EA007008B1 - Триамидзамещённые индолы, бензофураны и бензотиофены в качестве ингибиторов микросомального белка, переносящего триглицериды, (мтр) и/или ингибиторов секреции аполипопротеина в (аро в) - Google Patents
Триамидзамещённые индолы, бензофураны и бензотиофены в качестве ингибиторов микросомального белка, переносящего триглицериды, (мтр) и/или ингибиторов секреции аполипопротеина в (аро в) Download PDFInfo
- Publication number
- EA007008B1 EA007008B1 EA200301310A EA200301310A EA007008B1 EA 007008 B1 EA007008 B1 EA 007008B1 EA 200301310 A EA200301310 A EA 200301310A EA 200301310 A EA200301310 A EA 200301310A EA 007008 B1 EA007008 B1 EA 007008B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- alkyl
- methyl
- independently
- phenyl
- trifluoromethyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 40
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 title description 22
- 230000028327 secretion Effects 0.000 title description 8
- 150000002475 indoles Chemical class 0.000 title description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title description 2
- 101710095342 Apolipoprotein B Proteins 0.000 title description 2
- 102100040202 Apolipoprotein B-100 Human genes 0.000 title description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical class C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title 1
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 319
- 238000000034 method Methods 0.000 claims abstract description 129
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 208000008589 Obesity Diseases 0.000 claims abstract description 12
- 235000020824 obesity Nutrition 0.000 claims abstract description 12
- -1 phenyl- Chemical group 0.000 claims description 167
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 100
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 83
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 83
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- 150000003839 salts Chemical class 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 38
- 150000002367 halogens Chemical class 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 241001465754 Metazoa Species 0.000 claims description 29
- 125000004076 pyridyl group Chemical group 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 230000015572 biosynthetic process Effects 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
- 125000004429 atom Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 150000001408 amides Chemical class 0.000 claims description 14
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
- 150000001299 aldehydes Chemical class 0.000 claims description 13
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 13
- 125000002950 monocyclic group Chemical group 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 229910052700 potassium Inorganic materials 0.000 claims description 13
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 12
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 10
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- YXBMGPJKBYDLAK-UHFFFAOYSA-N 2-amino-2-phenyl-n-propylacetamide Chemical compound CCCNC(=O)C(N)C1=CC=CC=C1 YXBMGPJKBYDLAK-UHFFFAOYSA-N 0.000 claims description 3
- XDCULFDDDMBXFA-UHFFFAOYSA-N 3-chloro-1-methyl-5-[methyl-[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylic acid Chemical compound C=1C=C2N(C)C(C(O)=O)=C(Cl)C2=CC=1N(C)C(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 XDCULFDDDMBXFA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- OUMKBAHMPRLISR-UHFFFAOYSA-N 1-phenyl-4-(trifluoromethyl)benzene Chemical group C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1 OUMKBAHMPRLISR-UHFFFAOYSA-N 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 11
- 102000018616 Apolipoproteins B Human genes 0.000 abstract description 3
- 108010027006 Apolipoproteins B Proteins 0.000 abstract description 3
- 150000002632 lipids Chemical class 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 description 133
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- 239000000243 solution Substances 0.000 description 99
- 239000002904 solvent Substances 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- 239000000047 product Substances 0.000 description 67
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 46
- 239000002253 acid Substances 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 239000003795 chemical substances by application Substances 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 30
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 27
- 150000001412 amines Chemical class 0.000 description 27
- OJPPLAWORTYMLZ-UHFFFAOYSA-N 2-amino-n-benzyl-n-methyl-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(N)C(=O)N(C)CC1=CC=CC=C1 OJPPLAWORTYMLZ-UHFFFAOYSA-N 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
- 150000003626 triacylglycerols Chemical class 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 17
- 238000010586 diagram Methods 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- 239000012043 crude product Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 239000003826 tablet Substances 0.000 description 16
- 239000003054 catalyst Substances 0.000 description 15
- 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 15
- 239000007788 liquid Substances 0.000 description 15
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 14
- 206010012601 diabetes mellitus Diseases 0.000 description 14
- 235000019359 magnesium stearate Nutrition 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 239000000651 prodrug Substances 0.000 description 13
- 229940002612 prodrug Drugs 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 238000000634 powder X-ray diffraction Methods 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 238000000926 separation method Methods 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 108090000854 Oxidoreductases Proteins 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 239000012453 solvate Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 229930195725 Mannitol Natural products 0.000 description 10
- 102000004316 Oxidoreductases Human genes 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 125000002619 bicyclic group Chemical group 0.000 description 10
- 150000001718 carbodiimides Chemical class 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 150000002430 hydrocarbons Chemical group 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 239000000594 mannitol Substances 0.000 description 10
- 235000010355 mannitol Nutrition 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 239000012265 solid product Substances 0.000 description 10
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 210000000936 intestine Anatomy 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 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 8
- 208000035150 Hypercholesterolemia Diseases 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 239000000883 anti-obesity agent Substances 0.000 description 8
