JP2007522159A - テトラヒドロベンゾ［ｄ］アゼピン−２−オン誘導体および心臓血管疾患を処置するためのその使用 - Google Patents
テトラヒドロベンゾ［ｄ］アゼピン−２−オン誘導体および心臓血管疾患を処置するためのその使用 Download PDFInfo
- Publication number
- JP2007522159A JP2007522159A JP2006552501A JP2006552501A JP2007522159A JP 2007522159 A JP2007522159 A JP 2007522159A JP 2006552501 A JP2006552501 A JP 2006552501A JP 2006552501 A JP2006552501 A JP 2006552501A JP 2007522159 A JP2007522159 A JP 2007522159A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- formula
- compound
- mmol
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 208000024172 Cardiovascular disease Diseases 0.000 title abstract description 9
- DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical class O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 title abstract description 4
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 83
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 11
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 10
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 9
- 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 8
- 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 208000037803 restenosis Diseases 0.000 claims abstract description 7
- 230000006806 disease prevention Effects 0.000 claims abstract description 6
- 208000028867 ischemia Diseases 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 201
- -1 hydroxy, amino, carboxyl Chemical group 0.000 claims description 64
- 239000002904 solvent Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
- 239000012453 solvate Substances 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 241001465754 Metazoa Species 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000012442 inert solvent Substances 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
- 230000009435 amidation Effects 0.000 claims description 5
- 238000007112 amidation reaction Methods 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 150000001735 carboxylic acids Chemical class 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
- GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical compound CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims 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 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- 102000007592 Apolipoproteins Human genes 0.000 claims description 3
- 108010071619 Apolipoproteins Proteins 0.000 claims description 3
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 3
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 3
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 230000032050 esterification Effects 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 183
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 114
- 239000000243 solution Substances 0.000 description 101
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 67
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 58
- 239000000203 mixture Substances 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 239000012074 organic phase Substances 0.000 description 50
- 239000011541 reaction mixture Substances 0.000 description 46
- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
- 229910052938 sodium sulfate Inorganic materials 0.000 description 45
- 235000011152 sodium sulphate Nutrition 0.000 description 45
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000003480 eluent Substances 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 30
- 238000002953 preparative HPLC Methods 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- 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 22
- 235000019253 formic acid Nutrition 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- 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 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 239000002585 base Substances 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 229940031439 squalene Drugs 0.000 description 13
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 12
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 230000037396 body weight Effects 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 102100037997 Squalene synthase Human genes 0.000 description 10
- 239000008186 active pharmaceutical agent Substances 0.000 description 10
- 229940088679 drug related substance Drugs 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 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 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 6
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
- BTUGGGLMQBJCBN-UHFFFAOYSA-N 1-iodo-2-methylpropane Chemical compound CC(C)CI BTUGGGLMQBJCBN-UHFFFAOYSA-N 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- 150000001993 dienes Chemical class 0.000 description 5
