ES2446419T3 - Moduladores de GPR40 de ácidos bifenilfenoxi, tiofenil y aminofenilpropanoico sustituidos - Google Patents
Moduladores de GPR40 de ácidos bifenilfenoxi, tiofenil y aminofenilpropanoico sustituidos Download PDFInfo
- Publication number
- ES2446419T3 ES2446419T3 ES08742774.6T ES08742774T ES2446419T3 ES 2446419 T3 ES2446419 T3 ES 2446419T3 ES 08742774 T ES08742774 T ES 08742774T ES 2446419 T3 ES2446419 T3 ES 2446419T3
- Authority
- ES
- Spain
- Prior art keywords
- mmol
- compound
- et0ac
- methyl
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 title description 48
- 102100026148 Free fatty acid receptor 1 Human genes 0.000 title description 46
- 125000001544 thienyl group Chemical group 0.000 title description 4
- HTCSFFGLRQDZDE-UHFFFAOYSA-N 2-azaniumyl-2-phenylpropanoate Chemical class OC(=O)C(N)(C)C1=CC=CC=C1 HTCSFFGLRQDZDE-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 302
- 239000000203 mixture Substances 0.000 claims abstract description 211
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 30
- 239000012453 solvate Substances 0.000 claims abstract description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 15
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 14
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 126
- 239000003814 drug Substances 0.000 claims description 27
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 317
- 239000000243 solution Substances 0.000 description 147
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 129
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 112
- -1 acids fatty acids Chemical class 0.000 description 110
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 92
- 238000003756 stirring Methods 0.000 description 88
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 87
- 238000006243 chemical reaction Methods 0.000 description 79
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
- 238000003818 flash chromatography Methods 0.000 description 73
- 239000000047 product Substances 0.000 description 69
- 239000011541 reaction mixture Substances 0.000 description 65
- 238000000034 method Methods 0.000 description 64
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 63
- 235000019341 magnesium sulphate Nutrition 0.000 description 63
- 239000000741 silica gel Substances 0.000 description 63
- 229910002027 silica gel Inorganic materials 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 63
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 59
- 239000012074 organic phase Substances 0.000 description 56
- 239000002253 acid Substances 0.000 description 49
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 48
- 238000005160 1H NMR spectroscopy Methods 0.000 description 43
- 235000019198 oils Nutrition 0.000 description 42
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 41
- 229910000024 caesium carbonate Inorganic materials 0.000 description 41
- 239000003921 oil Substances 0.000 description 41
- 239000012230 colorless oil Substances 0.000 description 40
- 239000000499 gel Substances 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
- 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 36
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 34
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 32
- 239000012043 crude product Substances 0.000 description 32
- 239000012267 brine Substances 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 201000010099 disease Diseases 0.000 description 26
- 239000011734 sodium Substances 0.000 description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 23
- 238000007792 addition Methods 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 21
- 229910052739 hydrogen Inorganic materials 0.000 description 21
- 239000001257 hydrogen Substances 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 125000001424 substituent group Chemical group 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- 239000007832 Na2SO4 Substances 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- 125000003118 aryl group Chemical group 0.000 description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
- 102000004877 Insulin Human genes 0.000 description 18
- 108090001061 Insulin Proteins 0.000 description 18
- 229940125396 insulin Drugs 0.000 description 18
- 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 16
- 239000002904 solvent Substances 0.000 description 16
- 229940124597 therapeutic agent Drugs 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000010898 silica gel chromatography Methods 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 13
- 208000031226 Hyperlipidaemia Diseases 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 125000004429 atom Chemical group 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 235000014113 dietary fatty acids Nutrition 0.000 description 11
- 239000000194 fatty acid Substances 0.000 description 11
- 229930195729 fatty acid Natural products 0.000 description 11
- 208000017169 kidney disease Diseases 0.000 description 11
- 101150041968 CDC13 gene Proteins 0.000 description 10
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 206010030113 Oedema Diseases 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 150000004665 fatty acids Chemical class 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 150000002367 halogens Chemical class 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 208000032928 Dyslipidaemia Diseases 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 208000017170 Lipid metabolism disease Diseases 0.000 description 8
