TW200306184A - Heterocyclic amide derivatives for the treatment of diabetes and other diseases - Google Patents

Info

Publication number

TW200306184A

TW200306184A TW092105025A TW92105025A TW200306184A TW 200306184 A TW200306184 A TW 200306184A TW 092105025 A TW092105025 A TW 092105025A TW 92105025 A TW92105025 A TW 92105025A TW 200306184 A TW200306184 A TW 200306184A

Authority

TW

Taiwan

Prior art keywords

group

compound

carbon atoms

item

substituted

Prior art date

2002-03-08

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• -1 Heterocyclic amide Chemical class 0.000 title claims description 212
• 206010012601 diabetes mellitus Diseases 0.000 title claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 31
• 201000010099 disease Diseases 0.000 title abstract description 27
• 150000001875 compounds Chemical class 0.000 claims abstract description 244
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 65
• 150000003839 salts Chemical class 0.000 claims abstract description 46
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 30
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 29
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 29
• 150000002632 lipids Chemical class 0.000 claims abstract description 25
• 230000037356 lipid metabolism Effects 0.000 claims abstract description 24
• 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 19
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 15
• 230000023852 carbohydrate metabolic process Effects 0.000 claims abstract description 14
• 206010006187 Breast cancer Diseases 0.000 claims abstract description 13
• 235000021256 carbohydrate metabolism Nutrition 0.000 claims abstract description 13
• 229910052796 boron Inorganic materials 0.000 claims abstract description 11
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims abstract description 3
• 125000004432 carbon atom Chemical group C* 0.000 claims description 100
• 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 claims description 85
• 239000000203 mixture Substances 0.000 claims description 69
• 125000000217 alkyl group Chemical group 0.000 claims description 66
• 150000001412 amines Chemical class 0.000 claims description 64
• 125000001424 substituent group Chemical group 0.000 claims description 63
• 239000001257 hydrogen Substances 0.000 claims description 59
• 238000000034 method Methods 0.000 claims description 54
• 125000003118 aryl group Chemical group 0.000 claims description 52
• 125000001072 heteroaryl group Chemical group 0.000 claims description 46
• 125000003545 alkoxy group Chemical group 0.000 claims description 42
• 241001465754 Metazoa Species 0.000 claims description 36
• 210000004027 cell Anatomy 0.000 claims description 32
• 210000002966 serum Anatomy 0.000 claims description 32
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 29
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
• 239000008103 glucose Substances 0.000 claims description 29
• 241000699670 Mus sp. Species 0.000 claims description 28
• 125000003277 amino group Chemical group 0.000 claims description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
• 230000004069 differentiation Effects 0.000 claims description 24
• 229910052757 nitrogen Inorganic materials 0.000 claims description 24
• 125000000962 organic group Chemical group 0.000 claims description 23
• 238000006243 chemical reaction Methods 0.000 claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims description 22
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
• 150000001409 amidines Chemical group 0.000 claims description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
• 210000001789 adipocyte Anatomy 0.000 claims description 18
• 239000002243 precursor Substances 0.000 claims description 17
• 125000003107 substituted aryl group Chemical group 0.000 claims description 17
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
• 230000004060 metabolic process Effects 0.000 claims description 16
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
• 241000700159 Rattus Species 0.000 claims description 15
• 201000011510 cancer Diseases 0.000 claims description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
• 210000004369 blood Anatomy 0.000 claims description 14
• 239000008280 blood Substances 0.000 claims description 14
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
• 238000005859 coupling reaction Methods 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical class 0.000 claims description 14
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 14
• 239000000126 substance Substances 0.000 claims description 13
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 11
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 210000000229 preadipocyte Anatomy 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 238000010168 coupling process Methods 0.000 claims description 10
• 150000001720 carbohydrates Chemical class 0.000 claims description 9
• 235000014633 carbohydrates Nutrition 0.000 claims description 9
• 230000008878 coupling Effects 0.000 claims description 9
• 229910052740 iodine Inorganic materials 0.000 claims description 9
• 241000124008 Mammalia Species 0.000 claims description 8
• 241000699666 Mus <mouse, genus> Species 0.000 claims description 7
• 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
• 150000001768 cations Chemical class 0.000 claims description 7
• 125000004438 haloalkoxy group Chemical class 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
• CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 claims description 6
• 150000002148 esters Chemical class 0.000 claims description 6
• 210000003462 vein Anatomy 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
• 235000009200 high fat diet Nutrition 0.000 claims description 5
• 150000001450 anions Chemical class 0.000 claims description 4
• RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 229910052744 lithium Inorganic materials 0.000 claims description 4
• 239000011777 magnesium Substances 0.000 claims description 4
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 4
• 150000003254 radicals Chemical class 0.000 claims description 4
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
• 239000007983 Tris buffer Substances 0.000 claims description 3
• 229910052782 aluminium Inorganic materials 0.000 claims description 3
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
• 239000000460 chlorine Substances 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 125000004122 cyclic group Chemical group 0.000 claims description 3
• 230000006372 lipid accumulation Effects 0.000 claims description 3
• 229910052749 magnesium Inorganic materials 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 239000011734 sodium Substances 0.000 claims description 3