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 239000011630 iodine Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000000825 ultraviolet detection Methods 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 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 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 210000005228 liver tissue Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229940057061 mevalonolactone Drugs 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229930000044 secondary metabolite Natural products 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 4
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 description 3
- VWFJDQUYCIWHTN-UHFFFAOYSA-N Farnesyl pyrophosphate Natural products CC(C)=CCCC(C)=CCCC(C)=CCOP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-UHFFFAOYSA-N 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229950005499 carbon tetrachloride Drugs 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 229960001701 chloroform Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- RBESFTPUTXOFCD-UHFFFAOYSA-N ethyl 2-piperidin-4-ylacetate;hydrochloride Chemical compound Cl.CCOC(=O)CC1CCNCC1 RBESFTPUTXOFCD-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 210000001589 microsome Anatomy 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 3
- 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 2
- FOZFSEMFCIPOSZ-SPCKQMHLSA-N (2r,3r,4r,5s)-2-(hydroxymethyl)-1-[[(2r,3s,4s,5r,6s)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]methyl]piperidine-3,4,5-triol;trihydrate Chemical compound O.O.O.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 FOZFSEMFCIPOSZ-SPCKQMHLSA-N 0.000 description 2
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- MJBBWPDFYUSKKR-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(C(O)=O)CC1 MJBBWPDFYUSKKR-UHFFFAOYSA-N 0.000 description 2
- UMQUIRYNOVNYPA-UHFFFAOYSA-N 2-(4-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C=C1 UMQUIRYNOVNYPA-UHFFFAOYSA-N 0.000 description 2
- JVKUCNQGESRUCL-UHFFFAOYSA-N 2-Hydroxyethyl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OCCO JVKUCNQGESRUCL-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- GOJOZDJNNWARQG-UHFFFAOYSA-N 2-[1-[2-[5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(C)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(CC(O)=O)CC1 GOJOZDJNNWARQG-UHFFFAOYSA-N 0.000 description 2
- SJYICAYPBJXIFV-UHFFFAOYSA-N 2-[1-[2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(CC(O)=O)CC1 SJYICAYPBJXIFV-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- BTMWBQITKYTCTD-UHFFFAOYSA-N 2-[4-chloro-2-(2-methoxybenzoyl)phenyl]acetic acid Chemical compound COC1=CC=CC=C1C(=O)C1=CC(Cl)=CC=C1CC(O)=O BTMWBQITKYTCTD-UHFFFAOYSA-N 0.000 description 2
- IJZGBQZJIZOIMQ-UHFFFAOYSA-N 2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylprop-2-enyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetic acid Chemical compound C1N(CC(O)=O)C(=O)C(CC(=C)C)C2=CC=C(Cl)C=C2C1C1=CC=CC=C1Cl IJZGBQZJIZOIMQ-UHFFFAOYSA-N 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- ISRGONDNXBCDBM-UHFFFAOYSA-N 2-chlorostyrene Chemical compound ClC1=CC=CC=C1C=C ISRGONDNXBCDBM-UHFFFAOYSA-N 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 2
- ZZIBWSOOKYNNRH-UHFFFAOYSA-N 5-chloro-3-(2-methoxyphenyl)-1h-indene Chemical compound COC1=CC=CC=C1C1=CCC2=CC=C(Cl)C=C12 ZZIBWSOOKYNNRH-UHFFFAOYSA-N 0.000 description 2
- SMSGJDOJSQHQIW-UHFFFAOYSA-N 6-chloro-2,3-dihydroinden-1-one Chemical compound ClC1=CC=C2CCC(=O)C2=C1 SMSGJDOJSQHQIW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000004366 Glucosidases Human genes 0.000 description 2
- 108010056771 Glucosidases Proteins 0.000 description 2
- 101000656751 Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) 30S ribosomal protein S24e Proteins 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 229920001304 Solutol HS 15 Polymers 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 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 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229960002632 acarbose Drugs 0.000 description 2
- 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 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000010640 amide synthesis reaction Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000003392 amylase inhibitor Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical class OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 230000001906 cholesterol absorption Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- FFGHKPYGZLJZBV-UHFFFAOYSA-N methyl 2-[4-chloro-2-[cyano-(2,3-dimethoxyphenyl)methyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=C(Cl)C=C1C(C#N)C1=CC=CC(OC)=C1OC FFGHKPYGZLJZBV-UHFFFAOYSA-N 0.000 description 2