- 208000008589 Obesity Diseases 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- 238000013019 agitation Methods 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 235000020824 obesity Nutrition 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 206010020772 Hypertension Diseases 0.000 description 7
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 7
- 238000004296 chiral HPLC Methods 0.000 description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 7
- 201000006549 dyspepsia Diseases 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 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 7
- 230000004044 response Effects 0.000 description 7
- 208000011580 syndromic disease Diseases 0.000 description 7
- 201000001320 Atherosclerosis Diseases 0.000 description 6
- 208000024172 Cardiovascular disease Diseases 0.000 description 6
- 206010012689 Diabetic retinopathy Diseases 0.000 description 6
- 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 6
- 208000035150 Hypercholesterolemia Diseases 0.000 description 6
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 6
- 208000013016 Hypoglycemia Diseases 0.000 description 6
- 206010023379 Ketoacidosis Diseases 0.000 description 6
- 208000007976 Ketosis Diseases 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 6
- 201000001880 Sexual dysfunction Diseases 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 6
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000007900 aqueous suspension Substances 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 235000003599 food sweetener Nutrition 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 201000001421 hyperglycemia Diseases 0.000 description 6
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 6
- 201000008980 hyperinsulinism Diseases 0.000 description 6
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 6
- 208000006575 hypertriglyceridemia Diseases 0.000 description 6
- 230000002218 hypoglycaemic effect Effects 0.000 description 6
- 230000003914 insulin secretion Effects 0.000 description 6
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical group CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 231100000872 sexual dysfunction Toxicity 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 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 6
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 5
- 208000002705 Glucose Intolerance Diseases 0.000 description 5
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 5
- 206010022489 Insulin Resistance Diseases 0.000 description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid group Chemical group C(CCCCC)(=O)O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 5
- 239000013067 intermediate product Substances 0.000 description 5
- 239000011981 lindlar catalyst Substances 0.000 description 5
- 229960003105 metformin Drugs 0.000 description 5
- XRAMJHXWXCMGJM-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)propionate Chemical compound COC(=O)CCC1=CC=C(O)C=C1 XRAMJHXWXCMGJM-UHFFFAOYSA-N 0.000 description 5
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 235000019260 propionic acid Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical group O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 4
- YJLGZLXAAKBBJN-UHFFFAOYSA-N 1-tert-butyl-4-(chloromethyl)-2-(2-fluoro-5-methoxyphenyl)benzene Chemical group COC1=CC=C(F)C(C=2C(=CC=C(CCl)C=2)C(C)(C)C)=C1 YJLGZLXAAKBBJN-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 4
- 239000012981 Hank's balanced salt solution Substances 0.000 description 4
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229940123464 Thiazolidinedione Drugs 0.000 description 4
- 102100034195 Thrombopoietin Human genes 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- XAAMAAXKDLWBKO-UHFFFAOYSA-N methyl 3-(4-phenylmethoxyphenyl)propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1OCC1=CC=CC=C1 XAAMAAXKDLWBKO-UHFFFAOYSA-N 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000003944 tolyl group Chemical group 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 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 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000012053 oil suspension Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 3
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 235000018553 tannin Nutrition 0.000 description 3
- 239000001648 tannin Substances 0.000 description 3
- 229920001864 tannin Polymers 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- IPTZOWYBCLEBOE-UHFFFAOYSA-N (2-fluoro-5-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(F)C(B(O)O)=C1 IPTZOWYBCLEBOE-UHFFFAOYSA-N 0.000 description 2
- APGOHCBEJDAUOM-VYIIXAMBSA-N (2S)-2-amino-N-(1-diphenoxyphosphorylethyl)butanediamide Chemical compound C=1C=CC=CC=1OP(=O)(C(NC(=O)[C@@H](N)CC(N)=O)C)OC1=CC=CC=C1 APGOHCBEJDAUOM-VYIIXAMBSA-N 0.000 description 2
- BLSRGJPGRJBHQK-BUSXIPJBSA-N (2s)-2-amino-1-(2-diphenoxyphosphorylpyrrolidin-1-yl)propan-1-one Chemical compound C[C@H](N)C(=O)N1CCCC1P(=O)(OC=1C=CC=CC=1)OC1=CC=CC=C1 BLSRGJPGRJBHQK-BUSXIPJBSA-N 0.000 description 2
- JMVFRBIAXHMBPB-KKFHFHRHSA-N (3s)-3-amino-4-(2-diphenoxyphosphorylpyrrolidin-1-yl)-4-oxobutanamide Chemical compound NC(=O)C[C@H](N)C(=O)N1CCCC1P(=O)(OC=1C=CC=CC=1)OC1=CC=CC=C1 JMVFRBIAXHMBPB-KKFHFHRHSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FAHUKNBUIVOJJR-UHFFFAOYSA-N 1-(4-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine Chemical compound C1=CC(F)=CC=C1C1C2=CC=CN2CCN1 FAHUKNBUIVOJJR-UHFFFAOYSA-N 0.000 description 2
