CA2490109A1 - Ring-substituted diphenyl azetidinones, method for the production thereof, medicaments containing said compounds, and use thereof - Google Patents

Info

Publication number

CA2490109A1

CA2490109A1 CA002490109A CA2490109A CA2490109A1 CA 2490109 A1 CA2490109 A1 CA 2490109A1 CA 002490109 A CA002490109 A CA 002490109A CA 2490109 A CA2490109 A CA 2490109A CA 2490109 A1 CA2490109 A1 CA 2490109A1

Authority

CA

Canada

Prior art keywords

alkyl

phenyl

cooh

radical

agonists

Prior art date

2002-06-19

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 134
• 239000003814 drug Substances 0.000 title claims abstract description 14
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 5
• 238000000034 method Methods 0.000 title abstract description 8
• VDOXIAUNJCHYRC-UHFFFAOYSA-N 1,3-diphenylazetidin-2-one Chemical class O=C1C(C=2C=CC=CC=2)CN1C1=CC=CC=C1 VDOXIAUNJCHYRC-UHFFFAOYSA-N 0.000 title abstract description 3
• 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 143
• 229910052731 fluorine Inorganic materials 0.000 claims description 56
• -1 (C1-C6)-alkyl-phenyl Chemical group 0.000 claims description 50
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
• 239000000556 agonist Substances 0.000 claims description 35
• 239000000203 mixture Substances 0.000 claims description 34
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
• 229910052739 hydrogen Inorganic materials 0.000 claims description 28
• 125000004432 carbon atom Chemical group C* 0.000 claims description 24
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 20
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 19
• 150000003839 salts Chemical class 0.000 claims description 16
• 235000000346 sugar Nutrition 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 12
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 239000003112 inhibitor Substances 0.000 claims description 12
• 125000002015 acyclic group Chemical group 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 10
• 150000001413 amino acids Chemical class 0.000 claims description 10
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 10
• 239000011737 fluorine Substances 0.000 claims description 10
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
• 239000005557 antagonist Substances 0.000 claims description 8
• 102000004877 Insulin Human genes 0.000 claims description 7
• 108090001061 Insulin Proteins 0.000 claims description 7
• 229910006069 SO3H Inorganic materials 0.000 claims description 7
• 229940100389 Sulfonylurea Drugs 0.000 claims description 6
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 6
• 102000015636 Oligopeptides Human genes 0.000 claims description 5
• 108010038807 Oligopeptides Proteins 0.000 claims description 5
• 125000000539 amino acid group Chemical group 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 150000002337 glycosamines Chemical class 0.000 claims description 5
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 4
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 4
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 4
• 239000003613 bile acid Substances 0.000 claims description 4
• 230000001419 dependent effect Effects 0.000 claims description 4
• 239000000122 growth hormone Substances 0.000 claims description 4
• 230000037356 lipid metabolism Effects 0.000 claims description 4
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 4
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 3
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
• 102000018997 Growth Hormone Human genes 0.000 claims description 3
• 108010051696 Growth Hormone Proteins 0.000 claims description 3
• 102000016267 Leptin Human genes 0.000 claims description 3
• 108010092277 Leptin Proteins 0.000 claims description 3
• 102000004257 Potassium Channel Human genes 0.000 claims description 3
• 229940123464 Thiazolidinedione Drugs 0.000 claims description 3
• 238000010521 absorption reaction Methods 0.000 claims description 3
• 230000003178 anti-diabetic effect Effects 0.000 claims description 3
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims description 3
• 230000001906 cholesterol absorption Effects 0.000 claims description 3
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 claims description 3
• 229940039781 leptin Drugs 0.000 claims description 3
• 229950004994 meglitinide Drugs 0.000 claims description 3
• 238000002156 mixing Methods 0.000 claims description 3
• 108020001213 potassium channel Proteins 0.000 claims description 3
• 102000004146 ATP citrate synthases Human genes 0.000 claims description 2
• 108090000662 ATP citrate synthases Proteins 0.000 claims description 2
• 229940123208 Biguanide Drugs 0.000 claims description 2
• 102000013585 Bombesin Human genes 0.000 claims description 2
• 108010051479 Bombesin Proteins 0.000 claims description 2
• 101800002068 Galanin Proteins 0.000 claims description 2
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 2
• 102000000853 LDL receptors Human genes 0.000 claims description 2
• 108010001831 LDL receptors Proteins 0.000 claims description 2
• 108010013563 Lipoprotein Lipase Proteins 0.000 claims description 2
• 102100022119 Lipoprotein lipase Human genes 0.000 claims description 2
• 229940124757 MC-4 agonist Drugs 0.000 claims description 2
• 102000002512 Orexin Human genes 0.000 claims description 2
• 102000023984 PPAR alpha Human genes 0.000 claims description 2
• 108010028924 PPAR alpha Proteins 0.000 claims description 2