- 229960001110 miglitol Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229950008882 polysorbate Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical compound O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000011775 sodium fluoride Substances 0.000 description 2
- 235000013024 sodium fluoride Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000004059 squalene synthase inhibitor Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 2
- 229960001729 voglibose Drugs 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- VCIPQQCYKMORDY-KBYFLBCBSA-N (2r,3r,4s,5s,6r)-2-(hydroxymethyl)-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]piperidine-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)N[C@@H]1CO[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VCIPQQCYKMORDY-KBYFLBCBSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical class OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- 125000004161 1,4-diazepinyl group Chemical group 0.000 description 1
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
- RUPWPJCCZVVHOY-UHFFFAOYSA-N 1-[2-[1-(2,2-dimethylpropyl)-5-(2-methoxyphenyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound COC1=CC=CC=C1C1C2=CC(C(F)(F)F)=CC=C2C(CC(C)(C)C)C(=O)N(CC(=O)N2CCC(CC2)C(O)=O)C1 RUPWPJCCZVVHOY-UHFFFAOYSA-N 0.000 description 1
- HXJPOAMVOOGPKL-UHFFFAOYSA-N 1-[2-[5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Br)CN1CC(=O)N1CCC(C(O)=O)CC1 HXJPOAMVOOGPKL-UHFFFAOYSA-N 0.000 description 1
- PDYCGEVFXGJXRS-UHFFFAOYSA-N 1-[2-[5-(2-chlorophenyl)-1-(2,2-dimethylpropyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)(C)C)C2=CC=C(C(F)(F)F)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(C(O)=O)CC1 PDYCGEVFXGJXRS-UHFFFAOYSA-N 0.000 description 1
- YYCQKKHGEJTDOG-UHFFFAOYSA-N 1-[2-[5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(C(F)(F)F)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(C(O)=O)CC1 YYCQKKHGEJTDOG-UHFFFAOYSA-N 0.000 description 1
- RYLDKWZJTQXOTM-UHFFFAOYSA-N 1-[2-[5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(C)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(C(O)=O)CC1 RYLDKWZJTQXOTM-UHFFFAOYSA-N 0.000 description 1
- HMMRFIITYNKTFV-UHFFFAOYSA-N 1-[2-[5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound COC1=CC=CC=C1C1C2=CC(C(F)(F)F)=CC=C2C(CC(C)C)C(=O)N(CC(=O)N2CCC(CC2)C(O)=O)C1 HMMRFIITYNKTFV-UHFFFAOYSA-N 0.000 description 1
- WOZIHKLNBFQSMH-UHFFFAOYSA-N 1-[2-[7-chloro-1-(2,2-dimethylpropyl)-5-(2-methoxyphenyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound COC1=CC=CC=C1C1C2=CC(Cl)=CC=C2C(CC(C)(C)C)C(=O)N(CC(=O)N2CCC(CC2)C(O)=O)C1 WOZIHKLNBFQSMH-UHFFFAOYSA-N 0.000 description 1
- MHPRFIZEOJDZMD-UHFFFAOYSA-N 1-[2-[7-chloro-1-(2-methylpropyl)-5-naphthalen-1-yl-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C3=CC=CC=C3C=CC=2)CN1CC(=O)N1CCC(C(O)=O)CC1 MHPRFIZEOJDZMD-UHFFFAOYSA-N 0.000 description 1
- NGGCALNJZWMYFJ-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C=3OCCOC=3C=CC=2)CN1CC(=O)N1CCC(C(O)=O)CC1 NGGCALNJZWMYFJ-UHFFFAOYSA-N 0.000 description 1
- DPMUOGFZRDHBQP-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2,3-dimethoxyphenyl)-1-(2,2-dimethylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound COC1=CC=CC(C2C3=CC(Cl)=CC=C3C(CC(C)(C)C)C(=O)N(CC(=O)N3CCC(CC3)C(O)=O)C2)=C1OC DPMUOGFZRDHBQP-UHFFFAOYSA-N 0.000 description 1
- WMJMBQSUCFTOQK-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound COC1=CC=CC(C2C3=CC(Cl)=CC=C3C(CC(C)C)C(=O)N(CC(=O)N3CCC(CC3)C(O)=O)C2)=C1OC WMJMBQSUCFTOQK-UHFFFAOYSA-N 0.000 description 1
- FSLWPULYNYTGOV-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2,3-dimethylphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=C(C)C=CC=2)C)CN1CC(=O)N1CCC(C(O)=O)CC1 FSLWPULYNYTGOV-UHFFFAOYSA-N 0.000 description 1
- MYCJYVIWMUSSAC-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2,4-dimethylphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC(C)=CC=2)C)CN1CC(=O)N1CCC(C(O)=O)CC1 MYCJYVIWMUSSAC-UHFFFAOYSA-N 0.000 description 1
- NAMJQCACXARWAV-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2-chlorophenyl)-1-(2,2-dimethylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(C(O)=O)CC1 NAMJQCACXARWAV-UHFFFAOYSA-N 0.000 description 1
- QEMOQAWFTXFWSC-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2-ethynylphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)C#C)CN1CC(=O)N1CCC(C(O)=O)CC1 QEMOQAWFTXFWSC-UHFFFAOYSA-N 0.000 description 1