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- LWXCEYUVPGVRDQ-UHFFFAOYSA-N 2-bromo-1-butoxy-4-methoxybenzene Chemical compound CCCCOC1=CC=C(OC)C=C1Br LWXCEYUVPGVRDQ-UHFFFAOYSA-N 0.000 description 2
- LTMSUXSPKZRMAB-UHFFFAOYSA-N 2-bromo-4-methoxyphenol Chemical compound COC1=CC=C(O)C(Br)=C1 LTMSUXSPKZRMAB-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- QVWAEZJXDYOKEH-UHFFFAOYSA-N 3-(3-hydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(O)=C1 QVWAEZJXDYOKEH-UHFFFAOYSA-N 0.000 description 2
- SXXLKZCNJHJYFL-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,2]oxazolo[4,5-c]pyridin-5-ium-3-olate Chemical compound C1CNCC2=C1ONC2=O SXXLKZCNJHJYFL-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 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
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 240000008415 Lactuca sativa Species 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
- 239000000006 Nitroglycerin Substances 0.000 description 2
- YHIPILPTUVMWQT-UHFFFAOYSA-N Oplophorus luciferin Chemical compound C1=CC(O)=CC=C1CC(C(N1C=C(N2)C=3C=CC(O)=CC=3)=O)=NC1=C2CC1=CC=CC=C1 YHIPILPTUVMWQT-UHFFFAOYSA-N 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 101001032756 Rattus norvegicus Granzyme-like protein 1 Proteins 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 2
- 108010054082 Sterol O-acyltransferase Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- PNDPGZBMCMUPRI-XXSWNUTMSA-N [125I][125I] Chemical compound [125I][125I] PNDPGZBMCMUPRI-XXSWNUTMSA-N 0.000 description 2
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 230000023852 carbohydrate metabolic process Effects 0.000 description 2
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- JQFWSELAMIOZPM-UHFFFAOYSA-N ethyl 2-methylhex-4-enoate Chemical compound CCOC(=O)C(C)CC=CC JQFWSELAMIOZPM-UHFFFAOYSA-N 0.000 description 2
- NEXFMPAUGJAIHE-UHFFFAOYSA-N ethyl 3-(4-aminophenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(N)C=C1 NEXFMPAUGJAIHE-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229960003711 glyceryl trinitrate Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid group Chemical group C(CCCCCC)(=O)O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 102000052080 human FFAR1 Human genes 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 210000004153 islets of langerhan Anatomy 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000312 peanut oil Substances 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
- 238000002953 preparative HPLC Methods 0.000 description 2
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000028503 regulation of lipid metabolic process Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 235000012045 salad Nutrition 0.000 description 2
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229940011671 vitamin b6 Drugs 0.000 description 2
- JRPGMCRJPQJYPE-UHFFFAOYSA-N zinc;carbanide Chemical compound [CH3-].[CH3-].[Zn+2] JRPGMCRJPQJYPE-UHFFFAOYSA-N 0.000 description 2
- IPSRAFUHLHIWAR-UHFFFAOYSA-N zinc;ethane Chemical compound [Zn+2].[CH2-]C.[CH2-]C IPSRAFUHLHIWAR-UHFFFAOYSA-N 0.000 description 2
- GNLJBJNONOOOQC-UHFFFAOYSA-N $l^{3}-carbane;magnesium Chemical compound [Mg]C GNLJBJNONOOOQC-UHFFFAOYSA-N 0.000 description 1
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-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
- YOLVBJUSDXESQT-LSLKUGRBSA-N (2S)-2-amino-N-(1-diphenoxyphosphorylethyl)propanamide Chemical compound C=1C=CC=CC=1OP(=O)(C(C)NC(=O)[C@@H](N)C)OC1=CC=CC=C1 YOLVBJUSDXESQT-LSLKUGRBSA-N 0.000 description 1
- KUKBMDYLALFYFP-SSDOTTSWSA-N (2r)-3-(4-hydroxyphenyl)-2-methylpropanoic acid Chemical compound OC(=O)[C@H](C)CC1=CC=C(O)C=C1 KUKBMDYLALFYFP-SSDOTTSWSA-N 0.000 description 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- KUKBMDYLALFYFP-ZETCQYMHSA-N (2s)-3-(4-hydroxyphenyl)-2-methylpropanoic acid Chemical compound OC(=O)[C@@H](C)CC1=CC=C(O)C=C1 KUKBMDYLALFYFP-ZETCQYMHSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- 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 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
- RWIUTHWKQHRQNP-ZDVGBALWSA-N (9e,12e)-n-(1-phenylethyl)octadeca-9,12-dienamide Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(=O)NC(C)C1=CC=CC=C1 RWIUTHWKQHRQNP-ZDVGBALWSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- MUOAJTSAEFZWDX-SNAWJCMRSA-N (e)-4-(4-methoxy-2-methylphenyl)but-3-en-2-ol Chemical compound COC1=CC=C(\C=C\C(C)O)C(C)=C1 MUOAJTSAEFZWDX-SNAWJCMRSA-N 0.000 description 1
- GQOSBRKKZQFIKP-SNAWJCMRSA-N (e)-4-(4-methoxy-2-methylphenyl)but-3-en-2-one Chemical compound COC1=CC=C(\C=C\C(C)=O)C(C)=C1 GQOSBRKKZQFIKP-SNAWJCMRSA-N 0.000 description 1
- MUOAJTSAEFZWDX-YEZKRMTDSA-N (e,2s)-4-(4-methoxy-2-methylphenyl)but-3-en-2-ol Chemical compound COC1=CC=C(\C=C\[C@H](C)O)C(C)=C1 MUOAJTSAEFZWDX-YEZKRMTDSA-N 0.000 description 1
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
- 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- UIMPAOAAAYDUKQ-UHFFFAOYSA-N 1-methoxy-4-(4-methoxyphenyl)benzene Chemical group C1=CC(OC)=CC=C1C1=CC=C(OC)C=C1 UIMPAOAAAYDUKQ-UHFFFAOYSA-N 0.000 description 1
- QHMVQKOXILNZQR-UHFFFAOYSA-N 1-methoxyprop-1-ene Chemical compound COC=CC QHMVQKOXILNZQR-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-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
- 125000005955 1H-indazolyl group Chemical group 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
