NO329308B1 - N-aryl-piperidinsubstituerte bifenylkarboksamider som inhibitorer av apolipoprotein B-sekresjon - Google Patents

N-aryl-piperidinsubstituerte bifenylkarboksamider som inhibitorer av apolipoprotein B-sekresjon Download PDF

Info

Publication number: NO329308B1
Authority: NO; Norway
Prior art keywords: formula; compounds; compound; hydrogen; acid
Prior art date: 2002-08-12

Application number

NO20050563A

Other languages

English (en)

Norwegian (no)

Other versions

NO20050563L (no

Inventor

Leo Jacobus Jozef Backx

Peter Walter Maria Roevens

Lieven Meerpoel

Original Assignee

Janssen Pharmaceutica Nv

Priority date (The priority date 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 date listed.)

2002-08-12

Filing date

2005-01-31

Publication date

2010-09-27

2005-01-31 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2005-01-31 Publication of NO20050563L publication Critical patent/NO20050563L/no

2010-09-27 Publication of NO329308B1 publication Critical patent/NO329308B1/no

Links

239000003112 inhibitor Substances 0.000 title abstract description 19
GTKIGDZXPDCIKR-UHFFFAOYSA-N 2-phenylbenzamide Chemical class NC(=O)C1=CC=CC=C1C1=CC=CC=C1 GTKIGDZXPDCIKR-UHFFFAOYSA-N 0.000 title abstract description 12
102100040202 Apolipoprotein B-100 Human genes 0.000 title abstract description 10
101710095342 Apolipoprotein B Proteins 0.000 title abstract description 5
230000028327 secretion Effects 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 113
238000000034 method Methods 0.000 claims abstract description 35
239000003814 drug Substances 0.000 claims abstract description 14
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
230000008569 process Effects 0.000 claims abstract description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
239000001257 hydrogen Substances 0.000 claims description 31
229910052739 hydrogen Inorganic materials 0.000 claims description 31
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 21
229910052757 nitrogen Inorganic materials 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 13
238000006243 chemical reaction Methods 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 12
239000002904 solvent Substances 0.000 claims description 9
239000002585 base Substances 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 4
229910052727 yttrium Inorganic materials 0.000 claims description 4
ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 claims description 3
239000012458 free base Substances 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 2
150000004820 halides Chemical class 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
230000009466 transformation Effects 0.000 claims 1
208000031226 Hyperlipidaemia Diseases 0.000 abstract description 19
238000002360 preparation method Methods 0.000 abstract description 14
208000008589 Obesity Diseases 0.000 abstract description 8
235000020824 obesity Nutrition 0.000 abstract description 8
208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 85
239000000203 mixture Substances 0.000 description 48
239000000543 intermediate Substances 0.000 description 29
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
-1 biphenylcarboxamide compound Chemical class 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
108010007622 LDL Lipoproteins Proteins 0.000 description 19
102000007330 LDL Lipoproteins Human genes 0.000 description 19
108010062497 VLDL Lipoproteins Proteins 0.000 description 18
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 18
239000000243 solution Substances 0.000 description 18
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
239000011541 reaction mixture Substances 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 15
102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 13
108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 13
239000011347 resin Substances 0.000 description 13
229920005989 resin Polymers 0.000 description 13
201000001320 Atherosclerosis Diseases 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 11
150000002632 lipids Chemical class 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
235000012000 cholesterol Nutrition 0.000 description 8
229940079593 drug Drugs 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
229940107161 cholesterol Drugs 0.000 description 7
239000000796 flavoring agent Substances 0.000 description 7
108010010234 HDL Lipoproteins Proteins 0.000 description 6
102000015779 HDL Lipoproteins Human genes 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
238000002648 combination therapy Methods 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
235000019634 flavors Nutrition 0.000 description 6
239000007788 liquid Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
108010008150 Apolipoprotein B-100 Proteins 0.000 description 5
102000007592 Apolipoproteins Human genes 0.000 description 5
108010071619 Apolipoproteins Proteins 0.000 description 5
108010004103 Chylomicrons Proteins 0.000 description 5
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 5
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
239000003524 antilipemic agent Substances 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
235000003599 food sweetener Nutrition 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
239000011734 sodium Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
239000003765 sweetening agent Substances 0.000 description 5
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
102400000352 Apolipoprotein B-48 Human genes 0.000 description 4
101800001976 Apolipoprotein B-48 Proteins 0.000 description 4
102000002284 Hydroxymethylglutaryl-CoA Synthase Human genes 0.000 description 4
108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 4
208000035150 Hypercholesterolemia Diseases 0.000 description 4
102000004895 Lipoproteins Human genes 0.000 description 4
108090001030 Lipoproteins Proteins 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
208000029078 coronary artery disease Diseases 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
206010012601 diabetes mellitus Diseases 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
238000009472 formulation Methods 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000012289 standard assay Methods 0.000 description 4
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
238000012360 testing method Methods 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