- UIDVDWBJUGYMJC-UHFFFAOYSA-N 1-[2-[7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid Chemical compound COC1=CC=CC=C1C1C2=CC(Cl)=CC=C2C(CC(C)C)C(=O)N(CC(=O)N2CCC(CC2)C(O)=O)C1 UIDVDWBJUGYMJC-UHFFFAOYSA-N 0.000 description 1
- SSZOCHFYWWVSAI-UHFFFAOYSA-N 1-bromo-2-ethenylbenzene Chemical compound BrC1=CC=CC=C1C=C SSZOCHFYWWVSAI-UHFFFAOYSA-N 0.000 description 1
- OFNGHAYJUVTBAK-UHFFFAOYSA-N 2,3,3-trichlorooxepane Chemical compound ClC1OCCCCC1(Cl)Cl OFNGHAYJUVTBAK-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- LQLLNCGLZXJZOJ-UHFFFAOYSA-N 2-[1-[2-[1-(2,2-dimethylpropyl)-5-(2-methoxyphenyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound COC1=CC=CC=C1C1C2=CC(C(F)(F)F)=CC=C2C(CC(C)(C)C)C(=O)N(CC(=O)N2CCC(CC(O)=O)CC2)C1 LQLLNCGLZXJZOJ-UHFFFAOYSA-N 0.000 description 1
- AYQVCTFOPHOMSE-UHFFFAOYSA-N 2-[1-[2-[5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Br)CN1CC(=O)N1CCC(CC(O)=O)CC1 AYQVCTFOPHOMSE-UHFFFAOYSA-N 0.000 description 1
- XANAXABVEAKUSM-UHFFFAOYSA-N 2-[1-[2-[5-(2-chlorophenyl)-1-(2,2-dimethylpropyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)(C)C)C2=CC=C(C(F)(F)F)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(CC(O)=O)CC1 XANAXABVEAKUSM-UHFFFAOYSA-N 0.000 description 1
- HYQFHPXYAKJOHB-UHFFFAOYSA-N 2-[1-[2-[5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(C(F)(F)F)C=C2C(C=2C(=CC=CC=2)Cl)CN1CC(=O)N1CCC(CC(O)=O)CC1 HYQFHPXYAKJOHB-UHFFFAOYSA-N 0.000 description 1
- ILODTPSHWQLKAL-UHFFFAOYSA-N 2-[1-[2-[5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-7-(trifluoromethyl)-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound COC1=CC=CC=C1C1C2=CC(C(F)(F)F)=CC=C2C(CC(C)C)C(=O)N(CC(=O)N2CCC(CC(O)=O)CC2)C1 ILODTPSHWQLKAL-UHFFFAOYSA-N 0.000 description 1
- ANCKRBQAPBSYRD-UHFFFAOYSA-N 2-[1-[2-[7-chloro-1-(2-methylpropyl)-5-naphthalen-1-yl-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C3=CC=CC=C3C=CC=2)CN1CC(=O)N1CCC(CC(O)=O)CC1 ANCKRBQAPBSYRD-UHFFFAOYSA-N 0.000 description 1
- WHYJBQKHFUFJRW-UHFFFAOYSA-N 2-[1-[2-[7-chloro-5-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C=3OCCOC=3C=CC=2)CN1CC(=O)N1CCC(CC(O)=O)CC1 WHYJBQKHFUFJRW-UHFFFAOYSA-N 0.000 description 1
- XJXJTENENYVKMM-UHFFFAOYSA-N 2-[1-[2-[7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound COC1=CC=CC(C2C3=CC(Cl)=CC=C3C(CC(C)C)C(=O)N(CC(=O)N3CCC(CC(O)=O)CC3)C2)=C1OC XJXJTENENYVKMM-UHFFFAOYSA-N 0.000 description 1
- UCJFUABZQVJWQR-UHFFFAOYSA-N 2-[1-[2-[7-chloro-5-(2,3-dimethylphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=C(C)C=CC=2)C)CN1CC(=O)N1CCC(CC(O)=O)CC1 UCJFUABZQVJWQR-UHFFFAOYSA-N 0.000 description 1
- DWPHQRMKPMLBRN-UHFFFAOYSA-N 2-[1-[2-[7-chloro-5-(2,4-dimethylphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound O=C1C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC(C)=CC=2)C)CN1CC(=O)N1CCC(CC(O)=O)CC1 DWPHQRMKPMLBRN-UHFFFAOYSA-N 0.000 description 1
- RPKXJTOBLYDNPU-UHFFFAOYSA-N 2-[1-[2-[7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetic acid Chemical compound COC1=CC=CC=C1C1C2=CC(Cl)=CC=C2C(CC(C)C)C(=O)N(CC(=O)N2CCC(CC(O)=O)CC2)C1 RPKXJTOBLYDNPU-UHFFFAOYSA-N 0.000 description 1
- AZUXYDGJRUTTAR-UHFFFAOYSA-N 2-[4-chloro-2-[(2,3-dimethoxyphenyl)methyl]phenyl]acetic acid Chemical compound COC1=CC=CC(CC=2C(=CC=C(Cl)C=2)CC(O)=O)=C1OC AZUXYDGJRUTTAR-UHFFFAOYSA-N 0.000 description 1
- FIXFRXKZQMMDHW-UHFFFAOYSA-N 2-[5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetic acid Chemical compound C1N(CC(O)=O)C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C1C1=CC=CC=C1Br FIXFRXKZQMMDHW-UHFFFAOYSA-N 0.000 description 1
- GDJRPHAADWFEKK-UHFFFAOYSA-N 2-[5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetic acid Chemical compound C1N(CC(O)=O)C(=O)C(CC(C)C)C2=CC=C(C)C=C2C1C1=CC=CC=C1Cl GDJRPHAADWFEKK-UHFFFAOYSA-N 0.000 description 1
- AQYUGNGWEXBZGP-UHFFFAOYSA-N 2-[7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetic acid Chemical compound COC1=CC=CC(C2C3=CC(Cl)=CC=C3C(CC(C)C)C(=O)N(CC(O)=O)C2)=C1OC AQYUGNGWEXBZGP-UHFFFAOYSA-N 0.000 description 1
- ZEIRLQGOSHRPHQ-UHFFFAOYSA-N 2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetic acid Chemical compound C1N(CC(O)=O)C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C1C1=CC=CC=C1Cl ZEIRLQGOSHRPHQ-UHFFFAOYSA-N 0.000 description 1
- YBPYETHENAODPQ-UHFFFAOYSA-N 2-[7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetic acid Chemical compound COC1=CC=CC=C1C1C2=CC(Cl)=CC=C2C(CC(C)C)C(=O)N(CC(O)=O)C1 YBPYETHENAODPQ-UHFFFAOYSA-N 0.000 description 1