• 102000005630 Urocortins Human genes 0.000 claims description 2
• 108010059705 Urocortins Proteins 0.000 claims description 2
• 239000003963 antioxidant agent Substances 0.000 claims description 2
• DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 claims description 2
• 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 claims description 2
• 229960002802 bromocriptine Drugs 0.000 claims description 2
• 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 2
• 229940125753 fibrate Drugs 0.000 claims description 2
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 2
• 230000001771 impaired effect Effects 0.000 claims description 2
• 239000000411 inducer Substances 0.000 claims description 2
• 239000002697 lyase inhibitor Substances 0.000 claims description 2
• SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 claims description 2
• 230000002474 noradrenergic effect Effects 0.000 claims description 2
• 108060005714 orexin Proteins 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 102000004169 proteins and genes Human genes 0.000 claims description 2
• 108090000623 proteins and genes Proteins 0.000 claims description 2
• 229940076279 serotonin Drugs 0.000 claims description 2
• 239000000952 serotonin receptor agonist Substances 0.000 claims description 2
• 239000003772 serotonin uptake inhibitor Substances 0.000 claims description 2
• 230000002295 serotoninergic effect Effects 0.000 claims description 2
• 239000004059 squalene synthase inhibitor Substances 0.000 claims description 2
• 150000001467 thiazolidinediones Chemical class 0.000 claims description 2
• 239000000777 urocortin Substances 0.000 claims description 2
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 16
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 6
• 229910018828 PO3H2 Inorganic materials 0.000 claims 3
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 3
• 229940127470 Lipase Inhibitors Drugs 0.000 claims 2
• 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 claims 2
• 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 claims 2
• 102000019432 Galanin Human genes 0.000 claims 1
• 206010022489 Insulin Resistance Diseases 0.000 claims 1
• 102000004882 Lipase Human genes 0.000 claims 1
• 239000004367 Lipase Substances 0.000 claims 1
• 108090001060 Lipase Proteins 0.000 claims 1
• 102000057248 Lipoprotein(a) Human genes 0.000 claims 1
• 108010033266 Lipoprotein(a) Proteins 0.000 claims 1
• 102000000536 PPAR gamma Human genes 0.000 claims 1
• 108010016731 PPAR gamma Proteins 0.000 claims 1
• 229940124754 PPAR-alpha/gamma agonist Drugs 0.000 claims 1
• 239000003392 amylase inhibitor Substances 0.000 claims 1
• 150000004283 biguanides Chemical class 0.000 claims 1
• 150000001735 carboxylic acids Chemical class 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 239000004026 insulin derivative Substances 0.000 claims 1
• 235000019421 lipase Nutrition 0.000 claims 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 1
• 206010003210 Arteriosclerosis Diseases 0.000 abstract 1
• 208000035150 Hypercholesterolemia Diseases 0.000 abstract 1
• 208000011775 arteriosclerosis disease Diseases 0.000 abstract 1
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
• 239000000047 product Substances 0.000 description 31
• SDOFMBGMRVAJNF-UHFFFAOYSA-N 6-aminohexane-1,2,3,4,5-pentol Chemical compound NCC(O)C(O)C(O)C(O)CO SDOFMBGMRVAJNF-UHFFFAOYSA-N 0.000 description 24
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
• 239000007787 solid Substances 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 150000003254 radicals Chemical class 0.000 description 16
• 230000015572 biosynthetic process Effects 0.000 description 14
• 238000003786 synthesis reaction Methods 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
• 229910001868 water Inorganic materials 0.000 description 13
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• WVDRSXGPQWNUBN-UHFFFAOYSA-N 4-(4-carboxyphenoxy)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=C(C(O)=O)C=C1 WVDRSXGPQWNUBN-UHFFFAOYSA-N 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 9
• GOMUHAODASRBBA-UHFFFAOYSA-N 4-[4-(aminomethyl)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one Chemical compound C1=CC(CN)=CC=C1C1N(C=2C=CC(F)=CC=2)C(=O)C1CCC(O)C1=CC=C(F)C=C1 GOMUHAODASRBBA-UHFFFAOYSA-N 0.000 description 8
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
• 150000001768 cations Chemical class 0.000 description 8
• 235000001014 amino acid Nutrition 0.000 description 7
• 229940024606 amino acid Drugs 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 7
• ZIFWYCYPTCFKCS-UHFFFAOYSA-N 1-[4-(aminomethyl)phenyl]-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-methoxyphenyl)azetidin-2-one Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(CN)=CC=2)C(=O)C1CCC(O)C1=CC=C(F)C=C1 ZIFWYCYPTCFKCS-UHFFFAOYSA-N 0.000 description 6
• JCLXUZWNOJDWQK-UHFFFAOYSA-M 4-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one;bromide Chemical compound [Br-].C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(OCC=3C=CC(C[N+]45CCN(CC4)CC5)=CC=3)=CC=2)N1C1=CC=C(F)C=C1 JCLXUZWNOJDWQK-UHFFFAOYSA-M 0.000 description 6
• HAZPLGUZDJSPTI-UHFFFAOYSA-N 4-[4-[[4-[3-(3-hydroxy-3-phenylpropyl)-2-oxo-4-phenylazetidin-1-yl]phenyl]methylcarbamoyl]phenoxy]benzoic acid Chemical compound C=1C=CC=CC=1C(O)CCC(C1=O)C(C=2C=CC=CC=2)N1C(C=C1)=CC=C1CNC(=O)C(C=C1)=CC=C1OC1=CC=C(C(O)=O)C=C1 HAZPLGUZDJSPTI-UHFFFAOYSA-N 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 229940125396 insulin Drugs 0.000 description 6