MVUGBURUWNYPHI-UHFFFAOYSA-N 3-methyl-2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C1=CC=C(C(F)(F)F)C=C1 MVUGBURUWNYPHI-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
108010027006 Apolipoproteins B Proteins 0.000 description 3
102000018616 Apolipoproteins B Human genes 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
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 3
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 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
241000282412 Homo Species 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000000654 additive Substances 0.000 description 3
239000000872 buffer Substances 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000003795 chemical substances by application Substances 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
230000000875 corresponding effect Effects 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
239000003480 eluent Substances 0.000 description 3
IHSUFLCKRIHFGY-UHFFFAOYSA-N ethyl 2-piperidin-4-ylacetate Chemical compound CCOC(=O)CC1CCNCC1 IHSUFLCKRIHFGY-UHFFFAOYSA-N 0.000 description 3
239000008103 glucose Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
230000000968 intestinal effect Effects 0.000 description 3
210000000936 intestine Anatomy 0.000 description 3
210000004185 liver Anatomy 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
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
238000010532 solid phase synthesis reaction Methods 0.000 description 3
239000004059 squalene synthase inhibitor Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
238000013518 transcription Methods 0.000 description 3
230000035897 transcription Effects 0.000 description 3
238000013519 translation Methods 0.000 description 3
230000032258 transport Effects 0.000 description 3
CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 2
IQOMYCGTGFGDFN-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IQOMYCGTGFGDFN-UHFFFAOYSA-N 0.000 description 2
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 2
ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 2
208000007848 Alcoholism Diseases 0.000 description 2
206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 2
208000032841 Bulimia Diseases 0.000 description 2
206010006550 Bulimia nervosa Diseases 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
206010008635 Cholestasis Diseases 0.000 description 2
108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 2
102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
201000001376 Familial Combined Hyperlipidemia Diseases 0.000 description 2
206010059183 Familial hypertriglyceridaemia Diseases 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
MXPBQDFWIMBACQ-ACZMJKKPSA-N Glu-Cys-Cys Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(O)=O MXPBQDFWIMBACQ-ACZMJKKPSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 2
208000026350 Inborn Genetic disease Diseases 0.000 description 2
238000008214 LDL Cholesterol Methods 0.000 description 2
102100024640 Low-density lipoprotein receptor Human genes 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
206010029164 Nephrotic syndrome Diseases 0.000 description 2
208000018262 Peripheral vascular disease Diseases 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
229940123495 Squalene synthetase inhibitor Drugs 0.000 description 2
206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 2
ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
208000037919 acquired disease Diseases 0.000 description 2
206010001584 alcohol abuse Diseases 0.000 description 2
208000025746 alcohol use disease Diseases 0.000 description 2
238000003556 assay Methods 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
230000002490 cerebral effect Effects 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
230000007870 cholestasis Effects 0.000 description 2
231100000359 cholestasis Toxicity 0.000 description 2
239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 description 2
208000020832 chronic kidney disease Diseases 0.000 description 2
208000022831 chronic renal failure syndrome Diseases 0.000 description 2
208000026758 coronary atherosclerosis Diseases 0.000 description 2
239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 2
KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
235000013367 dietary fats Nutrition 0.000 description 2
ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 2
108010037444 diisopropylglutathione ester Proteins 0.000 description 2
239000007884 disintegrant Substances 0.000 description 2
201000001386 familial hypercholesterolemia Diseases 0.000 description 2
229940125753 fibrate Drugs 0.000 description 2
239000000499 gel Substances 0.000 description 2
208000016361 genetic disease Diseases 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
208000000522 hyperlipoproteinemia type IV Diseases 0.000 description 2
208000003532 hypothyroidism Diseases 0.000 description 2
230000002989 hypothyroidism Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
230000031891 intestinal absorption Effects 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000003446 ligand Substances 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
208000031225 myocardial ischemia Diseases 0.000 description 2
229960003512 nicotinic acid Drugs 0.000 description 2
235000001968 nicotinic acid Nutrition 0.000 description 2
239000011664 nicotinic acid Substances 0.000 description 2
235000013615 non-nutritive sweetener Nutrition 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000008188 pellet Substances 0.000 description 2
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
150000003904 phospholipids Chemical class 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
235000004252 protein component Nutrition 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
239000012453 solvate Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
229960005137 succinic acid Drugs 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
238000012546 transfer Methods 0.000 description 2
150000003626 triacylglycerols Chemical class 0.000 description 2
208000019553 vascular disease Diseases 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
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 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
NUFKRGBSZPCGQB-FLBSXDLDSA-N (3s)-3-amino-4-oxo-4-[[(2r)-1-oxo-1-[(2,2,4,4-tetramethylthietan-3-yl)amino]propan-2-yl]amino]butanoic acid;pentahydrate Chemical compound O.O.O.O.O.OC(=O)C[C@H](N)C(=O)N[C@H](C)C(=O)NC1C(C)(C)SC1(C)C.OC(=O)C[C@H](N)C(=O)N[C@H](C)C(=O)NC1C(C)(C)SC1(C)C NUFKRGBSZPCGQB-FLBSXDLDSA-N 0.000 description 1
YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 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
BZZXQZOBAUXLHZ-UHFFFAOYSA-N (c-methylsulfanylcarbonimidoyl)azanium;sulfate Chemical compound CSC(N)=N.CSC(N)=N.OS(O)(=O)=O BZZXQZOBAUXLHZ-UHFFFAOYSA-N 0.000 description 1
IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
OJYOOHSQOIDDOO-UHFFFAOYSA-N 1-(9h-fluoren-9-ylmethoxycarbonyl)piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 OJYOOHSQOIDDOO-UHFFFAOYSA-N 0.000 description 1
SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 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
VFDVBQMLLPCXNP-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoyl chloride Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(Cl)=O VFDVBQMLLPCXNP-UHFFFAOYSA-N 0.000 description 1
BAZVFQBTJPBRTJ-UHFFFAOYSA-N 2-chloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1 BAZVFQBTJPBRTJ-UHFFFAOYSA-N 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 description 1
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
VDXSUEUQROFWMB-UHFFFAOYSA-N 3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl chloride Chemical compound CC1=CC=CC(C(Cl)=O)=C1C1=CC=C(C(F)(F)F)C=C1 VDXSUEUQROFWMB-UHFFFAOYSA-N 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
KBIWNQVZKHSHTI-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,4-diamine;oxalic acid Chemical compound OC(=O)C(O)=O.CN(C)C1=CC=C(N)C=C1 KBIWNQVZKHSHTI-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
208000010470 Ageusia Diseases 0.000 description 1
239000004377 Alitame Substances 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
101150102415 Apob gene Proteins 0.000 description 1
108010011485 Aspartame Proteins 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
241000167854 Bourreria succulenta Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
238000007125 Buchwald synthesis reaction Methods 0.000 description 1
239000004322 Butylated hydroxytoluene Substances 0.000 description 1
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229940127328 Cholesterol Synthesis Inhibitors Drugs 0.000 description 1
229920001268 Cholestyramine Polymers 0.000 description 1
KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
229920002911 Colestipol Polymers 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-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
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
241000792859 Enema Species 0.000 description 1
VWFJDQUYCIWHTN-UHFFFAOYSA-N Farnesyl pyrophosphate Natural products CC(C)=CCCC(C)=CCCC(C)=CCOP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-UHFFFAOYSA-N 0.000 description 1
108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
235000016623 Fragaria vesca Nutrition 0.000 description 1
240000009088 Fragaria x ananassa Species 0.000 description 1
235000011363 Fragaria x ananassa Nutrition 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
229930091371 Fructose Natural products 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
230000005526 G1 to G0 transition Effects 0.000 description 1
HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
229940122498 Gene expression inhibitor Drugs 0.000 description 1
101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
108010028554 LDL Cholesterol Proteins 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
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-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
229930195725 Mannitol Natural products 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
108050004114 Monellin Proteins 0.000 description 1
125000000815 N-oxide group Chemical group 0.000 description 1
206010029897 Obsessive thoughts Diseases 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
241001494479 Pecora Species 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
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
240000001890 Ribes hudsonianum Species 0.000 description 1
235000016954 Ribes hudsonianum Nutrition 0.000 description 1
235000001466 Ribes nigrum Nutrition 0.000 description 1
235000011034 Rubus glaucus Nutrition 0.000 description 1
244000235659 Rubus idaeus Species 0.000 description 1
235000009122 Rubus idaeus Nutrition 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
229920002472 Starch Polymers 0.000 description 1
102000001494 Sterol O-Acyltransferase Human genes 0.000 description 1
108010054082 Sterol O-acyltransferase Proteins 0.000 description 1
UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
239000004376 Sucralose Substances 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
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 1
BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
208000004622 abetalipoproteinemia Diseases 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
235000010358 acesulfame potassium Nutrition 0.000 description 1
229960004998 acesulfame potassium Drugs 0.000 description 1
239000000619 acesulfame-K Substances 0.000 description 1
OJFDKHTZOUZBOS-CITAKDKDSA-N acetoacetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 OJFDKHTZOUZBOS-CITAKDKDSA-N 0.000 description 1
229940100228 acetyl coenzyme a Drugs 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
235000019666 ageusia Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
235000019409 alitame Nutrition 0.000 description 1
108010009985 alitame Proteins 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
239000008168 almond oil Substances 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
235000012211 aluminium silicate Nutrition 0.000 description 1
229960004909 aminosalicylic acid Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
230000000923 atherogenic effect Effects 0.000 description 1
230000003143 atherosclerotic effect Effects 0.000 description 1
229960005370 atorvastatin Drugs 0.000 description 1
230000009286 beneficial effect Effects 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
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
239000003613 bile acid Substances 0.000 description 1
229920000080 bile acid sequestrant Polymers 0.000 description 1
229940096699 bile acid sequestrants Drugs 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000036983 biotransformation Effects 0.000 description 1
235000015895 biscuits Nutrition 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000012267 brine Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
229940095259 butylated hydroxytoluene Drugs 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