- 239000004305 biphenyl Substances 0.000 description 8
- 125000002843 carboxylic acid group Chemical group 0.000 description 8
- 238000004821 distillation Methods 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000004059 squalene synthase inhibitor Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
- 201000001320 Atherosclerosis Diseases 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- 229940125710 antiobesity agent Drugs 0.000 description 7
- 125000002618 bicyclic heterocycle group Chemical class 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 7
- 238000002648 combination therapy Methods 0.000 description 7
- WPRKJQVJYKGTLF-UHFFFAOYSA-N ethyl 5-amino-1-methylindole-2-carboxylate Chemical compound NC1=CC=C2N(C)C(C(=O)OCC)=CC2=C1 WPRKJQVJYKGTLF-UHFFFAOYSA-N 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000000945 filler Substances 0.000 description 7
- 235000013355 food flavoring agent Nutrition 0.000 description 7
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 230000006340 racemization Effects 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 7
- IQOMYCGTGFGDFN-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IQOMYCGTGFGDFN-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 239000003963 antioxidant agent Substances 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000007884 disintegrant Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- LPGIJOKHQGNRDJ-UHFFFAOYSA-N ethyl 1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylate Chemical compound C=1C=C2N(C)C(C(=O)OCC)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 LPGIJOKHQGNRDJ-UHFFFAOYSA-N 0.000 description 6
- 125000005456 glyceride group Chemical group 0.000 description 6
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 6
- 150000004677 hydrates Chemical class 0.000 description 6
- 208000006575 hypertriglyceridemia Diseases 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 239000000314 lubricant Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 6
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical group NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 206010033645 Pancreatitis Diseases 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 230000001906 cholesterol absorption Effects 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 5
- 230000031891 intestinal absorption Effects 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 229940095064 tartrate Drugs 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 4
- 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 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 4
- 108090001030 Lipoproteins Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 238000013019 agitation Methods 0.000 description 4
- 125000003277 amino group Chemical class 0.000 description 4
- 239000011260 aqueous acid Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- DTGUXIWYZIAUIT-UHFFFAOYSA-N ethyl 1-methyl-5-nitroindole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2N(C)C(C(=O)OCC)=CC2=C1 DTGUXIWYZIAUIT-UHFFFAOYSA-N 0.000 description 4
- DVFJMQCNICEPAI-UHFFFAOYSA-N ethyl 5-nitro-1h-indole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2NC(C(=O)OCC)=CC2=C1 DVFJMQCNICEPAI-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000006178 methyl benzyl group Chemical group 0.000 description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 4
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011118 potassium hydroxide Nutrition 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 3
- ZCXLTWVZYXBHJS-UHFFFAOYSA-N 1,2-benzoxazepine Chemical class O1N=CC=CC2=CC=CC=C12 ZCXLTWVZYXBHJS-UHFFFAOYSA-N 0.000 description 3
- OEDWWZYYIXCAIW-UHFFFAOYSA-N 1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylic acid Chemical compound C=1C=C2N(C)C(C(O)=O)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 OEDWWZYYIXCAIW-UHFFFAOYSA-N 0.000 description 3
- MIMYTSWNVBMNRH-UHFFFAOYSA-N 1h-indol-6-amine Chemical compound NC1=CC=C2C=CNC2=C1 MIMYTSWNVBMNRH-UHFFFAOYSA-N 0.000 description 3
- KIYRSYYOVDHSPG-UHFFFAOYSA-N 2-amino-2-phenylacetamide Chemical class NC(=O)C(N)C1=CC=CC=C1 KIYRSYYOVDHSPG-UHFFFAOYSA-N 0.000 description 3
- GXBRYTMUEZNYJT-UHFFFAOYSA-N 2-anilinoacetamide Chemical compound NC(=O)CNC1=CC=CC=C1 GXBRYTMUEZNYJT-UHFFFAOYSA-N 0.000 description 3
- ZFGOPJASRDDARH-UHFFFAOYSA-N 3-[[10,13-dimethyl-17-(6-methylheptan-2-yl)-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-10,13-dimethyl-17-(6-methylheptan-2-yl)-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C12CCC3(C)C(C(C)CCCC(C)C)CCC3C2CC=C(C2)C1(C)CCC2OC1CC2=CCC3C4CCC(C(C)CCCC(C)C)C4(C)CCC3C2(C)CC1 ZFGOPJASRDDARH-UHFFFAOYSA-N 0.000 description 3
- ZEJAIFHFRMTBCN-UHFFFAOYSA-N 3-chloro-1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylic acid Chemical compound C=1C=C2N(C)C(C(O)=O)=C(Cl)C2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 ZEJAIFHFRMTBCN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- 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 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 241000282324 Felis Species 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 229940123934 Reductase inhibitor Drugs 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 239000003524 antilipemic agent Substances 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- 229960005370 atorvastatin Drugs 0.000 description 3
- 125000002393 azetidinyl group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 3
- 229960002802 bromocriptine Drugs 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000000113 differential scanning calorimetry Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229960001582 fenfluramine Drugs 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000001087 glyceryl triacetate Substances 0.000 description 3
- 235000013773 glyceryl triacetate Nutrition 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 230000003228 microsomal effect Effects 0.000 description 3
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 235000001968 nicotinic acid Nutrition 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 3
- 229960001243 orlistat Drugs 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229930195734 saturated hydrocarbon Natural products 0.000 description 3
- 229960004425 sibutramine Drugs 0.000 description 3
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 159000000000 sodium salts Chemical group 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 229960002622 triacetin Drugs 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- DSGKWFGEUBCEIE-UHFFFAOYSA-N (2-carbonochloridoylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1C(Cl)=O DSGKWFGEUBCEIE-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 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 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 2
- TTWRDTJGXVPENY-UHFFFAOYSA-N 1-ethyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylic acid Chemical compound C=1C=C2N(CC)C(C(O)=O)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 TTWRDTJGXVPENY-UHFFFAOYSA-N 0.000 description 2