• 210000004185 liver Anatomy 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• JUNQIUQYFKAGLJ-UHFFFAOYSA-N 4-[4-[[4-[3-[3-(4-fluorophenyl)-3-hydroxypropyl]-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]phenyl]methylcarbamoyl]phenoxy]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(CNC(=O)C=3C=CC(OC=4C=CC(=CC=4)C(O)=O)=CC=3)=CC=2)C(=O)C1CCC(O)C1=CC=C(F)C=C1 JUNQIUQYFKAGLJ-UHFFFAOYSA-N 0.000 description 5
• QJJCSDQJHLBCAS-UHFFFAOYSA-M 4-[4-[[4-[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]phenyl]methoxy]phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one;bromide Chemical compound [Br-].C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(OCC=3C=CC(=CC=3)C=3C=CC(C[N+]45CCN(CC4)CC5)=CC=3)=CC=2)N1C1=CC=C(F)C=C1 QJJCSDQJHLBCAS-UHFFFAOYSA-M 0.000 description 5
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 5
• 239000012973 diazabicyclooctane Substances 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• OLNTVTPDXPETLC-UHFFFAOYSA-N 1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(O)=CC=2)N1C1=CC=C(F)C=C1 OLNTVTPDXPETLC-UHFFFAOYSA-N 0.000 description 4
• PZRZUEDVBFTTIB-UHFFFAOYSA-N 1-[4-(aminomethyl)phenyl]-3-(3-hydroxy-3-phenylpropyl)-4-phenylazetidin-2-one Chemical compound C1=CC(CN)=CC=C1N1C(=O)C(CCC(O)C=2C=CC=CC=2)C1C1=CC=CC=C1 PZRZUEDVBFTTIB-UHFFFAOYSA-N 0.000 description 4
• JOTCOKADYWPVSC-UHFFFAOYSA-N 2-[4-(1-azoniabicyclo[2.2.2]octan-1-ylmethyl)phenyl]-n-[[4-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]phenyl]methyl]acetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(CNC(=O)CC=3C=CC(C[N+]45CCC(CC4)CC5)=CC=3)=CC=2)N1C1=CC=C(F)C=C1 JOTCOKADYWPVSC-UHFFFAOYSA-N 0.000 description 4
• IRTXHCJKYAHGDF-UHFFFAOYSA-N 2-[4-[(1,4-dimethylpiperazin-1-ium-1-yl)methyl]phenyl]-n-[[4-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]phenyl]methyl]acetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1CN(C)CC[N+]1(C)CC(C=C1)=CC=C1CC(=O)NCC1=CC=C(C2N(C(=O)C2CCC(O)C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)C=C1 IRTXHCJKYAHGDF-UHFFFAOYSA-N 0.000 description 4
• QKUYJAIVAPVXFH-UHFFFAOYSA-N 3-[3-(4-fluorophenyl)-3-hydroxypropyl]-1-(4-hydroxyphenyl)-4-(4-methoxyphenyl)azetidin-2-one Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(O)=CC=2)C(=O)C1CCC(O)C1=CC=C(F)C=C1 QKUYJAIVAPVXFH-UHFFFAOYSA-N 0.000 description 4
• RUWHEHABHPGZNK-UHFFFAOYSA-N 4-[3-[3-(4-fluorophenyl)-3-hydroxypropyl]-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(=CC=2)C#N)C(=O)C1CCC(O)C1=CC=C(F)C=C1 RUWHEHABHPGZNK-UHFFFAOYSA-N 0.000 description 4
• RFQNMZOCNZXPSA-UHFFFAOYSA-N 4-[3-[3-[tert-butyl(dimethyl)silyl]oxy-3-(4-fluorophenyl)propyl]-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(=CC=2)C#N)C(=O)C1CCC(O[Si](C)(C)C(C)(C)C)C1=CC=C(F)C=C1 RFQNMZOCNZXPSA-UHFFFAOYSA-N 0.000 description 4
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• 239000000470 constituent Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 4
• 229960003105 metformin Drugs 0.000 description 4
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
• QMQIVCJAGMPTIJ-UHFFFAOYSA-N n-[[4-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]phenyl]methyl]-2-[4-[[methyl(2,3,4,5,6-pentahydroxyhexyl)amino]methyl]phenyl]acetamide Chemical compound C1=CC(CN(CC(O)C(O)C(O)C(O)CO)C)=CC=C1CC(=O)NCC1=CC=C(C2N(C(=O)C2CCC(O)C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)C=C1 QMQIVCJAGMPTIJ-UHFFFAOYSA-N 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
• FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 4
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
• RBZMSGOBSOCYHR-UHFFFAOYSA-N 1,4-bis(bromomethyl)benzene Chemical compound BrCC1=CC=C(CBr)C=C1 RBZMSGOBSOCYHR-UHFFFAOYSA-N 0.000 description 3
• PNJNOLPOBDAXBT-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[3-hydroxy-3-(4-hydroxyphenyl)propyl]-4-(4-methoxyphenyl)azetidin-2-one Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(F)=CC=2)C(=O)C1CCC(O)C1=CC=C(O)C=C1 PNJNOLPOBDAXBT-UHFFFAOYSA-N 0.000 description 3
• YINJTCQYTVPZEK-UHFFFAOYSA-M 1-[4-[(1,4,7-trimethyl-1,4,7-triazonan-1-ium-1-yl)methyl]phenyl]propan-2-one;bromide Chemical compound [Br-].C1CN(C)CCN(C)CC[N+]1(C)CC1=CC=C(CC(C)=O)C=C1 YINJTCQYTVPZEK-UHFFFAOYSA-M 0.000 description 3
• FYOZZULRIJNEJZ-UHFFFAOYSA-M 1-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-methoxyphenyl)azetidin-2-one;bromide Chemical compound [Br-].C1=CC(OC)=CC=C1C1N(C=2C=CC(OCC=3C=CC(C[N+]45CCN(CC4)CC5)=CC=3)=CC=2)C(=O)C1CCC(O)C1=CC=C(F)C=C1 FYOZZULRIJNEJZ-UHFFFAOYSA-M 0.000 description 3
• VQWVQHLXLOLUMW-UHFFFAOYSA-N 2-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]benzonitrile Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C(=CC=CC=2)C#N)N1C1=CC=C(F)C=C1 VQWVQHLXLOLUMW-UHFFFAOYSA-N 0.000 description 3
• WZMVTUSHFCVSNP-UHFFFAOYSA-N 2-[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]acetic acid;bromide Chemical compound [Br-].C1=CC(CC(=O)O)=CC=C1C[N+]1(CC2)CCN2CC1 WZMVTUSHFCVSNP-UHFFFAOYSA-N 0.000 description 3
• HTIHMWRVGKFMIX-UHFFFAOYSA-N 2-[4-(1-azoniabicyclo[2.2.2]octan-1-ylmethyl)phenyl]acetic acid;bromide Chemical compound [Br-].C1=CC(CC(=O)O)=CC=C1C[N+]1(CC2)CCC2CC1 HTIHMWRVGKFMIX-UHFFFAOYSA-N 0.000 description 3
• PDWGIZDABYYHFX-UHFFFAOYSA-N 2-[4-[(1,4-dimethylpiperazin-1-ium-1-yl)methyl]phenyl]acetic acid;bromide Chemical compound [Br-].C1CN(C)CC[N+]1(C)CC1=CC=C(CC(O)=O)C=C1 PDWGIZDABYYHFX-UHFFFAOYSA-N 0.000 description 3