- VFLPYPDOSIEMQG-UHFFFAOYSA-N 2-(2-tert-butylphenyl)-1-fluoro-4-methoxybenzene Chemical group COC1=CC=C(F)C(C=2C(=CC=CC=2)C(C)(C)C)=C1 VFLPYPDOSIEMQG-UHFFFAOYSA-N 0.000 description 1
- UCYSBTTXLRLWMU-UHFFFAOYSA-N 2-[5-(chloromethyl)-2-cyclopropylphenyl]-1-fluoro-4-methoxybenzene Chemical group COC1=CC=C(F)C(C=2C(=CC=C(CCl)C=2)C2CC2)=C1 UCYSBTTXLRLWMU-UHFFFAOYSA-N 0.000 description 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 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
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- DBVTYDLZMXNRIN-UHFFFAOYSA-N 3-benzyl-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1CC1=CC=CC=C1 DBVTYDLZMXNRIN-UHFFFAOYSA-N 0.000 description 1
- SHBYNNKZVBDWRW-UHFFFAOYSA-N 3-bromo-4-tert-butylbenzoic acid Chemical compound CC(C)(C)C1=CC=C(C(O)=O)C=C1Br SHBYNNKZVBDWRW-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- OWXNQQUWPGXPMS-UHFFFAOYSA-N 3-cyclopropyl-3-(4-hydroxyphenyl)propanoic acid Chemical compound C=1C=C(O)C=CC=1C(CC(=O)O)C1CC1 OWXNQQUWPGXPMS-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 1
- UCFSYHMCKWNKAH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OBOC1(C)C UCFSYHMCKWNKAH-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-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
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-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
- GIHMRLIXZMBZPQ-UHFFFAOYSA-N 5-[cyclopropyl-(4-hydroxyphenyl)methyl]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound O=C1OC(C)(C)OC(=O)C1C(C=1C=CC(O)=CC=1)C1CC1 GIHMRLIXZMBZPQ-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108010058207 Anistreplase Proteins 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000589513 Burkholderia cepacia Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- ITQVRZQPIJQFKE-LJQANCHMSA-N CC(C)(C)c(ccc(COc1ccc([C@@H](CC(O)=O)C#C)cc1)c1)c1-c(cc(cc1)[O]=N)c1F Chemical compound CC(C)(C)c(ccc(COc1ccc([C@@H](CC(O)=O)C#C)cc1)c1)c1-c(cc(cc1)[O]=N)c1F ITQVRZQPIJQFKE-LJQANCHMSA-N 0.000 description 1
- RINWPVIHIGLXLQ-UHFFFAOYSA-N CC([Mg])=C Chemical compound CC([Mg])=C RINWPVIHIGLXLQ-UHFFFAOYSA-N 0.000 description 1
- 0 CCC[C@](CC(O)=O)c(cc1)cc(C)c1OCc1cc(-c2cc(*)ccc2F)c(C(C)(C)C)cc1 Chemical compound CCC[C@](CC(O)=O)c(cc1)cc(C)c1OCc1cc(-c2cc(*)ccc2F)c(C(C)(C)C)cc1 0.000 description 1
- 101100172886 Caenorhabditis elegans sec-6 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 229940127007 Compound 39 Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 108010066671 Enalaprilat Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- PTVSRINJXWDIKP-UHFFFAOYSA-N Ethyl 4-pentenoate Chemical compound CCOC(=O)CCC=C PTVSRINJXWDIKP-UHFFFAOYSA-N 0.000 description 1
- ICMAFTSLXCXHRK-UHFFFAOYSA-N Ethyl pentanoate Chemical compound CCCCC(=O)OCC ICMAFTSLXCXHRK-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- 108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 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
- LRULVYSBRWUVGR-FCHUYYIVSA-N GSK2879552 Chemical compound C1=CC(C(=O)O)=CC=C1CN1CCC(CN[C@H]2[C@@H](C2)C=2C=CC=CC=2)CC1 LRULVYSBRWUVGR-FCHUYYIVSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical class OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000007625 Hirudins Human genes 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 241000322338 Loeseliastrum Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- XYXISKZRUAYHOK-UHFFFAOYSA-N O=BOC1CC1 Chemical compound O=BOC1CC1 XYXISKZRUAYHOK-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 102000016978 Orphan receptors Human genes 0.000 description 1
- 108070000031 Orphan receptors Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910021120 PdC12 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920001774 Perfluoroether Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000005782 Squalene Monooxygenase Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229910010066 TiC14 Inorganic materials 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003537 Vitamin B3 Natural products 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 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
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 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
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229960003318 alteplase Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229960000983 anistreplase Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 229940076810 beta sitosterol Drugs 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 229940096699 bile acid sequestrants Drugs 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- INLLPKCGLOXCIV-UHFFFAOYSA-N bromoethene Chemical compound BrC=C INLLPKCGLOXCIV-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- WOFIDTFNJZRJRE-UHFFFAOYSA-N but-3-en-2-ol Chemical compound [CH2]C(O)C=C WOFIDTFNJZRJRE-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000001906 cholesterol absorption Effects 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
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 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
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- LTYMSROWYAPPGB-UHFFFAOYSA-N diphenyl sulfide Chemical compound C=1C=CC=CC=1SC1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-N 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229960002680 enalaprilat Drugs 0.000 description 1
- LZFZMUMEGBBDTC-QEJZJMRPSA-N enalaprilat (anhydrous) Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 LZFZMUMEGBBDTC-QEJZJMRPSA-N 0.000 description 1