- LHZCYMUDOGCJOW-UHFFFAOYSA-N 1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylic acid;hydrate Chemical compound O.C=1C=C2N(C)C(C(O)=O)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 LHZCYMUDOGCJOW-UHFFFAOYSA-N 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- YYMHHPFPTALMCY-UHFFFAOYSA-N 2-(methylamino)-2-phenylacetamide Chemical compound CNC(C(N)=O)C1=CC=CC=C1 YYMHHPFPTALMCY-UHFFFAOYSA-N 0.000 description 2
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 description 2
- MVUGBURUWNYPHI-UHFFFAOYSA-N 3-methyl-2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C1=CC=C(C(F)(F)F)C=C1 MVUGBURUWNYPHI-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 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 2
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 2
- LHFOJSCXLFKDIR-UHFFFAOYSA-N 5-nitro-1h-indole-2-carboxylic acid Chemical group [O-][N+](=O)C1=CC=C2NC(C(=O)O)=CC2=C1 LHFOJSCXLFKDIR-UHFFFAOYSA-N 0.000 description 2
- LZKWLHXJPIKJSJ-UHFFFAOYSA-N 5-nitrobenzofuran-2-carboxylic acid Chemical group [O-][N+](=O)C1=CC=C2OC(C(=O)O)=CC2=C1 LZKWLHXJPIKJSJ-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 2
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- 108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 2
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical group OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- 102000016267 Leptin Human genes 0.000 description 2
- 108010092277 Leptin Proteins 0.000 description 2
- 229910017976 MgO 4 Inorganic materials 0.000 description 2
- 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 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 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 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 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 2
- 229940123495 Squalene synthetase inhibitor Drugs 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 125000006267 biphenyl group Chemical group 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 150000001907 coumarones Chemical class 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000008157 edible vegetable oil Substances 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- XZPGYMKNLXTCOQ-UHFFFAOYSA-N ethyl 1-ethyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylate Chemical compound C=1C=C2N(CC)C(C(=O)OCC)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 XZPGYMKNLXTCOQ-UHFFFAOYSA-N 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 229960003765 fluvastatin Drugs 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 229940039781 leptin Drugs 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- 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 2
- 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 2
- 239000011777 magnesium Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- YIBQTOKSYBJZFG-UHFFFAOYSA-N methyl 3-methyl-2-[4-(trifluoromethyl)phenyl]benzoate Chemical compound COC(=O)C1=CC=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 YIBQTOKSYBJZFG-UHFFFAOYSA-N 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 239000008063 pharmaceutical solvent Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229960003562 phentermine Drugs 0.000 description 2
- 150000005331 phenylglycines Chemical class 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001184 polypeptide Chemical group 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- NLFMFWSRAVXVRP-UHFFFAOYSA-M potassium 1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylate hydrate Chemical compound O.[K+].Cn1c(cc2cc(NC(=O)c3ccccc3-c3ccc(cc3)C(F)(F)F)ccc12)C([O-])=O NLFMFWSRAVXVRP-UHFFFAOYSA-M 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 229960002965 pravastatin Drugs 0.000 description 2
- 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 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108090000765 processed proteins & peptides Chemical group 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 229940076372 protein antagonist Drugs 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- 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 2
- 238000007711 solidification Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000004034 viscosity adjusting agent Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 1
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 1
- DZLOHEOHWICNIL-QGZVFWFLSA-N (2R)-2-[6-(4-chlorophenoxy)hexyl]-2-oxiranecarboxylic acid ethyl ester Chemical compound C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)OCC)CO1 DZLOHEOHWICNIL-QGZVFWFLSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- 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 1
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YMOCGEHYJFNZQZ-UHFFFAOYSA-N 1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]pyridine-3-carbonyl]amino]indole-2-carboxylic acid Chemical compound C=1C=C2N(C)C(C(O)=O)=CC2=CC=1NC(=O)C1=CC=CN=C1C1=CC=C(C(F)(F)F)C=C1 YMOCGEHYJFNZQZ-UHFFFAOYSA-N 0.000 description 1
- RXHBEIXARTWQOU-UHFFFAOYSA-N 1-methyl-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylic acid Chemical compound CC1=CC=CC(C(=O)NC=2C=C3C=C(N(C)C3=CC=2)C(O)=O)=C1C1=CC=C(C(F)(F)F)C=C1 RXHBEIXARTWQOU-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- ZSTUEICKYWFYIC-UHFFFAOYSA-N 2-(4-methylphenyl)benzoic acid Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1C(O)=O ZSTUEICKYWFYIC-UHFFFAOYSA-N 0.000 description 1
- ZSOZYBIDCNHWSW-UHFFFAOYSA-N 2-[1-(3,3-diphenylpropyl)piperidin-4-yl]-3h-isoindol-1-one Chemical compound C1C2=CC=CC=C2C(=O)N1C(CC1)CCN1CCC(C=1C=CC=CC=1)C1=CC=CC=C1 ZSOZYBIDCNHWSW-UHFFFAOYSA-N 0.000 description 1
- TYZQFNOLWJGHRZ-UHFFFAOYSA-N 2-[2-(4,5-dihydro-1h-imidazol-2-yl)-1-phenylethyl]pyridine Chemical compound N=1CCNC=1CC(C=1N=CC=CC=1)C1=CC=CC=C1 TYZQFNOLWJGHRZ-UHFFFAOYSA-N 0.000 description 1
- VFDVBQMLLPCXNP-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoyl chloride Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(Cl)=O VFDVBQMLLPCXNP-UHFFFAOYSA-N 0.000 description 1
- BSJZOKLRDOUYFW-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1C1=CC=C(C(F)(F)F)C=C1 BSJZOKLRDOUYFW-UHFFFAOYSA-N 0.000 description 1
- ACZKTJZXXSHIGF-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1CCCCCC1(C(=O)O)CO1 ACZKTJZXXSHIGF-UHFFFAOYSA-N 0.000 description 1
- ANPFFDAQFQPIHE-UHFFFAOYSA-N 2-amino-n-benzyl-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(N)C(=O)NCC1=CC=CC=C1 ANPFFDAQFQPIHE-UHFFFAOYSA-N 0.000 description 1
- DDRNQKVAGAWDEE-UHFFFAOYSA-N 2-chlorobutanediamide Chemical compound NC(=O)CC(Cl)C(N)=O DDRNQKVAGAWDEE-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- FMKOJHQHASLBPH-OUBTZVSYSA-N 2-iodopropane Chemical compound CC([13CH3])I FMKOJHQHASLBPH-OUBTZVSYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical class O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 1
- 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 description 1
