NO314143B1 - Substituerte pyridiner og bifenyler, fremgangsmåte for fremstilling, farmasöytiske produkter inneholdende disse samt anvendelse forfremstilling av farmasöytiske preparater - Google Patents
Substituerte pyridiner og bifenyler, fremgangsmåte for fremstilling, farmasöytiske produkter inneholdende disse samt anvendelse forfremstilling av farmasöytiske preparater Download PDFInfo
- Publication number
- NO314143B1 NO314143B1 NO19990399A NO990399A NO314143B1 NO 314143 B1 NO314143 B1 NO 314143B1 NO 19990399 A NO19990399 A NO 19990399A NO 990399 A NO990399 A NO 990399A NO 314143 B1 NO314143 B1 NO 314143B1
- Authority
- NO
- Norway
- Prior art keywords
- diisopropyl
- substituted
- phenyl
- hydroxymethyl
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 154
- 150000003222 pyridines Chemical class 0.000 title claims description 38
- 238000002360 preparation method Methods 0.000 title claims description 37
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 27
- 229940127557 pharmaceutical product Drugs 0.000 title claims description 17
- 235000010290 biphenyl Nutrition 0.000 title claims description 12
- 150000004074 biphenyls Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 294
- -1 cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy Chemical group 0.000 claims description 122
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 102
- 125000004432 carbon atom Chemical group C* 0.000 claims description 94
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 86
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 80
- 125000001424 substituent group Chemical group 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 73
- 239000000460 chlorine Substances 0.000 claims description 59
- 238000011282 treatment Methods 0.000 claims description 59
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 42
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 42
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 41
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 38
- 229910052801 chlorine Inorganic materials 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 38
- 239000011737 fluorine Substances 0.000 claims description 36
- 229910052731 fluorine Inorganic materials 0.000 claims description 36
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 230000009467 reduction Effects 0.000 claims description 32
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 claims description 29
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 27
- 239000012442 inert solvent Substances 0.000 claims description 27
- 102000051325 Glucagon Human genes 0.000 claims description 26
- 108060003199 Glucagon Proteins 0.000 claims description 26
- 229960004666 glucagon Drugs 0.000 claims description 26
- 229910052794 bromium Inorganic materials 0.000 claims description 25
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 24
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 24
- 230000002829 reductive effect Effects 0.000 claims description 22
- 206010012601 diabetes mellitus Diseases 0.000 claims description 21
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 20
- 239000004305 biphenyl Substances 0.000 claims description 20
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 19
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 19
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
- 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 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
- 125000002541 furyl group Chemical group 0.000 claims description 13
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 108010063919 Glucagon Receptors Proteins 0.000 claims description 11
- 102100040890 Glucagon receptor Human genes 0.000 claims description 11
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 11
- 238000007239 Wittig reaction Methods 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 229940122904 Glucagon receptor antagonist Drugs 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000001041 indolyl group Chemical group 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000005493 quinolyl group Chemical group 0.000 claims description 6
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- XPINZAYSUKBJNK-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)-2,6-di(propan-2-yl)-5-propylpyridin-3-yl]ethanol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 XPINZAYSUKBJNK-UHFFFAOYSA-N 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 238000003747 Grignard reaction Methods 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 230000003042 antagnostic effect Effects 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- CGERYLIZDURBOY-UHFFFAOYSA-N [4-(4-fluorophenyl)-2,6-di(propan-2-yl)-5-propylpyridin-3-yl]methanol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 CGERYLIZDURBOY-UHFFFAOYSA-N 0.000 claims description 4
- XLGVIPRRJYUYBR-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-hexyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 XLGVIPRRJYUYBR-UHFFFAOYSA-N 0.000 claims description 4
- ZVOGRANCSDFRIU-UHFFFAOYSA-N [5-butyl-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 ZVOGRANCSDFRIU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical group C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 229930192474 thiophene Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical class 0.000 claims description 3
- 125000003113 cycloheptyloxy group Chemical group C1(CCCCCC1)O* 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000006373 (C2-C10) alkyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000004932 phenoxathinyl group Chemical group 0.000 claims description 2
- 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 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 4
- HTOIKIOVMJVPFB-UHFFFAOYSA-N 1-[3-ethyl-2-phenyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 HTOIKIOVMJVPFB-UHFFFAOYSA-N 0.000 claims 2
- MWVCACJLNJUMHL-UHFFFAOYSA-N 2-[2-(hydroxymethyl)-6-pentyl-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1O MWVCACJLNJUMHL-UHFFFAOYSA-N 0.000 claims 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims 1
- GHBDKPMSPLDASO-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-3-[(4-fluorophenyl)sulfanylmethyl]-4,6-di(propan-2-yl)phenyl]ethanol Chemical group C=1C=C(F)C=CC=1SCC=1C(C(C)C)=CC(C(C)C)=C(C(C)O)C=1C1=CC=C(Cl)C=C1 GHBDKPMSPLDASO-UHFFFAOYSA-N 0.000 claims 1
- MZVCXBXHXDZABD-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-3-[(4-methylphenyl)sulfanylmethyl]-4,6-di(propan-2-yl)phenyl]ethanol Chemical group C=1C=C(C)C=CC=1SCC=1C(C(C)C)=CC(C(C)C)=C(C(C)O)C=1C1=CC=C(Cl)C=C1 MZVCXBXHXDZABD-UHFFFAOYSA-N 0.000 claims 1
- WSNAAEJBQBMDJE-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-3-ethyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 WSNAAEJBQBMDJE-UHFFFAOYSA-N 0.000 claims 1
- FDZAGJMNNJBGGF-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-3-pentyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 FDZAGJMNNJBGGF-UHFFFAOYSA-N 0.000 claims 1
- IILZAAMYOKNOKR-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-4,6-di(propan-2-yl)-3-propylphenyl]ethanol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 IILZAAMYOKNOKR-UHFFFAOYSA-N 0.000 claims 1
- QZSWVMMECMZFLW-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)-3-hexyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 QZSWVMMECMZFLW-UHFFFAOYSA-N 0.000 claims 1
- VNZRUAGGCIAOJQ-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)-3-pentyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 VNZRUAGGCIAOJQ-UHFFFAOYSA-N 0.000 claims 1
- VPKLOZUZMAZBBV-UHFFFAOYSA-N 1-[2-(4-methylphenyl)-3-[(4-methylphenyl)sulfanylmethyl]-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CC(C)C1=CC(C(C)C)=C(C(C)O)C(C=2C=CC(C)=CC=2)=C1CSC1=CC=C(C)C=C1 VPKLOZUZMAZBBV-UHFFFAOYSA-N 0.000 claims 1
- NYNHEIHSNJLCHP-UHFFFAOYSA-N 1-[2-phenyl-4,6-di(propan-2-yl)-3-propylphenyl]ethanol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 NYNHEIHSNJLCHP-UHFFFAOYSA-N 0.000 claims 1
- QFUSNTBKZNNNCQ-UHFFFAOYSA-N 1-[3-[(4-methylphenyl)sulfanylmethyl]-2-phenyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CC(C)C1=CC(C(C)C)=C(C(C)O)C(C=2C=CC=CC=2)=C1CSC1=CC=C(C)C=C1 QFUSNTBKZNNNCQ-UHFFFAOYSA-N 0.000 claims 1
- PZWWHLZVCXOIGG-UHFFFAOYSA-N 1-[3-butyl-2-(4-chlorophenyl)-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 PZWWHLZVCXOIGG-UHFFFAOYSA-N 0.000 claims 1
- HGCYYLIYSGIJKE-UHFFFAOYSA-N 1-[3-butyl-2-(4-fluorophenyl)-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 HGCYYLIYSGIJKE-UHFFFAOYSA-N 0.000 claims 1
- JNDQCAVDIVEFIY-UHFFFAOYSA-N 1-[3-butyl-2-(4-methylphenyl)-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(C)C=C1 JNDQCAVDIVEFIY-UHFFFAOYSA-N 0.000 claims 1
- QVJRSJJPQAICMZ-UHFFFAOYSA-N 1-[3-butyl-2-phenyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 QVJRSJJPQAICMZ-UHFFFAOYSA-N 0.000 claims 1
- QGAVOQLRNNHPOG-UHFFFAOYSA-N 1-[3-ethyl-2-(4-fluorophenyl)-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 QGAVOQLRNNHPOG-UHFFFAOYSA-N 0.000 claims 1
- FYGICTMUJWLPCA-UHFFFAOYSA-N 1-[3-ethyl-2-(4-methylphenyl)-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(C)C=C1 FYGICTMUJWLPCA-UHFFFAOYSA-N 0.000 claims 1
- VSZDPPCYYXLWCS-UHFFFAOYSA-N 1-[3-hexyl-2-(4-methylphenyl)-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(C)C=C1 VSZDPPCYYXLWCS-UHFFFAOYSA-N 0.000 claims 1
- WMKBBDODMCTVQS-UHFFFAOYSA-N 1-[3-hexyl-2-phenyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 WMKBBDODMCTVQS-UHFFFAOYSA-N 0.000 claims 1
- LKJUIYNUZVVUAE-UHFFFAOYSA-N 1-[3-pentyl-2-phenyl-4,6-di(propan-2-yl)phenyl]ethanol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 LKJUIYNUZVVUAE-UHFFFAOYSA-N 0.000 claims 1
- ODKIEVZPQGGRJL-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-2,6-di(propan-2-yl)-5-propylpyridin-3-yl]ethanol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 ODKIEVZPQGGRJL-UHFFFAOYSA-N 0.000 claims 1
- NVBLBTMWYLOPBA-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-5-ethyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 NVBLBTMWYLOPBA-UHFFFAOYSA-N 0.000 claims 1
- UVMNNUANFUBCIB-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-5-hexyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 UVMNNUANFUBCIB-UHFFFAOYSA-N 0.000 claims 1
- RLSBIQPRZPNNKW-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-5-pentyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(Cl)C=C1 RLSBIQPRZPNNKW-UHFFFAOYSA-N 0.000 claims 1
- KDJSMIISTUVOAO-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)-5-hexyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 KDJSMIISTUVOAO-UHFFFAOYSA-N 0.000 claims 1
- PTKPSYLXJIYGGX-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)-5-pentyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 PTKPSYLXJIYGGX-UHFFFAOYSA-N 0.000 claims 1
- DYKCQSDKEUFCQK-UHFFFAOYSA-N 1-[4-(4-methylphenyl)-2,6-di(propan-2-yl)-5-propylpyridin-3-yl]ethanol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(C)C=C1 DYKCQSDKEUFCQK-UHFFFAOYSA-N 0.000 claims 1
- VSFMILGPYSOXEO-UHFFFAOYSA-N 1-[4-(4-methylphenyl)-5-pentyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(C)C=C1 VSFMILGPYSOXEO-UHFFFAOYSA-N 0.000 claims 1
- GTBWFXMMRPHUPC-UHFFFAOYSA-N 1-[5-butyl-4-(4-methylphenyl)-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(C)C=C1 GTBWFXMMRPHUPC-UHFFFAOYSA-N 0.000 claims 1