- NLOLAHBEMPOPGX-UHFFFAOYSA-N 2-[[2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]amino]acetic acid Chemical compound C1N(CC(=O)NCC(O)=O)C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C1C1=CC=CC=C1Cl NLOLAHBEMPOPGX-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- MPSXGPCFLAGJOM-UHFFFAOYSA-M 2-tert-butyl-5-methyl-1,2-oxazol-2-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC1=CC=[N+](C(C)(C)C)O1 MPSXGPCFLAGJOM-UHFFFAOYSA-M 0.000 description 1
- XVTAQSGZOGYIEY-UHFFFAOYSA-N 3,4-dihydroisocoumarin Chemical class C1=CC=C2C(=O)OCCC2=C1 XVTAQSGZOGYIEY-UHFFFAOYSA-N 0.000 description 1
- BBSLOKZINKEUCR-UHFFFAOYSA-N 3-(4-chlorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=C(Cl)C=C1 BBSLOKZINKEUCR-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 1
- USEGQJLHQSTGHW-UHFFFAOYSA-N 3-bromo-2-methylprop-1-ene Chemical compound CC(=C)CBr USEGQJLHQSTGHW-UHFFFAOYSA-N 0.000 description 1
- YRZRLBVFCJOAOX-UHFFFAOYSA-N 4-(2-bromophenyl)-6-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C12=CC(Cl)=CC=C2CC(=O)CC1C1=CC=CC=C1Br YRZRLBVFCJOAOX-UHFFFAOYSA-N 0.000 description 1
- KJFCTTWWFJVYSA-UHFFFAOYSA-N 4-(2-chlorophenyl)-6-methyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound C12=CC(C)=CC=C2CC(=O)CC1C1=CC=CC=C1Cl KJFCTTWWFJVYSA-UHFFFAOYSA-N 0.000 description 1
- PREGEQNUTKXTAX-UHFFFAOYSA-N 4-[[2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]amino]butanoic acid Chemical compound C1N(CC(=O)NCCCC(O)=O)C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C1C1=CC=CC=C1Cl PREGEQNUTKXTAX-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- YXMKRNCQHQKPRH-UHFFFAOYSA-N 5-(2-bromophenyl)-7-chloro-1,3,4,5-tetrahydro-3-benzazepin-2-one Chemical compound C12=CC(Cl)=CC=C2CC(=O)NCC1C1=CC=CC=C1Br YXMKRNCQHQKPRH-UHFFFAOYSA-N 0.000 description 1
- NRAVEFWDYJEVLW-UHFFFAOYSA-N 5-(2-chlorophenyl)-7-methyl-1,3,4,5-tetrahydro-3-benzazepin-2-one Chemical compound C12=CC(C)=CC=C2CC(=O)NCC1C1=CC=CC=C1Cl NRAVEFWDYJEVLW-UHFFFAOYSA-N 0.000 description 1
- WGVLMHVDTWNFET-UHFFFAOYSA-N 5-chloro-3-(2,3-dimethoxyphenyl)-1h-indene Chemical compound COC1=CC=CC(C=2C3=CC(Cl)=CC=C3CC=2)=C1OC WGVLMHVDTWNFET-UHFFFAOYSA-N 0.000 description 1
- KWYDBQOSVBWVND-UHFFFAOYSA-N 6-chloro-4-(2-chlorophenyl)-3,4-dihydro-1h-naphthalen-2-one Chemical compound C12=CC(Cl)=CC=C2CC(=O)CC1C1=CC=CC=C1Cl KWYDBQOSVBWVND-UHFFFAOYSA-N 0.000 description 1
- DHSSDEDRBUKTQY-UHFFFAOYSA-N 6-prop-2-enyl-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-2-amine Chemical compound C1CN(CC=C)CCC2=C1N=C(N)S2 DHSSDEDRBUKTQY-UHFFFAOYSA-N 0.000 description 1
- QNMWEXCDQMMLEQ-UHFFFAOYSA-N 7-chloro-5-(2,3-dimethoxyphenyl)-1,3,4,5-tetrahydro-3-benzazepin-2-one Chemical compound COC1=CC=CC(C2C3=CC(Cl)=CC=C3CC(=O)NC2)=C1OC QNMWEXCDQMMLEQ-UHFFFAOYSA-N 0.000 description 1
- VECVSFGZANHXJQ-UHFFFAOYSA-N 7-chloro-5-(2-methoxyphenyl)-1,3,4,5-tetrahydro-3-benzazepin-2-one Chemical compound COC1=CC=CC=C1C1C2=CC(Cl)=CC=C2CC(=O)NC1 VECVSFGZANHXJQ-UHFFFAOYSA-N 0.000 description 1
- VMCQFERNKVBDRT-UHFFFAOYSA-N 7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-3-(2-oxo-2-piperidin-1-ylethyl)-4,5-dihydro-1h-3-benzazepin-2-one Chemical compound COC1=CC=CC=C1C1C2=CC(Cl)=CC=C2C(CC(C)C)C(=O)N(CC(=O)N2CCCCC2)C1 VMCQFERNKVBDRT-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 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
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229940122816 Amylase inhibitor Drugs 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000036490 Arterial inflammations Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical group CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 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
- 239000005711 Benzoic acid Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical class OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VKBYPFKZDDIBFN-UHFFFAOYSA-N CC(C)CC(c1ccc(C(F)(F)F)cc1C(CN1CC(N2CCC(CC(O)=O)CC2)=O)c2cccc(OC)c2OC)C1=O Chemical compound CC(C)CC(c1ccc(C(F)(F)F)cc1C(CN1CC(N2CCC(CC(O)=O)CC2)=O)c2cccc(OC)c2OC)C1=O VKBYPFKZDDIBFN-UHFFFAOYSA-N 0.000 description 1
- ZXSCBTQRDWPUMB-UHFFFAOYSA-N COC1=CC=CC=C1[Mg] Chemical compound COC1=CC=CC=C1[Mg] ZXSCBTQRDWPUMB-UHFFFAOYSA-N 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 description 1
- 208000031288 Combined hyperlipidaemia Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010021024 Hypolipidaemia Diseases 0.000 description 1
- 229940125922 IBAT inhibitor Drugs 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- VCIPQQCYKMORDY-UHFFFAOYSA-N MDL 25637 Natural products OC1C(O)C(O)C(CO)NC1COC1C(O)C(O)C(O)C(CO)O1 VCIPQQCYKMORDY-UHFFFAOYSA-N 0.000 description 1