• QFSXTTPKLXFRRU-UHFFFAOYSA-N 2-[4-[(2,3,4,5,6-pentahydroxyhexylamino)methyl]phenyl]acetic acid Chemical compound OCC(O)C(O)C(O)C(O)CNCC1=CC=C(CC(O)=O)C=C1 QFSXTTPKLXFRRU-UHFFFAOYSA-N 0.000 description 3
• FSLFABUVTDXVTQ-UHFFFAOYSA-N 2-[4-[[methyl(2,3,4,5,6-pentahydroxyhexyl)amino]methyl]phenyl]acetic acid Chemical compound OCC(O)C(O)C(O)C(O)CN(C)CC1=CC=C(CC(O)=O)C=C1 FSLFABUVTDXVTQ-UHFFFAOYSA-N 0.000 description 3
• HIALIZQROKUEJE-UHFFFAOYSA-N 4-[1-(4-fluoroanilino)-5-(4-fluorophenyl)-5-hydroxy-2-(2-oxo-4-phenyl-1,3-oxazolidine-3-carbonyl)pentyl]benzonitrile Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C(=O)N1C(OCC1C=1C=CC=CC=1)=O)C(C=1C=CC(=CC=1)C#N)NC1=CC=C(F)C=C1 HIALIZQROKUEJE-UHFFFAOYSA-N 0.000 description 3
• XZTQJBRBVLPLBE-UHFFFAOYSA-M 4-[4-[[3-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one;bromide Chemical compound [Br-].C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(OCC=3C=C(C[N+]45CCN(CC4)CC5)C=CC=3)=CC=2)N1C1=CC=C(F)C=C1 XZTQJBRBVLPLBE-UHFFFAOYSA-M 0.000 description 3
• MHQMLFZLVUIOQF-UHFFFAOYSA-N 4-[[4-[[4-[3-[3-(4-fluorophenyl)-3-hydroxypropyl]-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]phenyl]methylcarbamoyl]phenyl]methyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(CNC(=O)C=3C=CC(CC=4C=CC(=CC=4)C(O)=O)=CC=3)=CC=2)C(=O)C1CCC(O)C1=CC=C(F)C=C1 MHQMLFZLVUIOQF-UHFFFAOYSA-N 0.000 description 3
• ITKUJUGSTGCXAR-UHFFFAOYSA-N 4-[[5-[tert-butyl(dimethyl)silyl]oxy-5-(4-fluorophenyl)-1-(4-methoxyphenyl)-2-(2-oxo-4-phenyl-1,3-oxazolidine-3-carbonyl)pentyl]amino]benzonitrile Chemical compound C1=CC(OC)=CC=C1C(C(CCC(O[Si](C)(C)C(C)(C)C)C=1C=CC(F)=CC=1)C(=O)N1C(OCC1C=1C=CC=CC=1)=O)NC1=CC=C(C#N)C=C1 ITKUJUGSTGCXAR-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 3
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 125000000217 alkyl group Chemical group 0.000 description 3
• BPGBVGUMPQVVAU-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1.O=C1CCN1 BPGBVGUMPQVVAU-UHFFFAOYSA-N 0.000 description 3
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 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
• 238000009472 formulation Methods 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 229940028435 intralipid Drugs 0.000 description 3
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
• 239000008194 pharmaceutical composition Substances 0.000 description 3
• 230000035790 physiological processes and functions Effects 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 229960002354 repaglinide Drugs 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 2
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
• RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
• SCUYUVZFXMGTTE-UHFFFAOYSA-N 1-[4-[[4-(bromomethyl)phenyl]methoxy]phenyl]-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-methoxyphenyl)azetidin-2-one Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(OCC=3C=CC(CBr)=CC=3)=CC=2)C(=O)C1CCC(O)C1=CC=C(F)C=C1 SCUYUVZFXMGTTE-UHFFFAOYSA-N 0.000 description 2
• XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 2
• NDVMCQUOSYOQMZ-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)C(C(N)=O)[Si](C)(C)C NDVMCQUOSYOQMZ-UHFFFAOYSA-N 0.000 description 2
• KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 2
• RKRFKYYQCKGDSM-UHFFFAOYSA-N 3-[3-[4-[[4-(bromomethyl)phenyl]methoxy]phenyl]-3-hydroxypropyl]-1-(4-fluorophenyl)-4-(4-methoxyphenyl)azetidin-2-one Chemical compound C1=CC(OC)=CC=C1C1N(C=2C=CC(F)=CC=2)C(=O)C1CCC(O)C(C=C1)=CC=C1OCC1=CC=C(CBr)C=C1 RKRFKYYQCKGDSM-UHFFFAOYSA-N 0.000 description 2
• CLUOAVYWRSUYEA-UHFFFAOYSA-N 4-[4-[[2-(bromomethyl)phenyl]methoxy]phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(OCC=3C(=CC=CC=3)CBr)=CC=2)N1C1=CC=C(F)C=C1 CLUOAVYWRSUYEA-UHFFFAOYSA-N 0.000 description 2
• HGSNYXKRLJJTKY-UHFFFAOYSA-N 4-[4-[[3-(bromomethyl)phenyl]methoxy]phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(OCC=3C=C(CBr)C=CC=3)=CC=2)N1C1=CC=C(F)C=C1 HGSNYXKRLJJTKY-UHFFFAOYSA-N 0.000 description 2
• RLBMYVHBZGJAGU-UHFFFAOYSA-N 4-[4-[[4-(bromomethyl)phenyl]methoxy]phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(OCC=3C=CC(CBr)=CC=3)=CC=2)N1C1=CC=C(F)C=C1 RLBMYVHBZGJAGU-UHFFFAOYSA-N 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class 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 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 229940086609 Lipase inhibitor Drugs 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-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
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000007868 Raney catalyst Substances 0.000 description 2
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
• 229910000564 Raney nickel Inorganic materials 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 108010077895 Sarcosine Proteins 0.000 description 2
• 241000978776 Senegalia senegal Species 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 229960002632 acarbose Drugs 0.000 description 2
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 235000003704 aspartic acid Nutrition 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 235000012000 cholesterol Nutrition 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 2
• 229960000815 ezetimibe Drugs 0.000 description 2
• 230000002550 fecal effect Effects 0.000 description 2
• 210000003608 fece Anatomy 0.000 description 2
• 239000000835 fiber Substances 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 229960004580 glibenclamide Drugs 0.000 description 2
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 2
• 229960001381 glipizide Drugs 0.000 description 2