- KMPOYFQAPNRMMQ-UHFFFAOYSA-N 1-[5-butyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 KMPOYFQAPNRMMQ-UHFFFAOYSA-N 0.000 claims 1
- POEINIBHNJSSFH-UHFFFAOYSA-N 1-[5-ethyl-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1 POEINIBHNJSSFH-UHFFFAOYSA-N 0.000 claims 1
- YYWYPNBURFKXJM-UHFFFAOYSA-N 1-[5-ethyl-4-(4-methylphenyl)-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(C)C=C1 YYWYPNBURFKXJM-UHFFFAOYSA-N 0.000 claims 1
- DEIYCRLILYZUFQ-UHFFFAOYSA-N 1-[5-ethyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 DEIYCRLILYZUFQ-UHFFFAOYSA-N 0.000 claims 1
- KGOSTSOKNOMANV-UHFFFAOYSA-N 1-[5-hexyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 KGOSTSOKNOMANV-UHFFFAOYSA-N 0.000 claims 1
- FAZNUZSICMFBKG-UHFFFAOYSA-N 1-[5-pentyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]ethanol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1 FAZNUZSICMFBKG-UHFFFAOYSA-N 0.000 claims 1
- ALLIZEAXNXSFGD-UHFFFAOYSA-N 1-methyl-2-phenylbenzene Chemical group CC1=CC=CC=C1C1=CC=CC=C1 ALLIZEAXNXSFGD-UHFFFAOYSA-N 0.000 claims 1
- XKJASAPQHBHQOY-UHFFFAOYSA-N 2-[2-(1-hydroxyethyl)-3,5-di(propan-2-yl)-6-propylphenyl]phenol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O XKJASAPQHBHQOY-UHFFFAOYSA-N 0.000 claims 1
- DUJXIEHMXDKLDD-UHFFFAOYSA-N 2-[2-(1-hydroxyethyl)-6-pentyl-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O DUJXIEHMXDKLDD-UHFFFAOYSA-N 0.000 claims 1
- ACOVCBIJGUDAOD-UHFFFAOYSA-N 2-[2-(hydroxymethyl)-3,5-di(propan-2-yl)-6-propylphenyl]phenol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1O ACOVCBIJGUDAOD-UHFFFAOYSA-N 0.000 claims 1
- HFVBJDQTCSGOGJ-UHFFFAOYSA-N 2-[2-[(4-fluorophenyl)sulfanylmethyl]-6-(hydroxymethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group C=1C=CC=C(O)C=1C1=C(CO)C(C(C)C)=CC(C(C)C)=C1CSC1=CC=C(F)C=C1 HFVBJDQTCSGOGJ-UHFFFAOYSA-N 0.000 claims 1
- QINIOXAZFYTZFM-UHFFFAOYSA-N 2-[2-butyl-6-(1-hydroxyethyl)-3,5-di(propan-2-yl)phenyl]-5-fluorophenol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1O QINIOXAZFYTZFM-UHFFFAOYSA-N 0.000 claims 1
- UZRSEEGOXIATIY-UHFFFAOYSA-N 2-[2-butyl-6-(1-hydroxyethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O UZRSEEGOXIATIY-UHFFFAOYSA-N 0.000 claims 1
- SAJYEBKGSSIGPH-UHFFFAOYSA-N 2-[2-butyl-6-(hydroxymethyl)-3,5-di(propan-2-yl)phenyl]-5-fluorophenol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1O SAJYEBKGSSIGPH-UHFFFAOYSA-N 0.000 claims 1
- IDWSBXGOPVSMSO-UHFFFAOYSA-N 2-[2-ethyl-6-(1-hydroxyethyl)-3,5-di(propan-2-yl)phenyl]-5-fluorophenol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1O IDWSBXGOPVSMSO-UHFFFAOYSA-N 0.000 claims 1
- OKWCFWHLRPMGND-UHFFFAOYSA-N 2-[2-ethyl-6-(1-hydroxyethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O OKWCFWHLRPMGND-UHFFFAOYSA-N 0.000 claims 1
- HMHRTQLGMXTEIO-UHFFFAOYSA-N 2-[2-ethyl-6-(hydroxymethyl)-3,5-di(propan-2-yl)phenyl]-5-fluorophenol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1O HMHRTQLGMXTEIO-UHFFFAOYSA-N 0.000 claims 1
- KRIYDQLRZDUBOI-UHFFFAOYSA-N 2-[2-ethyl-6-(hydroxymethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1O KRIYDQLRZDUBOI-UHFFFAOYSA-N 0.000 claims 1
- LJSLXUHOKKMJGA-UHFFFAOYSA-N 2-[2-hexyl-6-(hydroxymethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1O LJSLXUHOKKMJGA-UHFFFAOYSA-N 0.000 claims 1
- WJESFFWHDFTYIO-UHFFFAOYSA-N 2-[3-(1-hydroxyethyl)-5-pentyl-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O WJESFFWHDFTYIO-UHFFFAOYSA-N 0.000 claims 1
- MUNZGRRSIJJGQQ-UHFFFAOYSA-N 2-[3-[(4-fluorophenyl)sulfanylmethyl]-5-(1-hydroxyethyl)-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CC(C)C1=NC(C(C)C)=C(C(C)O)C(C=2C(=CC=CC=2)O)=C1CSC1=CC=C(F)C=C1 MUNZGRRSIJJGQQ-UHFFFAOYSA-N 0.000 claims 1
- ZQUADOVBJNKXNM-UHFFFAOYSA-N 2-[3-butyl-5-(1-hydroxyethyl)-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O ZQUADOVBJNKXNM-UHFFFAOYSA-N 0.000 claims 1
- LTIKFEWBVVXCDC-UHFFFAOYSA-N 2-[3-butyl-5-(hydroxymethyl)-2,6-di(propan-2-yl)pyridin-4-yl]-5-fluorophenol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1O LTIKFEWBVVXCDC-UHFFFAOYSA-N 0.000 claims 1
- MELQWPBUIARHFW-UHFFFAOYSA-N 2-[3-ethyl-5-(1-hydroxyethyl)-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O MELQWPBUIARHFW-UHFFFAOYSA-N 0.000 claims 1
- PXSYREXAUKZYSQ-UHFFFAOYSA-N 2-[3-ethyl-5-(hydroxymethyl)-2,6-di(propan-2-yl)pyridin-4-yl]-5-fluorophenol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1O PXSYREXAUKZYSQ-UHFFFAOYSA-N 0.000 claims 1
- MLGQIUNLKSZPQI-UHFFFAOYSA-N 2-[3-ethyl-5-(hydroxymethyl)-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1O MLGQIUNLKSZPQI-UHFFFAOYSA-N 0.000 claims 1
- SGEINOCVVOLQMX-UHFFFAOYSA-N 2-[3-hexyl-5-(1-hydroxyethyl)-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CCCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O SGEINOCVVOLQMX-UHFFFAOYSA-N 0.000 claims 1
- LPVFFFWENYWFFB-UHFFFAOYSA-N 5-fluoro-2-[2-(1-hydroxyethyl)-3,5-di(propan-2-yl)-6-propylphenyl]phenol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1O LPVFFFWENYWFFB-UHFFFAOYSA-N 0.000 claims 1
- GWHGHNLODWJQBS-UHFFFAOYSA-N 5-fluoro-2-[2-(1-hydroxyethyl)-6-[(4-methylphenyl)sulfanylmethyl]-3,5-di(propan-2-yl)phenyl]phenol Chemical group CC(C)C1=CC(C(C)C)=C(C(C)O)C(C=2C(=CC(F)=CC=2)O)=C1CSC1=CC=C(C)C=C1 GWHGHNLODWJQBS-UHFFFAOYSA-N 0.000 claims 1
- ZJKBBWZDGLZIOU-UHFFFAOYSA-N 5-fluoro-2-[2-(1-hydroxyethyl)-6-pentyl-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1O ZJKBBWZDGLZIOU-UHFFFAOYSA-N 0.000 claims 1
- UWLNTOMQVFFZNF-UHFFFAOYSA-N 5-fluoro-2-[2-(hydroxymethyl)-3,5-di(propan-2-yl)-6-propylphenyl]phenol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1O UWLNTOMQVFFZNF-UHFFFAOYSA-N 0.000 claims 1
- DNRBPPQOSNEYBV-UHFFFAOYSA-N 5-fluoro-2-[2-[(4-fluorophenyl)sulfanylmethyl]-6-(1-hydroxyethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group CC(C)C1=CC(C(C)C)=C(C(C)O)C(C=2C(=CC(F)=CC=2)O)=C1CSC1=CC=C(F)C=C1 DNRBPPQOSNEYBV-UHFFFAOYSA-N 0.000 claims 1
- IOZKFPJFMLXQSY-UHFFFAOYSA-N 5-fluoro-2-[2-hexyl-6-(1-hydroxyethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1O IOZKFPJFMLXQSY-UHFFFAOYSA-N 0.000 claims 1
- FMUHDSYKDGQDLF-UHFFFAOYSA-N 5-fluoro-2-[2-hexyl-6-(hydroxymethyl)-3,5-di(propan-2-yl)phenyl]phenol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1O FMUHDSYKDGQDLF-UHFFFAOYSA-N 0.000 claims 1
- XBLSHRACWAZFCN-UHFFFAOYSA-N 5-fluoro-2-[3-(hydroxymethyl)-2,6-di(propan-2-yl)-5-propylpyridin-4-yl]phenol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1O XBLSHRACWAZFCN-UHFFFAOYSA-N 0.000 claims 1
- YXOHTNLNADZFPN-UHFFFAOYSA-N 5-fluoro-2-[3-[(4-fluorophenyl)sulfanylmethyl]-5-(1-hydroxyethyl)-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CC(C)C1=NC(C(C)C)=C(C(C)O)C(C=2C(=CC(F)=CC=2)O)=C1CSC1=CC=C(F)C=C1 YXOHTNLNADZFPN-UHFFFAOYSA-N 0.000 claims 1
- ZTECBIPIFRUTJD-UHFFFAOYSA-N 5-fluoro-2-[3-hexyl-5-(1-hydroxyethyl)-2,6-di(propan-2-yl)pyridin-4-yl]phenol Chemical compound CCCCCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1O ZTECBIPIFRUTJD-UHFFFAOYSA-N 0.000 claims 1
- JFFBAPDAOIVQMG-UHFFFAOYSA-N [2-(4-chlorophenyl)-3-[(4-methylphenyl)sulfanylmethyl]-4,6-di(propan-2-yl)phenyl]methanol Chemical group C=1C=C(Cl)C=CC=1C1=C(CO)C(C(C)C)=CC(C(C)C)=C1CSC1=CC=C(C)C=C1 JFFBAPDAOIVQMG-UHFFFAOYSA-N 0.000 claims 1
- PUTFUMOKXPPZNZ-UHFFFAOYSA-N [2-(4-chlorophenyl)-3-ethyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(Cl)C=C1 PUTFUMOKXPPZNZ-UHFFFAOYSA-N 0.000 claims 1
- TURPLLZSUZDJBB-UHFFFAOYSA-N [2-(4-chlorophenyl)-3-hexyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(Cl)C=C1 TURPLLZSUZDJBB-UHFFFAOYSA-N 0.000 claims 1
- PKKZHDSSIJKFRV-UHFFFAOYSA-N [2-(4-chlorophenyl)-3-pentyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(Cl)C=C1 PKKZHDSSIJKFRV-UHFFFAOYSA-N 0.000 claims 1
- HQDCGXFULZSWGG-UHFFFAOYSA-N [2-(4-chlorophenyl)-4,6-di(propan-2-yl)-3-propylphenyl]methanol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(Cl)C=C1 HQDCGXFULZSWGG-UHFFFAOYSA-N 0.000 claims 1
- JCYGLCLMLMGSJN-UHFFFAOYSA-N [2-(4-fluorophenyl)-3-hexyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 JCYGLCLMLMGSJN-UHFFFAOYSA-N 0.000 claims 1
- PLWSZSDKTDBKNN-UHFFFAOYSA-N [2-(4-fluorophenyl)-3-pentyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 PLWSZSDKTDBKNN-UHFFFAOYSA-N 0.000 claims 1
- BKSUMRVNMGRFHU-UHFFFAOYSA-N [2-(4-fluorophenyl)-4,6-di(propan-2-yl)-3-propylphenyl]methanol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 BKSUMRVNMGRFHU-UHFFFAOYSA-N 0.000 claims 1
- FYUYDKHBFBLZLD-UHFFFAOYSA-N [2-(4-methylphenyl)-3-[(4-methylphenyl)sulfanylmethyl]-4,6-di(propan-2-yl)phenyl]methanol Chemical group C=1C=C(C)C=CC=1C1=C(CO)C(C(C)C)=CC(C(C)C)=C1CSC1=CC=C(C)C=C1 FYUYDKHBFBLZLD-UHFFFAOYSA-N 0.000 claims 1
- WDGFFVBPXPPTDH-UHFFFAOYSA-N [2-(4-methylphenyl)-4,6-di(propan-2-yl)-3-propylphenyl]methanol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(C)C=C1 WDGFFVBPXPPTDH-UHFFFAOYSA-N 0.000 claims 1
- JNXUZJPOLADVEY-UHFFFAOYSA-N [2-phenyl-4,6-di(propan-2-yl)-3-propylphenyl]methanol Chemical group CCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1 JNXUZJPOLADVEY-UHFFFAOYSA-N 0.000 claims 1
- LKASCORFCHMECB-UHFFFAOYSA-N [3-[(4-methylphenyl)sulfanylmethyl]-2-phenyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group C=1C=CC=CC=1C1=C(CO)C(C(C)C)=CC(C(C)C)=C1CSC1=CC=C(C)C=C1 LKASCORFCHMECB-UHFFFAOYSA-N 0.000 claims 1
- VYBLFXLXIQJOAU-UHFFFAOYSA-N [3-butyl-2-(4-fluorophenyl)-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 VYBLFXLXIQJOAU-UHFFFAOYSA-N 0.000 claims 1
- UHSNRAVFDZTHAF-UHFFFAOYSA-N [3-butyl-2-(4-methylphenyl)-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(C)C=C1 UHSNRAVFDZTHAF-UHFFFAOYSA-N 0.000 claims 1
- CYLKFMKLDJCXBT-UHFFFAOYSA-N [3-butyl-2-phenyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1 CYLKFMKLDJCXBT-UHFFFAOYSA-N 0.000 claims 1
- NJWAERVFODMHJU-UHFFFAOYSA-N [3-ethyl-2-(4-fluorophenyl)-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 NJWAERVFODMHJU-UHFFFAOYSA-N 0.000 claims 1
- IXQUWENXHBPVGZ-UHFFFAOYSA-N [3-ethyl-2-(4-methylphenyl)-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(C)C=C1 IXQUWENXHBPVGZ-UHFFFAOYSA-N 0.000 claims 1
- WPDSMFLJZQAKMX-UHFFFAOYSA-N [3-ethyl-2-phenyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1 WPDSMFLJZQAKMX-UHFFFAOYSA-N 0.000 claims 1
- DWAWOJQXSGUUHO-UHFFFAOYSA-N [3-hexyl-2-(4-methylphenyl)-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=C(C)C=C1 DWAWOJQXSGUUHO-UHFFFAOYSA-N 0.000 claims 1
- SSJCIBYNXAMYAK-UHFFFAOYSA-N [3-hexyl-2-phenyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1 SSJCIBYNXAMYAK-UHFFFAOYSA-N 0.000 claims 1
- MQENVMWCILRYRV-UHFFFAOYSA-N [3-pentyl-2-phenyl-4,6-di(propan-2-yl)phenyl]methanol Chemical group CCCCCC1=C(C(C)C)C=C(C(C)C)C(CO)=C1C1=CC=CC=C1 MQENVMWCILRYRV-UHFFFAOYSA-N 0.000 claims 1
- QVIPWSKJJIUWJN-UHFFFAOYSA-N [4-(4-chlorophenyl)-2,6-di(propan-2-yl)-5-propylpyridin-3-yl]methanol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(Cl)C=C1 QVIPWSKJJIUWJN-UHFFFAOYSA-N 0.000 claims 1
- MRAJXEJREVLHNF-UHFFFAOYSA-N [4-(4-chlorophenyl)-5-pentyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(Cl)C=C1 MRAJXEJREVLHNF-UHFFFAOYSA-N 0.000 claims 1
- LWMMKIZORZAKBC-UHFFFAOYSA-N [4-(4-methylphenyl)-2,6-di(propan-2-yl)-5-propylpyridin-3-yl]methanol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(C)C=C1 LWMMKIZORZAKBC-UHFFFAOYSA-N 0.000 claims 1