- 239000004425 Makrolon Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 238000011785 NMRI mouse Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- 229940126033 PPAR agonist Drugs 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 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
- OCTNNXHKAOLDJL-BMGYQPLYSA-N Salbostatin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)OC[C@@H]1N[C@@H]1[C@H](O)[C@@H](O)[C@H](O)C(CO)=C1 OCTNNXHKAOLDJL-BMGYQPLYSA-N 0.000 description 1
- OCTNNXHKAOLDJL-UHFFFAOYSA-N Salbostatin Natural products OC1C(O)C(CO)OCC1NC1C(O)C(O)C(O)C(CO)=C1 OCTNNXHKAOLDJL-UHFFFAOYSA-N 0.000 description 1
- 238000006085 Schmidt reaction Methods 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229930186167 Trestatin Natural products 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate 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-DQQFMEOOSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Chemical class OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 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
- 125000002785 azepinyl group Chemical group 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
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 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
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229950001261 camiglibose Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960002887 deanol Drugs 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000010410 dusting Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- DMXKCKYVKYQZFR-UHFFFAOYSA-N ethyl 1-[2-[7-chloro-1-(2-methylpropyl)-2-oxo-5-[2-(2-trimethylsilylethynyl)phenyl]-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CN1C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)C#C[Si](C)(C)C)C1 DMXKCKYVKYQZFR-UHFFFAOYSA-N 0.000 description 1
- ITAIKDVPJRQOJJ-UHFFFAOYSA-N ethyl 1-[2-[7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CN1C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=C(OC)C=CC=2)OC)C1 ITAIKDVPJRQOJJ-UHFFFAOYSA-N 0.000 description 1
- JXDQWDNOWWOCAA-UHFFFAOYSA-N ethyl 1-[2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CN1C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Cl)C1 JXDQWDNOWWOCAA-UHFFFAOYSA-N 0.000 description 1
- FPPBWOMEBGQVEB-UHFFFAOYSA-N ethyl 2-[1-[2-[5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C(=O)CN1C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Br)C1 FPPBWOMEBGQVEB-UHFFFAOYSA-N 0.000 description 1
- ORUYWEONTBVKBH-UHFFFAOYSA-N ethyl 2-[1-[2-[5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C(=O)CN1C(=O)C(CC(C)C)C2=CC=C(C)C=C2C(C=2C(=CC=CC=2)Cl)C1 ORUYWEONTBVKBH-UHFFFAOYSA-N 0.000 description 1
- FOEAAJGWOJHKJM-UHFFFAOYSA-N ethyl 2-[1-[2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetyl]piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C(=O)CN1C(=O)C(CC(C)C)C2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Cl)C1 FOEAAJGWOJHKJM-UHFFFAOYSA-N 0.000 description 1
- XQYWNTSFGFKAKS-UHFFFAOYSA-N ethyl 2-[5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(Cl)=CC=C2C(CC(C)C)C(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1Br XQYWNTSFGFKAKS-UHFFFAOYSA-N 0.000 description 1
- CZMYKPFHIOQMFR-UHFFFAOYSA-N ethyl 2-[5-(2-bromophenyl)-7-chloro-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(Cl)=CC=C2CC(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1Br CZMYKPFHIOQMFR-UHFFFAOYSA-N 0.000 description 1
- ZJDIHJIEEWZXHW-UHFFFAOYSA-N ethyl 2-[5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(C)=CC=C2C(CC(C)C)C(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1Cl ZJDIHJIEEWZXHW-UHFFFAOYSA-N 0.000 description 1
- QXDKPNBIGZYNFI-UHFFFAOYSA-N ethyl 2-[5-(2-chlorophenyl)-7-methyl-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(C)=CC=C2CC(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1Cl QXDKPNBIGZYNFI-UHFFFAOYSA-N 0.000 description 1
- QHNVBVBUPIIKAL-UHFFFAOYSA-N ethyl 2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylprop-2-enyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(Cl)=CC=C2C(CC(C)=C)C(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1Cl QHNVBVBUPIIKAL-UHFFFAOYSA-N 0.000 description 1
- TUGVWLAGOWTNBY-UHFFFAOYSA-N ethyl 2-[7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(Cl)=CC=C2C(CC(C)C)C(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1Cl TUGVWLAGOWTNBY-UHFFFAOYSA-N 0.000 description 1
- DNXXUQUMTRQXOJ-UHFFFAOYSA-N ethyl 2-[7-chloro-5-(2-chlorophenyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(Cl)=CC=C2CC(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1Cl DNXXUQUMTRQXOJ-UHFFFAOYSA-N 0.000 description 1
- YLTNUNPFRRBZKU-UHFFFAOYSA-N ethyl 2-[7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(Cl)=CC=C2C(CC(C)C)C(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1OC YLTNUNPFRRBZKU-UHFFFAOYSA-N 0.000 description 1