NNOYLBKZPCUCQT-UHFFFAOYSA-L calcium;1,1-dioxo-1,2-benzothiazol-3-olate;heptahydrate Chemical compound O.O.O.O.O.O.O.[Ca+2].C1=CC=C2C([O-])=NS(=O)(=O)C2=C1.C1=CC=C2C([O-])=NS(=O)(=O)C2=C1 NNOYLBKZPCUCQT-UHFFFAOYSA-L 0.000 description 1
235000013736 caramel Nutrition 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000001364 causal effect Effects 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
230000008859 change Effects 0.000 description 1
235000019693 cherries Nutrition 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
230000001906 cholesterol absorption Effects 0.000 description 1
229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 description 1
229960002174 ciprofibrate Drugs 0.000 description 1
KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
235000015165 citric acid Nutrition 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
229960001214 clofibrate Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
229960002604 colestipol Drugs 0.000 description 1
GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000000356 contaminant Substances 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
239000008120 corn starch Substances 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000007547 defect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
229940009976 deoxycholate Drugs 0.000 description 1
229960003964 deoxycholic acid Drugs 0.000 description 1
238000011161 development Methods 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction 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
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
WIKWPYFFKLRAIF-UHFFFAOYSA-N ethyl 2-[1-(4-aminophenyl)piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C1=CC=C(N)C=C1 WIKWPYFFKLRAIF-UHFFFAOYSA-N 0.000 description 1
USGOGXZJPANEHE-UHFFFAOYSA-N ethyl 2-[1-(4-nitrophenyl)piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C1=CC=C([N+]([O-])=O)C=C1 USGOGXZJPANEHE-UHFFFAOYSA-N 0.000 description 1
WZDWMXDXMFMTCA-UHFFFAOYSA-N ethyl 2-[1-(5-aminopyridin-2-yl)piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C1=CC=C(N)C=N1 WZDWMXDXMFMTCA-UHFFFAOYSA-N 0.000 description 1
XDHMVRQWCNZAKR-UHFFFAOYSA-N ethyl 2-[1-(5-aminopyrimidin-2-yl)piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C1=NC=C(N)C=N1 XDHMVRQWCNZAKR-UHFFFAOYSA-N 0.000 description 1
WJLRLKHGOFHNHW-UHFFFAOYSA-N ethyl 2-[1-(5-nitropyridin-2-yl)piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C1=CC=C([N+]([O-])=O)C=N1 WJLRLKHGOFHNHW-UHFFFAOYSA-N 0.000 description 1
LISMBJQYNHPDCT-UHFFFAOYSA-N ethyl 2-[1-(5-nitropyrimidin-2-yl)piperidin-4-yl]acetate Chemical compound C1CC(CC(=O)OCC)CCN1C1=NC=C([N+]([O-])=O)C=N1 LISMBJQYNHPDCT-UHFFFAOYSA-N 0.000 description 1
RBESFTPUTXOFCD-UHFFFAOYSA-N ethyl 2-piperidin-4-ylacetate;hydrochloride Chemical compound Cl.CCOC(=O)CC1CCNCC1 RBESFTPUTXOFCD-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 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
229960002297 fenofibrate Drugs 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000013020 final formulation Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
229960003765 fluvastatin Drugs 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000008369 fruit flavor Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
239000007789 gas Substances 0.000 description 1
229960003627 gemfibrozil Drugs 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
229960004275 glycolic acid Drugs 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
230000009931 harmful effect Effects 0.000 description 1
230000005802 health problem Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
210000003494 hepatocyte Anatomy 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
235000012907 honey Nutrition 0.000 description 1
102000045903 human LPA Human genes 0.000 description 1
239000003906 humectant Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
208000006575 hypertriglyceridemia Diseases 0.000 description 1
239000012133 immunoprecipitate Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
210000002490 intestinal epithelial cell Anatomy 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000000905 isomalt Substances 0.000 description 1
235000010439 isomalt Nutrition 0.000 description 1
HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960000448 lactic acid Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
108010052968 leupeptin Proteins 0.000 description 1
230000008604 lipoprotein metabolism Effects 0.000 description 1
239000002502 liposome Substances 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
229960004844 lovastatin Drugs 0.000 description 1
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
101150009970 mtp gene Proteins 0.000 description 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229920002113 octoxynol Polymers 0.000 description 1
239000002674 ointment Substances 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
229940116315 oxalic acid Drugs 0.000 description 1
150000002921 oxetanes Chemical class 0.000 description 1
150000002941 palladium compounds Chemical class 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
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920001592 potato starch Polymers 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
238000011533 pre-incubation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000002028 premature Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
238000011002 quantification Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229960002855 simvastatin Drugs 0.000 description 1
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229960001462 sodium cyclamate Drugs 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000000527 sonication Methods 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical class C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
229940031439 squalene Drugs 0.000 description 1
TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
229940013618 stevioside Drugs 0.000 description 1
OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
235000019202 steviosides Nutrition 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
235000019408 sucralose Nutrition 0.000 description 1
BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
238000005199 ultracentrifugation Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
150000003952 β-lactams Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Child & Adolescent Psychology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)

