C(CCC(O)=O)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 BXZSTNOKQQGVMY-JWQCQUIFSA-N 0.000 description 11
• 239000007821 HATU Substances 0.000 description 11
• 102000004877 Insulin Human genes 0.000 description 11
• 108090001061 Insulin Proteins 0.000 description 11
• 239000008280 blood Substances 0.000 description 11
• 210000004369 blood Anatomy 0.000 description 11
• 239000012230 colorless oil Substances 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• 229940125396 insulin Drugs 0.000 description 11
• 239000000463 material Substances 0.000 description 11
• 239000008213 purified water Substances 0.000 description 11
• 238000010992 reflux Methods 0.000 description 11
• 229910000029 sodium carbonate Inorganic materials 0.000 description 11
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 11
• KBMAOLDNCSMGSE-DHIUTWEWSA-N (3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepine-8-carbonitrile Chemical compound C1([C@@H]2C3=CC(OC)=C(C#N)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 KBMAOLDNCSMGSE-DHIUTWEWSA-N 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 10
• 150000001412 amines Chemical group 0.000 description 10
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 10
• 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 9
• PBIKLKFKYVHLRN-FYYLOGMGSA-N (3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepine-8-carboxylic acid Chemical compound C1([C@@H]2C3=CC(OC)=C(C(O)=O)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 PBIKLKFKYVHLRN-FYYLOGMGSA-N 0.000 description 9
• CZGVOBIGEBDYTP-VSGBNLITSA-N 3-[[(3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepin-8-yl]methylamino]pentanedioic acid Chemical compound C1([C@@H]2C3=CC(OC)=C(CNC(CC(O)=O)CC(O)=O)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 CZGVOBIGEBDYTP-VSGBNLITSA-N 0.000 description 9
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
• LHAYZDULSNURMY-FGZHOGPDSA-N [(3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepin-8-yl] trifluoromethanesulfonate Chemical compound C1([C@@H]2C3=CC(OC)=C(OS(=O)(=O)C(F)(F)F)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 LHAYZDULSNURMY-FGZHOGPDSA-N 0.000 description 9
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 239000003960 organic solvent Substances 0.000 description 9
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
• 230000028327 secretion Effects 0.000 description 9
• TWOIQRCUTTZFTJ-FGZHOGPDSA-N (3r,5r)-3-butyl-3-ethyl-8-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepin-7-ol Chemical compound C1([C@@H]2C3=CC(O)=C(OC)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 TWOIQRCUTTZFTJ-FGZHOGPDSA-N 0.000 description 8
• 150000001299 aldehydes Chemical class 0.000 description 8
• 150000003863 ammonium salts Chemical class 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 238000010511 deprotection reaction Methods 0.000 description 8
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 208000030159 metabolic disease Diseases 0.000 description 8
• 150000002825 nitriles Chemical class 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 238000005406 washing Methods 0.000 description 8
• CKFWDLFFXXVSBJ-DHIUTWEWSA-N (3r,5r)-3-butyl-3-ethyl-7,8-dimethoxy-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepine 1,1-dioxide Chemical compound C1([C@@H]2C3=CC(OC)=C(OC)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 CKFWDLFFXXVSBJ-DHIUTWEWSA-N 0.000 description 7
• RCOCWDOJSUPGPF-DHIUTWEWSA-N [(3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepin-8-yl]methanamine Chemical compound C1([C@@H]2C3=CC(OC)=C(CN)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 RCOCWDOJSUPGPF-DHIUTWEWSA-N 0.000 description 7
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 7
• 239000006260 foam Substances 0.000 description 7
• 150000002466 imines Chemical class 0.000 description 7
• 239000003112 inhibitor Substances 0.000 description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
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