- PLCZOEQHLALBOP-UHFFFAOYSA-N ethyl 2-[7-chloro-5-(2-methoxyphenyl)-2-oxo-4,5-dihydro-1h-3-benzazepin-3-yl]acetate Chemical compound C12=CC(Cl)=CC=C2CC(=O)N(CC(=O)OCC)CC1C1=CC=CC=C1OC PLCZOEQHLALBOP-UHFFFAOYSA-N 0.000 description 1
- IHSUFLCKRIHFGY-UHFFFAOYSA-N ethyl 2-piperidin-4-ylacetate Chemical compound CCOC(=O)CC1CCNCC1 IHSUFLCKRIHFGY-UHFFFAOYSA-N 0.000 description 1
- QVLJLWHOILVHJJ-UHFFFAOYSA-N ethyl 2-pyridin-4-ylacetate Chemical compound CCOC(=O)CC1=CC=NC=C1 QVLJLWHOILVHJJ-UHFFFAOYSA-N 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011156 evaluation 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
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Chemical class 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- YSLDOTFAFZJPOC-UHFFFAOYSA-N hydron;methyl 6-aminohexanoate;chloride Chemical compound Cl.COC(=O)CCCCCN YSLDOTFAFZJPOC-UHFFFAOYSA-N 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 208000026621 hypolipoproteinemia Diseases 0.000 description 1
- YIAPLDFPUUJILH-UHFFFAOYSA-N indan-1-ol Chemical compound C1=CC=C2C(O)CCC2=C1 YIAPLDFPUUJILH-UHFFFAOYSA-N 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000001023 inorganic pigment Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 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
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Chemical class 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical class [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- FCPRDUXJWIUVPZ-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=CC=[C-]1 FCPRDUXJWIUVPZ-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Chemical class 0.000 description 1
- 239000001630 malic acid Chemical class 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- TXRITZIBWTUFSI-UHFFFAOYSA-N methyl 2-[4-chloro-2-[cyano-(2-methoxyphenyl)methyl]phenyl]acetate Chemical compound COC(=O)CC1=CC=C(Cl)C=C1C(C#N)C1=CC=CC=C1OC TXRITZIBWTUFSI-UHFFFAOYSA-N 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 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
- 230000003228 microsomal effect Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- CJTQESMNKMUZAO-UHFFFAOYSA-N n-[tert-butylimino-(dimethylamino)-[[tris(dimethylamino)-$l^{5}-phosphanylidene]amino]-$l^{5}-phosphanyl]-n-methylmethanamine Chemical compound CC(C)(C)N=P(N(C)C)(N(C)C)N=P(N(C)C)(N(C)C)N(C)C CJTQESMNKMUZAO-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- KCXYZMFPZHYUFO-UHFFFAOYSA-N n-methyl-n-phosphanylmethanamine Chemical compound CN(C)P KCXYZMFPZHYUFO-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 238000001556 precipitation Methods 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
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical class O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 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
- 230000009863 secondary prevention Effects 0.000 description 1
- 229960002855 simvastatin Drugs 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
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000011975 tartaric acid Chemical class 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 150000003613 toluenes Chemical class 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004006325A DE102004006325A1 (de) | 2004-02-10 | 2004-02-10 | Tetrahydrobenzo[d]azepin-2-on-Derivate und ihre Verwendung |
| PCT/EP2005/000960 WO2005077907A1 (de) | 2004-02-10 | 2005-02-01 | Tetrahydrobenzo [d] azepin-2-on derivate und ihre verwendung zur behandlung von kardiovaskulären krankheiten |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007522159A true JP2007522159A (ja) | 2007-08-09 |
| JP2007522159A5 JP2007522159A5 (https=) | 2008-03-21 |
Family
ID=34801798
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006552501A Withdrawn JP2007522159A (ja) | 2004-02-10 | 2005-02-01 | テトラヒドロベンゾ［ｄ］アゼピン−２−オン誘導体および心臓血管疾患を処置するためのその使用 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7662956B2 (https=) |
| EP (1) | EP1716118B1 (https=) |
| JP (1) | JP2007522159A (https=) |
| CA (1) | CA2554996A1 (https=) |
| DE (2) | DE102004006325A1 (https=) |
| ES (1) | ES2304682T3 (https=) |
| WO (1) | WO2005077907A1 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2624102A1 (en) | 2005-09-29 | 2007-04-12 | Sanofi-Aventis | Phenyl- and pyridinyl- 1, 2 , 4 - oxadiazolone derivatives, processes for their preparation and their use as pharmaceuticals |
| EP2061767B1 (de) | 2006-08-08 | 2014-12-17 | Sanofi | Arylaminoaryl-alkyl-substituierte Imidazolidin-2,4-dione, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Arzneimittel und ihre Verwendung |