- 229950002375 englitazone Drugs 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- PGFGDJRYGGZGOE-SECBINFHSA-N ethyl (2r)-3-(4-hydroxyphenyl)-2-methylpropanoate Chemical compound CCOC(=O)[C@H](C)CC1=CC=C(O)C=C1 PGFGDJRYGGZGOE-SECBINFHSA-N 0.000 description 1
- HFAKUEIRAFSKCH-CYBMUJFWSA-N ethyl (3r)-3-(4-hydroxyphenyl)-4-methylpent-4-enoate Chemical compound CCOC(=O)C[C@H](C(C)=C)C1=CC=C(O)C=C1 HFAKUEIRAFSKCH-CYBMUJFWSA-N 0.000 description 1
- HXBKLFDMBSWHJU-INIZCTEOSA-N ethyl (3s)-3-(4-hydroxyphenyl)-3-phenylpropanoate Chemical compound C1([C@H](CC(=O)OCC)C=2C=CC(O)=CC=2)=CC=CC=C1 HXBKLFDMBSWHJU-INIZCTEOSA-N 0.000 description 1
- ZJMKYRDQXUYWLC-CYBMUJFWSA-N ethyl (3s)-3-(4-hydroxyphenyl)-5-methylhex-4-enoate Chemical compound CCOC(=O)C[C@@H](C=C(C)C)C1=CC=C(O)C=C1 ZJMKYRDQXUYWLC-CYBMUJFWSA-N 0.000 description 1
- PGFGDJRYGGZGOE-UHFFFAOYSA-N ethyl 3-(4-hydroxyphenyl)-2-methylpropanoate Chemical compound CCOC(=O)C(C)CC1=CC=C(O)C=C1 PGFGDJRYGGZGOE-UHFFFAOYSA-N 0.000 description 1
- HFAKUEIRAFSKCH-UHFFFAOYSA-N ethyl 3-(4-hydroxyphenyl)-4-methylpent-4-enoate Chemical compound CCOC(=O)CC(C(C)=C)C1=CC=C(O)C=C1 HFAKUEIRAFSKCH-UHFFFAOYSA-N 0.000 description 1
- JSEMUSFPVZYRSG-UHFFFAOYSA-N ethyl 3-(triphenyl-$l^{5}-phosphanylidene)propanoate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CCC(=O)OCC)C1=CC=CC=C1 JSEMUSFPVZYRSG-UHFFFAOYSA-N 0.000 description 1
- RBJLHYGZMJNFBK-UHFFFAOYSA-N ethyl hex-4-enoate Chemical compound CCOC(=O)CCC=CC RBJLHYGZMJNFBK-UHFFFAOYSA-N 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229940095884 glucophage Drugs 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
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 238000011141 high resolution liquid chromatography Methods 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000012528 insulin ELISA Methods 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229940090473 januvia Drugs 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- AAWGSOZCJNFZAG-UHFFFAOYSA-M magnesium;cyclopropane;chloride Chemical compound [Mg+2].[Cl-].C1C[CH-]1 AAWGSOZCJNFZAG-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229950008446 melinamide Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- FFGBPOHEZMOXPV-MRXNPFEDSA-N methyl (3r)-3-(3-bromo-4-phenylmethoxyphenyl)hexanoate Chemical compound BrC1=CC([C@@H](CC(=O)OC)CCC)=CC=C1OCC1=CC=CC=C1 FFGBPOHEZMOXPV-MRXNPFEDSA-N 0.000 description 1
- MEZYCNMPBPQTLK-ONEGZZNKSA-N methyl (e)-hex-4-enoate Chemical compound COC(=O)CC\C=C\C MEZYCNMPBPQTLK-ONEGZZNKSA-N 0.000 description 1
- CKCNYQURFFYZRU-UHFFFAOYSA-N methyl 2-[(4-hydroxyphenyl)methyl]butanoate Chemical compound COC(=O)C(CC)CC1=CC=C(O)C=C1 CKCNYQURFFYZRU-UHFFFAOYSA-N 0.000 description 1
- RTXXRMHGXZHTIN-UHFFFAOYSA-N methyl 2-bromo-4-tert-butylbenzoate Chemical compound COC(=O)c1ccc(cc1Br)C(C)(C)C RTXXRMHGXZHTIN-UHFFFAOYSA-N 0.000 description 1
- DANXMWWZKCBBAD-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)-2,2-dimethylpropanoate Chemical compound COC(=O)C(C)(C)CC1=CC=C(O)C=C1 DANXMWWZKCBBAD-UHFFFAOYSA-N 0.000 description 1
- CLRJXWANIVYEHH-UHFFFAOYSA-N methyl 3-bromo-4-chlorobenzoate Chemical compound COC(=O)C1=CC=C(Cl)C(Br)=C1 CLRJXWANIVYEHH-UHFFFAOYSA-N 0.000 description 1
- KXCQBZYCOHEWHO-UHFFFAOYSA-N methyl 3-bromo-4-tert-butylbenzoate Chemical compound COC(=O)C1=CC=C(C(C)(C)C)C(Br)=C1 KXCQBZYCOHEWHO-UHFFFAOYSA-N 0.000 description 1
- NKKKHHGOLLZXLN-UHFFFAOYSA-N methyl 3-cyclopropyl-3-(4-hydroxyphenyl)propanoate Chemical compound C=1C=C(O)C=CC=1C(CC(=O)OC)C1CC1 NKKKHHGOLLZXLN-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- JUYWKECPOZQAQT-UHFFFAOYSA-N methyl(sulfanylidene)borane Chemical compound CB=S JUYWKECPOZQAQT-UHFFFAOYSA-N 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- VLGWYKOEXANHJT-UHFFFAOYSA-N methylsulfanol Chemical compound CSO VLGWYKOEXANHJT-UHFFFAOYSA-N 0.000 description 1
- MKUWVMRNQOOSAT-UHFFFAOYSA-N methylvinylmethanol Natural products CC(O)C=C MKUWVMRNQOOSAT-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- LLYKPZOWCPVRPD-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine;n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=CC=N1 LLYKPZOWCPVRPD-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- AIKVCUNQWYTVTO-UHFFFAOYSA-N nicardipine hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 AIKVCUNQWYTVTO-UHFFFAOYSA-N 0.000 description 1
- 229960002289 nicardipine hydrochloride Drugs 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N pentanoic acid group Chemical group C(CCCC)(=O)O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229960005095 pioglitazone Drugs 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
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960002917 reteplase Drugs 0.000 description 1
- 108010051412 reteplase Proteins 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940083618 sodium nitroprusside Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000004059 squalene synthase inhibitor Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- DFQPZDGUFQJANM-UHFFFAOYSA-M tetrabutylphosphanium;hydroxide Chemical compound [OH-].CCCC[P+](CCCC)(CCCC)CCCC DFQPZDGUFQJANM-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960001641 troglitazone Drugs 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
- 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
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/72—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Ophthalmology & Optometry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US92501407P | 2007-04-16 | 2007-04-16 | |
| US925014P | 2007-04-16 | ||