- CGVPQHIRIGIDLE-UHFFFAOYSA-N 3-(2-aminooxyphenyl)propanoic acid Chemical compound NOC1=CC=CC=C1CCC(O)=O CGVPQHIRIGIDLE-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
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
- ALAISIMBNHEIBH-UHFFFAOYSA-N 3-[2-[benzyl(methyl)amino]-2-oxo-1-phenylethyl]-1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxamide Chemical compound C(C1=CC=CC=C1)N(C(C(C1=CC=CC=C1)C1=C(N(C2=CC=C(C=C12)NC(=O)C=1C(=CC=CC1)C1=CC=C(C=C1)C(F)(F)F)C)C(=O)N)=O)C ALAISIMBNHEIBH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- QXZBMSIDSOZZHK-DOPDSADYSA-N 31362-50-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CNC=N1 QXZBMSIDSOZZHK-DOPDSADYSA-N 0.000 description 1
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 description 1
- YAVSXFRYNGAFRN-UHFFFAOYSA-N 4,1-benzoxazepine Chemical class O1C=CN=C2C=CC=CC2=C1 YAVSXFRYNGAFRN-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
- ZSEHBLBYCASPDO-UHFFFAOYSA-N 4-phenyl-1,3-oxazolidine-2,5-dione Chemical compound O=C1OC(=O)NC1C1=CC=CC=C1 ZSEHBLBYCASPDO-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- DUSMDSXUPJPMBJ-UHFFFAOYSA-N 5-[(2-hydroxybenzoyl)amino]-1-methylindole-2-carboxylic acid Chemical compound C=1C=C2N(C)C(C(O)=O)=CC2=CC=1NC(=O)C1=CC=CC=C1O DUSMDSXUPJPMBJ-UHFFFAOYSA-N 0.000 description 1
- MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 1
- XDOYYGGLLVXWHM-UHFFFAOYSA-N 5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-1-benzofuran-2-carboxylic acid Chemical compound C=1C=C2OC(C(=O)O)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 XDOYYGGLLVXWHM-UHFFFAOYSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- KROYLRGNLSKXHM-UHFFFAOYSA-N 6-nitro-1-benzofuran-2-carboxylic acid Chemical compound C1=C([N+]([O-])=O)C=C2OC(C(=O)O)=CC2=C1 KROYLRGNLSKXHM-UHFFFAOYSA-N 0.000 description 1
- JIXJNWVLWQQNDB-UHFFFAOYSA-N 6-nitro-1h-indole-2-carboxylic acid Chemical compound C1=C([N+]([O-])=O)C=C2NC(C(=O)O)=CC2=C1 JIXJNWVLWQQNDB-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
- 108010051842 Advanced Oxidation Protein Products Proteins 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 102000013585 Bombesin Human genes 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 241000283725 Bos Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- GDHCFIDPKAIDKE-UHFFFAOYSA-N C(C1=CC=CC=C1)C(C(=O)N)C1=CC=CC=C1.Cl Chemical compound C(C1=CC=CC=C1)C(C(=O)N)C1=CC=CC=C1.Cl GDHCFIDPKAIDKE-UHFFFAOYSA-N 0.000 description 1
- DTPWZYSUQQHRKD-VIUAGAKSSA-N CC(O)=O.CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O Chemical compound CC(O)=O.CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O DTPWZYSUQQHRKD-VIUAGAKSSA-N 0.000 description 1
- AZKLBFXQHJLECP-UHFFFAOYSA-N CCc1c(C(O)=O)n(CC)c2ccc(cc12)[N+]([O-])=O Chemical compound CCc1c(C(O)=O)n(CC)c2ccc(cc12)[N+]([O-])=O AZKLBFXQHJLECP-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229940122820 Cannabinoid receptor antagonist Drugs 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 101710150887 Cholecystokinin A Proteins 0.000 description 1
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 241000701796 Fowl aviadenovirus 1 Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 102000019432 Galanin Human genes 0.000 description 1
- 101800002068 Galanin Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229940122498 Gene expression inhibitor Drugs 0.000 description 1
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 229940121931 Gluconeogenesis inhibitor Drugs 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
- 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
- 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical class CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 1
- 229940122942 Leptin receptor agonist Drugs 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 229940086609 Lipase inhibitor Drugs 0.000 description 1
- 108010000410 MSH receptor Proteins 0.000 description 1
- 229940111264 Melanocyte stimulating hormone receptor agonist Drugs 0.000 description 1
- 102000012539 Melanocyte-stimulating hormone receptors Human genes 0.000 description 1
- 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 1
- 208000031888 Mycoses Diseases 0.000 description 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical class CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 1
- 241001077878 Neurolaena lobata Species 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229940123730 Orexin receptor antagonist Drugs 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 1
- 108010054082 Sterol O-acyltransferase Proteins 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
- 241000282887 Suidae Species 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 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 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 102000005630 Urocortins Human genes 0.000 description 1
- 108010059705 Urocortins Proteins 0.000 description 1
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- OJFDKHTZOUZBOS-CITAKDKDSA-N acetoacetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 OJFDKHTZOUZBOS-CITAKDKDSA-N 0.000 description 1
- 229960001466 acetohexamide Drugs 0.000 description 1
- VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
- 229940100228 acetyl coenzyme a Drugs 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 229960003526 acipimox Drugs 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical group 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 229940072049 amyl acetate Drugs 0.000 description 1
- PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001346 anti-hypertriglyceridemic effect Effects 0.000 description 1
- 230000003243 anti-lipolytic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 108010014210 axokine Proteins 0.000 description 1
- DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- QXNDZONIWRINJR-UHFFFAOYSA-N azocane Chemical compound C1CCCNCCC1 QXNDZONIWRINJR-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 229960001264 benfluorex Drugs 0.000 description 1
- 229940054066 benzamide antipsychotics Drugs 0.000 description 1
- 150000003936 benzamides Chemical group 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 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
- CJAVTWRYCDNHSM-UHFFFAOYSA-N benzoic acid 2-[1-[3-(trifluoromethyl)phenyl]propan-2-ylamino]ethyl ester Chemical compound C=1C=CC=CC=1C(=O)OCCNC(C)CC1=CC=CC(C(F)(F)F)=C1 CJAVTWRYCDNHSM-UHFFFAOYSA-N 0.000 description 1
- HAVZTGSQJIEKPI-UHFFFAOYSA-N benzothiadiazine Chemical compound C1=CC=C2C=NNSC2=C1 HAVZTGSQJIEKPI-UHFFFAOYSA-N 0.000 description 1
- 229940085242 benzothiazepine derivative selective calcium channel blockers with direct cardiac effects Drugs 0.000 description 1
- 150000007657 benzothiazepines Chemical class 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229960004111 buformin Drugs 0.000 description 1
- XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229950001261 camiglibose Drugs 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000003536 cannabinoid receptor antagonist Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 210000003764 chromatophore Anatomy 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229950009226 ciglitazone Drugs 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229950006376 clomoxir Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- QQKNSPHAFATFNQ-UHFFFAOYSA-N darglitazone Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=O)C(C=C1)=CC=C1CC1SC(=O)NC1=O QQKNSPHAFATFNQ-UHFFFAOYSA-N 0.000 description 1
- 229950006689 darglitazone Drugs 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 238000000280 densification Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960004597 dexfenfluramine Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- 235000019821 dicalcium diphosphate Nutrition 0.000 description 1
- 229910000393 dicalcium diphosphate Inorganic materials 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 229950000269 emiglitate Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229950002375 englitazone Drugs 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction 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
- ZKVUIZMEWIDCAY-UHFFFAOYSA-N ethyl 1,3-diethyl-5-nitroindole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2N(CC)C(C(=O)OCC)=C(CC)C2=C1 ZKVUIZMEWIDCAY-UHFFFAOYSA-N 0.000 description 1
- WDFFCCSGOPZWDE-UHFFFAOYSA-N ethyl 1-ethyl-5-nitroindole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2N(CC)C(C(=O)OCC)=CC2=C1 WDFFCCSGOPZWDE-UHFFFAOYSA-N 0.000 description 1
- WZPPLBNWMYQMIW-UHFFFAOYSA-N ethyl 1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]pyridine-3-carbonyl]amino]indole-2-carboxylate Chemical compound C=1C=C2N(C)C(C(=O)OCC)=CC2=CC=1NC(=O)C1=CC=CN=C1C1=CC=C(C(F)(F)F)C=C1 WZPPLBNWMYQMIW-UHFFFAOYSA-N 0.000 description 1
- UDTZGLPLWZDASX-UHFFFAOYSA-N ethyl 1-methyl-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylate Chemical compound C=1C=C2N(C)C(C(=O)OCC)=CC2=CC=1NC(=O)C1=CC=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 UDTZGLPLWZDASX-UHFFFAOYSA-N 0.000 description 1
- DFPTYPKVAXICRU-UHFFFAOYSA-N ethyl 3-chloro-1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylate Chemical compound C=1C=C2N(C)C(C(=O)OCC)=C(Cl)C2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 DFPTYPKVAXICRU-UHFFFAOYSA-N 0.000 description 1
- NWWORXYTJRPSMC-QKPAOTATSA-N ethyl 4-[2-[(2r,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 NWWORXYTJRPSMC-QKPAOTATSA-N 0.000 description 1
- DVQHFONUWFIEAF-UHFFFAOYSA-N ethyl 5-amino-1-ethylindole-2-carboxylate Chemical compound NC1=CC=C2N(CC)C(C(=O)OCC)=CC2=C1 DVQHFONUWFIEAF-UHFFFAOYSA-N 0.000 description 1
- SOMZLSPJSSDTAP-UHFFFAOYSA-N ethyl 6-nitro-1h-indole-2-carboxylate Chemical compound C1=C([N+]([O-])=O)C=C2NC(C(=O)OCC)=CC2=C1 SOMZLSPJSSDTAP-UHFFFAOYSA-N 0.000 description 1
- 239000002038 ethyl acetate fraction Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229950006213 etomoxir Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 108010011129 farnesyl pyrophosphatase Proteins 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
- 229940126013 glucocorticoid receptor antagonist Drugs 0.000 description 1
- 239000003850 glucocorticoid receptor antagonist Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N homoserine Chemical compound OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- XPXMKIXDFWLRAA-UHFFFAOYSA-N hydrazinide Chemical compound [NH-]N XPXMKIXDFWLRAA-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- HPMRFMKYPGXPEP-UHFFFAOYSA-N idazoxan Chemical compound N1CCN=C1C1OC2=CC=CC=C2OC1 HPMRFMKYPGXPEP-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 150000002462 imidazolines Chemical class 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- HCUARRIEZVDMPT-UHFFFAOYSA-N indolyl-2-carboxylic acid Natural products C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 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
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229940058690 lanosterol Drugs 0.000 description 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical class C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 1
- 229910052745 lead Inorganic materials 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- JEJXTJUTLLQPGN-UHFFFAOYSA-N methyl 2-[4-(trifluoromethyl)phenyl]pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1C1=CC=C(C(F)(F)F)C=C1 JEJXTJUTLLQPGN-UHFFFAOYSA-N 0.000 description 1
- KEIDWEMUVVLVKL-UHFFFAOYSA-N methyl 5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-1-benzofuran-2-carboxylate Chemical compound C=1C=C2OC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 KEIDWEMUVVLVKL-UHFFFAOYSA-N 0.000 description 1
- OLLMSIUDBMURHQ-UHFFFAOYSA-N methyl 5-amino-1-benzofuran-2-carboxylate Chemical compound NC1=CC=C2OC(C(=O)OC)=CC2=C1 OLLMSIUDBMURHQ-UHFFFAOYSA-N 0.000 description 1
- FMFPOZLVAJOEHS-UHFFFAOYSA-N methyl 5-nitro-1-benzofuran-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2OC(C(=O)OC)=CC2=C1 FMFPOZLVAJOEHS-UHFFFAOYSA-N 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 229950001332 midaglizole Drugs 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229940126403 monoamine reuptake inhibitor Drugs 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- IMNDHOCGZLYMRO-UHFFFAOYSA-N n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1 IMNDHOCGZLYMRO-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- LNIVDAPIGFBRFB-UHFFFAOYSA-N n-(2-butyl-3,4-dihydro-1h-isoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCCC)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 LNIVDAPIGFBRFB-UHFFFAOYSA-N 0.000 description 1
- DJLMIXIBPMWLNC-UHFFFAOYSA-N n-[2-(2-acetamidoethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCNC(=O)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 DJLMIXIBPMWLNC-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- RQRAKXWAVSGUEZ-UHFFFAOYSA-N oxazireno[2,3-a]indole Chemical compound O1c2cc3ccccc3n12 RQRAKXWAVSGUEZ-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 150000002921 oxetanes Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000005009 perfluoropropyl group Chemical group FC(C(C(F)(F)F)(F)F)(F)* 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229960003243 phenformin Drugs 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000005541 phosphonamide group Chemical group 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- BFFWSXUFQWNHHK-UHFFFAOYSA-M potassium;1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylate Chemical compound [K+].C=1C=C2N(C)C(C([O-])=O)=CC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 BFFWSXUFQWNHHK-UHFFFAOYSA-M 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- 229960004457 pramlintide acetate Drugs 0.000 description 1
- 229960002847 prasterone Drugs 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 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
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 229960003908 pseudoephedrine Drugs 0.000 description 1