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 2
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 2
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 2
• 150000004703 alkoxides Chemical class 0.000 claims description 2
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
• 239000011575 calcium Substances 0.000 claims description 2
• 229910052791 calcium Inorganic materials 0.000 claims description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 2
• 229960001231 choline Drugs 0.000 claims description 2
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
• 229940043237 diethanolamine Drugs 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 229940012017 ethylenediamine Drugs 0.000 claims description 2
• 229960003194 meglumine Drugs 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
• 125000004043 oxo group Chemical group O=* 0.000 claims description 2
• 235000019371 penicillin G benzathine Nutrition 0.000 claims description 2
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
• 229960004919 procaine Drugs 0.000 claims description 2
• 229910052708 sodium Inorganic materials 0.000 claims description 2
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 12
• AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims 6
• SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical group CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 claims 1
• AISXBZVAYNUAKB-UHFFFAOYSA-N 1,1,4,4,6-pentamethyl-2,3-dihydronaphthalene Chemical compound CC1(C)CCC(C)(C)C=2C1=CC(C)=CC=2 AISXBZVAYNUAKB-UHFFFAOYSA-N 0.000 claims 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
• HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 claims 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims 1
• 210000004268 dentin Anatomy 0.000 claims 1
• 125000005594 diketone group Chemical group 0.000 claims 1
• DWRDBJCTLDOPFZ-UHFFFAOYSA-N imidazole-2,4-dione Chemical compound O=C1NC(=O)N=C1 DWRDBJCTLDOPFZ-UHFFFAOYSA-N 0.000 claims 1
• 229910052750 molybdenum Inorganic materials 0.000 claims 1
• 239000011733 molybdenum Substances 0.000 claims 1
• 125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
• 239000011591 potassium Substances 0.000 claims 1
• 229910052700 potassium Inorganic materials 0.000 claims 1
• 229910052722 tritium Inorganic materials 0.000 claims 1
• WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 abstract description 6
• 230000035755 proliferation Effects 0.000 abstract description 2
• UGWULZWUXSCWPX-UHFFFAOYSA-N 2-sulfanylideneimidazolidin-4-one Chemical group O=C1CNC(=S)N1 UGWULZWUXSCWPX-UHFFFAOYSA-N 0.000 abstract 1
• 150000001408 amides Chemical group 0.000 abstract 1
• KIWUVOGUEXMXSV-UHFFFAOYSA-N rhodanine Chemical compound O=C1CSC(=S)N1 KIWUVOGUEXMXSV-UHFFFAOYSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 181
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 126
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
• 239000000243 solution Substances 0.000 description 76
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 62
• 235000019439 ethyl acetate Nutrition 0.000 description 62
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 55
• 239000012267 brine Substances 0.000 description 54
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 54
• 101150041968 CDC13 gene Proteins 0.000 description 51
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
• 239000011541 reaction mixture Substances 0.000 description 39
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 37
• 235000012000 cholesterol Nutrition 0.000 description 33
• 238000005160 1H NMR spectroscopy Methods 0.000 description 31
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 31
• 229910052786 argon Inorganic materials 0.000 description 31
• 229940125846 compound 25 Drugs 0.000 description 31
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 27
• 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 26
• 239000000741 silica gel Substances 0.000 description 26
• 229910002027 silica gel Inorganic materials 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
• 230000000694 effects Effects 0.000 description 21
• 239000000543 intermediate Substances 0.000 description 21
• 238000005481 NMR spectroscopy Methods 0.000 description 20
• 229910052799 carbon Inorganic materials 0.000 description 19
• 125000000547 substituted alkyl group Chemical group 0.000 description 19
• 238000002844 melting Methods 0.000 description 18
• 230000008018 melting Effects 0.000 description 18
• 239000002253 acid Substances 0.000 description 17
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 17
• 238000012360 testing method Methods 0.000 description 17
• 125000005431 alkyl carboxamide group Chemical class 0.000 description 16
• 239000007864 aqueous solution Substances 0.000 description 16
• 230000002829 reductive effect Effects 0.000 description 16
• 238000010992 reflux Methods 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
• 239000002585 base Substances 0.000 description 15
• 239000010410 layer Substances 0.000 description 15
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 15
• 125000004001 thioalkyl group Chemical group 0.000 description 15
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 14
• 150000005347 biaryls Chemical group 0.000 description 14
• 229940125782 compound 2 Drugs 0.000 description 14
• 229940125961 compound 24 Drugs 0.000 description 14
• 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 14
• 229910000027 potassium carbonate Inorganic materials 0.000 description 14
• 239000004480 active ingredient Substances 0.000 description 13
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 12
• 125000004453 alkoxycarbonyl group Chemical class 0.000 description 12
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 12
• 235000005911 diet Nutrition 0.000 description 12
• 239000007788 liquid Substances 0.000 description 12
• 125000005415 substituted alkoxy group Chemical group 0.000 description 12
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 11
• 125000004429 atom Chemical group 0.000 description 11
• 150000001721 carbon Chemical group 0.000 description 11
• 125000005432 dialkylcarboxamide group Chemical group 0.000 description 11
• 230000037213 diet Effects 0.000 description 11
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 10
• 125000001905 inorganic group Chemical group 0.000 description 10
• 229910052760 oxygen Inorganic materials 0.000 description 10
• 239000001301 oxygen Substances 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• SSIVEDPNMAMSDY-UHFFFAOYSA-N 7-bromo-1-ethyl-4,4,6-trimethyl-3h-quinolin-2-one Chemical compound CC1=C(Br)C=C2N(CC)C(=O)CC(C)(C)C2=C1 SSIVEDPNMAMSDY-UHFFFAOYSA-N 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
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