| PCT/US2008/004701 WO2008130514A1 (en) | 2007-04-16 | 2008-04-10 | Substituted biphenyl phenoxy-, thiophenyl- and aminophenylpropanoic acid gpr40 modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2446419T3 true ES2446419T3 (es) | 2014-03-07 |
Family
ID=39610197
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08742774.6T Active ES2446419T3 (es) | 2007-04-16 | 2008-04-10 | Moduladores de GPR40 de ácidos bifenilfenoxi, tiofenil y aminofenilpropanoico sustituidos |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7572934B2 (OSRAM) |
| EP (1) | EP2139843B1 (OSRAM) |
| JP (1) | JP2010524932A (OSRAM) |
| AU (1) | AU2008241490B2 (OSRAM) |
| CA (1) | CA2683751C (OSRAM) |
| ES (1) | ES2446419T3 (OSRAM) |
| WO (1) | WO2008130514A1 (OSRAM) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8030354B2 (en) | 2007-10-10 | 2011-10-04 | Amgen Inc. | Substituted biphenyl GPR40 modulators |
| CA2716352C (en) * | 2008-03-06 | 2013-05-28 | Amgen Inc. | Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders |
| MX2011003917A (es) * | 2008-10-15 | 2011-05-31 | Amgen Inc | Moduladores de grp40 espirociclicos. |
| AR074760A1 (es) | 2008-12-18 | 2011-02-09 | Metabolex Inc | Agonistas del receptor gpr120 y usos de los mismos en medicamentos para el tratamiento de diabetes y el sindrome metabolico. |
| AR078948A1 (es) * | 2009-11-30 | 2011-12-14 | Lilly Co Eli | Compuestos de espiropiperidina, composicion farmaceutica que lo comprenden y su uso para preparar un medicamento util para tratar la diabetes |
| US8476287B2 (en) | 2009-12-25 | 2013-07-02 | Mochida Pharmaceutical Co., Ltd. | 3-hydroxy-5-arylisothiazole derivative |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8299117B2 (en) | 2010-06-16 | 2012-10-30 | Metabolex Inc. | GPR120 receptor agonists and uses thereof |
| JP5746334B2 (ja) * | 2010-06-16 | 2015-07-08 | シマベイ セラピューティクス， インコーポレーテッド | Ｇｐｒ１２０受容体作動薬及びその使用 |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| JP5809157B2 (ja) | 2010-10-08 | 2015-11-10 | 持田製薬株式会社 | 環状アミド誘導体 |
| US8557766B2 (en) | 2011-04-27 | 2013-10-15 | Mochida Pharmaceutical Co., Ltd. | 3-hydroxyisothiazole 1-oxide derivatives |
| AU2012248627A1 (en) | 2011-04-28 | 2013-11-14 | Mochida Pharmaceutical Co., Ltd. | Cyclic amide derivative |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013122028A1 (ja) * | 2012-02-13 | 2013-08-22 | 武田薬品工業株式会社 | 芳香環化合物 |
| CA2878625A1 (en) | 2012-07-11 | 2014-01-16 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
| US9527875B2 (en) | 2012-08-02 | 2016-12-27 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| WO2014064215A1 (en) | 2012-10-24 | 2014-05-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | TPL2 KINASE INHIBITORS FOR PREVENTING OR TREATING DIABETES AND FOR PROMOTING β-CELL SURVIVAL |
| TWI692469B (zh) | 2012-11-09 | 2020-05-01 | 南韓商Ｌｇ化學股份有限公司 | Ｇｐｒ４０受體促效劑，製造該促效劑的方法以及含有該促效劑作爲活性劑的醫藥組成物 |
| WO2014078610A1 (en) | 2012-11-16 | 2014-05-22 | Bristol-Myers Squibb Company | Dihydropyrazole gpr40 modulators |
| MX2015010935A (es) | 2013-02-22 | 2015-10-29 | Merck Sharp & Dohme | Compuestos biciclicos antidiabeticos. |
| CN108017603B (zh) * | 2013-02-28 | 2021-07-23 | 株式会社蒂奥姆生物 | 三环化合物及其用途 |
| CN104109115B (zh) * | 2013-04-16 | 2016-11-23 | 中国科学院上海药物研究所 | 一种含氮杂环链接的苯丙酸类化合物、其药物组合物、制备方法和用途 |
| KR101569522B1 (ko) * | 2013-04-18 | 2015-11-17 | 현대약품 주식회사 | 신규한 3-(4-(벤질옥시)페닐)헥스-4-이노익 산 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 대사성 질환의 예방 또는 치료용 약학적 조성물 |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| HK1221465A1 (zh) | 2013-11-14 | 2017-06-02 | Cadila Healthcare Limited | 新型杂环化合物 |
| US10519115B2 (en) | 2013-11-15 | 2019-12-31 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| EP3076959B1 (en) | 2013-12-04 | 2018-07-04 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| WO2015089809A1 (en) | 2013-12-19 | 2015-06-25 | Merck Sharp & Dohme Corp. | Antidiabetic substituted heteroaryl compounds |
| EP3102198B1 (en) * | 2014-02-06 | 2020-08-26 | Merck Sharp & Dohme Corp. | Antidiabetic compounds |
| US9850225B2 (en) | 2014-04-14 | 2017-12-26 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| WO2015176267A1 (en) | 2014-05-22 | 2015-11-26 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| EP3177287B1 (en) | 2014-08-08 | 2022-02-23 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| WO2016019587A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | [7, 6]-fused bicyclic antidiabetic compounds |
| WO2016022448A1 (en) | 2014-08-08 | 2016-02-11 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| US10100042B2 (en) | 2014-08-08 | 2018-10-16 | Merck Sharp & Dohme Corp. | [5,6]—fused bicyclic antidiabetic compounds |
| MX387086B (es) * | 2014-10-17 | 2025-03-19 | Hyundai Pharm Co Ltd | Preparacion compuesta, que contiene derivado novedoso de acido 3-(4-(benciloxi)fenil)hex-4-inoico y otro ingrediente activo, para prevenir o tratar enfermedades metabolicas |
| US10426818B2 (en) | 2015-03-24 | 2019-10-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Method and pharmaceutical composition for use in the treatment of diabetes |
| US10745382B2 (en) | 2015-10-15 | 2020-08-18 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| US10676458B2 (en) | 2016-03-29 | 2020-06-09 | Merch Sharp & Dohne Corp. Rahway | Antidiabetic bicyclic compounds |
| US10144706B2 (en) | 2016-09-01 | 2018-12-04 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| EP3551176A4 (en) | 2016-12-06 | 2020-06-24 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| WO2018118670A1 (en) | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