• 239000000174 gluconic acid Substances 0.000 description 2
• 235000012208 gluconic acid Nutrition 0.000 description 2
• 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 2
• 239000001257 hydrogen Substances 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 230000002218 hypoglycaemic effect Effects 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 229960004844 lovastatin Drugs 0.000 description 2
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 235000012054 meals Nutrition 0.000 description 2
• HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 2
• SPBJGJIBKKVPAJ-UHFFFAOYSA-N n-[[4-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]phenyl]methyl]-2-[4-[(1,4,7-trimethyl-1,4,7-triazonan-1-ium-1-yl)methyl]phenyl]acetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C1CN(C)CCN(C)CC[N+]1(C)CC(C=C1)=CC=C1CC(=O)NCC1=CC=C(C2N(C(=O)C2CCC(O)C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)C=C1 SPBJGJIBKKVPAJ-UHFFFAOYSA-N 0.000 description 2
• WZJSHGLOQWLHLO-UHFFFAOYSA-N n-[[4-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]phenyl]methyl]-2-[4-[(2,3,4,5,6-pentahydroxyhexylamino)methyl]phenyl]acetamide Chemical compound C1=CC(CNCC(O)C(O)C(O)C(O)CO)=CC=C1CC(=O)NCC1=CC=C(C2N(C(=O)C2CCC(O)C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)C=C1 WZJSHGLOQWLHLO-UHFFFAOYSA-N 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 2
• 229960001243 orlistat Drugs 0.000 description 2
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
• 229960005095 pioglitazone Drugs 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 229960004586 rosiglitazone Drugs 0.000 description 2
• 238000007493 shaping process Methods 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 239000011975 tartaric acid Substances 0.000 description 2
• 235000002906 tartaric acid Nutrition 0.000 description 2
• VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 2
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
• 229960005371 tolbutamide Drugs 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 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
• DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 1
• OVRSTXSKBHTEJU-BPLKJJMMSA-N (2S)-4-amino-2-(ethylamino)-4-oxobutanoic acid (2S,5R)-2,6-diamino-5-hydroxyhexanoic acid (2S,3S)-3-methyl-2-(methylamino)pentanoic acid Chemical compound N[C@@H](CC[C@@H](O)CN)C(=O)O.CN[C@@H]([C@@H](C)CC)C(=O)O.C(C)N[C@@H](CC(N)=O)C(=O)O OVRSTXSKBHTEJU-BPLKJJMMSA-N 0.000 description 1
• SDOFMBGMRVAJNF-SLPGGIOYSA-N (2r,3r,4r,5s)-6-aminohexane-1,2,3,4,5-pentol Chemical compound NC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO SDOFMBGMRVAJNF-SLPGGIOYSA-N 0.000 description 1
• VEVRNHHLCPGNDU-MUGJNUQGSA-N (2s)-2-amino-5-[1-[(5s)-5-amino-5-carboxypentyl]-3,5-bis[(3s)-3-amino-3-carboxypropyl]pyridin-1-ium-4-yl]pentanoate Chemical compound OC(=O)[C@@H](N)CCCC[N+]1=CC(CC[C@H](N)C(O)=O)=C(CCC[C@H](N)C([O-])=O)C(CC[C@H](N)C(O)=O)=C1 VEVRNHHLCPGNDU-MUGJNUQGSA-N 0.000 description 1
• VVQIIIAZJXTLRE-QMMMGPOBSA-N (2s)-2-amino-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC[C@H](N)C(O)=O VVQIIIAZJXTLRE-QMMMGPOBSA-N 0.000 description 1
• SNZIFNXFAFKRKT-NSHDSACASA-N (2s)-2-azaniumyl-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoate Chemical compound CC(C)(C)OC1=CC=C(C[C@H]([NH3+])C([O-])=O)C=C1 SNZIFNXFAFKRKT-NSHDSACASA-N 0.000 description 1
• MXWMFBYWXMXRPD-YFKPBYRVSA-N (2s)-2-azaniumyl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoate Chemical compound CC(C)(C)OC(=O)C[C@H](N)C(O)=O MXWMFBYWXMXRPD-YFKPBYRVSA-N 0.000 description 1
• ONOURAAVVKGJNM-SCZZXKLOSA-N (2s,3r)-2-azaniumyl-3-phenylmethoxybutanoate Chemical compound [O-]C(=O)[C@@H]([NH3+])[C@@H](C)OCC1=CC=CC=C1 ONOURAAVVKGJNM-SCZZXKLOSA-N 0.000 description 1
• LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• KGKAYWMGPDWLQZ-UHFFFAOYSA-N 1,2-bis(bromomethyl)benzene Chemical compound BrCC1=CC=CC=C1CBr KGKAYWMGPDWLQZ-UHFFFAOYSA-N 0.000 description 1
• OXHOPZLBSSTTBU-UHFFFAOYSA-N 1,3-bis(bromomethyl)benzene Chemical compound BrCC1=CC=CC(CBr)=C1 OXHOPZLBSSTTBU-UHFFFAOYSA-N 0.000 description 1
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• KZNQNBZMBZJQJO-UHFFFAOYSA-N 1-(2-azaniumylacetyl)pyrrolidine-2-carboxylate Chemical compound NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
• HMUGRILXVBKBID-UHFFFAOYSA-N 1-(bromomethyl)-4-[4-(bromomethyl)phenyl]benzene Chemical group C1=CC(CBr)=CC=C1C1=CC=C(CBr)C=C1 HMUGRILXVBKBID-UHFFFAOYSA-N 0.000 description 1
• BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
• PMGZJNCIQHGNLT-UHFFFAOYSA-N 1-[bis(2,2-dimethylpropanoyloxymethoxy)phosphoryl]-4-(3-phenoxyphenyl)butane-1-sulfonic acid Chemical compound CC(C)(C)C(=O)OCOP(=O)(OCOC(=O)C(C)(C)C)C(S(O)(=O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 PMGZJNCIQHGNLT-UHFFFAOYSA-N 0.000 description 1
• OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
• GUSVHVVOABZHAH-OPZWKQDFSA-N 1aw8p77hkj Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@H](C)CC1)O5)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GUSVHVVOABZHAH-OPZWKQDFSA-N 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• YKQGUJZZCQAQDE-UHFFFAOYSA-N 2-(benzylideneamino)benzonitrile Chemical compound N#CC1=CC=CC=C1N=CC1=CC=CC=C1 YKQGUJZZCQAQDE-UHFFFAOYSA-N 0.000 description 1
• ZEVUGJRUEGVFCU-UHFFFAOYSA-N 2-[3-(bromomethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CBr)=C1 ZEVUGJRUEGVFCU-UHFFFAOYSA-N 0.000 description 1