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 229940045847 receptor mimetic Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- DCPZMFAGTRHXAH-UHFFFAOYSA-M sodium 1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxylate hydrate Chemical compound O.[Na+].Cn1c(cc2cc(NC(=O)c3ccccc3-c3ccc(cc3)C(F)(F)F)ccc12)C([O-])=O DCPZMFAGTRHXAH-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229940075620 somatostatin analogue Drugs 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical class C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- 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 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- DIORMHZUUKOISG-UHFFFAOYSA-N sulfoformic acid Chemical class OC(=O)S(O)(=O)=O DIORMHZUUKOISG-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000000777 urocortin Substances 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
-
- 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
-
- 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
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Furan Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30164401P | 2001-06-28 | 2001-06-28 | |
| PCT/IB2002/001876 WO2003002533A1 (en) | 2001-06-28 | 2002-05-24 | Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (mtp) and/or apolipoprotein b (apo b) secretion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200301310A1 EA200301310A1 (ru) | 2004-06-24 |
| EA007008B1 true EA007008B1 (ru) | 2006-06-30 |
Family
ID=23164253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200301310A EA007008B1 (ru) | 2001-06-28 | 2002-05-24 | Триамидзамещённые индолы, бензофураны и бензотиофены в качестве ингибиторов микросомального белка, переносящего триглицериды, (мтр) и/или ингибиторов секреции аполипопротеина в (аро в) |
Country Status (46)
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE502928T1 (de) | 2000-11-01 | 2011-04-15 | Millennium Pharm Inc | Stickstoffhaltige heterozyklische verbindungen und verfahren zu deren herstellung |
| SI1404653T1 (sl) * | 2001-06-28 | 2008-12-31 | Pfizer Prod Inc | S triamidom substituirani indoli, benzofurani in benzotiofeni kot zaviralci mikrosomske prenašalnebeljakovine za trigliceride (MTP) in/ali izločanja apolipoproteina B (APO B) |
| WO2003057175A2 (en) * | 2002-01-02 | 2003-07-17 | Visen Medical, Inc. | Amine functionalized superparamagnetic nanoparticles for the synthesis of bioconjugates and uses therefor |
| EP1594439A2 (en) * | 2003-02-13 | 2005-11-16 | Albert Einstein College Of Medicine Of Yeshiva University | REGULATION OF FOOD INTAKE AND GLUCOSE PRODUCTION BY MODULATION OF LONG-CHAIN FATTY ACYL-CoA LEVELS IN THE HYPOTHALAMUS |
| WO2004112695A2 (en) * | 2003-05-20 | 2004-12-29 | Erimos Pharmaceutical Llc | Methods and compositions for delivery of catecholic butanes for treatment of obesity |
| JP5133561B2 (ja) | 2003-06-19 | 2013-01-30 | メルク セローノ ソシエテ アノニム | プリオン変換を調節する因子の使用 |
| AU2004289110A1 (en) * | 2003-11-14 | 2005-05-26 | Pfizer Products Inc. | Solid amorphous dispersions of an MTP inhibitor for treatment of obesity |
| WO2005080373A1 (en) | 2004-02-04 | 2005-09-01 | Pfizer Products Inc. | Substituted quinoline compounds |
| JP5697296B2 (ja) | 2004-03-05 | 2015-04-08 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 高脂血症および高コレステロール血症に関連する障害または疾患を、副作用を最小限にしつつ処置するための方法 |
| FR2873694B1 (fr) | 2004-07-27 | 2006-12-08 | Merck Sante Soc Par Actions Si | Nouveaux aza-indoles inhibiteurs de la mtp et apob |
| WO2006041922A2 (en) * | 2004-10-08 | 2006-04-20 | Dara Biosciences, Inc. | Agents and methods for administration to the central nervous system |
| PA8660701A1 (es) | 2005-02-04 | 2006-09-22 | Pfizer Prod Inc | Agonistas de pyy y sus usos |
| US20090012067A1 (en) * | 2005-02-14 | 2009-01-08 | Luciano Rossetti | Modulation of Hypothalamic Atp-Sensitive Potassium Channels |
| WO2006129193A2 (en) * | 2005-05-27 | 2006-12-07 | Pfizer Products Inc. | Combination of a cannabinoid-1- receptor-antagonist and a microsomal triglyceride transfer protein inhibitor for treating obesity or mainataining weight loss |
| DE102005027274A1 (de) * | 2005-06-08 | 2006-12-14 | Schering Ag | Inhibitoren der löslichen Adenylatzyklase |
| US7417066B2 (en) | 2005-06-08 | 2008-08-26 | Schering Ag | Inhibitors of soluble adenylate cyclase |
| CA2617654A1 (en) * | 2005-08-04 | 2007-02-08 | Pfizer Limited | Piperidinoyl-pyrrolidine and piperidinoyl-piperidine compounds |
| US20080253985A1 (en) * | 2005-10-18 | 2008-10-16 | Wisler Gerald L | Compositions for Lowering Serum Cholesterol and/or Triglycerides |
| US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
| EP1954137A4 (en) * | 2005-11-18 | 2008-12-17 | Janssen Pharmaceutica Nv | 2-KETO-OXAZOLE AS MODULATORS OF FATTY ACID AMIDHYDROLASE |
| US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| EP1973575B1 (en) | 2005-12-22 | 2019-07-24 | Visen Medical, Inc. | Biocompatible fluorescent metal oxide nanoparticles |
| US8383660B2 (en) | 2006-03-10 | 2013-02-26 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
| ES2882684T3 (es) * | 2006-04-07 | 2021-12-02 | Vertex Pharma | Preparación de moduladores de transportadores del casete de unión a ATP |
| US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US10022352B2 (en) | 2006-04-07 | 2018-07-17 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| EP2084127A1 (en) | 2006-11-13 | 2009-08-05 | Pfizer Products Inc. | Diaryl, dipyridinyl and aryl-pyridinyl derivatives and uses thereof |
| ATE547394T1 (de) | 2006-12-01 | 2012-03-15 | Bristol Myers Squibb Co | N-((3-benzyl)-2,2-(bis-phenyl)-propan-1- aminderivate als cetp-hemmer für die behandlung von atherosklerose und herz-kreislauf- erkrankungen |
| AU2007338625A1 (en) * | 2006-12-21 | 2008-07-03 | Aegerion Pharmaceuticals, Inc. | Methods for treating obesity with a combination comprising a MTP inhibitor and a cholesterol absorption inhibitor |
| WO2008100423A1 (en) * | 2007-02-09 | 2008-08-21 | Sirtris Pharmaceuticals, Inc. | Gut microsomal triglyceride transport protein inhibitors |
| ES2670852T3 (es) | 2007-02-09 | 2018-06-01 | Visen Medical, Inc. | Colorantes con policiclo y uso de los mismos |
| CN103450077B (zh) | 2007-06-08 | 2016-07-06 | 满康德股份有限公司 | IRE-1α抑制剂 |
| WO2009014674A1 (en) * | 2007-07-23 | 2009-01-29 | Sirtris Pharmaceuticals, Inc. | Heterocyclylamides as gut microsomal triglyceride transport protein inhibitors |
| WO2009090210A2 (en) * | 2008-01-16 | 2009-07-23 | Janssen Pharmaceutica Nv | Combination of metformin and an mtp inhibitor |
| US20090197947A1 (en) * | 2008-02-01 | 2009-08-06 | The Research Foundation Of State University Of New York | Medicaments and methods for lowering plasma lipid levels and screening drugs |
| JP5711151B2 (ja) * | 2010-01-06 | 2015-04-30 | 武田薬品工業株式会社 | インドール誘導体 |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| RU2569678C2 (ru) | 2010-04-22 | 2015-11-27 | Вертекс Фармасьютикалз Инкорпорейтед | Способ получения циклоалкилкарбоксамидо-индольных соединений |