| US11225471B2 (en) | 2017-11-16 | 2022-01-18 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| AU2019205093B2 (en) | 2018-01-08 | 2024-03-07 | Celon Pharma S.A. | 3-phenyl-4-hexynoic acid derivatives as GPR40 agonists |
| CR20200347A (es) | 2018-02-13 | 2020-09-23 | Gilead Sciences Inc | Inhibidores pd-1/pd-l1 |
| KR102591947B1 (ko) | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| PT3820572T (pt) | 2018-07-13 | 2023-11-10 | Gilead Sciences Inc | Inibidores pd-1/pd-l1 |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ， インコーポレイテッド | Ｐｄ－１／ｐｄ－ｌ１阻害剤 |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE305216B (OSRAM) | 1965-09-17 | 1968-10-21 | Astra Apotekarnes Kem Fab | |
| FR2359135A1 (fr) | 1976-07-22 | 1978-02-17 | Hexachimie | Nouvelles phenoxyhydroxypropylamines, procede pour les preparer et leur application en therapeutique |
| US4760089A (en) | 1985-09-09 | 1988-07-26 | Smithkline Beckman Corporation | Irreversible dopamine-β-hydroxylase inhibitors |
| DK303887A (da) | 1986-06-19 | 1987-12-20 | Smithkline Beckman Corp | Dopamin-beta-hydroxylaseinhibitorer og fremgangsmaade til fremstilling deraf |
| GB8917069D0 (en) | 1989-07-26 | 1989-09-13 | Merck Sharp & Dohme | Therapeutic agents |
| CA2135173A1 (en) | 1992-05-20 | 1993-11-25 | Bruce E. Witzel | Ester derivatives of 4-aza-steroids |
| AU668180B2 (en) | 1992-05-20 | 1996-04-26 | Merck & Co., Inc. | 17-ethers and thioethers of 4-aza-steroids |
| DE4241632A1 (de) | 1992-12-10 | 1994-06-16 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| HUT73813A (en) | 1993-06-30 | 1996-09-30 | Wellcome Found | Anti-athero-sclerotic diaryl compounds, process to prepare them and pharmaceutical compositions contg. them |
| US5463063A (en) | 1993-07-02 | 1995-10-31 | Celgene Corporation | Ring closure of N-phthaloylglutamines |
| US6037367A (en) | 1995-07-14 | 2000-03-14 | Smithkline Beecham Corporation | Substituted-pent-4-ynoic acids |
| US5795900A (en) | 1995-10-03 | 1998-08-18 | Abbott Laboratories | Symmetrical bis-heteroaryl-methoxy-phenylalkyl carboxylates as inhibitors of leukotriene biosynthesis |
| JPH10316641A (ja) | 1997-03-14 | 1998-12-02 | Sankyo Co Ltd | カルボン酸誘導体 |
| AU8750298A (en) | 1997-08-28 | 1999-03-22 | Ono Pharmaceutical Co. Ltd. | Peroxisome proliferator-activated receptor controllers |
| US6645939B1 (en) | 1997-11-24 | 2003-11-11 | Merck & Co., Inc. | Substituted β-alanine derivatives as cell adhesion inhibitors |
| DE69941777D1 (de) | 1998-03-10 | 2010-01-21 | Ono Pharmaceutical Co | Carbonsäurederivate und medikamente die diese als aktiven wirkstoff enthalten |
| DE19941567A1 (de) | 1998-09-05 | 2000-04-20 | Merck Patent Gmbh | Neue flüssigkristalline Verbindungen |
| AU3958200A (en) | 1999-04-20 | 2000-11-02 | Novo Nordisk A/S | New compounds, their preparation and use |
| DE60009480T2 (de) | 1999-05-05 | 2005-09-01 | Aventis Pharma Ltd., West Malling | Harnstoffe als modulatoren der zelladhäsion |
| GB9914977D0 (en) | 1999-06-25 | 1999-08-25 | Glaxo Group Ltd | Chemical compounds |
| GB9927056D0 (en) | 1999-11-17 | 2000-01-12 | Karobio Ab | Thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
| US6677473B1 (en) | 1999-11-19 | 2004-01-13 | Corvas International Inc | Plasminogen activator inhibitor antagonists |
| JP2001242165A (ja) | 2000-02-25 | 2001-09-07 | Dai Ichi Seiyaku Co Ltd | 採血用試薬 |
| JP2002003368A (ja) | 2000-06-23 | 2002-01-09 | Saitama Daiichi Seiyaku Kk | 経皮吸収又は経粘膜吸収用の製剤 |
| GB0031107D0 (en) | 2000-12-20 | 2001-01-31 | Glaxo Group Ltd | Chemical compounds |
| GB0031527D0 (en) | 2000-12-22 | 2001-02-07 | Smithkline Beecham Plc | New use |
| DE60139025D1 (de) | 2000-12-28 | 2009-07-30 | Takeda Pharmaceutical | Alkansäurederivate, verfahren zu deren herstellung und deren verwendung |
| TWI311133B (en) | 2001-04-20 | 2009-06-21 | Eisai R&D Man Co Ltd | Carboxylic acid derivativeand the salt thereof |
| CN1578659A (zh) | 2001-06-07 | 2005-02-09 | 伊莱利利公司 | 过氧化物酶体增殖剂激活的受体(ppar)的调节剂 |
| JP4705756B2 (ja) | 2002-02-07 | 2011-06-22 | 仁 遠藤 | 芳香族アミノ酸誘導体及び医薬組成物 |
| ATE466030T1 (de) | 2002-02-14 | 2010-05-15 | Takeda Pharmaceutical | Neues screening-verfahren |
| US20030207924A1 (en) | 2002-03-07 | 2003-11-06 | Xue-Min Cheng | Compounds that modulate PPAR activity and methods of preparation |
| US6875780B2 (en) | 2002-04-05 | 2005-04-05 | Warner-Lambert Company | Compounds that modulate PPAR activity and methods for their preparation |
| US20060148858A1 (en) | 2002-05-24 | 2006-07-06 | Tsuyoshi Maekawa | 1, 2-Azole derivatives with hypoglycemic and hypolipidemic activity |
| GB0214149D0 (en) | 2002-06-19 | 2002-07-31 | Glaxo Group Ltd | Chemical compounds |
| EP1535915A4 (en) | 2002-09-06 | 2005-10-05 | Takeda Pharmaceutical | FURANOIC OR THIOPHENE DERIVATIVES AND THEIR MEDICAL USE |
| US7960369B2 (en) * | 2002-11-08 | 2011-06-14 | Takeda Pharmaceutical Company Limited | Receptor function regulator |
| JP4594611B2 (ja) * | 2002-11-08 | 2010-12-08 | 武田薬品工業株式会社 | 受容体機能調節剤 |
| US20060258683A1 (en) | 2003-04-07 | 2006-11-16 | Liu Kevin | Para-sulfonyl substituted phenyl compounds as modulators of ppars |
| WO2004106276A1 (ja) | 2003-05-30 | 2004-12-09 | Takeda Pharmaceutical Company Limited | 縮合環化合物 |
| JP4805552B2 (ja) * | 2003-05-30 | 2011-11-02 | 武田薬品工業株式会社 | 縮合環化合物 |
| US7834013B2 (en) | 2003-11-19 | 2010-11-16 | Glaxosmithkline Llc | Aminophenylcyclopropyl carboxylic acids and derivatives as agonists to GPR40 |
| WO2005058848A1 (en) | 2003-12-17 | 2005-06-30 | Merck & Co., Inc. | (3,4-disubstituted)propanoic carboxylates as s1p (edg) receptor agonists |