| DE102007005045B4 (de) | 2007-01-26 | 2008-12-18 | Sanofi-Aventis | Phenothiazin Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE102007054497B3 (de) | 2007-11-13 | 2009-07-23 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung |
| UY31968A (es) | 2008-07-09 | 2010-01-29 | Sanofi Aventis | Nuevos derivados heterocíclicos, sus procesos para su preparación, y sus usos terapéuticos |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| KR20120060207A (ko) | 2009-08-26 | 2012-06-11 | 사노피 | 신규한 결정성 헤테로방향족 플루오로글리코시드 수화물, 이들 화합물을 포함하는 약제 및 이들의 용도 |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120058A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit benzyl- oder heteromethylengruppen substituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8828994B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| US8895547B2 (en) | 2011-03-08 | 2014-11-25 | Sanofi | Substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120051A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit adamantan- oder noradamantan substituierte benzyl-oxathiazinderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683702B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| AU2019318209B2 (en) | 2018-08-10 | 2025-09-25 | Diapin Therapeutics, Llc | Tri-peptides and treatment of metabolic, cardiovascular and inflammatory disorders |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2401697A (en) * | 1996-06-20 | 1998-01-07 | Pfizer Inc. | 4,1-benzoxazepines or 4,1-benzothiazepines and their use as squalene synthetase inhibitors |
| PL360243A1 (en) * | 2000-06-23 | 2004-09-06 | Takeda Chemical Industries,Ltd | Benzoxazepinones and their use as squalene synthase inhibitors |
| FR2819512B1 (fr) | 2001-01-18 | 2003-02-21 | Servier Lab | Nouveaux composes cyclo[d] azepane, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
-
2004
- 2004-02-10 DE DE102004006325A patent/DE102004006325A1/de not_active Withdrawn
-
2005
- 2005-02-01 EP EP05701287A patent/EP1716118B1/de not_active Expired - Lifetime
- 2005-02-01 ES ES05701287T patent/ES2304682T3/es not_active Expired - Lifetime
- 2005-02-01 CA CA002554996A patent/CA2554996A1/en not_active Abandoned
- 2005-02-01 JP JP2006552501A patent/JP2007522159A/ja not_active Withdrawn
- 2005-02-01 WO PCT/EP2005/000960 patent/WO2005077907A1/de not_active Ceased
- 2005-02-01 US US10/588,862 patent/US7662956B2/en not_active Expired - Fee Related
- 2005-02-01 DE DE502005003904T patent/DE502005003904D1/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US7662956B2 (en) | 2010-02-16 |
| DE102004006325A1 (de) | 2005-08-25 |
| EP1716118A1 (de) | 2006-11-02 |
| US20070287698A1 (en) | 2007-12-13 |
| ES2304682T3 (es) | 2008-10-16 |
| EP1716118B1 (de) | 2008-04-30 |
| CA2554996A1 (en) | 2005-08-25 |
| WO2005077907A1 (de) | 2005-08-25 |
| DE502005003904D1 (de) | 2008-06-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2007522159A (ja) | テトラヒドロベンゾ［ｄ］アゼピン−２−オン誘導体および心臓血管疾患を処置するためのその使用 | |
| US11014922B2 (en) | Cyclobutane- and azetidine-containing mono and spirocyclic compounds as αV integrin inhibitors | |
| JP6896113B2 (ja) | ジアザ二環式置換イミダゾピリミジンおよび呼吸障害を治療するためのその使用 | |
| KR102444687B1 (ko) | 치환된 디아자헤테로비시클릭 화합물 및 그의 용도 | |
| US10414765B2 (en) | Substituted perhydropyrrolo[3,4-c]pyrrole derivatives and the use of same | |
| US10717736B2 (en) | Pyrrole amides as alpha V integrin inhibitors | |
| JP2019537603A (ja) | アルファｖインテグリン阻害剤としてのアゾールアミドおよびアミン | |
| CN114929694B (zh) | 肾上腺素能受体adrac2拮抗剂 | |
| TWI826492B (zh) | 經取代四氫環戊[c]吡咯、經取代二氫吡咯，其類似物及使用其之方法 | |
| JP2009542590A (ja) | 置換ベンゾキセピノ−イソキサゾール類およびそれらの使用 | |
| JP2007517817A (ja) | 心血管障害の処置に使用されるスクアレンシンターゼ阻害剤としての三環式ベンズアゼピン誘導体およびそれらの使用 | |
| HK40085269A (en) | Diazabicyclic substituted imidazopyrimidines and their use for the treatment of breathing disorders | |
| HK40085266A (en) | Diazabicyclic substituted imidazopyrimidines and their use for the treatment of breathing disorders | |
| HK40085267A (en) | Diazabicyclic substituted imidazopyrimidines and their use for the treatment of breathing disorders | |
| HK40074244A (en) | Inhibitors of adrenoreceptor adrac2 | |
| HK40085266B (zh) | 二氮杂双环取代的咪唑并嘧啶及其用於治疗呼吸障碍的用途 | |
| MXPA06007981A (en) | Tricyclic benzazepine derivatives as squalene synthase inhibitors used for the treatment of cardiovascular diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080128 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080128 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A712 Effective date: 20091022 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20100127 |