• KEXMHAISSHPSAL-UHFFFAOYSA-O 2-[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]-n-[[4-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]phenyl]methyl]acetamide Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(CNC(=O)CC=3C=CC(C[N+]45CCN(CC4)CC5)=CC=3)=CC=2)N1C1=CC=C(F)C=C1 KEXMHAISSHPSAL-UHFFFAOYSA-O 0.000 description 1
• VWMNHDWGQFYAHK-UHFFFAOYSA-N 2-[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]-n-[[4-[3-(3-hydroxy-3-phenylpropyl)-2-oxo-4-phenylazetidin-1-yl]phenyl]methyl]acetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C=1C=CC=CC=1C(O)CCC(C(N1C=2C=CC(CNC(=O)CC=3C=CC(C[N+]45CCN(CC4)CC5)=CC=3)=CC=2)=O)C1C1=CC=CC=C1 VWMNHDWGQFYAHK-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• JXRBFOXQBINRSN-UHFFFAOYSA-N 2-aminohexanedioic acid 3-aminohexanedioic acid 2-amino-2-methylpropanoic acid 3-amino-2-methylpropanoic acid Chemical compound NCC(C)C(O)=O.CC(C)(N)C(O)=O.OC(=O)CC(N)CCC(O)=O.OC(=O)C(N)CCCC(O)=O JXRBFOXQBINRSN-UHFFFAOYSA-N 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• UVHJKWZVAXTMDS-UHFFFAOYSA-M 3-[3-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3-hydroxypropyl]-1-(4-fluorophenyl)-4-(4-methoxyphenyl)azetidin-2-one;bromide Chemical compound [Br-].C1=CC(OC)=CC=C1C1N(C=2C=CC(F)=CC=2)C(=O)C1CCC(O)C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 UVHJKWZVAXTMDS-UHFFFAOYSA-M 0.000 description 1
• SDWXLVHKJGRAMK-UHFFFAOYSA-N 3-[4-(aminomethyl)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one Chemical compound C1=CC(CN)=CC=C1C1(CCC(O)C=2C=CC(F)=CC=2)C(=O)N(C=2C=CC(F)=CC=2)C1 SDWXLVHKJGRAMK-UHFFFAOYSA-N 0.000 description 1
• AVAZNWOHQJYCEL-UHFFFAOYSA-N 3-[5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O)CCCC(=O)N(C(OC1)=O)C1C1=CC=CC=C1 AVAZNWOHQJYCEL-UHFFFAOYSA-N 0.000 description 1
• CQXYQHZDPOQVGG-UHFFFAOYSA-N 3-[5-[tert-butyl(dimethyl)silyl]oxy-5-(4-fluorophenyl)pentanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O[Si](C)(C)C(C)(C)C)CCCC(=O)N(C(OC1)=O)C1C1=CC=CC=C1 CQXYQHZDPOQVGG-UHFFFAOYSA-N 0.000 description 1
• LRXBZTWIFDRJSG-UHFFFAOYSA-N 3-[5-[tert-butyl(dimethyl)silyl]oxy-5-phenylpentanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C=1C=CC=CC=1C(O[Si](C)(C)C(C)(C)C)CCCC(=O)N(C(OC1)=O)C1C1=CC=CC=C1 LRXBZTWIFDRJSG-UHFFFAOYSA-N 0.000 description 1
• ZRWIZRDYISWISY-UHFFFAOYSA-N 3-[5-hydroxy-5-(4-hydroxyphenyl)pentanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C=1C=C(O)C=CC=1C(O)CCCC(=O)N(C(OC1)=O)C1C1=CC=CC=C1 ZRWIZRDYISWISY-UHFFFAOYSA-N 0.000 description 1
• KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• NCTCGHLIHJJIBK-UHFFFAOYSA-N 3-phenyl-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1C1=CC=CC=C1 NCTCGHLIHJJIBK-UHFFFAOYSA-N 0.000 description 1
• VTDMBRAUHKUOON-UHFFFAOYSA-N 4-[(4-carboxyphenyl)methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CC1=CC=C(C(O)=O)C=C1 VTDMBRAUHKUOON-UHFFFAOYSA-N 0.000 description 1
• DRTPXERKQCJQAJ-UHFFFAOYSA-N 4-[(4-fluorophenyl)iminomethyl]benzonitrile Chemical compound C1=CC(F)=CC=C1N=CC1=CC=C(C#N)C=C1 DRTPXERKQCJQAJ-UHFFFAOYSA-N 0.000 description 1
• ASVSTYQWCPHCFY-UHFFFAOYSA-N 4-[(4-methoxyphenyl)iminomethyl]benzonitrile Chemical compound C1=CC(OC)=CC=C1N=CC1=CC=C(C#N)C=C1 ASVSTYQWCPHCFY-UHFFFAOYSA-N 0.000 description 1
• YONXPYGTYHMKDH-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methylideneamino]phenol Chemical compound C1=CC(OC)=CC=C1C=NC1=CC=C(O)C=C1 YONXPYGTYHMKDH-UHFFFAOYSA-N 0.000 description 1
• MKJKHZAZINOMFQ-UHFFFAOYSA-N 4-[4-[[4-[4-(bromomethyl)phenyl]phenyl]methoxy]phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O)CCC(C1=O)C(C=2C=CC(OCC=3C=CC(=CC=3)C=3C=CC(CBr)=CC=3)=CC=2)N1C1=CC=C(F)C=C1 MKJKHZAZINOMFQ-UHFFFAOYSA-N 0.000 description 1
• QBQLYIISSRXYKL-UHFFFAOYSA-N 4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,2-oxazolidine-3,5-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1C(=O)NOC1=O QBQLYIISSRXYKL-UHFFFAOYSA-N 0.000 description 1
• AUEUBSJNKBZSKK-UHFFFAOYSA-N 5-benzylsulfonyl-2-[2-(dimethylamino)ethyl-ethylamino]-n,n-diethyl-4-(4-phenylpiperidin-1-yl)benzamide Chemical compound C1=C(N(CC)CCN(C)C)C(C(=O)N(CC)CC)=CC(S(=O)(=O)CC=2C=CC=CC=2)=C1N(CC1)CCC1C1=CC=CC=C1 AUEUBSJNKBZSKK-UHFFFAOYSA-N 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• MBBZMMPHUWSWHV-UHFFFAOYSA-N 6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound CNCC(O)C(O)C(O)C(O)CO MBBZMMPHUWSWHV-UHFFFAOYSA-N 0.000 description 1
• FVRKTWQQVGYNFQ-UHFFFAOYSA-N 6-aminohexane-1,1,1,6,6-pentol Chemical compound NC(O)(O)CCCCC(O)(O)O FVRKTWQQVGYNFQ-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• PTQXTEKSNBVPQJ-UHFFFAOYSA-N Avasimibe Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1CC(=O)NS(=O)(=O)OC1=C(C(C)C)C=CC=C1C(C)C PTQXTEKSNBVPQJ-UHFFFAOYSA-N 0.000 description 1
• XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
• YKCLKCUSOBPITL-RVUZOZDGSA-N CCNCC(O)=O.NCC(N)C(O)=O.NCCCCCC(O)=O.OC(=O)N1CCCCC1.CCCCCC(N)C(O)=O.OC(=O)C(N)C1=CC=CS1.OC(=O)[C@@H](N)CC1=CC=CS1.OC(=O)C(N)(N)CCCCC(O)=O Chemical compound CCNCC(O)=O.NCC(N)C(O)=O.NCCCCCC(O)=O.OC(=O)N1CCCCC1.CCCCCC(N)C(O)=O.OC(=O)C(N)C1=CC=CS1.OC(=O)[C@@H](N)CC1=CC=CS1.OC(=O)C(N)(N)CCCCC(O)=O YKCLKCUSOBPITL-RVUZOZDGSA-N 0.000 description 1
• DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
• 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
• 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose 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)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
• YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 description 1
• CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
• CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
• YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-MGCNEYSASA-N D-galactonic acid Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-MGCNEYSASA-N 0.000 description 1
• DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
• HAIWUXASLYEWLM-UHFFFAOYSA-N D-manno-Heptulose Natural products OCC1OC(O)(CO)C(O)C(O)C1O HAIWUXASLYEWLM-UHFFFAOYSA-N 0.000 description 1
• RGHNJXZEOKUKBD-MBMOQRBOSA-N D-mannonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O RGHNJXZEOKUKBD-MBMOQRBOSA-N 0.000 description 1
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 206010056474 Erythrosis Diseases 0.000 description 1
• 229930091371 Fructose Natural products 0.000 description 1
• 239000005715 Fructose Substances 0.000 description 1
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
• 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
• DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
• 102400001370 Galanin Human genes 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 102400000321 Glucagon Human genes 0.000 description 1
• 108060003199 Glucagon Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 102000004366 Glucosidases Human genes 0.000 description 1
• 108010056771 Glucosidases Proteins 0.000 description 1
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108010057186 Insulin Glargine 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
• 229940122355 Insulin sensitizer Drugs 0.000 description 1
• 208000007976 Ketosis Diseases 0.000 description 1
• SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• AGPKZVBTJJNPAG-UHNVWZDZSA-N L-allo-Isoleucine Chemical compound CC[C@@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-UHNVWZDZSA-N 0.000 description 1
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
• HSNZZMHEPUFJNZ-UHFFFAOYSA-N L-galacto-2-Heptulose Natural products OCC(O)C(O)C(O)C(O)C(=O)CO HSNZZMHEPUFJNZ-UHFFFAOYSA-N 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• QEFRNWWLZKMPFJ-YGVKFDHGSA-N L-methionine S-oxide Chemical compound CS(=O)CC[C@H](N)C(O)=O QEFRNWWLZKMPFJ-YGVKFDHGSA-N 0.000 description 1
• SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 238000008214 LDL Cholesterol Methods 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• 108090001030 Lipoproteins Proteins 0.000 description 1
• 229940122014 Lyase inhibitor Drugs 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
• 241000699673 Mesocricetus auratus Species 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
• 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 1
• IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• DBYQMASTXGHZES-UHFFFAOYSA-N NCCCC(=O)O.NC(C(=O)O)CCN.NC(C(=O)O)CC.NC(C(=O)O)CCCCC(=O)O.NCCC(=O)O Chemical compound NCCCC(=O)O.NC(C(=O)O)CCN.NC(C(=O)O)CC.NC(C(=O)O)CCCCC(=O)O.NCCC(=O)O DBYQMASTXGHZES-UHFFFAOYSA-N 0.000 description 1
• 238000011785 NMRI mouse Methods 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• KAFHLONDOVSENM-HNNXBMFYSA-N O-Benzyl-L-tyrosine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1OCC1=CC=CC=C1 KAFHLONDOVSENM-HNNXBMFYSA-N 0.000 description 1
• CRVWDBRZGSXPEN-KAJBOZBZSA-N OC1[C@H](NCC1)C(=O)O.CN[C@@H](C(C)C)C(=O)O Chemical compound OC1[C@H](NCC1)C(=O)O.CN[C@@H](C(C)C)C(=O)O CRVWDBRZGSXPEN-KAJBOZBZSA-N 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
• 229940127315 Potassium Channel Openers Drugs 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 102100040918 Pro-glucagon Human genes 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• HAIWUXASLYEWLM-AZEWMMITSA-N Sedoheptulose Natural products OC[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@](O)(CO)O1 HAIWUXASLYEWLM-AZEWMMITSA-N 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 229910007161 Si(CH3)3 Inorganic materials 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 229940123495 Squalene synthetase inhibitor Drugs 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
• IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
• 150000001323 aldoses Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 229920006318 anionic polymer Polymers 0.000 description 1
• 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
• 230000002402 anti-lipaemic effect Effects 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• RCHHVVGSTHAVPF-ZPHPLDECSA-N apidra 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=3N=CNC=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](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(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](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CNC=N1 RCHHVVGSTHAVPF-ZPHPLDECSA-N 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 150000005840 aryl radicals Chemical class 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 229950010046 avasimibe Drugs 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
• 229960000516 bezafibrate Drugs 0.000 description 1
• IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 239000013553 cell monolayer Substances 0.000 description 1
• 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
• 229960005110 cerivastatin Drugs 0.000 description 1
• SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 150000003841 chloride salts Chemical class 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 description 1
• YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
• 229950009226 ciglitazone Drugs 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 229960001214 clofibrate Drugs 0.000 description 1
• KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 229960004597 dexfenfluramine Drugs 0.000 description 1
• BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000001278 effect on cholesterol Effects 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• ZZCHHVUQYRMYLW-HKBQPEDESA-N farglitazar Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZCHHVUQYRMYLW-HKBQPEDESA-N 0.000 description 1
• 229960001582 fenfluramine Drugs 0.000 description 1
• 229960002297 fenofibrate Drugs 0.000 description 1
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 235000012631 food intake Nutrition 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 238000003304 gavage Methods 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 229960000346 gliclazide Drugs 0.000 description 1
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
• 229960004666 glucagon Drugs 0.000 description 1
• 230000004110 gluconeogenesis Effects 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 230000004190 glucose uptake Effects 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 230000004116 glycogenolysis Effects 0.000 description 1
• 235000014168 granola/muesli bars Nutrition 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 210000004347 intestinal mucosa Anatomy 0.000 description 1
• RGXCTRIQQODGIZ-UHFFFAOYSA-O isodesmosine Chemical compound OC(=O)C(N)CCCC[N+]1=CC(CCC(N)C(O)=O)=CC(CCC(N)C(O)=O)=C1CCCC(N)C(O)=O RGXCTRIQQODGIZ-UHFFFAOYSA-O 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 150000002584 ketoses Chemical class 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229940099563 lactobionic acid Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229940060975 lantus Drugs 0.000 description 1
• 229960003566 lomitapide Drugs 0.000 description 1
• QKVKOFVWUHNEBX-UHFFFAOYSA-N lomitapide mesylate Chemical compound CS(O)(=O)=O.C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCC1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 QKVKOFVWUHNEBX-UHFFFAOYSA-N 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960000299 mazindol Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 229960001110 miglitol Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• ZICFPEHQRZAFBZ-UHFFFAOYSA-N n-(4-fluorophenyl)-1-(4-methoxyphenyl)methanimine Chemical compound C1=CC(OC)=CC=C1C=NC1=CC=C(F)C=C1 ZICFPEHQRZAFBZ-UHFFFAOYSA-N 0.000 description 1
• LYAUICDWKQJAGX-UHFFFAOYSA-N n-(7-hydroxy-2,2,4,6-tetramethyl-1,3-dihydroinden-1-yl)-2-[4-(3-methoxyphenyl)piperazin-1-yl]acetamide Chemical compound COC1=CC=CC(N2CCN(CC(=O)NC3C(CC4=C3C(=C(C)C=C4C)O)(C)C)CC2)=C1 LYAUICDWKQJAGX-UHFFFAOYSA-N 0.000 description 1
• MVRHRGTVYZFTKV-UHFFFAOYSA-N n-[[4-[1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl]phenyl]methyl]-2-[4-[(4-methylmorpholin-4-ium-4-yl)methyl]phenyl]acetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C=1C=C(CC(=O)NCC=2C=CC(=CC=2)C2N(C(=O)C2CCC(O)C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)C=CC=1C[N+]1(C)CCOCC1 MVRHRGTVYZFTKV-UHFFFAOYSA-N 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• YDCVQGAUCOROHB-UHFFFAOYSA-N oxadiazolidine-4,5-dione Chemical class O=C1NNOC1=O YDCVQGAUCOROHB-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
• VWMZIGBYZQUQOA-QEEMJVPDSA-N pamaqueside Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC(=O)[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@H](C)CC1)O5)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VWMZIGBYZQUQOA-QEEMJVPDSA-N 0.000 description 1
• 229950005482 pamaqueside Drugs 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 229960001639 penicillamine Drugs 0.000 description 1
• 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• 229960003562 phentermine Drugs 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000003825 pressing Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 239000000700 radioactive tracer Substances 0.000 description 1
• 229960000672 rosuvastatin Drugs 0.000 description 1
• BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
• 229940043230 sarcosine Drugs 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• HSNZZMHEPUFJNZ-SHUUEZRQSA-N sedoheptulose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(=O)CO HSNZZMHEPUFJNZ-SHUUEZRQSA-N 0.000 description 1
• 229960004425 sibutramine Drugs 0.000 description 1
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 235000000891 standard diet Nutrition 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 150000005846 sugar alcohols Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
• XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 150000004044 tetrasaccharides Chemical class 0.000 description 1
• 238000002560 therapeutic procedure Methods 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
• YSMODUONRAFBET-WHFBIAKZSA-N threo-5-hydroxy-L-lysine Chemical compound NC[C@@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-WHFBIAKZSA-N 0.000 description 1
• 229950004437 tiqueside Drugs 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• KSBFAJFIWLUUBJ-UHFFFAOYSA-N triazonane Chemical compound C1CCCNNNCC1 KSBFAJFIWLUUBJ-UHFFFAOYSA-N 0.000 description 1
• SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
• 150000004043 trisaccharides Chemical class 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
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000007762 w/o emulsion Substances 0.000 description 1
• JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 description 1