- DKPPNWZCOYMYMW-UHFFFAOYSA-N [4-phenyl-2,6-di(propan-2-yl)-5-propylpyridin-3-yl]methanol Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 DKPPNWZCOYMYMW-UHFFFAOYSA-N 0.000 claims 1
- SWMYJAYRAUFGNN-UHFFFAOYSA-N [5-butyl-4-(4-chlorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(Cl)C=C1 SWMYJAYRAUFGNN-UHFFFAOYSA-N 0.000 claims 1
- UJKXEXCMBOOOKM-UHFFFAOYSA-N [5-butyl-4-(4-methylphenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(C)C=C1 UJKXEXCMBOOOKM-UHFFFAOYSA-N 0.000 claims 1
- XFYIVTJITOBNBO-UHFFFAOYSA-N [5-butyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 XFYIVTJITOBNBO-UHFFFAOYSA-N 0.000 claims 1
- YKTJDOAGPITATA-UHFFFAOYSA-N [5-ethyl-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 YKTJDOAGPITATA-UHFFFAOYSA-N 0.000 claims 1
- PHCWOCRFYJSPST-UHFFFAOYSA-N [5-ethyl-4-(4-methylphenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(C)C=C1 PHCWOCRFYJSPST-UHFFFAOYSA-N 0.000 claims 1
- YXZAOVVNIMGSEO-UHFFFAOYSA-N [5-ethyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 YXZAOVVNIMGSEO-UHFFFAOYSA-N 0.000 claims 1
- LPUWXQZNBDQHBM-UHFFFAOYSA-N [5-hexyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 LPUWXQZNBDQHBM-UHFFFAOYSA-N 0.000 claims 1
- JJSFGIZTXNWLSJ-UHFFFAOYSA-N [5-pentyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 JJSFGIZTXNWLSJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- JSJLLHPAMPKWIX-UHFFFAOYSA-N chembl116413 Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=CC=C1O JSJLLHPAMPKWIX-UHFFFAOYSA-N 0.000 claims 1
- WPUCRISSEKWRQP-UHFFFAOYSA-N chembl323913 Chemical compound CCCC1=C(C(C)C)N=C(C(C)C)C(C(C)O)=C1C1=CC=C(F)C=C1O WPUCRISSEKWRQP-UHFFFAOYSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 568
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 500
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 200
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 193
- 235000019439 ethyl acetate Nutrition 0.000 description 189
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 143
- 238000005481 NMR spectroscopy Methods 0.000 description 124
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 119
- 239000000243 solution Substances 0.000 description 98
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 94
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 85
- 239000000203 mixture Substances 0.000 description 77
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
- 239000002904 solvent Substances 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000543 intermediate Substances 0.000 description 33
- 239000007787 solid Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000002585 base Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- 238000003786 synthesis reaction Methods 0.000 description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 26
- 239000003921 oil Substances 0.000 description 26
- 235000019198 oils Nutrition 0.000 description 26
- 239000000741 silica gel Substances 0.000 description 26
- 229910002027 silica gel Inorganic materials 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
- 239000000047 product Substances 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 229910052786 argon Inorganic materials 0.000 description 24
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 24
- XCLDSQRVMMXWMS-UHFFFAOYSA-N ethyl 4-methyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)C XCLDSQRVMMXWMS-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 230000003647 oxidation Effects 0.000 description 21
- 238000007254 oxidation reaction Methods 0.000 description 21
- 239000003208 petroleum Substances 0.000 description 21
- 239000000126 substance Substances 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 20
- 239000012280 lithium aluminium hydride Substances 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 20
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 19
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 18
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 18
- 150000001299 aldehydes Chemical class 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 239000003638 chemical reducing agent Substances 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- 239000012267 brine Substances 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 239000012312 sodium hydride Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 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 10
- 108090001030 Lipoproteins Proteins 0.000 description 10
- 102000004895 Lipoproteins Human genes 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 239000007800 oxidant agent Substances 0.000 description 10
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 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 9
- 108010010234 HDL Lipoproteins Proteins 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- NIDVFKIOOJTTCI-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-pentyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 NIDVFKIOOJTTCI-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 238000012546 transfer Methods 0.000 description 9
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 235000011054 acetic acid Nutrition 0.000 description 8
- 150000001336 alkenes Chemical class 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- 235000012000 cholesterol Nutrition 0.000 description 8
- 230000026030 halogenation Effects 0.000 description 8
- 238000005658 halogenation reaction Methods 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 239000010410 layer 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
- 229910052987 metal hydride Inorganic materials 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 8
- 239000002798 polar solvent Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 7
- 239000005695 Ammonium acetate Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- 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 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 7
- 239000003513 alkali Substances 0.000 description 7
- 235000019257 ammonium acetate Nutrition 0.000 description 7
- 229940043376 ammonium acetate Drugs 0.000 description 7
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 7
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 229930195733 hydrocarbon Natural products 0.000 description 7
- 150000002430 hydrocarbons Chemical class 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- 229940125396 insulin Drugs 0.000 description 7
- 229910052744 lithium Inorganic materials 0.000 description 7
- 239000011777 magnesium Substances 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 6
- 108090001061 Insulin Proteins 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 150000003863 ammonium salts Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000004296 chiral HPLC Methods 0.000 description 6
- 229960001701 chloroform Drugs 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000003995 emulsifying agent Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 150000007529 inorganic bases Chemical class 0.000 description 6
- 238000010829 isocratic elution Methods 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 150000004681 metal hydrides Chemical class 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 6
- 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 5
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 5
- 239000007818 Grignard reagent Substances 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 5
- 229960002632 acarbose Drugs 0.000 description 5
- 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 5
- 229950005499 carbon tetrachloride Drugs 0.000 description 5
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 230000009229 glucose formation Effects 0.000 description 5
- 150000008282 halocarbons Chemical class 0.000 description 5
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 5
- 201000001421 hyperglycemia Diseases 0.000 description 5
- 208000001022 morbid obesity Diseases 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000006187 pill Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 229960001729 voglibose Drugs 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 206010003210 Arteriosclerosis Diseases 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 102000004366 Glucosidases Human genes 0.000 description 4
- 108010056771 Glucosidases Proteins 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- 241000699673 Mesocricetus auratus Species 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 4
- IBNFSCUPUJVZMA-XNTDXEJSSA-N [4-(4-fluorophenyl)-5-[(e)-2-(4-methylphenyl)ethenyl]-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound C=1C=C(F)C=CC=1C1=C(CO)C(C(C)C)=NC(C(C)C)=C1\C=C\C1=CC=C(C)C=C1 IBNFSCUPUJVZMA-XNTDXEJSSA-N 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 239000003392 amylase inhibitor Substances 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 description 4
- 150000007514 bases Chemical class 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 238000009395 breeding Methods 0.000 description 4
- 230000001488 breeding effect Effects 0.000 description 4
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 4
- 150000001840 cholesterol esters Chemical class 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 229940039227 diagnostic agent Drugs 0.000 description 4
- 239000000032 diagnostic agent Substances 0.000 description 4
- 238000000502 dialysis Methods 0.000 description 4
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- XPTNRLJHTLXFML-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-5-formyl-2,6-di(propan-2-yl)pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=C(C(C)C)C(C=O)=C1C1=CC=C(F)C=C1 XPTNRLJHTLXFML-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 210000004731 jugular vein Anatomy 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- ZKJHYLAGFXZELO-UHFFFAOYSA-N methyl 4-(4-fluorophenyl)-5-(2-oxoethyl)-2,6-di(propan-2-yl)pyridine-3-carboxylate Chemical compound COC(=O)C1=C(C(C)C)N=C(C(C)C)C(CC=O)=C1C1=CC=C(F)C=C1 ZKJHYLAGFXZELO-UHFFFAOYSA-N 0.000 description 4
- 229960001110 miglitol Drugs 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 230000004141 reverse cholesterol transport Effects 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- LXLLNPOQJNQQOL-UHFFFAOYSA-N (2,6-dimethyl-5-pent-1-enyl-4-phenylpyridin-3-yl)methanol Chemical compound CCCC=CC1=C(C)N=C(C)C(CO)=C1C1=CC=CC=C1 LXLLNPOQJNQQOL-UHFFFAOYSA-N 0.000 description 3
- BYMZQANAFPYIOB-UHFFFAOYSA-N (5-ethenyl-2,6-diethyl-4-phenylpyridin-3-yl)methanol Chemical compound CCC1=NC(CC)=C(C=C)C(C=2C=CC=CC=2)=C1CO BYMZQANAFPYIOB-UHFFFAOYSA-N 0.000 description 3
- QDVBKXJMLILLLB-UHFFFAOYSA-N 1,4'-bipiperidine Chemical compound C1CCCCN1C1CCNCC1 QDVBKXJMLILLLB-UHFFFAOYSA-N 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 3
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 3
- PRRBQHNMYJRHFW-UHFFFAOYSA-M 3-oxoheptanoate Chemical compound CCCCC(=O)CC([O-])=O PRRBQHNMYJRHFW-UHFFFAOYSA-M 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 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 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- HPHQUFZLYVLCKP-UHFFFAOYSA-N [4-(4-fluorophenyl)-2,6-di(propan-2-yl)-5-prop-1-enylpyridin-3-yl]methanol Chemical compound CC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 HPHQUFZLYVLCKP-UHFFFAOYSA-N 0.000 description 3