NO20050563A 2002-08-12 2005-01-31 N-aryl-piperidinsubstituerte bifenylkarboksamider som inhibitorer av apolipoprotein B-sekresjon NO329308B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP02078309		2002-08-12
PCT/EP2003/008694 WO2004017969A1 (en)	2002-08-12	2003-08-05	N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b secretion

Publications (2)

Publication Number	Publication Date
NO20050563L NO20050563L (no)	2005-01-31
NO329308B1 true NO329308B1 (no)	2010-09-27

Family

ID=31896911

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20050563A NO329308B1 (no)	2002-08-12	2005-01-31	N-aryl-piperidinsubstituerte bifenylkarboksamider som inhibitorer av apolipoprotein B-sekresjon

Country Status (31)

Country	Link
US (2)	US20060040989A1 (es)
EP (1)	EP1536796B1 (es)
JP (1)	JP4559856B2 (es)
KR (1)	KR101052204B1 (es)
CN (3)	CN100366252C (es)
AR (1)	AR040968A1 (es)
AT (1)	ATE385796T1 (es)
AU (1)	AU2003250215B2 (es)
BR (1)	BR0313377A (es)
CA (1)	CA2494208C (es)
CY (1)	CY1107945T1 (es)
DE (1)	DE60319097T2 (es)
DK (1)	DK1536796T3 (es)
EA (1)	EA008061B1 (es)
EG (1)	EG25699A (es)
ES (1)	ES2301873T3 (es)
HR (1)	HRP20050103B1 (es)
IL (1)	IL166795A (es)
IS (1)	IS2726B (es)
MX (1)	MXPA05001712A (es)
MY (1)	MY136632A (es)
NO (1)	NO329308B1 (es)
NZ (1)	NZ538680A (es)
PA (1)	PA8579901A1 (es)
PL (1)	PL212405B1 (es)
PT (1)	PT1536796E (es)
SI (1)	SI1536796T1 (es)
TW (1)	TWI342775B (es)
UA (1)	UA79300C2 (es)
WO (1)	WO2004017969A1 (es)
ZA (1)	ZA200501225B (es)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA83510C2 (en) *	2003-12-09	2008-07-25	Янссен Фармацевтика Н.В.	N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b
FR2883000B1 (fr) *	2005-03-14	2007-06-01	Merck Sante Soc Par Actions Si	Derives de trifluoromethylbenzamide et leurs utilisations en therapeutique
US7754717B2 (en)	2005-08-15	2010-07-13	Amgen Inc.	Bis-aryl amide compounds and methods of use
WO2007053436A1 (en)	2005-10-31	2007-05-10	Janssen Pharmaceutica N.V.	Substituted piperazines and piperidines as modulators of the neuropeptide y2 receptor
CA2648132C (en)	2006-04-03	2019-05-28	Santaris Pharma A/S	Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
EP2666859B1 (en) *	2006-04-03	2019-01-02	Roche Innovation Center Copenhagen A/S	Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
WO2008100423A1 (en) *	2007-02-09	2008-08-21	Sirtris Pharmaceuticals, Inc.	Gut microsomal triglyceride transport protein inhibitors
CA2681406A1 (en) *	2007-03-22	2008-09-25	Santaris Pharma A/S	Rna antagonist compounds for the inhibition of apo-b100 expression
WO2008113832A2 (en) *	2007-03-22	2008-09-25	Santaris Pharma A/S	SHORT RNA ANTAGONIST COMPOUNDS FOR THE MODULATION OF TARGET mRNA
WO2009027527A2 (en) *	2007-08-30	2009-03-05	Santaris Pharma A/S	Rna antagonist compounds for the modulation of fabp4/ap2
ES2360929T3 (es) *	2007-09-20	2011-06-10	Amgen Inc.	Derivados del ácido 1-(4-(4-bencilbenzamido)-bencil)azetidin-3-carboxílico y compuestos relacionados como moduladores del receptor s1p para el tratamiento de trastornos inmunitarios.
EP2623599B1 (en) *	2007-10-04	2019-01-02	Roche Innovation Center Copenhagen A/S	Micromirs
EP2268811A1 (en) *	2008-03-07	2011-01-05	Santaris Pharma A/S	Pharmaceutical compositions for treatment of microrna related diseases
ES2541442T3 (es)	2008-08-01	2015-07-20	Roche Innovation Center Copenhagen A/S	Modulación mediada por microARN de factores estimulantes de colonias
ES2599979T3 (es) *	2009-04-24	2017-02-06	Roche Innovation Center Copenhagen A/S	Composiciones farmacéuticas para el tratamiento de pacientes de VHC que no responden al interferón