| EP2665708A4 (en) * | 2011-01-20 | 2014-07-09 | Univ Colorado Regents | MODULATORS OF THE TLR3 / DSRNA COMPLEX AND APPLICATIONS THEREOF |
| CN102108070B (zh) * | 2011-01-26 | 2013-05-22 | 上海优贝德生物医药有限公司 | 5-氨基苯并呋喃-2-甲酸酯及其中间体的制备方法 |
| US9012496B2 (en) | 2012-07-16 | 2015-04-21 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide and administration thereof |
| EP2963013A4 (en) | 2013-02-27 | 2016-09-14 | Shionogi & Co | INDOLE AND AZAINDOLE DERIVATIVES HAVING AMPK ACTIVATION ACTIVITY EACH |
| WO2015121877A2 (en) * | 2014-02-17 | 2015-08-20 | Hetero Research Foundation | Polymorphs of lomitapide and its salts |
| CN103880797B (zh) * | 2014-03-26 | 2015-12-02 | 沈阳大学 | 苯并呋喃类化合物及其医药用途 |
| PT3131582T (pt) | 2014-04-15 | 2018-10-08 | Vertex Pharma | Composições farmacêuticas para o tratamento de doenças mediadas pelo regulador de condutância transmembranar da fibrose quística |
| PT3203840T (pt) | 2014-10-06 | 2020-10-27 | Vertex Pharma | Moduladores do regulador da condutância transmembranar da fibrose quística |
| US10738030B2 (en) | 2016-03-31 | 2020-08-11 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| LT3519401T (lt) | 2016-09-30 | 2021-11-25 | Vertex Pharmaceuticals Incorporated | Cistinės fibrozės transmembraninio laidumo reguliavimo moduliatorius, farmacinės kompozicijos, gydymo būdai ir moduliatoriaus gamybos būdas |
| MX2021013639A (es) | 2016-12-09 | 2022-09-30 | Vertex Pharma | Forma cristalina del compuesto 1, un modulador del regulador de conductancia transmembrana de fibrosis quística, procesos para su preparación, composiciones farmacéuticas del compuesto 1, y su uso en el tratamiento de fibrosis quística. |
| CA3066084A1 (en) | 2017-06-08 | 2018-12-13 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| AU2018304168B2 (en) | 2017-07-17 | 2023-05-04 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| CN111051280B (zh) | 2017-08-02 | 2023-12-22 | 弗特克斯药品有限公司 | 制备吡咯烷化合物的方法 |
| TWI719349B (zh) | 2017-10-19 | 2021-02-21 | 美商維泰克斯製藥公司 | Cftr調節劑之結晶形式及組合物 |
| MA51039A (fr) | 2017-12-08 | 2020-10-14 | Vertex Pharma | Procédés pour préparer des modulateurs du régulateur de la conductance transmembranaire de la mucoviscidose |
| TWI810243B (zh) | 2018-02-05 | 2023-08-01 | 美商維泰克斯製藥公司 | 用於治療囊腫纖化症之醫藥組合物 |
| EP3774825A1 (en) | 2018-04-13 | 2021-02-17 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator |
| AU2021316011A1 (en) | 2020-07-29 | 2023-02-09 | Amryt Pharmaceuticals Inc. | Lomitapide for use in methods of treating hyperlipidemia and hypercholesterolemia in pediatric patients |
| US12029718B2 (en) | 2021-11-09 | 2024-07-09 | Cct Sciences, Llc | Process for production of essentially pure delta-9-tetrahydrocannabinol |
| CN112608271A (zh) * | 2020-11-26 | 2021-04-06 | 安润医药科技(苏州)有限公司 | 酰胺衍生物及其在制备ep4受体拮抗剂中的应用 |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4022900A (en) | 1970-09-09 | 1977-05-10 | Marion Laboratories, Inc. | Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents |
| US4397855A (en) | 1981-06-26 | 1983-08-09 | Warner-Lambert Company | 4-(Substituted)-α, α-dimethyl-1-piperazine pentanoic acids and derivatives as anti-arteriosclerotic agents and method |
| US4647576A (en) * | 1984-09-24 | 1987-03-03 | Warner-Lambert Company | Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of cholesterol synthesis |
| US5416009A (en) | 1991-01-23 | 1995-05-16 | The United States Of America | Nucleotide molecule encoding a specific Onchocerca volvulus antigen for the immunodiagnosis of onchocerciasis |
| US5595872A (en) | 1992-03-06 | 1997-01-21 | Bristol-Myers Squibb Company | Nucleic acids encoding microsomal trigyceride transfer protein |
| CA2091102C (en) | 1992-03-06 | 2009-05-26 | John R. Ii Wetterau | Microsomal triglyceride transfer protein |
| GB9225141D0 (en) | 1992-12-01 | 1993-01-20 | Smithkline Beecham Corp | Chemical compounds |
| US5739135A (en) | 1993-09-03 | 1998-04-14 | Bristol-Myers Squibb Company | Inhibitors of microsomal triglyceride transfer protein and method |
| FR2723739B1 (fr) * | 1994-08-19 | 1997-02-14 | Sanofi Sa | Derives de glycinamide, procedes pour leur preparation et medicaments les contenant. |
| EP0832069B1 (en) * | 1995-06-07 | 2003-03-05 | Pfizer Inc. | BIPHENYL-2-CARBOXYLIC ACID-TETRAHYDRO-ISOQUINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND/OR APOLIPOPROTEIN B (Apo B) SECRETION |
| DK0832069T3 (da) | 1995-06-07 | 2003-04-22 | Pfizer | Biphenyl-2-carboxylsyre-tetrahydroisoquinolin-6-ylamidderivater, deres fremstilling og deres anvendelse som inhibitorer af sekretion af mikrosomalt triglyceridoverførselsprotein og/eller apolipoprotein B (Apo B) |
| ES2191706T3 (es) | 1995-06-07 | 2003-09-16 | Pfizer | Derivados de tetrahidro-isoquinolinil-6-il amida del acido bifenil-2-carboxilico, su preparacion y su uso como inhibidores de la proteina de transferencia de trigliceridos microsomal y/o secrecion de apolipoproteina b (apo b). |
| JP2000505360A (ja) | 1996-02-02 | 2000-05-09 | ブリギッテ メリット | 塑性的な材料から成るストランドを加工するための装置 |
| US5827875A (en) | 1996-05-10 | 1998-10-27 | Bristol-Myers Squibb Company | Inhibitors of microsomal triglyceride transfer protein and method |
| CA2272719C (en) | 1996-11-27 | 2002-10-01 | Pfizer Limited | Apo b-secretion/mtp inhibitory amides |
| WO1998027979A1 (en) | 1996-12-20 | 1998-07-02 | Bristol-Myers Squibb Company | Heterocyclic inhibitors of microsomal triglyceride transfer protein and method |
| US6066653A (en) | 1997-01-17 | 2000-05-23 | Bristol-Myers Squibb Co. | Method of treating acid lipase deficiency diseases with an MTP inhibitor and cholesterol lowering drugs |
| US5968950A (en) | 1997-06-23 | 1999-10-19 | Pfizer Inc | Apo B-secretion/MTP inhibitor hydrochloride salt |
| TW460478B (en) * | 1997-08-15 | 2001-10-21 | Chugai Pharmaceutical Co Ltd | Phenethylamine derivatives |
| JP2959765B2 (ja) | 1997-12-12 | 1999-10-06 | 日本たばこ産業株式会社 | 3−ピペリジル−4−オキソキナゾリン誘導体及びそれを含有してなる医薬組成物 |
| ES2241194T3 (es) | 1997-12-24 | 2005-10-16 | Aventis Pharma Deutschland Gmbh | Derivados de indol en calidad de inhibidores de factor xa. |
| AU3170699A (en) | 1998-05-22 | 1999-12-13 | Nippon Shinyaku Co. Ltd. | Mtp activity-lowering compositions |
| AU4543899A (en) | 1998-06-08 | 1999-12-30 | Advanced Medicine, Inc. | Multibinding inhibitors of microsomal triglyceride transferase protein |
| CO5090829A1 (es) * | 1998-07-21 | 2001-10-30 | Novartis Ag | Compuestos organicos de la formula i, utiles como inhibido res de la proteina de transferencia de triglicerido microso mal y de la secrecion de la apolipoproteina b. |
| US6197798B1 (en) | 1998-07-21 | 2001-03-06 | Novartis Ag | Amino-benzocycloalkane derivatives |
| CA2375920A1 (en) * | 1999-06-14 | 2000-12-21 | Eli Lilly And Company | Compounds |
| DE19933926A1 (de) | 1999-07-20 | 2001-01-25 | Boehringer Ingelheim Pharma | Biphenylderivate, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE19945594A1 (de) * | 1999-09-23 | 2001-03-29 | Boehringer Ingelheim Pharma | Substituierte Piperazinderivate, ihre Herstellung und ihre Verwendung als Arzneimittel |