- NLEUNXZBFYHPAP-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-(3-methylbut-1-enyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CC(C)C=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 NLEUNXZBFYHPAP-UHFFFAOYSA-N 0.000 description 3
- ZXZKAQLRBTVMKX-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-(3-phenylprop-2-enyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound C=1C=C(F)C=CC=1C1=C(CO)C(C(C)C)=NC(C(C)C)=C1CC=CC1=CC=CC=C1 ZXZKAQLRBTVMKX-UHFFFAOYSA-N 0.000 description 3
- MHPAZTPXOBBERU-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-(4-methylpent-1-enyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CC(C)CC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 MHPAZTPXOBBERU-UHFFFAOYSA-N 0.000 description 3
- QVRWGFDLXGTXSM-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-(4-phenylbut-1-enyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound C=1C=C(F)C=CC=1C1=C(CO)C(C(C)C)=NC(C(C)C)=C1C=CCCC1=CC=CC=C1 QVRWGFDLXGTXSM-UHFFFAOYSA-N 0.000 description 3
- ZFOLBRQAFUSITK-NTEUORMPSA-N [4-(4-fluorophenyl)-5-[(e)-2-(3-methylphenyl)ethenyl]-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound C=1C=C(F)C=CC=1C1=C(CO)C(C(C)C)=NC(C(C)C)=C1\C=C\C1=CC=CC(C)=C1 ZFOLBRQAFUSITK-NTEUORMPSA-N 0.000 description 3
- XDJCYJFEQWZEPA-XNTDXEJSSA-N [4-(4-fluorophenyl)-5-[(e)-2-phenylethenyl]-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound C=1C=C(F)C=CC=1C1=C(CO)C(C(C)C)=NC(C(C)C)=C1\C=C\C1=CC=CC=C1 XDJCYJFEQWZEPA-XNTDXEJSSA-N 0.000 description 3
- QCIZDFMOHQXKNA-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-hept-1-enyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCCC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 QCIZDFMOHQXKNA-UHFFFAOYSA-N 0.000 description 3
- MZKAODXDWOKVJN-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-hex-1-enyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 MZKAODXDWOKVJN-UHFFFAOYSA-N 0.000 description 3
- DCDDRTFOSDNAQA-UHFFFAOYSA-N [5-but-1-enyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 DCDDRTFOSDNAQA-UHFFFAOYSA-N 0.000 description 3
- ZFZPEIBRJAXQGX-UHFFFAOYSA-N [5-ethenyl-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CC(C)C1=NC(C(C)C)=C(C=C)C(C=2C=CC(F)=CC=2)=C1CO ZFZPEIBRJAXQGX-UHFFFAOYSA-N 0.000 description 3
- SXSTXSFUVBIIPQ-UHFFFAOYSA-N [5-pent-1-enyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 SXSTXSFUVBIIPQ-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 230000009435 amidation Effects 0.000 description 3
- 238000007112 amidation reaction Methods 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 150000001543 aryl boronic acids Chemical class 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 3
- 229910001863 barium hydroxide Inorganic materials 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 3
- 150000005690 diesters Chemical class 0.000 description 3
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
- 208000030172 endocrine system disease Diseases 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- AEXYGJRYLCZIJM-UHFFFAOYSA-N ethyl 3-amino-4-methylpent-2-enoate Chemical compound CCOC(=O)C=C(N)C(C)C AEXYGJRYLCZIJM-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- 150000004679 hydroxides Chemical class 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
- 229910000105 potassium hydride Inorganic materials 0.000 description 3
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 3
- 229940074439 potassium sodium tartrate Drugs 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical class O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical compound CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- HHBXWXJLQYJJBW-UHFFFAOYSA-M triphenyl(propan-2-yl)phosphanium;iodide Chemical compound [I-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(C)C)C1=CC=CC=C1 HHBXWXJLQYJJBW-UHFFFAOYSA-M 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- RPXTYLOWRQIAAU-UHFFFAOYSA-N (2,6-diethyl-5-pent-1-enyl-4-phenylpyridin-3-yl)methanol Chemical compound CCCC=CC1=C(CC)N=C(CC)C(CO)=C1C1=CC=CC=C1 RPXTYLOWRQIAAU-UHFFFAOYSA-N 0.000 description 2
- XDCQNYYELACHOT-UHFFFAOYSA-M (2-methylphenyl)methyl-triphenylphosphanium;bromide Chemical compound [Br-].CC1=CC=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XDCQNYYELACHOT-UHFFFAOYSA-M 0.000 description 2
- VCIPQQCYKMORDY-KBYFLBCBSA-N (2r,3r,4s,5s,6r)-2-(hydroxymethyl)-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]piperidine-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)N[C@@H]1CO[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VCIPQQCYKMORDY-KBYFLBCBSA-N 0.000 description 2
- BIYHITCBCNGOIR-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;bromide Chemical compound [Br-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BIYHITCBCNGOIR-UHFFFAOYSA-M 0.000 description 2
- CEEKCHGNKYVTTM-UHFFFAOYSA-M (4-methylphenyl)methyl-triphenylphosphanium;bromide Chemical compound [Br-].C1=CC(C)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 CEEKCHGNKYVTTM-UHFFFAOYSA-M 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 2
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical compound CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- RWXUNIMBRXGNEP-UHFFFAOYSA-N 1-bromo-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1Br RWXUNIMBRXGNEP-UHFFFAOYSA-N 0.000 description 2
- ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical class CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-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
- FTYAXYWEDPWJCJ-UHFFFAOYSA-N 2-pentan-3-ylpyridine Chemical compound CCC(CC)C1=CC=CC=N1 FTYAXYWEDPWJCJ-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical class NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- KJXRDJKQNGCWJL-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-pentyl-2,6-di(propan-2-yl)pyridine-3-carbaldehyde Chemical compound CCCCCC1=C(C(C)C)N=C(C(C)C)C(C=O)=C1C1=CC=C(F)C=C1 KJXRDJKQNGCWJL-UHFFFAOYSA-N 0.000 description 2
- 108010032229 AI 3688 Proteins 0.000 description 2
- 241000349731 Afzelia bipindensis Species 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 229940122816 Amylase inhibitor Drugs 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 229930003347 Atropine Natural products 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 108010023302 HDL Cholesterol Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101001030705 Homo sapiens Huntingtin Proteins 0.000 description 2
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- VCIPQQCYKMORDY-UHFFFAOYSA-N MDL 25637 Natural products OC1C(O)C(O)C(CO)NC1COC1C(O)C(O)C(O)C(CO)O1 VCIPQQCYKMORDY-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- OCTNNXHKAOLDJL-BMGYQPLYSA-N Salbostatin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)OC[C@@H]1N[C@@H]1[C@H](O)[C@@H](O)[C@H](O)C(CO)=C1 OCTNNXHKAOLDJL-BMGYQPLYSA-N 0.000 description 2
- OCTNNXHKAOLDJL-UHFFFAOYSA-N Salbostatin Natural products OC1C(O)C(CO)OCC1NC1C(O)C(O)C(O)C(CO)=C1 OCTNNXHKAOLDJL-UHFFFAOYSA-N 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- XHKWUZOFXYGQTG-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-(phenylsulfanylmethyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound C=1C=C(F)C=CC=1C1=C(CO)C(C(C)C)=NC(C(C)C)=C1CSC1=CC=CC=C1 XHKWUZOFXYGQTG-UHFFFAOYSA-N 0.000 description 2
- CVJNLHODQSTSOD-UHFFFAOYSA-N [4-phenyl-2,6-di(propan-2-yl)-5-prop-1-enylpyridin-3-yl]methanol Chemical compound CC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 CVJNLHODQSTSOD-UHFFFAOYSA-N 0.000 description 2
- DWLGERDWFIXFKS-UHFFFAOYSA-N [5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CC(C)C1=NC(C(C)C)=C(CO[Si](C)(C)C(C)(C)C)C(C=2C=CC(F)=CC=2)=C1CO DWLGERDWFIXFKS-UHFFFAOYSA-N 0.000 description 2
- XOVGBSWXWLDFMQ-UHFFFAOYSA-N [5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methyl methanesulfonate Chemical compound CC(C)C1=NC(C(C)C)=C(COS(C)(=O)=O)C(C=2C=CC(F)=CC=2)=C1CO[Si](C)(C)C(C)(C)C XOVGBSWXWLDFMQ-UHFFFAOYSA-N 0.000 description 2
- BJIXNBGCRXYREJ-UHFFFAOYSA-N [5-hex-1-enyl-4-phenyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=CC=C1 BJIXNBGCRXYREJ-UHFFFAOYSA-N 0.000 description 2
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229940092980 adalat Drugs 0.000 description 2
- COAIBTZEXXESAS-TZSLYBJXSA-N adiposin Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1N[C@@H]1[C@H](O)[C@@H](O)[C@H](O)C(CO)=C1 COAIBTZEXXESAS-TZSLYBJXSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- BYFGZMCJNACEKR-UHFFFAOYSA-N aluminium(i) oxide Chemical compound [Al]O[Al] BYFGZMCJNACEKR-UHFFFAOYSA-N 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 229940125708 antidiabetic agent Drugs 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 2
- 229960000396 atropine Drugs 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- WTEPWWCRWNCUNA-UHFFFAOYSA-M benzyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=C1 WTEPWWCRWNCUNA-UHFFFAOYSA-M 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- IKWKJIWDLVYZIY-UHFFFAOYSA-M butyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCC)C1=CC=CC=C1 IKWKJIWDLVYZIY-UHFFFAOYSA-M 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 229910052593 corundum Inorganic materials 0.000 description 2
- 229960002887 deanol Drugs 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000001085 differential centrifugation Methods 0.000 description 2
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 2
- 125000005594 diketone group Chemical group 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 229950000269 emiglitate Drugs 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical class CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- NWWORXYTJRPSMC-QKPAOTATSA-N ethyl 4-[2-[(2r,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 NWWORXYTJRPSMC-QKPAOTATSA-N 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000021588 free fatty acids Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 102000054185 human HTT Human genes 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 150000002440 hydroxy compounds Chemical class 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Chemical class 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 2
- FMUJIJVVYZXXIU-UHFFFAOYSA-N lithium;trifluoromethylbenzene Chemical compound [Li+].FC(F)(F)C1=CC=[C-]C=C1 FMUJIJVVYZXXIU-UHFFFAOYSA-N 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- RLWNSGVNYSJFQE-UHFFFAOYSA-N methyl 5-(bromomethyl)-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridine-3-carboxylate Chemical compound COC(=O)C1=C(C(C)C)N=C(C(C)C)C(CBr)=C1C1=CC=C(F)C=C1 RLWNSGVNYSJFQE-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 2
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- JJYKJUXBWFATTE-UHFFFAOYSA-N mosher's acid Chemical compound COC(C(O)=O)(C(F)(F)F)C1=CC=CC=C1 JJYKJUXBWFATTE-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- ARZGTTMMEJDPHG-UHFFFAOYSA-N n-benzyl-2-(2,2-dimethyl-4-phenyloxan-4-yl)ethanamine Chemical compound C1COC(C)(C)CC1(C=1C=CC=CC=1)CCNCC1=CC=CC=C1 ARZGTTMMEJDPHG-UHFFFAOYSA-N 0.000 description 2