US8563528B2 (en)	2009-07-21	2013-10-22	Santaris Pharma A/S	Antisense oligomers targeting PCSK9
ES2770667T3 (es)	2013-06-27	2020-07-02	Roche Innovation Ct Copenhagen As	Oligómeros antisentido y conjugados que se dirigen a PCSK9
US9790237B2 (en)	2014-06-16	2017-10-17	Johnson Matthey Public Limited Company	Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4231938A (en) *	1979-06-15	1980-11-04	Merck & Co., Inc.	Hypocholesteremic fermentation products and process of preparation
US4444784A (en) *	1980-08-05	1984-04-24	Merck & Co., Inc.	Antihypercholesterolemic compounds
MX7065E (es) *	1980-06-06	1987-04-10	Sankyo Co	Un procedimiento microbiologico para preparar derivados de ml-236b
US4739073A (en) *	1983-11-04	1988-04-19	Sandoz Pharmaceuticals Corp.	Intermediates in the synthesis of indole analogs of mevalonolactone and derivatives thereof
US4647576A (en) *	1984-09-24	1987-03-03	Warner-Lambert Company	Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of cholesterol synthesis
US4847271A (en) *	1986-01-27	1989-07-11	Merck & Co., Inc.	Antihypercholesterolemic β-lactones
US5041432A (en) *	1987-01-30	1991-08-20	E. I. Du Pont De Nemours And Company	Steroid derivatives useful as hypocholesterolemics
US5064856A (en) *	1989-07-31	1991-11-12	Merck & Co., Inc.	Novel hmg-coa synthase inhibitors
US5120729A (en) *	1990-06-20	1992-06-09	Merck & Co., Inc.	Beta-lactams as antihypercholesterolemics
US5177080A (en)	1990-12-14	1993-01-05	Bayer Aktiengesellschaft	Substituted pyridyl-dihydroxy-heptenoic acid and its salts
EP0618803A4 (en) *	1991-12-19	1995-03-22	Southwest Found Biomed Res	POLYPEPTIDE INHIBITING PROTEIN TRANSFER TO CHOLESTERYL ESTERS, ANTIBODIES AGAINST SYNTHETIC POLYPEPTIDE AND ANTI-ATHEROSCLEROSIS PROPHYLACTIC AND THERAPEUTIC TREATMENTS.
DE69332792T2 (de)	1992-04-20	2004-01-15	Takeda Chemical Industries Ltd	4,1-Benzoxazepinderivate als Squalen-Synthetase Inhibitoren und ihre Verwendung zur Behandlung von Hypercholesterämie und als Fungizide
AU678503B2 (en)	1993-09-24	1997-05-29	Takeda Chemical Industries Ltd.	Condensed heterocyclic compounds and their use as squalene synthetase inhibitors
EP0784612A1 (en)	1994-10-04	1997-07-23	Fujisawa Pharmaceutical Co., Ltd.	Urea derivatives and their use as acat-inhibitors
US5510379A (en) *	1994-12-19	1996-04-23	Warner-Lambert Company	Sulfonate ACAT inhibitors
GB9504066D0 (en)	1995-03-01	1995-04-19	Pharmacia Spa	Phosphate derivatives of ureas and thioureas
US6147214A (en) *	1997-04-18	2000-11-14	Pfizer Inc	Process and intermediates for the preparation of 4'-trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide
GB9826412D0 (en) *	1998-12-03	1999-01-27	Glaxo Group Ltd	Chemical compounds
GB0013383D0 (en) *	2000-06-01	2000-07-26	Glaxo Group Ltd	Therapeutic benzamide derivatives
GB0013378D0 (en) *	2000-06-01	2000-07-26	Glaxo Group Ltd	Use of therapeutic benzamide derivatives
JO2654B1 (en) *	2000-09-04	2012-06-17	شركة جانسين فارماسوتيكا ان. في	Multiple aryl caroxa amides are useful as lipid - lowering agents
JO2409B1 (en) *	2000-11-21	2007-06-17	شركة جانسين فارماسوتيكا ان. في	Second-phenyl carboxy amides are useful as lipid-lowering agents
JO2390B1 (en) *	2001-04-06	2007-06-17	شركة جانسين فارماسوتيكا ان. في	Diphenylcarboxamides act as lipid-lowering agents
US6884750B2 (en) *	2001-06-27	2005-04-26	Rs Tech Corp.	Chiral salen catalyst and methods for the preparation of chiral compounds from racemic epoxides by using new catalyst
GB0129015D0 (en) *	2001-12-04	2002-01-23	Glaxo Group Ltd	Compounds