| TW200523247A (en) | 2003-12-25 | 2005-07-16 | Takeda Pharmaceutical | 3-(4-benzyloxyphenyl) propanoic acid derivatives |
| JP4074616B2 (ja) * | 2003-12-25 | 2008-04-09 | 武田薬品工業株式会社 | ３−（４−ベンジルオキシフェニル）プロパン酸誘導体 |
| JP4855777B2 (ja) * | 2003-12-26 | 2012-01-18 | 武田薬品工業株式会社 | フェニルプロパン酸誘導体 |
| US7816367B2 (en) * | 2004-02-27 | 2010-10-19 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders |
| US7786165B2 (en) | 2004-03-15 | 2010-08-31 | Takeda Pharmaceutical Company Limited | Aminophenylpropanoic acid derivative |
| EP1731505B1 (en) * | 2004-03-30 | 2015-01-14 | Takeda Pharmaceutical Company Limited | Alkoxyphenylpropanoic acid derivatives |
| JP2007269630A (ja) | 2004-06-23 | 2007-10-18 | Toudai Tlo Ltd | インスリン分泌促進剤 |
| US20060003344A1 (en) | 2004-06-30 | 2006-01-05 | Pfizer Inc. | Methods related to a single nucleotide polymorphism of the G protein coupled receptor, GPR40 |
| JP2007284350A (ja) | 2004-07-27 | 2007-11-01 | Takeda Chem Ind Ltd | 糖尿病治療剤 |
| JP2008520683A (ja) * | 2004-11-18 | 2008-06-19 | ジ インスチチュート フォー ファーマシューティカル ディスカバリー、エルエルシー | タンパク質チロシンホスファターゼ阻害剤としてのヘテロシクリルビフェニル誘導体 |
| US20080090865A1 (en) | 2005-01-28 | 2008-04-17 | Min Ge | Antidiabetic Bicyclic Compounds |
| AU2006210954A1 (en) | 2005-01-31 | 2006-08-10 | Merck & Co., Inc. | Antidiabetic bicyclic compounds |
| US7465804B2 (en) | 2005-05-20 | 2008-12-16 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders |
| AU2006291234A1 (en) | 2005-09-14 | 2007-03-22 | Amgen Inc. | Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders |
| MX2008011615A (es) | 2006-03-14 | 2008-09-22 | Amgen Inc | Derivados de acidos carboxilicos biciclicos utiles para tratar trastornos metabolicos. |
| TW200815377A (en) | 2006-04-24 | 2008-04-01 | Astellas Pharma Inc | Oxadiazolidinedione compound |
| DE102006021878A1 (de) | 2006-05-11 | 2007-11-15 | Sanofi-Aventis | Phenylamino-benzoxazol substituierte Carbonsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE102006021872B4 (de) | 2006-05-11 | 2008-04-17 | Sanofi-Aventis | 4,5-Diphenyl-pyrimidinyl-oxy oder -mercapto substituierte Carbonsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE102006021874B4 (de) | 2006-05-11 | 2008-03-27 | Sanofi-Aventis | 4,5-Diphenyl-pyrimidinyl-amino substituierte Carbonsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| WO2007136572A2 (en) | 2006-05-15 | 2007-11-29 | Merck & Co., Inc. | Antidiabetic bicyclic compounds |
| CA2662242C (en) | 2006-09-07 | 2012-06-12 | Amgen Inc. | Benzo-fused compounds for use in treating metabolic disorders |
| AU2007293028B2 (en) | 2006-09-07 | 2012-05-31 | Amgen Inc. | Heterocyclic GPR40 modulators |
-
2008
- 2008-04-10 EP EP08742774.6A patent/EP2139843B1/en active Active
- 2008-04-10 WO PCT/US2008/004701 patent/WO2008130514A1/en not_active Ceased
- 2008-04-10 CA CA2683751A patent/CA2683751C/en not_active Expired - Fee Related
- 2008-04-10 US US12/082,645 patent/US7572934B2/en not_active Expired - Fee Related
- 2008-04-10 JP JP2010504053A patent/JP2010524932A/ja active Pending
- 2008-04-10 AU AU2008241490A patent/AU2008241490B2/en not_active Ceased
- 2008-04-10 ES ES08742774.6T patent/ES2446419T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010524932A (ja) | 2010-07-22 |
| AU2008241490B2 (en) | 2011-07-21 |
| EP2139843B1 (en) | 2013-12-25 |
| US20090111859A1 (en) | 2009-04-30 |
| CA2683751A1 (en) | 2008-10-30 |
| WO2008130514A1 (en) | 2008-10-30 |
| AU2008241490A1 (en) | 2008-10-30 |
| CA2683751C (en) | 2013-01-08 |
| EP2139843A1 (en) | 2010-01-06 |
| US7572934B2 (en) | 2009-08-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2446419T3 (es) | Moduladores de GPR40 de ácidos bifenilfenoxi, tiofenil y aminofenilpropanoico sustituidos | |
| ES2450567T3 (es) | Moduladores de GPR40 espirocíclicos | |
| ES2375936T3 (es) | Compuestos, sus composiciones farmacéuticas y su uso en el tratamiento de trastornos metabólicos. | |
| ES2433466T3 (es) | Compuestos, composiciones farmacéuticas y métodos para su uso en el tratamiento de trastornos metabólicos | |
| ES2530235T3 (es) | Compuestos para el tratamiento de trastornos metabólicos | |
| KR100704142B1 (ko) | 사람 퍼옥시좀 증식 활성화 수용체(ＰＰＡＲ)α의 효능제로서의 치환된 페닐프로피온산 유도체 | |
| JP2011515341A (ja) | 代謝障害の治療に有用な立体配座的に制限されたカルボン酸誘導体 | |
| ES2714207T3 (es) | Antagonistas de glucagón | |
| CA2646430A1 (en) | Bicyclic carboxylic acid derivatives useful for treating metabolic disorders | |
| JP2012503595A (ja) | 代謝病の治療用の化合物 | |
| CA2905448A1 (en) | Oxabicyclo [2.2.2] acid gpr120 modulators | |
| TW200812992A (en) | Antidiabetic tricyclic compounds | |
| UA121871C2 (uk) | Гетероциклічна сполука | |
| US11974997B2 (en) | RORgamma modulators and uses thereof | |
| JP6310931B2 (ja) | Ｇｐｒ１２０アゴニストとしてのチオアリール誘導体 | |
| CA2858285C (en) | 1,3-diphenylpropane derivatives, preparations and uses thereof | |
| TW201317229A (zh) | 稠合雜環衍生物 | |
| JP2010111692A (ja) | 高度不飽和脂肪酸誘導体およびそれを含有する医薬組成物 | |
| ES2350101T3 (es) | Nuevos ácidos arilhexadienoicos substituidos y sus ésteres que pueden ser empleados para el tratamiento y la prevención de la diabetes, de la dislipidemia y de la aterosclerosis, composiciones farmacéuticas que los comprenden y procedimientos para la preparación de los mismos. | |
| CN120247772A (zh) | 一类新型fabp1/fabp4双重抑制剂、其制备方法及其作为药物的用途 | |
| AU2004263254A1 (en) | Butenoic acid derivatives, processes for the preparation thereof, pharmaceutical compositions comprising them, and use for the treatment of dyslipidaemia, atherosclerosis and diabetes | |
| JPWO2000053563A1 (ja) | 核内リセプターｐｐａｒの新規リガンド |