- 229940105631 nembutal Drugs 0.000 description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- VAUKWMSXUKODHR-UHFFFAOYSA-M pentyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC)C1=CC=CC=C1 VAUKWMSXUKODHR-UHFFFAOYSA-M 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000011975 tartaric acid Chemical class 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 229950001790 tendamistat Drugs 0.000 description 2
- 108010037401 tendamistate Proteins 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- XMQSELBBYSAURN-UHFFFAOYSA-M triphenyl(propyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCC)C1=CC=CC=C1 XMQSELBBYSAURN-UHFFFAOYSA-M 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229910001845 yogo sapphire Inorganic materials 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 1
- IRICHAOGAOFEQI-UHFFFAOYSA-N (1-bromo-2,2,2-trifluoroethyl)benzene Chemical compound FC(F)(F)C(Br)C1=CC=CC=C1 IRICHAOGAOFEQI-UHFFFAOYSA-N 0.000 description 1
- VKTQADPEPIVMHK-UHFFFAOYSA-N (2-phenylphenyl)methanol Chemical group OCC1=CC=CC=C1C1=CC=CC=C1 VKTQADPEPIVMHK-UHFFFAOYSA-N 0.000 description 1
- FOZFSEMFCIPOSZ-SPCKQMHLSA-N (2r,3r,4r,5s)-2-(hydroxymethyl)-1-[[(2r,3s,4s,5r,6s)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]methyl]piperidine-3,4,5-triol;trihydrate Chemical compound O.O.O.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 FOZFSEMFCIPOSZ-SPCKQMHLSA-N 0.000 description 1
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
- COLPLFZHPXIFCQ-UHFFFAOYSA-N 1,4-dihydropyridine-3,5-dicarboxylic acid Chemical class OC(=O)C1=CNC=C(C(O)=O)C1 COLPLFZHPXIFCQ-UHFFFAOYSA-N 0.000 description 1
- BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 description 1
- PTUPIHXFSSYBFY-VAWYXSNFSA-N 1-hexoxy-4-[(e)-2-phenylethenyl]benzene Chemical compound C1=CC(OCCCCCC)=CC=C1\C=C\C1=CC=CC=C1 PTUPIHXFSSYBFY-VAWYXSNFSA-N 0.000 description 1
- FMFAHVFEPAMZQL-UHFFFAOYSA-N 1-methyl-2-methylsulfinylbenzene Chemical compound CC1=CC=CC=C1S(C)=O FMFAHVFEPAMZQL-UHFFFAOYSA-N 0.000 description 1
- FEVALTJSQBFLEU-UHFFFAOYSA-N 1-methyl-4-methylsulfinylbenzene Chemical compound CC1=CC=C(S(C)=O)C=C1 FEVALTJSQBFLEU-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 1
- UVAMFBJPMUMURT-UHFFFAOYSA-N 2,3,4,5,6-pentafluorobenzenethiol Chemical compound FC1=C(F)C(F)=C(S)C(F)=C1F UVAMFBJPMUMURT-UHFFFAOYSA-N 0.000 description 1
- ZKHSPLCIOVILMA-UHFFFAOYSA-N 2-(2-phenylphenyl)ethanol Chemical group OCCC1=CC=CC=C1C1=CC=CC=C1 ZKHSPLCIOVILMA-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- YIIHEMGEQQWSMA-UHFFFAOYSA-M 2-(dimethylamino)ethyl-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCN(C)C)C1=CC=CC=C1 YIIHEMGEQQWSMA-UHFFFAOYSA-M 0.000 description 1
- DSCJETUEDFKYGN-UHFFFAOYSA-N 2-Methoxybenzenethiol Chemical compound COC1=CC=CC=C1S DSCJETUEDFKYGN-UHFFFAOYSA-N 0.000 description 1
- LXUNZSDDXMPKLP-UHFFFAOYSA-N 2-Methylbenzenethiol Chemical compound CC1=CC=CC=C1S LXUNZSDDXMPKLP-UHFFFAOYSA-N 0.000 description 1
- GBGPVUAOTCNZPT-UHFFFAOYSA-N 2-Methylcumarone Chemical compound C1=CC=C2OC(C)=CC2=C1 GBGPVUAOTCNZPT-UHFFFAOYSA-N 0.000 description 1
- RFCQDOVPMUSZMN-UHFFFAOYSA-N 2-Naphthalenethiol Chemical compound C1=CC=CC2=CC(S)=CC=C21 RFCQDOVPMUSZMN-UHFFFAOYSA-N 0.000 description 1
- APSMUYYLXZULMS-UHFFFAOYSA-N 2-bromonaphthalene Chemical compound C1=CC=CC2=CC(Br)=CC=C21 APSMUYYLXZULMS-UHFFFAOYSA-N 0.000 description 1
- VIKPDPHNYHUZQW-UHFFFAOYSA-M 2-methylpropyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC(C)C)C1=CC=CC=C1 VIKPDPHNYHUZQW-UHFFFAOYSA-M 0.000 description 1
- ZMRFRBHYXOQLDK-UHFFFAOYSA-N 2-phenylethanethiol Chemical compound SCCC1=CC=CC=C1 ZMRFRBHYXOQLDK-UHFFFAOYSA-N 0.000 description 1
- CESBAYSBPMVAEI-UHFFFAOYSA-N 3,5-dimethylbenzenethiol Chemical compound CC1=CC(C)=CC(S)=C1 CESBAYSBPMVAEI-UHFFFAOYSA-N 0.000 description 1
- SSWPSKSQQSJKKF-UHFFFAOYSA-M 3-(dimethylamino)propyl-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCN(C)C)C1=CC=CC=C1 SSWPSKSQQSJKKF-UHFFFAOYSA-M 0.000 description 1
- SCURCOWZQJIUGR-UHFFFAOYSA-N 3-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=CC(S)=C1 SCURCOWZQJIUGR-UHFFFAOYSA-N 0.000 description 1
- QMVAZEHZOPDGHA-UHFFFAOYSA-N 3-methoxybenzenethiol Chemical compound COC1=CC=CC(S)=C1 QMVAZEHZOPDGHA-UHFFFAOYSA-N 0.000 description 1
- WRXOZRLZDJAYDR-UHFFFAOYSA-N 3-methylbenzenethiol Chemical compound CC1=CC=CC(S)=C1 WRXOZRLZDJAYDR-UHFFFAOYSA-N 0.000 description 1
- GZLGTVRDLCJQTO-UHFFFAOYSA-M 3-methylbutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCC(C)C)C1=CC=CC=C1 GZLGTVRDLCJQTO-UHFFFAOYSA-M 0.000 description 1
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- WCMLRSZJUIKVCW-UHFFFAOYSA-N 4-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=C(S)C=C1 WCMLRSZJUIKVCW-UHFFFAOYSA-N 0.000 description 1
- MWMMMRLOZIXOQA-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-5-(hydroxymethyl)-2,6-di(propan-2-yl)pyridin-3-yl]butanal Chemical compound CC(C)C1=NC(C(C)C)=C(CCCC=O)C(C=2C=CC(F)=CC=2)=C1CO MWMMMRLOZIXOQA-UHFFFAOYSA-N 0.000 description 1
- MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 1
- WIGIZIANZCJQQY-UHFFFAOYSA-N 4-ethyl-3-methyl-N-[2-[4-[[[(4-methylcyclohexyl)amino]-oxomethyl]sulfamoyl]phenyl]ethyl]-5-oxo-2H-pyrrole-1-carboxamide Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCC(C)CC2)C=C1 WIGIZIANZCJQQY-UHFFFAOYSA-N 0.000 description 1
- WWQQPHUHTAZWDH-UHFFFAOYSA-N 4-ethylbenzenethiol Chemical compound CCC1=CC=C(S)C=C1 WWQQPHUHTAZWDH-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 1
- WLHCBQAPPJAULW-UHFFFAOYSA-N 4-methylbenzenethiol Chemical compound CC1=CC=C(S)C=C1 WLHCBQAPPJAULW-UHFFFAOYSA-N 0.000 description 1
- AXBVSRMHOPMXBA-UHFFFAOYSA-N 4-nitrothiophenol Chemical compound [O-][N+](=O)C1=CC=C(S)C=C1 AXBVSRMHOPMXBA-UHFFFAOYSA-N 0.000 description 1
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 1
- APDUDRFJNCIWAG-UHFFFAOYSA-N 4-propan-2-ylbenzenethiol Chemical compound CC(C)C1=CC=C(S)C=C1 APDUDRFJNCIWAG-UHFFFAOYSA-N 0.000 description 1
- RRZOEIKXUHOANL-UHFFFAOYSA-N 5-ethoxycarbonyl-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridine-3-carboxylic acid Chemical compound CCOC(=O)C1=C(C(C)C)N=C(C(C)C)C(C(O)=O)=C1C1=CC=C(F)C=C1 RRZOEIKXUHOANL-UHFFFAOYSA-N 0.000 description 1
- RKWYTEQZGJNJNM-UHFFFAOYSA-N 5-o-ethyl 3-o-methyl 2-cyclopentyl-6-ethyl-4-(4-fluorophenyl)pyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C=2C=CC(F)=CC=2)C(C(=O)OCC)=C(CC)N=C1C1CCCC1 RKWYTEQZGJNJNM-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- PZLDFIXLOSUHCW-UHFFFAOYSA-N COC(=O)C(C=C)C1CCC(N)C1 Chemical compound COC(=O)C(C=C)C1CCC(N)C1 PZLDFIXLOSUHCW-UHFFFAOYSA-N 0.000 description 1
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229910021556 Chromium(III) chloride Inorganic materials 0.000 description 1
- 238000005821 Claisen rearrangement reaction Methods 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 102100027593 Cystatin-9 Human genes 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 208000001380 Diabetic Ketoacidosis Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- 101000725909 Homo sapiens Cystatin-9 Proteins 0.000 description 1
- 101000725906 Homo sapiens Cystatin-9-like Proteins 0.000 description 1
- 108010057186 Insulin Glargine Proteins 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- 206010023379 Ketoacidosis Diseases 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 101000725922 Mus musculus Cystatin-9 Proteins 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- BUIQRTDBPCHRIR-UHFFFAOYSA-L O[Cr](Cl)(=O)=O Chemical compound O[Cr](Cl)(=O)=O BUIQRTDBPCHRIR-UHFFFAOYSA-L 0.000 description 1
- 208000016222 Pancreatic disease Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102100040918 Pro-glucagon Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- UOLADDQJYFLUAC-UHFFFAOYSA-N [4-(3-bromophenyl)-2,6-dimethyl-5-(2-methylpropyl)pyridin-3-yl]methanol Chemical compound CC(C)CC1=C(C)N=C(C)C(CO)=C1C1=CC=CC(Br)=C1 UOLADDQJYFLUAC-UHFFFAOYSA-N 0.000 description 1
- UQQHTXWCCDFFTA-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-[(4-fluorophenyl)methyl]-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound C=1C=C(F)C=CC=1C1=C(CO)C(C(C)C)=NC(C(C)C)=C1CC1=CC=C(F)C=C1 UQQHTXWCCDFFTA-UHFFFAOYSA-N 0.000 description 1
- OBYNALDENJHJTL-UHFFFAOYSA-N [4-(4-fluorophenyl)-5-oct-1-enyl-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCCCCCC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 OBYNALDENJHJTL-UHFFFAOYSA-N 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- VCEBRCKKMSWMFN-UHFFFAOYSA-N [5-but-1-enyl-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridin-3-yl]methanol Chemical compound CCC=CC1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 VCEBRCKKMSWMFN-UHFFFAOYSA-N 0.000 description 1
- PZXYVYALFDSDBJ-UHFFFAOYSA-N [Br-].C(CCC)[PH2+]C1=CC=CC=C1 Chemical compound [Br-].C(CCC)[PH2+]C1=CC=CC=C1 PZXYVYALFDSDBJ-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 239000003288 aldose reductase inhibitor Substances 0.000 description 1
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 150000001356 alkyl thiols Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 150000003975 aryl alkyl amines Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 150000005347 biaryls Chemical group 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-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
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 229950001261 camiglibose Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 description 1
- 239000011636 chromium(III) chloride Substances 0.000 description 1
- 235000007831 chromium(III) chloride Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000003997 cyclic ketones Chemical class 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 238000006262 cycloaromatization reaction Methods 0.000 description 1
- WZYWSVSFFTZZPE-UHFFFAOYSA-M cyclopentyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C1CCCC1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WZYWSVSFFTZZPE-UHFFFAOYSA-M 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229960004597 dexfenfluramine Drugs 0.000 description 1
- 235000020805 dietary restrictions Nutrition 0.000 description 1
- XUNFXBODHIHPJX-UHFFFAOYSA-N diethyl 4-(4-fluorophenyl)-2,6-di(propan-2-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C(C)C)NC(C(C)C)=C(C(=O)OCC)C1C1=CC=C(F)C=C1 XUNFXBODHIHPJX-UHFFFAOYSA-N 0.000 description 1
- HLPUJCAGCALAKI-UHFFFAOYSA-N diethyl 4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=C(C(C)C)C(C(=O)OCC)=C1C1=CC=C(F)C=C1 HLPUJCAGCALAKI-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
- 229950010170 epalrestat Drugs 0.000 description 1
- CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- UDRCONFHWYGWFI-UHFFFAOYSA-N ethyl 3-oxopentanoate Chemical compound CCOC(=O)CC(=O)CC UDRCONFHWYGWFI-UHFFFAOYSA-N 0.000 description 1
- JHDIVQXLYLLVFY-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-5-(hydroxymethyl)-2,6-di(propan-2-yl)pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 JHDIVQXLYLLVFY-UHFFFAOYSA-N 0.000 description 1
- QOTMNZLKPASNPJ-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-5-formyl-6-methoxy-2-propan-2-ylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=C(OC)C(C=O)=C1C1=CC=C(F)C=C1 QOTMNZLKPASNPJ-UHFFFAOYSA-N 0.000 description 1
- IEYOSARNUPROQF-UHFFFAOYSA-N ethyl 5-[2-(1,3-benzoxazol-2-yl)ethenyl]-4-(4-fluorophenyl)-6-methoxy-2-propan-2-ylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=C(OC)C(C=CC=2OC3=CC=CC=C3N=2)=C1C1=CC=C(F)C=C1 IEYOSARNUPROQF-UHFFFAOYSA-N 0.000 description 1