2003
- 2003-05-08 UA UAA200501990A patent/UA79300C2/uk unknown
- 2003-08-02 EG EG2003080749A patent/EG25699A/xx active
- 2003-08-05 BR BR0313377-0A patent/BR0313377A/pt not_active Application Discontinuation
- 2003-08-05 EP EP03792260A patent/EP1536796B1/en not_active Expired - Lifetime
- 2003-08-05 MX MXPA05001712A patent/MXPA05001712A/es active IP Right Grant
- 2003-08-05 PT PT03792260T patent/PT1536796E/pt unknown
- 2003-08-05 CA CA2494208A patent/CA2494208C/en not_active Expired - Fee Related
- 2003-08-05 EA EA200500348A patent/EA008061B1/ru not_active IP Right Cessation
- 2003-08-05 SI SI200331203T patent/SI1536796T1/sl unknown
- 2003-08-05 DK DK03792260T patent/DK1536796T3/da active
- 2003-08-05 NZ NZ538680A patent/NZ538680A/en not_active IP Right Cessation
- 2003-08-05 CN CNB03818592XA patent/CN100366252C/zh not_active Expired - Fee Related
- 2003-08-05 WO PCT/EP2003/008694 patent/WO2004017969A1/en not_active Ceased
- 2003-08-05 AT AT03792260T patent/ATE385796T1/de active
- 2003-08-05 US US10/524,051 patent/US20060040989A1/en not_active Abandoned
- 2003-08-05 JP JP2004530089A patent/JP4559856B2/ja not_active Expired - Fee Related
- 2003-08-05 HR HRP20050103AA patent/HRP20050103B1/hr not_active IP Right Cessation
- 2003-08-05 ES ES03792260T patent/ES2301873T3/es not_active Expired - Lifetime
- 2003-08-05 DE DE60319097T patent/DE60319097T2/de not_active Expired - Lifetime
- 2003-08-05 CN CN2007101866730A patent/CN101165052B/zh not_active Expired - Fee Related
- 2003-08-05 KR KR1020057000829A patent/KR101052204B1/ko not_active Expired - Fee Related
- 2003-08-05 AU AU2003250215A patent/AU2003250215B2/en not_active Ceased
- 2003-08-05 PL PL373379A patent/PL212405B1/pl unknown
- 2003-08-05 CN CNA2007101866745A patent/CN101165053A/zh active Pending
- 2003-08-07 PA PA20038579901A patent/PA8579901A1/es unknown
- 2003-08-08 MY MYPI20033022A patent/MY136632A/en unknown
- 2003-08-11 TW TW092121938A patent/TWI342775B/zh not_active IP Right Cessation
- 2003-08-11 AR ARP030102901A patent/AR040968A1/es not_active Application Discontinuation
2004
- 2004-12-29 IS IS7622A patent/IS2726B/is unknown
2005
- 2005-01-31 NO NO20050563A patent/NO329308B1/no not_active IP Right Cessation
- 2005-02-10 IL IL166795A patent/IL166795A/en unknown
- 2005-02-10 ZA ZA200501225A patent/ZA200501225B/en unknown
2008
- 2008-05-13 CY CY20081100504T patent/CY1107945T1/el unknown
2009
- 2009-01-09 US US12/351,385 patent/US8258304B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CY1107945T1 (el)	2013-09-04
IS7622A (is)	2004-12-29
SI1536796T1 (sl)	2008-08-31
CN1674900A (zh)	2005-09-28
US20060040989A1 (en)	2006-02-23
NZ538680A (en)	2006-01-27
PL373379A1 (en)	2005-08-22
MXPA05001712A (es)	2005-04-19
DK1536796T3 (da)	2008-06-09
IL166795A0 (en)	2006-01-15
KR20050026483A (ko)	2005-03-15
PL212405B1 (pl)	2012-09-28
IS2726B (is)	2011-03-15
UA79300C2 (en)	2007-06-11
ATE385796T1 (de)	2008-03-15
PA8579901A1 (es)	2005-03-03
HRP20050103B1 (hr)	2013-09-30
CN100366252C (zh)	2008-02-06
US8258304B2 (en)	2012-09-04
WO2004017969A1 (en)	2004-03-04
EA008061B1 (ru)	2007-02-27
MY136632A (en)	2008-11-28
AU2003250215B2 (en)	2009-01-22
ES2301873T3 (es)	2008-07-01
DE60319097D1 (de)	2008-03-27
DE60319097T2 (de)	2009-06-04
TWI342775B (en)	2011-06-01
AR040968A1 (es)	2005-04-27
CA2494208C (en)	2011-05-10
HK1083451A1 (en)	2006-07-07
EP1536796B1 (en)	2008-02-13
HRP20050103A2 (en)	2006-09-30
EA200500348A1 (ru)	2005-08-25
JP4559856B2 (ja)	2010-10-13
ZA200501225B (en)	2006-07-26
CN101165053A (zh)	2008-04-23
IL166795A (en)	2010-11-30
NO20050563L (no)	2005-01-31
CN101165052B (zh)	2012-04-18
TW200412954A (en)	2004-08-01
BR0313377A (pt)	2005-07-12
KR101052204B1 (ko)	2011-07-29
CN101165052A (zh)	2008-04-23
EP1536796A1 (en)	2005-06-08
JP2006500371A (ja)	2006-01-05
PT1536796E (pt)	2008-05-13
CA2494208A1 (en)	2004-03-04
EG25699A (en)	2012-05-22
US20090156623A1 (en)	2009-06-18
AU2003250215A1 (en)	2004-03-11