| CA2325358C (en) * | 1999-11-10 | 2005-08-02 | Pfizer Products Inc. | 7-¬(4'-trifluoromethyl-biphenyl-2-carbonyl)amino|-quinoline-3-carboxylic acid amides, and methods of inhibiting the secretion of apolipoprotein b |
| DE19963235A1 (de) | 1999-12-27 | 2001-07-05 | Boehringer Ingelheim Pharma | Substituierte Piperazinderivate, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE19963234A1 (de) * | 1999-12-27 | 2002-01-24 | Boehringer Ingelheim Pharma | Substituierte Piperazinderivate, ihre Herstellung und ihre Verwendung als Arzneimittel |
| WO2001053260A1 (en) | 2000-01-18 | 2001-07-26 | Novartis Ag | Carboxamides useful as inhibitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion |
| AU2001262185A1 (en) | 2000-04-10 | 2001-10-23 | Novartis Ag | Substituted (hetero)aryl carboxamide derivatives as microsomal triglyceride transfer protein (mtp) and apolipoprotein b (apo b) secretion |
| GB0013346D0 (en) | 2000-06-01 | 2000-07-26 | Glaxo Group Ltd | Therapeutic benzamide derivatives |
| GB0013378D0 (en) | 2000-06-01 | 2000-07-26 | Glaxo Group Ltd | Use of therapeutic benzamide derivatives |
| GB0013383D0 (en) | 2000-06-01 | 2000-07-26 | Glaxo Group Ltd | Therapeutic benzamide derivatives |
| DE10033337A1 (de) | 2000-07-08 | 2002-01-17 | Boehringer Ingelheim Pharma | Biphenylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| US20020032238A1 (en) | 2000-07-08 | 2002-03-14 | Henning Priepke | Biphenylcarboxylic acid amides, the preparation thereof and the use thereof as medicaments |
| FR2816940A1 (fr) | 2000-11-23 | 2002-05-24 | Lipha | Derives de 4-(biphenylcarbonylamino)-piperidine, compositions les contenant et leur utilisation |
| GB0109287D0 (en) | 2001-04-12 | 2001-05-30 | Glaxo Group Ltd | Therapeutic benzamide derivatives |
| SI1404653T1 (sl) * | 2001-06-28 | 2008-12-31 | Pfizer Prod Inc | S triamidom substituirani indoli, benzofurani in benzotiofeni kot zaviralci mikrosomske prenašalnebeljakovine za trigliceride (MTP) in/ali izločanja apolipoproteina B (APO B) |
| CN101838218A (zh) | 2002-02-28 | 2010-09-22 | 日本烟草产业株式会社 | 酯化合物及其医药用途 |
-
2002
- 2002-05-24 SI SI200230732T patent/SI1404653T1/sl unknown
- 2002-05-24 CZ CZ20033558A patent/CZ20033558A3/cs unknown
- 2002-05-24 BR BR0210616-7A patent/BR0210616A/pt active Search and Examination
- 2002-05-24 AU AU2002307839A patent/AU2002307839B2/en not_active Ceased
- 2002-05-24 GE GEAP20027236A patent/GEP20063720B/en unknown
- 2002-05-24 CN CN028130219A patent/CN1522246B/zh not_active Expired - Fee Related
- 2002-05-24 HU HU0400348A patent/HU229551B1/hu not_active IP Right Cessation
- 2002-05-24 RS YUP-1004/03A patent/RS50712B/sr unknown
- 2002-05-24 GE GE5350A patent/GEP20053720B/en unknown
- 2002-05-24 KR KR1020037017167A patent/KR100575919B1/ko not_active Expired - Fee Related
- 2002-05-24 IL IL15851602A patent/IL158516A0/xx not_active IP Right Cessation
- 2002-05-24 EA EA200301310A patent/EA007008B1/ru not_active IP Right Cessation
- 2002-05-24 AT AT02780923T patent/ATE405548T1/de active
- 2002-05-24 ES ES02780923T patent/ES2307799T3/es not_active Expired - Lifetime
- 2002-05-24 MX MXPA03011707A patent/MXPA03011707A/es active IP Right Grant
- 2002-05-24 EP EP02780923A patent/EP1404653B1/en not_active Expired - Lifetime
- 2002-05-24 CA CA002451474A patent/CA2451474C/en not_active Expired - Fee Related
- 2002-05-24 PT PT02780923T patent/PT1404653E/pt unknown
- 2002-05-24 KR KR1020057025027A patent/KR100575944B1/ko not_active Expired - Fee Related
- 2002-05-24 JP JP2003508914A patent/JP4139325B2/ja not_active Expired - Lifetime
- 2002-05-24 SK SK1610-2003A patent/SK287806B6/sk not_active IP Right Cessation
- 2002-05-24 CN CN2006100941142A patent/CN1880304B/zh not_active Expired - Fee Related
- 2002-05-24 EE EEP200400040A patent/EE05452B1/xx not_active IP Right Cessation
- 2002-05-24 HR HR20031051A patent/HRP20031051B1/xx not_active IP Right Cessation
- 2002-05-24 DK DK02780923T patent/DK1404653T3/da active
- 2002-05-24 OA OA1200300327A patent/OA12626A/en unknown
- 2002-05-24 WO PCT/IB2002/001876 patent/WO2003002533A1/en not_active Ceased
- 2002-05-24 NZ NZ528752A patent/NZ528752A/en not_active IP Right Cessation
- 2002-05-24 TN TNPCT/IB2002/001876A patent/TNSN03146A1/fr unknown
- 2002-05-24 UA UA20031212657A patent/UA75660C2/uk unknown
- 2002-05-24 DE DE60228447T patent/DE60228447D1/de not_active Expired - Lifetime
- 2002-05-24 PL PL02367680A patent/PL367680A1/xx unknown
- 2002-06-20 US US10/177,858 patent/US6720351B2/en not_active Expired - Fee Related
- 2002-06-21 TW TW091113664A patent/TWI313264B/zh not_active IP Right Cessation
- 2002-06-21 TW TW094146513A patent/TW200628447A/zh unknown
- 2002-06-26 AR ARP020102408A patent/AR036158A1/es active IP Right Grant
- 2002-06-26 MY MYPI20022415A patent/MY129328A/en unknown
- 2002-06-27 AP APAP/P/2002/002567A patent/AP1649A/en active
- 2002-06-27 GT GT200200136A patent/GT200200136A/es unknown
- 2002-06-27 PE PE2002000580A patent/PE20030135A1/es not_active Application Discontinuation
- 2002-06-27 UY UY27360A patent/UY27360A1/es unknown
- 2002-06-28 PA PA20028549301A patent/PA8549301A1/es unknown
-
2003
- 2003-08-13 US US10/639,855 patent/US6949572B2/en not_active Expired - Fee Related
- 2003-08-13 US US10/639,854 patent/US6979692B2/en not_active Expired - Fee Related
- 2003-10-07 ZA ZA200307818A patent/ZA200307818B/en unknown
- 2003-10-09 IS IS6988A patent/IS2603B/is unknown
- 2003-11-17 CR CR7151A patent/CR7151A/es not_active Application Discontinuation
- 2003-12-16 NO NO20035607A patent/NO326700B1/no not_active IP Right Cessation
- 2003-12-22 BG BG108487A patent/BG108487A/bg unknown
- 2003-12-22 MA MA27457A patent/MA27045A1/fr unknown
- 2003-12-23 EC EC2003004925A patent/ECSP034925A/es unknown
-
2005
- 2005-08-02 US US11/196,563 patent/US7482368B2/en not_active Expired - Fee Related
-
2006
- 2006-02-10 US US11/351,571 patent/US7348355B2/en not_active Expired - Fee Related
-
2008
- 2008-10-13 CY CY20081101126T patent/CY1108407T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA007008B1 (ru) | Триамидзамещённые индолы, бензофураны и бензотиофены в качестве ингибиторов микросомального белка, переносящего триглицериды, (мтр) и/или ингибиторов секреции аполипопротеина в (аро в) | |
| AU2002307839A1 (en) | Triamide-substituted indoles, benzofuranes and benzothiophenes as inhibitors of microsomal triglyceride transfer protein (MTP) and/or apolipoprotein B (Apo B) secretion | |
| AU2009232836A1 (en) | Indolinone compound | |
| JP5628937B2 (ja) | 5−ht6受容体リガンドとしてのスルホン化合物 | |
| WO2017183723A1 (ja) | Kcnq2~5チャネル活性化剤 | |
| HK1064369B (en) | Triamide-substituted indoles, benzofuranes and benzothiophenes | |
| HK1096665B (en) | Triamide-substituted indoles, benzofuranes and benzothiophenes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM |
|
| PC4A | Registration of transfer of a eurasian patent by assignment | ||
| TC4A | Change in name of a patent proprietor in a eurasian patent | ||
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): RU |