- ADDIUXFOAOKWCG-UHFFFAOYSA-N ethyl 5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyridine-3-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=C(C(C)C)C(CO[Si](C)(C)C(C)(C)C)=C1C1=CC=C(F)C=C1 ADDIUXFOAOKWCG-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 150000004673 fluoride salts Chemical class 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000027119 gastric acid secretion Effects 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
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 229960004580 glibenclamide 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
- 125000005843 halogen group Chemical group 0.000 description 1
- WCZSOHSGMBVYFW-UHFFFAOYSA-M heptyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCC)C1=CC=CC=C1 WCZSOHSGMBVYFW-UHFFFAOYSA-M 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PWDFZWZPWFYFTC-UHFFFAOYSA-M hexyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCC)C1=CC=CC=C1 PWDFZWZPWFYFTC-UHFFFAOYSA-M 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 230000000871 hypocholesterolemic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 210000002660 insulin-secreting cell Anatomy 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 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
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
- DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
- PBMNTKWQPYMDHA-UHFFFAOYSA-N methyl 3-amino-3-(4-fluorophenyl)prop-2-enoate Chemical compound COC(=O)C=C(N)C1=CC=C(F)C=C1 PBMNTKWQPYMDHA-UHFFFAOYSA-N 0.000 description 1
- FDFDDQJLQHAQAN-UHFFFAOYSA-N methyl 4-(4-fluorophenyl)-5-(hydroxymethyl)-2,6-di(propan-2-yl)pyridine-3-carboxylate Chemical compound COC(=O)C1=C(C(C)C)N=C(C(C)C)C(CO)=C1C1=CC=C(F)C=C1 FDFDDQJLQHAQAN-UHFFFAOYSA-N 0.000 description 1
- HNNFDXWDCFCVDM-UHFFFAOYSA-N methyl 4-methyl-3-oxopentanoate Chemical compound COC(=O)CC(=O)C(C)C HNNFDXWDCFCVDM-UHFFFAOYSA-N 0.000 description 1
- QJQYPZZUKLQGGT-UHFFFAOYSA-N methyl hypobromite Chemical compound COBr QJQYPZZUKLQGGT-UHFFFAOYSA-N 0.000 description 1
- AZFQCTBZOPUVOW-UHFFFAOYSA-N methyl(triphenyl)phosphanium Chemical class C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 AZFQCTBZOPUVOW-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-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
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- SEXOVMIIVBKGGM-UHFFFAOYSA-N naphthalene-1-thiol Chemical compound C1=CC=C2C(S)=CC=CC2=C1 SEXOVMIIVBKGGM-UHFFFAOYSA-N 0.000 description 1
- 125000001326 naphthylalkyl group Chemical group 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 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 1
- 208000024691 pancreas disease Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 150000005359 phenylpyridines Chemical class 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- TZIRZGBAFTZREM-MKAGXXMWSA-N pramlintide Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)CSSC1)[C@@H](C)O)C(C)C)C1=CC=CC=C1 TZIRZGBAFTZREM-MKAGXXMWSA-N 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- GAPYKZAARZMMGP-UHFFFAOYSA-N pyridin-1-ium;acetate Chemical compound CC(O)=O.C1=CC=NC=C1 GAPYKZAARZMMGP-UHFFFAOYSA-N 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical class 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
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 239000012047 saturated solution 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
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- CRLYHSUSQLYCCZ-UHFFFAOYSA-M sodium;azanide;methyl(triphenyl)phosphanium;bromide Chemical compound [NH2-].[Na+].[Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 CRLYHSUSQLYCCZ-UHFFFAOYSA-M 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
- 229960003069 tolrestat Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- RPUZOJFXAPSSJD-UHFFFAOYSA-M triphenyl(3-phenylpropyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CCCC1=CC=CC=C1 RPUZOJFXAPSSJD-UHFFFAOYSA-M 0.000 description 1
- GGAUJFNZKFHHGA-UHFFFAOYSA-M triphenyl-[[3-(trifluoromethyl)phenyl]methyl]phosphanium;bromide Chemical compound [Br-].FC(F)(F)C1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 GGAUJFNZKFHHGA-UHFFFAOYSA-M 0.000 description 1
- NCPXQVVMIXIKTN-UHFFFAOYSA-N trisodium;phosphite Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])[O-] NCPXQVVMIXIKTN-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 230000003820 β-cell dysfunction Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
- C07D213/34—Sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US69011196A | 1996-07-31 | 1996-07-31 | |
PCT/US1997/013248 WO1998004528A2 (en) | 1996-07-31 | 1997-07-29 | Substituted pyridines and biphenyls as anti-hypercholesterinemic, anti-hyperlipoproteinemic and anti-hyperglycemic agents |
Publications (3)
Publication Number | Publication Date |
---|---|
NO990399D0 NO990399D0 (no) | 1999-01-28 |
NO990399L NO990399L (no) | 1999-03-29 |
NO314143B1 true NO314143B1 (no) | 2003-02-03 |
Family
ID=24771137
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19990399A NO314143B1 (no) | 1996-07-31 | 1999-01-28 | Substituerte pyridiner og bifenyler, fremgangsmåte for fremstilling, farmasöytiske produkter inneholdende disse samt anvendelse forfremstilling av farmasöytiske preparater |
Country Status (24)
Country | Link |
---|---|
US (1) | US6218431B1 (es) |
EP (1) | EP0934274A1 (es) |
JP (1) | JP2001512416A (es) |
KR (1) | KR20000029723A (es) |
CN (1) | CN1239474A (es) |
AR (2) | AR008789A1 (es) |
AU (1) | AU3897197A (es) |
BG (1) | BG103200A (es) |
BR (1) | BR9710637A (es) |
CA (1) | CA2262434A1 (es) |
CO (1) | CO4900061A1 (es) |
CZ (1) | CZ30899A3 (es) |
HR (1) | HRP970425A2 (es) |
HU (1) | HUP0100324A3 (es) |
ID (1) | ID19422A (es) |
IL (1) | IL128251A0 (es) |
NO (1) | NO314143B1 (es) |
NZ (1) | NZ333951A (es) |
PL (1) | PL333465A1 (es) |
RU (1) | RU2195443C2 (es) |
TR (3) | TR199902325T2 (es) |
TW (1) | TW520360B (es) |
WO (1) | WO1998004528A2 (es) |
ZA (1) | ZA976730B (es) |
Families Citing this family (147)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6613942B1 (en) | 1997-07-01 | 2003-09-02 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
WO1999041237A1 (en) * | 1998-02-13 | 1999-08-19 | G.D. Searle & Co. | Substituted pyridines useful for inhibiting cholesteryl ester transfer protein activity |
AU761267C (en) | 1998-09-09 | 2007-08-09 | Metabasis Therapeutics, Inc. | Novel heteroaromatic inhibitors of fructose 1,6-bisphosphatase |
US7919109B2 (en) | 1999-02-08 | 2011-04-05 | Intarcia Therapeutics, Inc. | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
US7258869B1 (en) | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
US6503949B1 (en) | 1999-05-17 | 2003-01-07 | Noro Nordisk A/S | Glucagon antagonists/inverse agonists |
DK1248604T4 (da) | 2000-01-21 | 2012-05-21 | Novartis Ag | Kombinationer indeholdende dipeptidylpeptidase-IV-inhibitorer og antidiabetiske midler |
US6562807B2 (en) | 2000-06-23 | 2003-05-13 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
SI1303490T1 (sl) * | 2000-07-14 | 2008-10-31 | Hoffmann La Roche | N-oksidi kot predzdravila NK 1 receptorskega antagonista 4-fenil-piridin derivatov |
US7115279B2 (en) | 2000-08-03 | 2006-10-03 | Curatolo William J | Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors |
EP1345890A1 (en) | 2000-11-17 | 2003-09-24 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
US6821960B2 (en) | 2000-11-17 | 2004-11-23 | Noyo Nordisk Pharmaceuticals, Inc. | Glucagon antagonists/inverse agonists |
US6706744B2 (en) | 2000-11-17 | 2004-03-16 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
WO2002094799A2 (en) * | 2001-05-22 | 2002-11-28 | Neurogen Corporation | Melanin concentrating hormone receptor ligands: substituted 1-benzyl-4-aryl piperazine analogues |
EP1935885A3 (en) * | 2001-05-22 | 2008-10-15 | Neurogen Corporation | Melanin concentrating hormone receptor ligands : substituted 1-benzyl-4-aryl piperazine analogues. |
CN1523979A (zh) | 2001-06-22 | 2004-08-25 | �Ʒ� | 非晶形药物吸附物的药物组合物 |
ES2333645T3 (es) | 2001-06-22 | 2010-02-25 | Bend Research, Inc. | Composiciones farmaceuticas de dispersiones de medicamentos y polimeros neutros. |
UA74912C2 (en) | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
US6740776B2 (en) | 2001-07-16 | 2004-05-25 | Novartis Ag | Air oxidation of an aromatic aldehyde to an aromatic acid |
US6881746B2 (en) | 2001-12-03 | 2005-04-19 | Novo Nordick A/S | Glucagon antagonists/inverse agonists |
US7094801B2 (en) | 2001-12-19 | 2006-08-22 | Atherogenics, Inc. | Chalcone derivatives and their use to treat diseases |
AU2002361811A1 (en) | 2001-12-19 | 2003-07-09 | Atherogenics, Inc. | 1,3-bis-(substituted-phenyl)-2-propyn-1-ones and their use to treat disorders |
AR038375A1 (es) | 2002-02-01 | 2005-01-12 | Pfizer Prod Inc | Composiciones farmaceuticas de inhibidores de la proteina de transferencia de esteres de colesterilo |
BR0307344A (pt) | 2002-02-01 | 2004-12-14 | Pfizer Prod Inc | Composições farmacêuticas de dispersões amorfas de fármacos e materiais formadores de microfase lipofìlica |
KR100634195B1 (ko) | 2002-08-30 | 2006-10-16 | 니뽄 다바코 산교 가부시키가이샤 | 디벤질아민 화합물 및 그 의약 용도 |
US7196106B2 (en) | 2002-11-05 | 2007-03-27 | Merck & Co., Inc | Cyanothiophene derivatives, compositions containing such compounds and methods of use |
US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
EP1961419B1 (en) | 2002-12-20 | 2010-03-24 | Pfizer Products Inc. | Dosage forms comprising a CETP inhibitor and an HMG-CoA reductase inhibitor |
US20040209928A1 (en) * | 2002-12-30 | 2004-10-21 | Ravi Kurukulasuriya | Glucagon receptor antagonists/inverse agonists |
JP2006516572A (ja) | 2003-01-14 | 2006-07-06 | アリーナ ファーマシューティカルズ, インコーポレイテッド | 代謝モジュレーターとしての1,2,3−トリ置換アリール誘導体および1,2,3−トリ置換ヘテロアリール誘導体ならびにこれらの誘導体に関連する糖尿病および高血糖のような障害の予防および処置 |
WO2004069158A2 (en) | 2003-01-27 | 2004-08-19 | Merck & Co., Inc. | Substituted pyrazoles, compositions containing such compounds and methods of use |
BRPI0407620A (pt) * | 2003-02-24 | 2006-02-21 | Arena Pharm Inc | derivados de arila e heteroarila substituìdos como moduladores do metabolismo da glicose e a profilaxia e tratamento de seus distúrbios |
CA2519432C (en) | 2003-03-17 | 2009-06-09 | Japan Tobacco Inc. | Pharmaceutical compositions comprising cetp inhibitors and a water-insoluble concentration-enhancing additive for the treatment of cardiovascular disease |
WO2004082675A1 (en) | 2003-03-17 | 2004-09-30 | Japan Tobacco Inc. | Method for increasing the oral bioavailability of s-[2- ([[1- (2-ethylbutyl) cyclohexyl] carbonyl] amino) phenyl] 2-methylpropanethioate |
WO2004103310A2 (en) * | 2003-05-20 | 2004-12-02 | New England Medical Center Hospitals, Inc. | Methods and compositions for the treatment of metabolic disorders |
AR045047A1 (es) * | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
CL2004001884A1 (es) | 2003-08-04 | 2005-06-03 | Pfizer Prod Inc | Procedimiento de secado por pulverizacion para la formacion de dispersiones solidas amorfas de un farmaco y polimeros. |
KR20070087197A (ko) | 2003-09-26 | 2007-08-27 | 니뽄 다바코 산교 가부시키가이샤 | 잔여 리포프로테인 생산 저해 방법 |