Legal Events

Date	Code	Title	Description
2019-03-25	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
US8258304B2 (en)	2012-09-04	N-aryl piperidine substituted biphenylcarboxamides
EP1339685B1 (en)	2006-11-02	Biphenylcarboxamides useful as lipid lowering agents
AU2007310925A1 (en)	2008-05-02	Piperidine or piperazine substituted tetrahydro-naphthalene-1-carboxylic acid MTP inhibiting compounds
AU2002219115A1 (en)	2002-08-08	Biphenylcarboxamides useful as lipid lowering agents
IL158252A (en)	2011-01-31	Pharmaceutical compounds for the preparation of biphenylcarboxamides for fat reduction
KR101125120B1 (ko)	2012-03-21	아포리포프로테인 ｂ 저해제로서의 ｎ-아릴 피페리딘치환된 비페닐카복사미드
JP5525261B2 (ja)	2014-06-18	Ｍｔｐ阻害性テトラヒドロ−ナフタレン−１−カルボン酸誘導体
HK1083451B (en)	2008-11-28	N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b secretion
HK1100559B (en)	2010-05-14	N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b
HK1137011B (en)	2013-10-11	Mtp inhibiting tetrahydro-naphthalene-1-carboxylic acid derivatives
MXPA06006507A (es)	2006-10-17	Bifenilcarboxamidas sustituidas con n-aril piperidina como inhibidores de apolipoproteina b