PE20050444A1 (es) * | 2003-10-31 | 2005-08-09 | Takeda Pharmaceutical | Compuestos de piridina como inhibidores de la peptidasa |
AU2004312001B2 (en) * | 2003-12-19 | 2009-08-27 | Merck & Co., Inc. | Cyclic guanidines, compositions containing such compounds and methods of use |
CA2548374C (en) | 2003-12-23 | 2014-05-27 | Astex Therapeutics Limited | Pyrazole derivatives as protein kinase modulators |
MY143599A (en) * | 2004-06-04 | 2011-06-15 | Merck Sharp & Dohme | Pyrazole derivatives, compositions containing such compounds and methods of use |
EA011671B1 (ru) * | 2004-06-04 | 2009-04-28 | Арена Фармасьютикалз, Инк. | Замещенные производные арила и гетероарила в качестве модуляторов метаболизма и для профилактики и лечения связанных с ним расстройств |
ATE449604T1 (de) * | 2004-07-07 | 2009-12-15 | Merck & Co Inc | Pyrazolamid-derivate, diese verbindungen enthaltende zusammensetzungen und anwendungsverfahren |
EP1773330B1 (en) * | 2004-07-22 | 2010-05-26 | Merck Sharp & Dohme Corp. | Substituted pyrazoles, compositions containing such compounds and methods of use |
DK1848430T3 (da) | 2004-12-31 | 2017-11-06 | Dr Reddys Laboratories Ltd | Nye benzylamin-derivativer som cetp-inhibitors |
US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
CN101141964B (zh) | 2005-01-10 | 2013-06-05 | 科尔泰多投资公司 | 治疗糖尿病、代谢综合症和其它病症的组合物及方法 |
DOP2006000010A (es) | 2005-01-10 | 2006-07-31 | Arena Pharm Inc | Procedimiento para preparar eteres aromáticos |
MY148521A (en) * | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
EP1844078B1 (en) | 2005-02-03 | 2016-09-28 | Bend Research, Inc | Pharmaceutical compositions with enhanced performance |
WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
JP2008533200A (ja) | 2005-03-21 | 2008-08-21 | メルク エンド カムパニー インコーポレーテッド | 置換アリールおよびヘテロアリール誘導体、かかる化合物を含有する組成物および使用法 |
US7803951B2 (en) | 2005-03-30 | 2010-09-28 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
WO2006136821A1 (en) | 2005-06-22 | 2006-12-28 | Astex Therapeutics Limited | Pharmaceutical compounds |
US8541461B2 (en) | 2005-06-23 | 2013-09-24 | Astex Therapeutics Limited | Pharmaceutical combinations comprising pyrazole derivatives as protein kinase modulators |
WO2007015999A2 (en) | 2005-07-26 | 2007-02-08 | Merck & Co., Inc. | Process for synthesizing a substituted pyrazole |
MY159522A (en) | 2005-09-14 | 2017-01-13 | Takeda Pharmaceuticals Co | Administration of dipeptidyl peptidase inhibitors |
JP2009508861A (ja) * | 2005-09-16 | 2009-03-05 | アリーナ ファーマシューティカルズ, インコーポレイテッド | 代謝の調節因子および代謝に関連する障害の処置 |
TW200745031A (en) | 2005-10-13 | 2007-12-16 | Merck & Co Inc | Acyl indoles, compositions containing such compounds and methods of use |
PT1951658E (pt) * | 2005-11-17 | 2012-11-12 | Lilly Co Eli | Antagonistas do receptor do glucagon, preparação e utilizações terapêuticas |
EP1801098A1 (en) | 2005-12-16 | 2007-06-27 | Merck Sante | 2-Adamantylurea derivatives as selective 11B-HSD1 inhibitors |
AU2006330072B2 (en) * | 2005-12-28 | 2012-08-02 | Dr. Reddy's Laboratories Ltd. | Selective benzylamine derivatives and their utility as cholesterol ester-transfer protein inhibitors |
DE102006012548A1 (de) | 2006-03-18 | 2007-09-20 | Bayer Healthcare Ag | Substituierte Chromanol-Derivate und ihre Verwendung |
EP2001472A2 (en) | 2006-03-23 | 2008-12-17 | Merck and Co., Inc. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
WO2007136577A2 (en) | 2006-05-16 | 2007-11-29 | Merck & Co., Inc. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
CA2651855C (en) | 2006-05-30 | 2011-08-02 | Intarcia Therapeutics, Inc. | Two-piece, internal-channel osmotic delivery system flow modulator |
TW200811140A (en) * | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
TW200811147A (en) * | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
EP2359808B1 (en) | 2006-08-09 | 2013-05-22 | Intarcia Therapeutics, Inc | Osmotic delivery systems and piston assemblies |
MEP8509A (en) | 2006-09-07 | 2011-12-20 | Combination treatment for diabetes mellitus | |
BRPI0719835A2 (pt) | 2006-10-02 | 2014-05-06 | Cortendo Invest Ab | Enantiômero de cetoconazol em humanos |
TW200821284A (en) | 2006-10-03 | 2008-05-16 | Merck & Co Inc | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
EP1935420A1 (en) | 2006-12-21 | 2008-06-25 | Merck Sante | 2-Adamantyl-butyramide derivatives as selective 11beta-HSD1 inhibitors |
GB0704932D0 (en) | 2007-03-14 | 2007-04-25 | Astex Therapeutics Ltd | Pharmaceutical compounds |
ES2402172T3 (es) | 2007-04-23 | 2013-04-29 | Intarcia Therapeutics, Inc | Formulación en suspensión de péptidos insulinotrópicos y usos de los mismos |
US8436028B2 (en) * | 2007-06-20 | 2013-05-07 | Merck Sharp & Dohme Corp | CETP inhibitors derived from benzoxazole arylamides |
EP2170058B1 (en) * | 2007-06-20 | 2013-07-03 | Merck Sharp & Dohme Corp. | Cetp inhibitors derived from benzoxazole arylamides |
CA2689525A1 (en) * | 2007-06-20 | 2008-12-24 | Merck Sharp & Dohme Corp. | Cetp inhibitors derived from benzoxazole arylamides |
EP2240155B1 (en) | 2008-02-13 | 2012-06-06 | Intarcia Therapeutics, Inc | Devices, formulations, and methods for delivery of multiple beneficial agents |
EP2110374A1 (en) | 2008-04-18 | 2009-10-21 | Merck Sante | Benzofurane, benzothiophene, benzothiazol derivatives as FXR modulators |
JO2870B1 (en) | 2008-11-13 | 2015-03-15 | ميرك شارب اند دوهم كورب | Amino Tetra Hydro Pirans as Inhibitors of Peptide Dipeptide IV for the Treatment or Prevention of Diabetes |
AU2009314200B2 (en) | 2008-11-17 | 2011-11-17 | Merck Sharp & Dohme Corp. | Substituted bicyclic amines for the treatment of diabetes |
CA2768577A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
WO2011011506A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
WO2011019538A1 (en) | 2009-08-13 | 2011-02-17 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment |
CN102595897A (zh) | 2009-09-02 | 2012-07-18 | 默沙东公司 | 作为用于糖尿病的治疗或预防的二肽基肽酶-iv抑制剂的氨基四氢吡喃 |
EP3323423B1 (en) | 2009-09-28 | 2020-06-17 | Intarcia Therapeutics, Inc | Rapid establishment and/or termination of substantial steady-state drug delivery |
WO2011041293A1 (en) | 2009-09-30 | 2011-04-07 | Takeda Pharmaceutical Company Limited | Pyrazolo [1, 5-a] pyrimidine derivatives as apoptosis signal-regulating kinase 1 inhibitors |
EP2501685A1 (en) | 2009-11-16 | 2012-09-26 | Mellitech | [1,5]-diazocin derivatives |
CA2784799C (en) | 2009-12-30 | 2014-06-10 | Shanghai Fochon Pharmaceutical Co Ltd | Certain dipeptidyl peptidase inhibtors |
EP2528894A1 (en) | 2010-01-27 | 2012-12-05 | Arena Pharmaceuticals, Inc. | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
RS53176B (en) | 2010-02-03 | 2014-06-30 | Takeda Pharmaceutical Company Limited | KINASE INHIBITORS 1 REGULATING SIGNALS IN APOPTOSIS |
US8853212B2 (en) | 2010-02-22 | 2014-10-07 | Merck Sharp & Dohme Corp | Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes |
US8980929B2 (en) | 2010-05-21 | 2015-03-17 | Merck Sharp & Dohme Corp. | Substituted seven-membered heterocyclic compounds as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes |
WO2012024183A1 (en) | 2010-08-18 | 2012-02-23 | Merck Sharp & Dohme Corp. | Spiroxazolidinone compounds |
CA2812061A1 (en) | 2010-09-22 | 2012-03-29 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
EP2630136A1 (en) * | 2010-10-21 | 2013-08-28 | Universität des Saarlandes | Selective cyp11b1 inhibitors for the treatment of cortisol dependent diseases |
WO2012085745A1 (en) | 2010-12-23 | 2012-06-28 | Pfizer Inc. | Glucagon receptor modulators |
EA023517B1 (ru) | 2011-02-08 | 2016-06-30 | Пфайзер Инк. | Модуляторы глюкагонового рецептора |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
WO2012138845A1 (en) | 2011-04-08 | 2012-10-11 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment |
US20140088124A1 (en) | 2011-06-02 | 2014-03-27 | Robert J. DeVita | Imidazole derivatives |
AU2012271009A1 (en) | 2011-06-16 | 2013-11-14 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds, and methods of treatment |
CN103732578B (zh) | 2011-07-22 | 2015-08-12 | 辉瑞大药厂 | 喹啉基胰高血糖素受体调节剂 |
JP5964965B2 (ja) | 2011-08-18 | 2016-08-03 | ドクター レディズ ラボラトリーズ リミテッド | コレステリルエステル転送タンパク質(cetp)インヒビターとしての置換複素環式アミン化合物 |
CA2850022C (en) | 2011-09-27 | 2018-05-01 | Dr. Reddy's Laboratories, Ltd. | 5 - benzylaminomethyl - 6 - aminopyrazolo [3,4-b] pyridine derivatives as cholesteryl ester-transfer protein (cetp) inhibitors useful for the treatment of atherosclerosis |
US9422266B2 (en) | 2011-09-30 | 2016-08-23 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment |
US9018200B2 (en) | 2011-10-24 | 2015-04-28 | Merck Sharp & Dohme Corp. | Substituted piperidinyl compounds useful as GPR119 agonists |
WO2013068328A1 (en) | 2011-11-07 | 2013-05-16 | Intervet International B.V. | Bicyclo [2.2.2] octan-1-ylcarboxylic acid compounds as dgat-1 inhibitors |
WO2013068439A1 (en) | 2011-11-09 | 2013-05-16 | Intervet International B.V. | 4-amino-5-oxo-7,8-dihydropyrimido[5, 4 -f] [1, 4] oxazepine compounds as dgat1 inhibitors |
AU2012339870B2 (en) | 2011-11-15 | 2017-06-29 | Merck Sharp & Dohme Corp. | Substituted cyclopropyl compounds useful as GPR119 agonists |
EP2814485A4 (en) | 2012-02-17 | 2015-08-26 | Merck Sharp & Dohme | DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES |
EP2838906A4 (en) | 2012-04-16 | 2015-07-15 | Kaneq Pharma Inc | FUSED AROMATIC PHOSPHONATE DERIVATIVES AS PRECURSORS OF PTP-1B INHIBITORS |
EP2874622A4 (en) | 2012-07-23 | 2015-12-30 | Merck Sharp & Dohme | TREATMENT OF DIABETES WITH DIPEPTIDYLPEPTIDASE IV INHIBITORS |
CA2873295A1 (en) * | 2012-08-24 | 2014-02-27 | F. Hoffmann-La Roche Ag | New bicyclicpyridine derivatives |
US9649294B2 (en) | 2013-11-04 | 2017-05-16 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
EA201690938A1 (ru) | 2013-11-05 | 2016-11-30 | Бен-Гурион Юниверсити Оф Дзе Негев Рисерч Энд Дивелопмент Оторити | Соединения для лечения диабета и осложнений, возникающих из-за этого заболевания |
US10065945B2 (en) | 2014-01-24 | 2018-09-04 | Merck Sharp & Dohme Corp. | Isoquinoline derivatives as MGAT2 inhibitors |
CA2945681A1 (en) | 2014-04-17 | 2015-10-22 | Merck Sharp & Dohme Corp. | Sitagliptin tannate complex |
US9988374B2 (en) | 2014-08-11 | 2018-06-05 | Angion Biomedica Corp. | Cytochrome P450 inhibitors and uses thereof |
US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
TW201625672A (zh) | 2014-10-24 | 2016-07-16 | 默沙東藥廠 | 升糖素及glp-1受體之共促效劑 |
AU2015374231B2 (en) | 2014-12-31 | 2020-07-23 | Angion Biomedica Corp. | Methods and agents for treating disease |
EP3242666A1 (en) | 2015-01-06 | 2017-11-15 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
AU2016270984B2 (en) | 2015-06-03 | 2021-02-25 | Intarcia Therapeutics, Inc. | Implant placement and removal systems |
CN108349891B (zh) | 2015-06-22 | 2022-04-05 | 艾尼纳制药公司 | 用于s1p1受体相关病症的化合物的结晶l-精氨酸盐 |
WO2017062334A1 (en) | 2015-10-05 | 2017-04-13 | Merck Sharp & Dohme Corp. | Antibody peptide conjugates that have agonist activity at both the glucagon and glucagon-like peptide 1 receptors |
KR20240037175A (ko) | 2016-05-16 | 2024-03-21 | 인타르시아 세라퓨틱스 인코포레이티드 | 글루카곤-수용체 선택적 폴리펩티드 및 이들의 이용 방법 |
USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
NZ750414A (en) * | 2016-07-05 | 2023-02-24 | Guangzhou Maxinovel Pharmaceuticals Co Ltd | Aromatic acetylene or aromatic ethylene compound, intermediate, preparation method, pharmaceutical composition and use thereof |
EP3496715B1 (en) | 2016-08-15 | 2021-11-03 | Merck Sharp & Dohme Corp. | Compounds useful for altering the levels of bile acids for the treatment of diabetes and cardiometabolic disease |
WO2018034918A1 (en) | 2016-08-15 | 2018-02-22 | Merck Sharp & Dohme Corp. | Compounds useful for altering the levels of bile acids for the treatment of diabetes and cardiometabolic disease |
IL307966A (en) | 2017-01-03 | 2023-12-01 | Intarcia Therapeutics Inc | Methods involving continuous administration of a GLP-1 receptor agonist and co-administration of a drug |
US11534424B2 (en) | 2017-02-16 | 2022-12-27 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
AU2018398887B2 (en) | 2017-12-29 | 2024-03-14 | Guangzhou Maxinovel Pharmaceuticals Co., Ltd | Aromatic vinyl or aromatic ethyl derivative, preparation method therefor, intermediate, pharmaceutical composition, and application |
CN108558847A (zh) * | 2018-05-31 | 2018-09-21 | 马文军 | 一种酯类衍生物及其在防治心脑血管疾病中的应用 |
CN108484573B (zh) * | 2018-06-26 | 2019-10-29 | 王先化 | 一种吲哚类衍生物及其在糖尿病中的应用 |
CN110833550B (zh) * | 2018-08-15 | 2023-03-24 | 广西梧州制药(集团)股份有限公司 | 吡唑并嘧啶衍生物在治疗急性胰腺炎致肝损伤的用途 |
EP3863634A1 (en) | 2018-10-12 | 2021-08-18 | Strongbridge Dublin Limited | Levoketoconazole for treatment of congenital adrenal hyperplasia and primary aldosteronism |
US20220177465A1 (en) | 2019-04-04 | 2022-06-09 | Merck Sharp & Dohme Corp. | Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes |
EP3842061A1 (en) | 2019-12-23 | 2021-06-30 | Merck Sharp & Dohme Corp. | Stapled triazole co-agonists of the glucagon and glp-1 receptors |
EP3842060A1 (en) | 2019-12-23 | 2021-06-30 | Merck Sharp & Dohme Corp. | Stapled lactam co-agonists of the glucagon and glp-1 receptors |
EP3842449A1 (en) | 2019-12-23 | 2021-06-30 | Merck Sharp & Dohme Corp. | Stapled olefin co-agonists of the glucagon and glp-1 receptors |
CN116077492B (zh) * | 2023-02-07 | 2024-03-15 | 华中科技大学协和深圳医院 | 胰高血糖素受体拮抗剂-3用于制备抗革兰氏阳性菌感染药物中的应用 |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5169857A (en) | 1988-01-20 | 1992-12-08 | Bayer Aktiengesellschaft | 7-(polysubstituted pyridyl)-hept-6-endates useful for treating hyperproteinaemia, lipoproteinaemia or arteriosclerosis |
ES8506627A1 (es) | 1983-08-11 | 1985-08-01 | Monsanto Co | Un procedimiento para preparar derivados de piridina sustituidos en las posiciones 2 y 6 |
US4698093A (en) | 1984-11-06 | 1987-10-06 | Monsanto Company | Herbicidal (2 or 6)-fluoroalkyl-4-amino pyridine derivatives |
US4655816A (en) | 1984-11-06 | 1987-04-07 | Monsanto Company | Herbicidal 2-trifluoromethyl 3-pyridine carboxylic acid derivatives |
JPH0778059B2 (ja) | 1986-03-11 | 1995-08-23 | ダイセル化学工業株式会社 | ピロン−3−カルボキサミド誘導体及び除草剤 |
NO881411L (no) | 1987-04-14 | 1988-10-17 | Bayer Ag | Substituerte pyrroler. |
DE3817808A1 (de) | 1987-07-21 | 1989-02-02 | Bayer Ag | Verfahren zur herstellung von 2-substituierten pyrrolen |
US4906624A (en) | 1987-09-08 | 1990-03-06 | Warner-Lambert Company | 6-(((Substituted)pyridin-3-yl)alkyl)-and alkenyl)-tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis |
US4997837A (en) | 1987-09-08 | 1991-03-05 | Warner-Lambert Company | 6-(((substituted)pyridin-3-yl)alkyl)-and alkenyl)-tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis |
NO177005C (no) * | 1988-01-20 | 1995-07-05 | Bayer Ag | Analogifremgangsmåte for fremstilling av substituerte pyridiner, samt mellomprodukter til bruk ved fremstillingen |
NO890046L (no) * | 1988-01-20 | 1989-07-21 | Bayer Ag | Disubstituerte pyridiner. |
DD283612A5 (de) | 1988-02-25 | 1990-10-17 | Bayer Aktiengesellschaft,De | Verfahren zur herstellung von substituierten imidazolinonen und imidazolinthionen |
NO890521L (no) | 1988-02-25 | 1989-08-28 | Bayer Ag | Substituerte pyrimidiner. |
NO890522L (no) | 1988-02-25 | 1989-08-28 | Bayer Ag | Substituerte imidazolinoner og imidazolinthioner. |
NO890988L (no) | 1988-03-24 | 1989-09-25 | Bayer Ag | Disubstituerte pyrroler. |
EP0339342A1 (de) | 1988-04-23 | 1989-11-02 | Bayer Ag | N-Substituierte N-Amino-pyrrole |
EP0352575A3 (de) | 1988-07-28 | 1991-08-21 | Bayer Ag | Substituierte anellierte Pyrrole |
US5032602A (en) | 1988-12-14 | 1991-07-16 | Bayer Aktiengesellschaft | Inhibiting HMG-CoA reductase with novel substituted 2-pyridones and pyrid-2-thiones |
US5164506A (en) | 1988-12-14 | 1992-11-17 | Bayer Aktiengesellschaft | Substituted 2-pyridones and pyrid-2-thiones compounds |
AU618158B2 (en) | 1989-01-07 | 1991-12-12 | Bayer Aktiengesellschaft | New substituted pyrido(2,3-d)pyrimidines |
DE3905908A1 (de) | 1989-02-25 | 1990-09-06 | Bayer Ag | Substituierte chinoline, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln |
DE3909378A1 (de) | 1989-03-22 | 1990-09-27 | Bayer Ag | Substituierte biphenyle |
DE3911064A1 (de) | 1989-04-06 | 1990-10-11 | Bayer Ag | Substituierte 1,8-naphthyridine |
US5145959A (en) | 1989-07-18 | 1992-09-08 | Bayer Aktiengesellschaft | Substituted pyrido (2,3-d) pyrimidines as intermediates |
US5183897A (en) | 1989-08-03 | 1993-02-02 | Bayer Aktiengesellschaft | Certain intermediate imino-substituted pyridines |
US5072023A (en) | 1990-02-15 | 1991-12-10 | E. R. Squibb & Sons, Inc. | Process for preparing highly substituted phenyls |
ZA911046B (en) * | 1990-02-26 | 1992-10-28 | Squibb & Sons Inc | Quinoline and pyridine anchors for hmg-coa reductase inhibitors |
DE4022414A1 (de) | 1990-07-13 | 1992-01-16 | Bayer Ag | Substituierte pyrrolo-pyridine |
DE4023308A1 (de) | 1990-07-21 | 1992-01-23 | Bayer Ag | Substituierte pyrido-oxazine |
DE4244029A1 (de) * | 1992-12-24 | 1994-06-30 | Bayer Ag | Neue substituierte Pyridine |
EP0742208A1 (en) * | 1995-05-05 | 1996-11-13 | Grelan Pharmaceutical Co., Ltd. | 2-Ureido-benzamide derivatives |
DE19610932A1 (de) * | 1996-03-20 | 1997-09-25 | Bayer Ag | 2-Aryl-substituierte Pyridine |
-
1997
- 1997-07-28 AR ARP970103411A patent/AR008789A1/es unknown
- 1997-07-29 EP EP97936259A patent/EP0934274A1/en not_active Withdrawn
- 1997-07-29 CZ CZ99308A patent/CZ30899A3/cs unknown
- 1997-07-29 CN CN97198258A patent/CN1239474A/zh active Pending
- 1997-07-29 PL PL97333465A patent/PL333465A1/xx unknown
- 1997-07-29 HU HU0100324A patent/HUP0100324A3/hu unknown
- 1997-07-29 JP JP50906898A patent/JP2001512416A/ja not_active Ceased
- 1997-07-29 CO CO97043316A patent/CO4900061A1/es unknown
- 1997-07-29 IL IL12825197A patent/IL128251A0/xx unknown
- 1997-07-29 ZA ZA9706730A patent/ZA976730B/xx unknown
- 1997-07-29 NZ NZ333951A patent/NZ333951A/xx unknown
- 1997-07-29 WO PCT/US1997/013248 patent/WO1998004528A2/en not_active Application Discontinuation
- 1997-07-29 BR BR9710637-2A patent/BR9710637A/pt not_active IP Right Cessation
- 1997-07-29 TR TR1999/02325T patent/TR199902325T2/xx unknown
- 1997-07-29 TW TW086110851A patent/TW520360B/zh not_active IP Right Cessation
- 1997-07-29 AU AU38971/97A patent/AU3897197A/en not_active Abandoned
- 1997-07-29 HR HR08/690,111A patent/HRP970425A2/hr not_active Application Discontinuation
- 1997-07-29 TR TR1999/00163T patent/TR199900163T2/xx unknown
- 1997-07-29 KR KR1019997000826A patent/KR20000029723A/ko not_active Application Discontinuation
- 1997-07-29 TR TR1999/02326T patent/TR199902326T2/xx unknown
- 1997-07-29 RU RU99104527/04A patent/RU2195443C2/ru not_active IP Right Cessation
- 1997-07-29 CA CA002262434A patent/CA2262434A1/en not_active Abandoned
- 1997-07-31 US US08/904,119 patent/US6218431B1/en not_active Expired - Fee Related
- 1997-07-31 ID IDP972662A patent/ID19422A/id unknown
-
1999
- 1999-01-28 NO NO19990399A patent/NO314143B1/no not_active IP Right Cessation
- 1999-02-23 BG BG103200A patent/BG103200A/xx unknown
-
2002
- 2002-11-11 AR ARP020104321A patent/AR037300A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
CO4900061A1 (es) | 2000-03-27 |
ID19422A (id) | 1998-07-09 |
TR199902326T2 (xx) | 2000-05-22 |
BR9710637A (pt) | 2000-10-31 |
BG103200A (en) | 1999-11-30 |
CZ30899A3 (cs) | 1999-05-12 |
WO1998004528A2 (en) | 1998-02-05 |
TW520360B (en) | 2003-02-11 |
NO990399L (no) | 1999-03-29 |
HUP0100324A2 (hu) | 2001-05-28 |
AU3897197A (en) | 1998-02-20 |
NZ333951A (en) | 2000-09-29 |
TR199902325T2 (xx) | 2000-02-21 |
WO1998004528A3 (en) | 1999-11-11 |
CN1239474A (zh) | 1999-12-22 |
AR008789A1 (es) | 2000-02-23 |
TR199900163T2 (xx) | 1999-04-21 |
HRP970425A2 (en) | 1998-08-31 |
CA2262434A1 (en) | 1998-02-05 |
PL333465A1 (en) | 1999-12-20 |
ZA976730B (en) | 1999-07-29 |
US6218431B1 (en) | 2001-04-17 |
IL128251A0 (en) | 1999-11-30 |
NO990399D0 (no) | 1999-01-28 |
EP0934274A1 (en) | 1999-08-11 |
RU2195443C2 (ru) | 2002-12-27 |
KR20000029723A (ko) | 2000-05-25 |
HUP0100324A3 (en) | 2001-06-28 |
JP2001512416A (ja) | 2001-08-21 |
AR037300A2 (es) | 2004-11-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO314143B1 (no) | Substituerte pyridiner og bifenyler, fremgangsmåte for fremstilling, farmasöytiske produkter inneholdende disse samt anvendelse forfremstilling av farmasöytiske preparater | |
EP3806955B9 (en) | Glp-1 receptor agonists and uses thereof | |
JP3816922B2 (ja) | Ppar活性を調節する化合物、及び該化合物の製造方法 | |
DE69532808T2 (de) | Tri-substituierte phenyl-derivate verwendbar als pde iv hemmer | |
CZ143989A3 (cs) | Thiazolidindionové deriváty a způsob jejich přípravy | |
SK279037B6 (sk) | Deriváty benzopyránu, medziprodukty pre ich výrobu | |
EP1507763A1 (de) | Tetrahydroisochinolin-derivate | |
CZ287168B6 (en) | Process for preparing 13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2 esters and intermediates for this preparation process | |
NO312100B1 (no) | Nytt tiazolidindion-2-derivat, fremgangsmåter for dets fremstilling, mellomproduktforbindelser, samt farmasöytiskepreparater som inneholder det | |
KR100423188B1 (ko) | 1,4-디하이드로피리딘 화합물의 제조방법 | |
FR2566404A1 (fr) | Nouveaux derives de la 1,4-dihydropyridine, leurs sels, procede pour les preparer, et compositions pharmaceutiques les contenant | |
DE19835324A1 (de) | Cyclopentabenzofuran-Derivate und ihre Verwendung | |
JPH021478A (ja) | 二置換ピリジン類 | |
DE2408476A1 (de) | Tetrahydropyridin- und piperidinderivate und verfahren zu ihrer herstellung | |
JP2632877B2 (ja) | 置換1h−イミダゾール化合物 | |
DK158517B (da) | 1-alkylsubstituerede 1,4-dihydropyridinlactoner og deres anvendelse i laegemidler | |
HU211554A9 (en) | Circulation-active dibenzo/1,5/dioxocin-5-ones | |
JP2007519640A (ja) | 非ヌクレオシド逆転写酵素インヒビター | |
CZ379197A3 (cs) | 4,4-(disubstituované)cyklohexan-l-olové monomery a odvozené sloučeniny, farmaceutický prostředek a použití | |
IE59450B1 (en) | Hydroxyacetic acid derivatives for the treatment of diabetic complications | |
HUT61997A (en) | Process for producing benzopyran derivatives, as well as antihypertensive and vasodilator pharmaceutical compositions comprising such compounds | |
US5190971A (en) | Substituted dibenz-oxa-thiocinones, -12-oxides and -12,12-dioxides, a process for their preparation and their use in medicaments | |
JPS61293972A (ja) | 1,4−ジヒドロピリジンスルホン誘導体およびその製法 | |
AT340921B (de) | Verfahren zur herstellung von neuen tetrahydropyridin- und piperidinderivaten und ihren saureadditionssalzen | |
FR2586417A1 (fr) | Composes heterocycliques, leur preparation et composition pharmaceutique |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |